The Chemistry Spark Presents

Top Name Reactions And

Rearrangements For CSIR
NET, IIT-JAM, GATE & JEE
Exams

(Detailed Mechanism, Exam-Tips,

Key Points, Examples)

Sudhir Nama
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 Content

Section A – Named Reactions

1. Aldol Condensation
2. Baeyer–Villiger Oxidation
3. Beckmann Rearrangement (noted both as named reaction and
rearrangement)
4. Birch Reduction
5. Cannizzaro Reaction
6. Claisen Condensation
7. Claisen Rearrangement
8. Cope Rearrangement
9. Curtius Rearrangement
10. Dakin Reaction
11. Diazotization Reaction
12. Diels–Alder Reaction
13. Doebner Reaction
14. Ene Reaction
15. Favorskii Rearrangement
16. Fischer Indole Synthesis
17. Friedel–Crafts Alkylation/Acylation
18. Gabriel Synthesis
19. Gattermann–Koch Formylation
20. Gomberg Reaction
21. Grignard Reaction
22. Hell–Volhard–Zelinsky Reaction
23. Hofmann Rearrangement (Degradation)
24. Hunsdiecker Reaction
25. Knoevenagel Condensation
26. Kolbe Electrolysis
27. Mannich Reaction
28. Michael Addition
29. Oppenauer Oxidation
30. Perkin Reaction
31. Reformatsky Reaction
32. Reimer–Tiemann Reaction
33. Rosenmund Reduction
34. Sandmeyer Reaction
35. Schmidt Reaction
36. Skraup Synthesis
37. Staudinger Reaction
38. Stevens Rearrangement
39. Suzuki Coupling
40. Swern Oxidation
41. Ullmann Coupling
42. Vilsmeier–Haack Formylation
 43. Williamson Ether Synthesis
44. Wittig Reaction
45. Wohl–Ziegler Bromination
46. Wolf–Kishner Reduction
47. Corey–Fuchs Reaction
48. Chan–Lam Coupling
49. Sonogashira Coupling
50. Corey–Chaykovsky Reaction
51. Meerwein Arylation
52. Buchwald–Hartwig Amination
53. Negishi Coupling

Section B - Rearrangements

1. Baeyer–Villiger Rearrangement
2. Beckmann Rearrangement
3. Benzil–Benzilic Acid Rearrangement
4. Claisen Rearrangement
5. Cope Rearrangement
6. Curtius Rearrangement
7. Pinacol–Pinacolone Rearrangement
8. Stevens Rearrangement
9. Schmidt Rearrangement
10. Tiffeneau–Demjanov Rearrangement
11. Wolff Rearrangement
12. Wagner–Meerwein Rearrangement
13. Favorskii Rearrangement
14. Fries Rearrangement
15. Neber Rearrangement
16. Lossen Rearrangement
17. Hofmann Rearrangement
18. Beckmann Fragmentation (special cases)
19. Benzidine Rearrangement
20. Demjanov Rearrangement
21. Bouvet Rearrangement
22. Sommelet Rearrangement
23. Payne Rearrangement
24. Overman Rearrangement
25. Johnson–Claisen Rearrangement
26. Ireland–Claisen Rearrangement
27. Eschenmoser–Claisen Rearrangement
28. Mumm Rearrangement
29. Bamberger Rearrangement
30. Boekelheide Rearrangement
31. Orton Rearrangement
32. Brook Rearrangement
33. Carroll Rearrangement
34. Barton Rearrangement
35. von Richter Rearrangement
36. Hunsdiecker Rearrangement (sometimes debated)
37. Winstein Rearrangement
38. Willgerodt Rearrangement
39. Wohl Rearrangement
40. Wharton Rearrangement
41. Pummerer Rearrangement
42. Smiles Rearrangement
43. Schenck Rearrangement
44. Hofmann–Martius Rearrangement
45. Neumann–Kopp Rearrangement
46. Mumm Rearrangement (O N acyl shift, included for completeness)
47. Bamberger (detailed again with nitrosobenzene)
48. Boekelheide (oxidative N-oxide rearrangement)
49. Wohler Rearrangement
50. Benzidine Rearrangement (detailed in aromatic amines)
51. Beckmann–Bergmann Rearrangement
52. Oppenauer Rearrangement (oxidative shift)
53. Nametkin Rearrangement
54. Neber Rearrangement (oxime α-aminoketone, already covered but
included)
55. Eschenmoser–Tanabe Rearrangement
56. Tiemann Rearrangement
57. Cornforth Rearrangement
58. Boulton–Katritzky Rearrangement
59. Bamberger Rearrangement (again, classical nitroso migration)
60. Willgerodt–Kindler Rearrangement
 Named Organic Reactions

1. Aldol Condensation

Introduction
Aldol condensation is an important C–C bond forming reaction in organic chemistry. It
involves the enolate ion of an aldehyde or ketone attacking another carbonyl compound,
giving a β-hydroxy carbonyl compound, which on dehydration yields an α,β-unsaturated
carbonyl compound.

General Reaction
(Acetaldehyde gives crotonaldehyde)

Mechanism (Stepwise)
Enolate Formation
o A base (OH⁻ or alkoxide) abstracts an α-hydrogen from the aldehyde/ketone.
o Forms an enolate ion (resonance-stabilized).

Nucleophilic Attack
 o The enolate ion attacks the carbonyl carbon of another molecule of
aldehyde/ketone.
o Forms an alkoxide intermediate.
Protonation
o The alkoxide abstracts a proton from water, giving a β-hydroxy aldehyde
(aldol).
Dehydration (on heating)
o Loss of water forms α,β-unsaturated carbonyl compound.

Reaction Steps :

Key Points
 Requires α-Hydrogen Methanal (HCHO) does not undergo aldol.

 Crossed Aldol possible if both partners have α-H.

 Industrial example: Synthesis of pentaerythritol (used in explosives, resins).

Exam Tips
 Remember: “Aldol = Aldehyde + Alcohol” (β-hydroxy product).

 Frequently asked in IIT-JEE & NET with dehydration step.

 Identify α-hydrogen – crucial check in exam questions.

2. Baeyer–Villiger Oxidation

Introduction
Baeyer–Villiger oxidation is the oxidation of ketones to esters (or cyclic ketones to
lactones) using peracids (like MCPBA, peracetic acid).
 General Reaction

Example: Cyclohexanone ε-Caprolactone

Mechanism
Nucleophilic attack of carbonyl oxygen on peracid forms Criegee intermediate.
Rearrangement migration of one alkyl/aryl group from carbon to oxygen.
Breakdown ester or lactone + carboxylic acid.

Step 1

Step 2

Key Points
 Migratory aptitude order: tertiary alkyl > cyclohexyl > secondary alkyl ≈ phenyl >
primary alkyl > methyl.

 Used in nylon-6 synthesis (ε-caprolactone precursor).

 Exam Tips
 Migration step is selective – expected question in CSIR NET.

 Remember “BVO = Baeyer–Villiger Oxidation = Ketone Ester/Lactone”.

3. Beckmann Rearrangement

Introduction
Beckmann rearrangement converts oximes into amides (or lactams, if cyclic).

General Reaction
 Mechanism
Protonation of oxime hydroxyl group.
Loss of water formation of nitrenium ion.
1,2-Shift (migration) of group anti to –OH across nitrogen.
Rearranged cation reacts with water gives amide/lactam.

Key Points
 Anti-group migration rule: the group anti to –OH migrates.

 Industrial application: nylon-6 manufacture.

Exam Tips
 Always check anti-orientation in exam problems.

 Compare with Beckmann fragmentation (different pathway).

4. Birch Reduction

Introduction
Birch reduction is the reduction of aromatic rings to 1,4-cyclohexadienes using alkali
metals (Na, Li, K) in liquid ammonia with an alcohol (ROH).
General Reaction
 Mechanism
Electron transfer from Na to aromatic ring radical anion.
Protonation by alcohol.
Second electron transfer carbanion.
Final protonation 1,4-diene product.

General Arenes Mechanism :

Anisole Reaction Mechanism :

Key Points
 Electron-withdrawing groups reduction at ortho/para positions.

 Electron-donating groups reduction at meta positions.

 Used in partial reduction of aromatic rings (synthetic intermediates).

 Exam Tips
 “Birch = Benzene Breaker” benzene loses aromaticity.

 Location of reduction depends on substituents.

5. Cannizzaro Reaction

Introduction
Cannizzaro reaction is the disproportionation of non-enolizable aldehydes (without α-H)
in presence of strong base, forming one molecule of alcohol and one molecule of
carboxylate salt.

General Reaction

Mechanism
Nucleophilic attack of hydroxide on aldehyde carbonyl carbon.
Hydride transfer from one aldehyde to another.
Formation of carboxylate + alcohol.
Benzaldehyde Mechanism :

Key Points
 Requires no α-Hydrogen (distinguishes from Aldol).

 Common aldehydes: formaldehyde, benzaldehyde.

 Crossed Cannizzaro also possible (e.g., HCHO + benzaldehyde).

Exam Tips
 Identify aldehydes with no α-H in multiple-choice questions.

 Formaldehyde always oxidized to formate in crossed Cannizzaro.

6. Claisen Condensation
Introduction
Claisen condensation is the base-catalyzed condensation of two esters (or one ester +
carbonyl compound) to form a β-keto ester or a β-diketone.

General Reaction (Ethyl acetate Ethyl acetoacetate)

Mechanism
Enolate Formation: Base (alkoxide) abstracts α-hydrogen of ester enolate.
Nucleophilic Attack: Enolate attacks carbonyl carbon of another ester molecule.
Tetrahedral Intermediate forms alkoxide leaves.
Proton transfer β-keto ester.
 Key Points
 Strong base required (same alkoxide as ester group to avoid transesterification).

 Reaction is irreversible because β-keto ester is resonance stabilized.

 Intramolecular version Dieckmann condensation.

Exam Tips
 Aldol = aldehyde/ketone, Claisen = ester.

 Products are β-keto esters used in malonic ester & acetoacetic ester synthesis.

7. Claisen Rearrangement
Introduction
Claisen rearrangement is a [3,3]-sigmatropic rearrangement where an allyl vinyl ether
rearranges to a γ,δ-unsaturated carbonyl compound.

General Reaction
Mechanism
 Concerted pericyclic reaction involving a six-membered cyclic transition state.

 Bond shifts occur simultaneously (suprafacial shift).

Key Points
 Thermal rearrangement, no catalyst needed.

 Evidence of pericyclic nature: stereospecific, orbital symmetry controlled.

 Aromatic Claisen rearrangement phenol derivatives.

Exam Tips
 Typical sigmatropic rearrangement asked in CSIR-NET.

 Remember [3,3] three atoms shift on both sides.

8. Cope Rearrangement

Introduction
Cope rearrangement is a [3,3]-sigmatropic rearrangement of 1,5-dienes into an isomeric
1,5-diene.

General Reaction

Mechanism
 Concerted reaction via a six-membered cyclic transition state.

 No external reagent needed (thermal process).

Key Points
 Example of pericyclic reaction controlled by Woodward–Hoffmann rules.

 Variants: Oxy-Cope (OH-substituted dienes), Anionic Oxy-Cope (much faster).

Exam Tips
 Don’t confuse with Claisen rearrangement (has oxygen).

 Useful to demonstrate orbital symmetry rules in exams.

9. Curtius Rearrangement

Introduction
Curtius rearrangement is the thermal decomposition of acyl azides to form isocyanates,
which can be further hydrolyzed to amines.

General Reaction

Mechanism
Acyl azide formation (from acyl chloride + NaN₃ ).
Thermal decomposition nitrene intermediate.
1,2-Shift of R group with loss of N₂ isocyanate.
Hydrolysis primary amine.

Key Points
 Similar to Hofmann, Lossen, Schmidt rearrangements.

 Key step = migration of acyl group with N₂ elimination.

 Industrial use: urethane & amine synthesis.

Exam Tips
 Always forms amine with one less carbon than parent acid.

 Compare with Hofmann rearrangement (amide amine).

10. Dakin Reaction

Introduction
Dakin reaction is the oxidation of ortho- or para-hydroxy aromatic aldehydes/ketones
with hydrogen peroxide (H₂ O₂ ) in alkaline medium, producing hydroxyphenols.

General Reaction

Example: p-Hydroxybenzaldehyde Hydroquinone

Mechanism
Peroxide anion attack on carbonyl carbon.
Rearrangement migration of aryl group to oxygen.
Release of formic acid (if aldehyde) or acetic acid (if ketone).
Product = di-hydroxy aromatic compound.

Key Points
 Requires activated aromatic aldehyde/ketone (–OH group present).

 Gives hydroquinone, catechol, resorcinol derivatives.

 Important in industrial dye & pharmaceutical synthesis.

Exam Tips
 “Dakin = Di-hydroxy phenol” easy mnemonic.

 Often asked as name-reaction product question.

11. Diazotization Reaction

Introduction
Diazotization is the conversion of primary aromatic amines into diazonium salts (Ar–
N₂ ⁺ X⁻ ) by treatment with nitrous acid (HNO₂ ) at low temperature (0–5 °C).

General Reaction

Mechanism

Generation of Nitrous Acid:

Formation of nitrosonium ion (NO⁺ )
Attack of amine: –NH₂ group of aniline reacts with NO⁺ N-nitrosamine.
Protonation & dehydration diazonium ion (Ar–N₂ ⁺ ).
 Key Points
 Temperature critical above 5 °C, diazonium decomposes.

 Aliphatic amines form unstable diazonium salts not isolable.

 Key precursor for azo dyes, Sandmeyer reactions, coupling reactions.

Exam Tips
 CSIR often asks: “Identify condition for stable diazonium salt formation.”

 Remember: Only aromatic diazonium salts are stable at low temperature.

 Mnemonic: “Diazo = Two nitrogen atoms together.”

12. Diels–Alder Reaction

Introduction
The Diels–Alder reaction is a [4+2] cycloaddition between a conjugated diene and a
dienophile, producing a cyclohexene derivative.

General Reaction
 Mechanism
 Concerted pericyclic reaction via a cyclic transition state.

 Diene (HOMO) overlaps with dienophile (LUMO).

 Bonds rearrange simultaneously no intermediates.

Stereochemistry
 Suprafacial addition retains stereochemistry.

 Endo rule: electron-withdrawing substituents prefer endo position (secondary orbital

overlap).
 Key Points
 Thermal, pericyclic reaction governed by Woodward–Hoffmann rules.

 Requires s-cis conformation of diene.

 Electron-withdrawing groups on dienophile accelerate reaction.

Exam Tips
 Typical NET question: “Predict product stereochemistry (endo/exo).”

 Remember: “Diels–Alder = Diene + Dienophile Six-membered ring.”

13. Doebner Reaction

Introduction
Doebner reaction synthesizes α,β-unsaturated carboxylic acids by condensation of an
aromatic aldehyde, aniline, and α,β-unsaturated acid (like pyruvic acid).

General Reaction
 Mechanism
Formation of Schiff Base: aldehyde + aniline imine.
Condensation with pyruvic acid.
Decarboxylation & tautomerization α,β-unsaturated acid.

Key Points
 Useful in preparation of cinnamic acid derivatives.

 Related to Perkin reaction (benzaldehyde + acetic anhydride).

Exam Tips
 CSIR often asks difference between Doebner vs Perkin.

 Mnemonic: “Doebner Double bond + Carboxylic acid.”

14. Ene Reaction

Introduction
The Ene reaction is a pericyclic reaction where an alkene with an allylic hydrogen (ene)
reacts with an enophile (electron-deficient double bond), giving a new σ-bond and shifted
double bond.
 General Reaction

Mechanism
 Concerted process with a six-membered cyclic transition state.

 Allylic H migrates enophile forms bond.

 Double bond shifts to new position.

Key Points
 Thermal reaction, no catalyst needed.

 Substituent effects: electron-withdrawing groups on enophile enhance reactivity.

 Example: Hydroformylation step in industrial chemistry.

Exam Tips
 Key feature = allylic hydrogen shift.

 Compare with Diels–Alder (but Ene involves H-shift instead of [4+2] addition).

15. Favorskii Rearrangement

Introduction
Favorskii rearrangement involves α-haloketones reacting with base to give carboxylic acid
derivatives (esters, amides, salts), usually with ring contraction in cyclic systems.
 General Reaction

Mechanism
Base abstraction of α-H enolate.
Intramolecular attack cyclopropanone intermediate.
Ring opening & rearrangement carboxylate.
Protonation/esterification final product.

Key Points
 Unique feature = cyclopropanone intermediate.

 Cyclic ketones ring contraction products.

 Industrial use in steroid chemistry.

Exam Tips
 CSIR frequently tests recognition of ring contraction.

 Mnemonic: “Favorskii = Fewer carbons in ring.”

16. Fischer Indole Synthesis

Introduction
The Fischer Indole Synthesis is one of the most important methods for synthesizing
indoles (heteroaromatic compounds found in tryptophan, serotonin, alkaloids). It involves
the acid-catalyzed rearrangement of aryl hydrazones derived from ketones/aldehydes.

General Reaction

Mechanism
Formation of hydrazone: Carbonyl compound + aryl hydrazine hydrazone.
Tautomerization to ene-hydrazine.
[3,3]-Sigmatropic rearrangement migration of aryl group.
Cyclization (intramolecular attack on iminium).
Dehydration indole nucleus.
 Key Points
 Acid catalyzed (HCl, H₂ SO₄ , Lewis acids).

 Widely used for drug synthesis (indomethacin, tryptamine derivatives).

 Mechanism involves sigmatropic rearrangement (important for exam).

Exam Tips
 CSIR often asks: “Name the rearrangement step in Fischer synthesis.” [3,3]-
sigmatropic shift.

 Mnemonic: Fischer = “Find Indole”.

17. Friedel–Crafts Alkylation / Acylation

Introduction
Friedel–Crafts reactions introduce alkyl (R–) or acyl (R–CO–) groups onto aromatic rings
using Lewis acids (AlCl₃ , FeCl₃ ) as catalysts.

General Reactions
 Alkylation:
  Acylation:

Mechanism
Generation of electrophile:
o R⁺ (carbocation) in alkylation.
o Acylium ion (R–C≡O⁺ ) in acylation.
Electrophilic substitution: aromatic π-electrons attack.
Aromaticity restored substitution product.

Alkylation :
Acylation :

Key Points
 Alkylation limitations: carbocation rearrangements, polyalkylation.

 Acylation advantages: acylium ion stable, no rearrangements.

 Cannot occur on deactivated rings (–NO₂ , –CF₃ ).

Exam Tips
 Identify if rearrangement possible only in alkylation.

 Acylation products resistant to further substitution (deactivating COR group).

18. Gabriel Synthesis

Introduction
Gabriel synthesis prepares primary amines using potassium phthalimide and alkyl
halides, avoiding multiple alkylation.

General Reaction

Mechanism
Formation of nucleophile: Potassium phthalimide.
SN2 reaction with alkyl halide N-alkyl phthalimide.
Hydrolysis or hydrazinolysis primary amine.

Key Points
 Works only for 1° alkyl halides (SN2 mechanism).

 Does not work for aryl/secondary/tertiary halides.

  Clean method no secondary or tertiary amine byproducts.

Exam Tips
 CSIR often gives tricky options (aryl halide won’t work).

 Mnemonic: “Gabriel gives Genuine (Primary) amines.”

19. Gattermann–Koch Formylation

Introduction

The Gattermann–Koch reaction introduces a formyl group (–CHO) into an aromatic ring
using CO + HCl in presence of AlCl₃ /CuCl.

General Reaction

Mechanism
Generation of electrophile: CO + HCl + AlCl₃ /CuCl formyl cation (HCO⁺ ).
Electrophilic substitution: Ar–H + HCO⁺ Ar–CHO.
Aromaticity restored benzaldehyde derivative.

Key Points
 Direct method for preparing aromatic aldehydes.

 Works best with activated rings (–OH, –NH₂ groups).

 In deactivated rings, yield is poor.

 Exam Tips
 Differentiate from Gattermann Reaction (uses HCN + HCl formyl group
introduction via iminium).

 Mnemonic: Gattermann–Koch = “CO for CHO.”

20. Gomberg Reaction

Introduction

The Gomberg reaction is the generation of free radicals from triphenylmethyl chloride in
presence of metals. It was the first demonstration of a free radical (trityl radical).

General Reaction

Mechanism
Homolytic cleavage of C–Cl bond promoted by Ag/metal.
Formation of trityl radical (stabilized by resonance over 3 phenyl rings).
Radical dimerization or substitution occurs.

Key Points
 Historical significance: first stable radical identified (1900).

 Stability due to resonance delocalization of radical center.

 Modern relevance: radical chemistry & polymerization initiators.

Exam Tips
 CSIR may test “Which radical was first discovered?” Triphenylmethyl radical
(Gomberg).

 Mnemonic: Gomberg = “Great Old Radical.”

21. Grignard Reaction

Overview
The Grignard reaction is one of the most fundamental carbon–carbon bond-forming
reactions in organic chemistry. It involves the reaction of an organomagnesium halide
(Grignard reagent, RMgX) with electrophiles such as aldehydes, ketones, esters, CO₂ ,
and epoxides.

General Reaction

 Aldehyde Secondary Alcohol

 Ketone Tertiary Alcohol

 Formaldehyde Primary Alcohol

 Esters/Acid chlorides Tertiary Alcohol (via 2 additions)

Reaction Mind Map :

Mechanism
1. Formation of Grignard reagent
2. Nucleophilic attack
3. Protonation (work-up with H₃ O⁺ )

Key Points

 Requires anhydrous ether (Et₂ O or THF) as solvent.

 Sensitive to moisture (RMgX hydrolyzes).

 Attacks epoxides extended chain alcohols.

Exam Tips

 Remember Grignard + CO₂ Carboxylic Acid.

 Important in synthesis planning (C–C bond extension).

 Competes with Cannizzaro / Aldol under wrong conditions.

22. Hell–Volhard–Zelinsky (HVZ) Reaction

Overview
The HVZ reaction involves the α-halogenation of carboxylic acids in the presence of red
phosphorus and halogen (Cl₂ /Br₂ ).
General Reaction

Mechanism

Activation
Carboxylic acid reacts with Br₂ /P Acyl bromide formed.
Enol formation
Acyl bromide tautomerizes to enol form.
Halogenation
Enol reacts with Br₂ α-bromoacyl bromide.
Hydrolysis
α-bromoacyl bromide hydrolyzes α-bromo acid.

Key Points

 Selective α-halogenation.

 Requires red phosphorus (catalytic).

 Further substitution possible if excess Br₂ used.

Exam Tips
 α-bromo acids starting point for amino acids (Strecker synthesis).
  Watch for mechanistic steps in MCQs.

23. Hofmann Rearrangement (Degradation)

Overview

Converts primary amides primary amines with loss of one carbon atom using Br₂
and strong base.

General Reaction

Mechanism
Formation of N-bromoamide.
Base abstracts a proton rearrangement forms isocyanate.
Hydrolysis of isocyanate primary amine + CO₂ .
Key Points
 Decreases carbon count by 1.

 Intermediate: isocyanate (very important).

Exam Tips
 Differentiate from Curtius & Schmidt rearrangements (similar transformations).

 Frequently asked: “What is the intermediate?” Answer: Isocyanate.

24. Hunsdiecker Reaction

Overview

The Hunsdiecker reaction involves the decarboxylation of silver salts of carboxylic

acids with halogens, producing alkyl halides.
General Reaction

Mechanism
Silver salt of acid reacts with Br₂ unstable acyloxy radical.
Decarboxylation alkyl radical.
Recombination with Br radical alkyl bromide.

Key Points
 Useful for converting acids halides with 1 carbon loss.

 Radical mechanism.

Exam Tips
 Compared with Kolbe electrolysis (radical decarboxylation).

 Often asked: product prediction with different halogens.

25. Knoevenagel Condensation

Overview
The Knoevenagel condensation is a reaction of aldehydes/ketones with active
methylene compounds (malononitrile, ethyl acetoacetate) in the presence of a weak base
(piperidine, pyridine).

General Reaction
Mechanism
Base abstracts proton from active methylene carbanion.
Carbanion attacks aldehyde/ketone alkoxide.
Dehydration α,β-unsaturated compound.

Key Points
 Base-catalyzed.

 Produces C=C bond conjugated with electron-withdrawing groups.

Exam Tips
 Application in drug synthesis and industrial dyes.

 Differentiate from Aldol condensation (similar steps but methylene group

involvement).

26. Kolbe Electrolysis

Introduction
 The Kolbe electrolysis (also known as Kolbe reaction) is a decarboxylative
dimerization of carboxylate anions using electrochemical oxidation.
  First reported by Hermann Kolbe in 1847.

 It is a green electro-organic reaction since it avoids strong reagents and uses

electrical energy as the driving force.

 General reaction:

Mechanism (Stepwise)
Anodic oxidation of the carboxylate anion
The unstable carboxyl radical decomposes
Radical dimerization at the anode surface

Mechanism Path 2

Key Features
 Works best with aliphatic carboxylates (RCOONa, RCOOK).

 Radical coupling makes it non-selective sometimes.

 Electrochemical cell: platinum or graphite electrodes in aqueous/alcoholic solution.

Applications
 Synthesis of hydrocarbons from cheap carboxylic acids.

 Used in the Kolbe synthesis of ethane from sodium acetate.

 Industrial use: in the preparation of dimers, fragrances, and polymer building blocks.
Exam Tips
 Remember: Anodic decarboxylation Radical Coupling.

 Question trick: Kolbe electrolysis of sodium acetate gives ethane, not methane.

 Sometimes asked as: “Kolbe’s method of hydrocarbon synthesis”.

27. Mannich Reaction

Introduction
 The Mannich reaction is a carbon–carbon bond forming reaction involving an
amine, formaldehyde, and an active methylene compound.

 First reported by Carl Mannich in 1912.

 It is a nucleophilic substitution reaction that gives β-aminocarbonyl compounds

(Mannich bases).

General Scheme:

Mechanism
Imine (Schiff base) formation
Enolate formation from active methylene compound.
Nucleophilic attack of enolate on iminium ion β-aminocarbonyl product.
Key Features
 Requires an α-H acidic compound (acetone, β-keto esters, malonates, etc.).

 Formaldehyde is the most common aldehyde used.

 Both primary and secondary amines are used, but tertiary amines cannot form
iminium ions.

Applications
 Very important in pharmaceutical chemistry.

 Used in synthesis of alkaloids, peptides, and biologically active molecules.

 Precursor to morphine derivatives and quinine analogues.

Exam Tips
 Mnemonic: "Amine + Aldehyde + Active methylene = Mannich base".

 In CSIR-NET, often asked: "Identify the active methylene compound in Mannich

condensation".

28. Michael Addition

Introduction
 The Michael addition (or Michael reaction) is the 1,4-conjugate addition of a
nucleophile to an α,β-unsaturated carbonyl compound.

 Discovered by Arthur Michael (1887).

 It is a C–C bond forming reaction widely used in total synthesis.

General Scheme:

Mechanism
Base deprotonates the donor (e.g., enolate, nitroalkane, malonate).
Nucleophile attacks β-carbon of α,β-unsaturated carbonyl (conjugate addition).
Protonation gives Michael adduct.

Key Points
 Soft nucleophiles (enolates, thiolates, nitroalkanes) are preferred.

 Electrophile must be conjugated (enone, acrylate).

 Stereoselective versions (asymmetric Michael) are important in modern organic

synthesis.
Applications
 Central to Robinson annulation and synthesis of cyclic ketones.

 Used in formation of complex alkaloids and steroids.

 Widely applied in drug synthesis (e.g., warfarin).

Exam Tips
 Always think 1,4-addition (not 1,2).

 Asked in NET: “Which nucleophiles participate in Michael addition?” Enolates,

nitroalkanes, β-ketoesters.

29. Oppenauer Oxidation

Introduction
 The Oppenauer oxidation converts secondary alcohols ketones using an
aluminum alkoxide catalyst and a hydride acceptor (ketone such as acetone).

 First reported by R. Oppenauer (1937).

 It is the reverse of Meerwein–Ponndorf–Verley (MPV) reduction.

General Scheme:

Mechanism
Secondary alcohol coordinates with Al(OR)₃ .
Hydride transfer from alcohol to ketone (acetone).
 Formation of ketone product + isopropanol.

Key Features
 Selective for secondary alcohols.

 No over-oxidation, since it uses mild conditions.

 Environmentally friendly since no strong oxidants used.

Applications
 Used in steroid synthesis (conversion of alcohols in ring systems to ketones).

 Selective oxidation in complex natural product synthesis.

 Green alternative to Cr(VI) oxidation.

Exam Tips
 Remember: Oppenauer = Oxidation, MPV = Reduction.

 NET trick: If both MPV and Oppenauer are options, decide based on
oxidation/reduction.
30. Perkin Reaction

Introduction
 The Perkin reaction is the condensation of aromatic aldehydes with acid
anhydrides in presence of an alkali salt of the acid to form α,β-unsaturated
aromatic acids.

 Discovered by William Henry Perkin (1868).

General Scheme:

Mechanism
Formation of enolate ion from acetic anhydride using sodium acetate.
Enolate attacks aldehyde carbonyl aldol-like addition.
Elimination of acetate α,β-unsaturated acid (Perkin product).
Key Features
 Works best with aromatic aldehydes (benzaldehyde).

 Aliphatic aldehydes fail due to side reactions.

 Provides cinnamic acids, important in fragrance industry.

Applications
 Industrial synthesis of cinnamic acid and derivatives.

 Used in manufacturing of flavoring agents (styrene, coumarin).

 Important in fine chemical synthesis.

Exam Tips
 NET often asks: “Why aromatic aldehyde is preferred in Perkin reaction?”
Stabilization of intermediate and reduced side reactions.

 Mnemonic: Perkin = Perfume (cinnamic acid fragrances).

Summary (26–30)
Reaction Transformation Key Point CSIR Tip
Kolbe Carboxylate Radical coupling at Product = dimer, not
Electrolysis Hydrocarbon + CO₂ anode monomer
Mannich Aldehyde + Amine + β-aminocarbonyl Used in drug synthesis
Active methylene (Mannich base)
Michael Nu α,β-unsaturated 1,4-Addition Enolates/nitroalkanes
Addition carbonyl
Reaction Transformation Key Point CSIR Tip
Oppenauer 2° Alcohol Ketone Reverse of MPV Uses Al(OR)₃ , acetone
Oxidation
Perkin ArCHO + Acid α,β-unsaturated Cinnamic acid synthesis
anhydride aromatic acid

31. Reformatsky Reaction

Introduction
The Reformatsky reaction (1887, Sergey Reformatsky) is a carbon–carbon bond forming
reaction where α-halo esters (like ethyl bromoacetate) react with aldehydes/ketones in the
presence of zinc metal to give β-hydroxy esters.
This is conceptually similar to the aldol reaction, but instead of enolate ions, we use zinc-
mediated organometallic reagents called Reformatsky reagents.

General Reaction Scheme

Mechanism (Step-by-Step)
Activation of α-halo ester
o Zinc inserts into the C–Br bond of the α-halo ester.
o Forms a zinc enolate species:
 Nucleophilic Attack on Carbonyl
o The zinc enolate attacks the aldehyde/ketone carbonyl carbon.
o Forms a tetrahedral alkoxide intermediate.
Protonation
o On work-up (H₂ O, dilute acid), the alkoxide gets protonated.
o Final product: β-hydroxy ester.

Key Points
 Works best with aldehydes > ketones.

 No reaction with esters or acid chlorides (zinc enolate not reactive enough).

 Stereoselectivity: Reaction can produce syn/anti isomers (important in exams).

 Reformatsky reagent is milder than Grignard: does not attack esters.

Exam Tips
 Difference from Grignard reaction: Grignards attack esters alcohols, while
Reformatsky stops at β-hydroxy esters.

 Can be intramolecular gives lactones.

 Often asked: "Which metal is essential in Reformatsky?" Zinc.

 CSIR may test selectivity questions: aldehyde reacts but ester remains untouched.

Applications
 Synthesis of β-hydroxy esters (precursors for β-lactams, steroids).

 Used in synthesis of natural products like Erythromycin intermediates.

32. Reimer–Tiemann Reaction

Introduction
The Reimer–Tiemann reaction (1876, Karl Reimer & Ferdinand Tiemann) is a formylation
of phenols.
Phenols treated with chloroform (CHCl₃ ) + strong base (NaOH/KOH) give ortho-formyl
phenols (salicylaldehyde derivatives).

General Reaction Scheme

Mechanism (Step-by-Step)
Generation of Dichlorocarbene
o Base deprotonates chloroform:
o Dichlorocarbene (:CCl₂ ) is a reactive electrophile.
Phenoxide Formation
o Phenol is deprotonated by base phenoxide ion.
o Resonance in phenoxide makes ortho/para positions electron-rich.
Carbene Attack
o :CCl₂ attacks ortho position (major) of phenoxide.
o Intermediate formed: Ar–CCl₂ .
Hydrolysis
o Strong base hydrolyzes dichloromethyl group –CHO group.
o Product: ortho-hydroxybenzaldehyde (salicylaldehyde).
 Key Points
 Major product: ortho-formyl phenol; minor product: para.

 Carbene intermediate (:CCl₂ ) important exam highlight.

 Requires chloroform + base.

 Reaction fails without phenolic OH (phenoxide required).

Exam Tips
 Asked in CSIR frequently: Which carbene intermediate is formed? :CCl₂ .

 Difference with Gattermann reaction: Reimer–Tiemann uses CHCl₃ /NaOH,

Gattermann uses CO + HCl/AlCl₃ –CuCl.

 Important: ortho-selectivity (due to H-bonding stabilization in product).

Applications
 Industrial synthesis of salicylaldehyde, precursor for dyes, drugs, perfumes.

 Salicylaldehyde Schiff base ligands coordination complexes.

33. Rosenmund Reduction

Introduction
The Rosenmund reduction (1918, Karl Wilhelm Rosenmund) reduces acid chlorides into
aldehydes using H₂ gas over Pd/BaSO₄ (poisoned catalyst).
 General Reaction Scheme

Catalyst: Pd/BaSO₄ , often poisoned with quinoline or sulfur.

Mechanism
Adsorption of H₂ on catalyst surface.
Hydrogenation of acid chloride occurs selectively to aldehyde.
Further reduction to alcohol is prevented due to catalyst poisoning.

Key Points
 Acid chloride aldehyde only (not alcohol).

 Poisoned catalyst prevents over-reduction.

 Works best with aromatic acid chlorides.

 Exam Tips
 Asked: Why not alcohol? Catalyst poisoned, stops at aldehyde.

 Difference with Stephen reduction: Stephen uses nitrile + SnCl₂ /HCl, Rosenmund
uses acid chloride + H₂ /Pd–BaSO₄ .

 Industrial application: synthesis of benzaldehyde.

34. Sandmeyer Reaction

Introduction
The Sandmeyer reaction (1884, Traugott Sandmeyer) involves the replacement of
diazonium salts with halogens or CN using Cu(I) salts.

General Reaction Scheme

Mechanism
Formation of Diazonium Salt
o Aromatic amine + NaNO₂ /HCl (0–5 °C).
o Produces Ar–N₂ ⁺ Cl⁻ .
Radical Substitution Pathway
o Cu(I) reduces diazonium salt Ar· radical.
o Radical couples with halogen or CN.
 Product Formation
o Stable aryl halide / nitrile formed.
o N₂ gas escapes (driving force).

Key Points
 Works only for aromatic diazonium salts.

 Reagents: CuCl, CuBr, CuCN.

 Not useful for iodination (done by KI directly).

Exam Tips
 Asked: Which gas evolves? N₂ .

 Key difference with Gattermann reaction (CO/HCl vs diazonium salts).

 Industrial application: aryl nitriles (important intermediates).

35. Schmidt Reaction

Introduction
The Schmidt reaction converts carboxylic acids, ketones, or aldehydes into amines or
amides using hydrazoic acid (HN₃ ) + acid catalyst.

General Reaction Scheme

 With carboxylic acid:

 With ketone:

With Aldehyde :

Mechanism
Protonation of substrate by strong acid (H₂ SO₄ ).
Nucleophilic attack of HN₃ .
Rearrangement (R shift) with N₂ loss.
Formation of amine or amide depending on substrate.
Carboxylic Acid Mechanism :

Acids which do not form acyl cation :

Ketones Mechanism :

Key Points
 Carboxylic acids primary amines.

 Ketones amides.

 Resembles Curtius/Hofmann rearrangements.

Exam Tips
 Frequently asked: Which gas evolves? N₂ + CO₂ .

 Order of migratory aptitude (R-shift): tertiary > secondary > primary > methyl.

 Reagent: HN₃ + conc. H₂ SO₄ .

 Summary
 Reformatsky Reaction β-hydroxy esters (Zn enolate).

 Reimer–Tiemann ortho-formyl phenols (dichlorocarbene).

 Rosenmund Reduction aldehydes from acid chlorides (poisoned Pd).

 Sandmeyer halides/nitriles from diazonium salts (Cu salts).

 Schmidt Reaction amines/amides via azide rearrangement.

36. Skraup Synthesis

Introduction
The Skraup Synthesis (1880, by Zdenko Hans Skraup) is a classical method for the
synthesis of quinolines from aniline derivatives, glycerol, and an oxidizing agent
(commonly nitrobenzene or arsenic acid) in the presence of an acid catalyst (sulfuric
acid). Quinolines are extremely important heterocycles in medicinal chemistry, dyes, and
materials science.

General Reaction Scheme:

Mechanism (Stepwise)
Dehydration of glycerol forms acrolein (CH₂ =CH–CHO).
Nucleophilic attack by aniline on acrolein forms β-aminopropanal intermediate.
Cyclization occurs leads to dihydroquinoline.
Oxidation (by nitrobenzene or arsenic acid) converts dihydroquinoline to quinoline.
Applications
 Large-scale synthesis of quinoline and substituted quinolines.

 Quinolines are used in antimalarial drugs (chloroquine, quinine derivatives).

 Intermediates in dyes and agrochemicals.

Key Points
 Requires strong acid catalyst.

 The reaction is highly exothermic requires temperature control.

 Oxidizing agents: Nitrobenzene, Arsenic acid, Ferric salts.

Exam Tips
 Acrolein intermediate is crucial (formed from glycerol).

 Oxidizing agent commonly nitrobenzene (reduced to aniline).

 Product: quinoline skeleton.

 Expected CSIR Question: “Write the mechanism of Skraup synthesis and explain the
role of nitrobenzene.”

37. Staudinger Reaction

Introduction
The Staudinger Reaction (1919, by Hermann Staudinger) involves the reduction of organic
azides (R–N₃ ) to primary amines (R–NH₂ ) using triphenylphosphine (PPh₃ ).

General Reaction Scheme:

Mechanism

Attack of PPh₃ on terminal nitrogen of azide formation of phosphazide.

Loss of N₂ yields iminophosphorane intermediate (R–N=PPh₃ ).
 Hydrolysis of iminophosphorane gives amine (R–NH₂ ) and
triphenylphosphine oxide (OPPh₃ ).

Applications
 Synthesis of primary amines from azides (mild conditions).

 Used in bioorthogonal chemistry: modified as Staudinger ligation for biomolecule

tagging.

Key Points
 Byproduct: triphenylphosphine oxide (OPPh₃ ).

 Azides are reactive but toxic careful handling.

 Staudinger ligation is a click-chemistry reaction important in chemical biology.

Exam Tips
 Intermediate: iminophosphorane.

 Reducing agent: PPh₃ .

 Product: primary amine.

 Common CSIR Question: “Explain Staudinger reaction and differentiate it from

Staudinger ligation.”

38. Stevens Rearrangement

Introduction
The Stevens Rearrangement is a rearrangement reaction of quaternary ammonium
salts or sulfonium salts under basic conditions to give amines or sulfides with new C–
C bonds.
General Reaction:

Mechanism
Deprotonation at α-position generates a carbanion adjacent to
ammonium/sulfonium center.
1,2-Migration one substituent migrates to the carbanion center.
Rearranged amine/sulfide obtained.

Applications
 C–C bond formation in heterocyclic synthesis.

 Formation of amine derivatives important in pharmaceuticals.

Key Points
 Involves 1,2-shift.

 Requires strong base (NaNH₂ , NaH).

 Works with quaternary ammonium salts or sulfonium salts.

Exam Tips
 Intermediate: ylide.

 Migration is 1,2 shift.

 Similar but distinct from Sommelet–Hauser rearrangement.

 Expected Question: “Compare Stevens and Sommelet–Hauser rearrangements.”

39. Suzuki Coupling

Introduction
The Suzuki Coupling (1979, Akira Suzuki, Nobel Prize 2010) is a palladium-catalyzed
cross-coupling reaction between aryl/alkenyl halides and organoboron compounds
(boronic acids or esters) to form biaryl or substituted alkenes.
General Reaction Scheme:

Mechanism
Oxidative Addition: Pd(0) inserts into Ar–X bond forms Ar–Pd(II)–X.
Transmetalation: Exchange between Pd complex and boronic acid transfers Ar'
group to Pd.
Reductive Elimination: Coupling of Ar and Ar' gives Ar–Ar' and regenerates
Pd(0).
Applications
 Widely used in drug synthesis (biaryl motifs).

 Essential in polymer and material synthesis.

 Found in synthesis of OLED materials, agrochemicals, and pharmaceuticals.

Key Points
 Catalyst: Pd(0).

 Reagents: Boronic acids + aryl halides.

 Base (K₂ CO₃ , NaOH) assists transmetalation.

Exam Tips
 Key step: Transmetalation.

 Catalyst: Palladium.

 Product: C–C bond (biaryl/alkene).

 Expected CSIR Question: “Write the catalytic cycle of Suzuki reaction.”

40. Swern Oxidation

Introduction
The Swern Oxidation is a mild oxidation reaction converting primary alcohols to
aldehydes and secondary alcohols to ketones using DMSO + oxalyl chloride + base
(Et₃ N) at low temperature.

General Reaction Scheme:

Mechanism
Activation of DMSO by oxalyl chloride forms chlorodimethylsulfonium ion.
Alcohol attack alkoxysulfonium ion.
Deprotonation (Et₃ N) elimination to form carbonyl compound.
Byproducts: CO, CO₂ , DMS (dimethyl sulfide, foul odor).

Applications
 Mild conditions sensitive substrates can be oxidized.

 Compatible with complex natural product synthesis.

Key Points
 Converts primary alcohol aldehyde (no overoxidation).

 Byproduct: dimethyl sulfide (bad smell).

 Reagents: (COCl)₂ , DMSO, Et₃ N.

Exam Tips
 No chromium reagents used safer, green chemistry.

 Low temperature (–60 °C).

 Expected CSIR Question: “Differentiate Swern oxidation from PCC oxidation.”

 Summary Table

Reaction Key Reagents Product Formed Key Intermediate

Skraup Aniline, Glycerol, Quinoline Acrolein,
Synthesis Nitrobenzene Dihydroquinoline
Staudinger Azides, PPh₃ , H₂ O Primary Amines Iminophosphorane
Reaction
Stevens Quaternary Rearranged Ylide, 1,2-shift
Rearrangement ammonium/sulfonium amine/sulfide
salts + Base
Suzuki Coupling Aryl halide + Boronic acid Biaryls/alkenes Pd(II) intermediates
+ Pd
Swern Oxidation DMSO, Oxalyl chloride, Aldehydes/Ketones Alkoxysulfonium ion
Et₃ N

41. Ullmann Coupling Reaction

Introduction
 The Ullmann Coupling Reaction is a copper-catalyzed coupling of aryl halides to
form biaryl compounds (Ar–Ar).

 Developed by Fritz Ullmann in 1901, it is a fundamental name reaction in C–C bond

formation.

 Important for making pharmaceuticals, agrochemicals, conducting polymers,

and natural product synthesis.

General Reaction
Mechanism
Oxidative Addition
o The aryl halide reacts with copper to form an aryl–copper intermediate.
Transmetalation / Association
o Another equivalent of aryl–copper forms.
Reductive Elimination
o Two aryl groups couple and regenerate copper catalyst.
Key Points
 Works best with aryl iodides > bromides > chlorides.

 Requires high temperature (200–300 °C).

 Modern versions use ligand-stabilized Cu catalysts (Ullmann-type couplings).

 Extended to C–N, C–O, and C–S couplings (Ullmann ether, Ullmann amination).

Applications
 Biaryl motifs in pharmaceuticals (antitumor drugs, NSAIDs).

 Construction of ligands and polymers (biphenyl scaffolds).

 Precursor step in cross-coupling chemistry.

Exam Tips
 Ullmann = Cu-catalyzed, biaryl formation.

 Compare with Suzuki Coupling (Pd-catalyzed, milder conditions).

 CSIR-NET often asks: "Which catalyst is used in Ullmann?" Copper.

42. Vilsmeier–Haack Formylation

Introduction
 The Vilsmeier–Haack Reaction is a formylation reaction where an aromatic
compound is converted into an aryl aldehyde using DMF + POCl₃ .

 Discovered in 1927 by Anton Vilsmeier and Albrecht Haack.

General Reaction
Mechanism

Activation of DMF
Electrophilic Attack
o The activated complex acts as an electrophilic iminium ion.
o Aromatic ring attacks gives aryl iminium salt.
Hydrolysis
o Aqueous work-up hydrolyzes iminium salt aryl aldehyde.
Key Points
 Works well on electron-rich aromatics (anisole, phenols, indoles).

 Does not work well on deactivated benzene rings.

 Selective ortho/para substitution.

Applications
 Preparation of heteroaryl aldehydes (indole-3-carboxaldehyde).

 Widely used in drug synthesis and fine chemicals.

Exam Tips
 Reagent pair POCl₃ + DMF.

 Product formylated arene (–CHO group).

 Compare with Reimer–Tiemann reaction (–CHO group introduction on phenols).

43. Williamson Ether Synthesis

Introduction

 The Williamson Ether Synthesis forms ethers (R–O–R') from alkoxide ions + alkyl
halides.

 Developed in 1850 by Alexander Williamson.

 A classical SN2 substitution reaction.

General Reaction

Mechanism
Formation of Alkoxide
SN2 Attack
The alkoxide nucleophile attacks the alkyl halide forms ether.
Key Points
 Works best with primary alkyl halides (SN2).

 Secondary halides slower, elimination competes.

 Tertiary halides elimination dominates (E2).

Applications
 Preparation of unsymmetrical ethers.

 Industrial ether production (MTBE, diethyl ether).

Exam Tips
 Williamson = SN2, not SN1.

 Best with primary halides.

 Side reaction: elimination in bulky substrates.

44. Wittig Reaction

Introduction
 The Wittig Reaction forms alkenes by reaction of aldehydes/ketones with
phosphonium ylides.

 Discovered by Georg Wittig (Nobel Prize 1979).

 A cornerstone in C=C bond formation.

General Reaction
Mechanism
Ylide Formation
Nucleophilic Attack
o Ylide attacks carbonyl forms betain intermediate.
Oxaphosphetane Formation
o Four-membered ring intermediate forms.
Decomposition
o Oxaphosphetane collapses alkene + Ph₃ P=O.

Key Points
 Gives alkenes with defined stereochemistry.

 Stabilized ylides (E)-alkenes.

 Unstabilized ylides (Z)-alkenes.

Applications
 Synthesis of alkenes in natural products.

 Useful for chain extension in carbonyl compounds.

Exam Tips
 Wittig = C=O C=C.

 Side product always Ph₃ P=O.

 Stabilized vs. unstabilized ylides decide stereochemistry.

45. Wohl–Ziegler Bromination

Introduction
 The Wohl–Ziegler Reaction is a benzylic and allylic bromination using N-
bromosuccinimide (NBS).

 Developed by Wohl & Ziegler in 1942.

General Reaction

Mechanism
Radical Initiation
o Heat or light forms Br• radicals.
Propagation
o Br• abstracts H benzylic radical.
o Radical reacts with NBS regenerates Br•.
Termination
o Radicals recombine.
Key Points
 Selective for benzylic & allylic hydrogens.

 Mild and controlled reaction.

 Solvent: CCl₄ (inert).

Applications
 Preparation of benzyl bromides (synthetic intermediates).

 Step in polymer & pharmaceutical synthesis.

Exam Tips
 Reagent: NBS.

 Selectivity: benzylic/allylic positions.

 Mechanism: free radical substitution.

46. Wolff–Kishner Reduction

Introduction
 Wolff–Kishner Reduction reduces aldehydes and ketones alkanes using
NH₂ NH₂ + base.

 Discovered by Ludwig Wolff and Nikolai Kishner (1911).

 Complementary to Clemmensen Reduction.

General Reaction
Mechanism

Hydrazone Formation
Base-Induced Deprotonation
Elimination of N₂
Protonation

Key Points
 Works under strongly basic, high temperature.

 Removes carbonyl oxygen as N₂ gas.

 Alternative Clemmensen (Zn–Hg/HCl) (acidic).

Applications
 Deoxygenation in organic synthesis.

 Used in steroid, terpenoid synthesis.

Exam Tips
 Wolff–Kishner = basic reduction.

 Clemmensen = acidic reduction.

 Product alkane.

47. Corey–Fuchs Reaction

Definition / Introduction
The Corey–Fuchs Reaction is a two-step transformation of aldehydes terminal
alkynes using carbon tetrabromide (CBr₄ ) and triphenylphosphine (PPh₃ ), followed by a
strong base (e.g., BuLi).
It is a highly useful method for preparing alkynes from aldehydes.

General Scheme:

Stepwise Detailed Mechanism

Wittig-type reaction
o PPh₃ reacts with CBr₄ forms Ph₃ P⁺ –CBr₃ (a phosphonium salt).
o Deprotonation gives dibromomethylene ylide (Ph₃ P=CBr₂ ).
o Reaction with aldehyde:
R–CHO + Ph₃ P=CBr₂ ⟶ R–CHBr₂
Formation of gem-dibromide
o The aldehyde reacts to form the dibromoalkene (gem-dibromide).
Base-induced elimination
 o Strong base (e.g., n-BuLi) abstracts proton eliminates 2Br⁻ forms
terminal alkyne.
o R–CHBr₂ + 2 BuLi ⟶ R–C≡CH

Real-World Examples / Applications

 Conversion of benzaldehyde phenylacetylene.

 Used in synthesis of alkyne building blocks in natural product synthesis.

Key Points & Common Confusions

 Converts aldehyde alkyne (not ketones).

 Requires strong base (BuLi, LDA).

 Two-step process: dibromoolefin formation, then elimination.

Exam Tricks & Tips
 Shortcut memory: “Fuchs makes alkynes from aldehydes” Corey–Fuchs.

 Likely CSIR Question: Which reaction converts aldehydes into terminal alkynes?
(Ans: Corey–Fuchs).

 Compare with Seyferth–Gilbert reaction (aldehyde alkyne via diazo reagents).

48. Chan–Lam Coupling

Definition / Introduction
The Chan–Lam Coupling is a copper(II)-mediated oxidative coupling of boronic acids
with nucleophiles such as amines, alcohols, or thiols, to form C–N, C–O, or C–S bonds.

General Scheme:

Stepwise Detailed Mechanism

Formation of Cu(II)-amine complex
o Nucleophile coordinates to Cu(II).
Transmetalation
o Arylboronic acid transfers the aryl group to copper.
Oxidative coupling
o Ar–Cu(III)–Nu species undergoes reductive elimination.
Regeneration
o Air reoxidizes Cu(I) Cu(II).

Real-World Examples / Applications

 Synthesis of aryl amines, aryl ethers, and aryl thioethers.

 Important in pharmaceutical chemistry (C–N bond construction in drug molecules).

Key Points & Common Confusions

 Mild conditions (room temperature, air as oxidant).

 Complements Suzuki and Buchwald reactions.

 Works best with electron-rich boronic acids.

Exam Tricks & Tips

 Memory aid: “Chan loves Copper” Chan–Lam uses Cu.

 Often compared with Buchwald–Hartwig (Pd) Expect MCQ comparing catalysts.

 CSIR NET Tip: If “aryl boronic acid + amine/alcohol under Cu(II)” Think Chan–Lam.

49. Sonogashira Coupling

Definition / Introduction
The Sonogashira Reaction is a Pd–Cu catalyzed cross-coupling of a terminal alkyne
with an aryl or vinyl halide to form a Csp–Csp² bond.

General Scheme:
Stepwise Detailed Mechanism
Oxidative addition
o Ar–X + Pd(0) Ar–Pd(II)–X.
Alkyne activation
o Terminal alkyne + CuI + base copper acetylide.
Transmetalation
o Copper acetylide transfers C≡C–R to Pd.
Reductive elimination
o Ar–C≡C–R forms. Pd(0) regenerated.

Real-World Examples / Applications

 Synthesis of enynes and natural products.

 Used in drug molecules (e.g., anticancer agents).

Key Points & Common Confusions
 Requires Pd(0) catalyst + CuI cocatalyst.

 Base (amine, Et₃ N) essential.

 Can undergo Glaser homocoupling (side reaction).

Exam Tricks & Tips

 Shortcut: “Sonogashira makes sp–sp² bonds.”

 NET Question style: Which coupling forms alkynyl-aryl bonds? (Ans: Sonogashira).

 Compare with Suzuki (Boron), Heck (alkene), Negishi (Zn), Kumada (Mg).

50. Corey–Chaykovsky Reaction

Definition / Introduction
The Corey–Chaykovsky Reaction involves the use of sulfonium or sulfoxonium ylides
to convert aldehydes/ketones epoxides or imines aziridines.

General Reaction
Stepwise Detailed Mechanism
Ylide formation
o Dimethylsulfonium/sulfoxonium salt + base CH₂ –SMe₂ ⁺ ylide.
Nucleophilic attack
o Ylide attacks carbonyl betaine intermediate.
Ring closure
o Intramolecular displacement epoxide formed.

Real-World Examples / Applications

 Epoxidation of α,β-unsaturated ketones.

 Aziridination of imines (important for heterocyclic drugs).

Key Points & Common Confusions
 Reagent: Dimethyloxosulfonium methylide (Corey–Chaykovsky ylide).

 Epoxide/aziridine formation without strong oxidants.

Exam Tricks & Tips

 “Chaykovsky makes small rings (epoxide, aziridine).”

 CSIR Trap: Don’t confuse with Corey–Fuchs (alkynes).

51. Meerwein Arylation

Definition / Introduction
The Meerwein Arylation is the radical arylation of alkenes with aryl diazonium salts,
giving substituted aromatic–alkene adducts.
Stepwise Detailed Mechanism

Real-World Examples / Applications

 Arylation of acrylonitrile to give useful intermediates.

Key Points & Common Confusions

 Free radical mechanism.

 Involves diazonium salts.

 Useful in polymer chemistry.

Exam Tricks & Tips

 “Meerwein loves radicals.”

 If diazonium + alkene in NET question think Meerwein.

52. Buchwald–Hartwig Amination

Definition / Introduction
The Buchwald–Hartwig Reaction is a Pd-catalyzed cross-coupling of aryl halides with
amines to form C–N bonds.

Stepwise Detailed Mechanism

Real-World Examples / Applications

 Key method for synthesis of arylamines (found in drugs, dyes, agrochemicals).

Key Points & Common Confusions

 Catalyst: Pd(0) with bulky phosphine ligands.
  Amines: Primary, secondary amines, anilines.

Exam Tricks & Tips

 Shortcut: “Buchwald Builds Bonds with Pd (C–N).”

 NET Trap: Differentiate from Chan–Lam (Cu, boronic acid).

53. Negishi Coupling

Definition / Introduction
The Negishi Coupling is a Pd- or Ni-catalyzed cross-coupling of organohalides with
organozinc reagents.

Stepwise Detailed Mechanism

Oxidative addition
o R–X + Pd(0) R–Pd(II)–X.
Transmetalation
o R′–ZnX + R–Pd–X R–Pd–R′.
Reductive elimination
o R–R′ (new C–C bond).
Real-World Examples / Applications
 Synthesis of polyenes, aromatic hydrocarbons.

Key Points & Common Confusions

 Organozinc reagents are mild, compatible with many groups.

 Complements Suzuki (Boron), Kumada (Mg), Stille (Sn).

Exam Tricks & Tips

 Shortcut: “Negishi needs Zn.”

 NET Question: If organozinc reagent present think Negishi.

Summary Exam Shortcuts

 Corey–Fuchs aldehyde alkyne.

 Chan–Lam boronic acid + amine/alcohol C–N/C–O.

 Sonogashira alkyne + aryl halide sp–sp².

 Corey–Chaykovsky epoxide/aziridine via ylide.

 Meerwein diazonium + alkene radical arylation.

 Buchwald–Hartwig aryl halide + amine C–N (Pd).

 Negishi organozinc + aryl halide C–C.

 Section-B : Rearrangement

1. Baeyer–Villiger Rearrangement

Definition & Historical Background

The Baeyer–Villiger rearrangement is one of the most important oxidation reactions in

organic chemistry. It involves the transformation of a ketone into an ester (or, in the case of
cyclic ketones, a lactone) using peracids as oxidants. The key feature is the insertion of
an oxygen atom between the carbonyl carbon and one of its adjacent substituents. This
reaction was first discovered by Adolf von Baeyer and Victor Villiger in 1899, and since then
it has become a fundamental method in both laboratory synthesis and industrial processes.
The general transformation can be represented as:

Thus, ketones become esters, and cyclic ketones form lactones.

Detailed Mechanism
The mechanism proceeds through the following key stages:
Protonation of the carbonyl oxygen
o The reaction begins with proton transfer from the peracid to the ketone.
o This makes the carbonyl carbon more electrophilic and therefore more
susceptible to nucleophilic attack.
Nucleophilic attack by peracid oxygen
o The peracid oxygen (-OOH group) attacks the carbonyl carbon.
o A tetrahedral intermediate is formed.
 Formation of the Criegee intermediate
o Rearrangement occurs when one of the adjacent groups migrates to the
oxygen atom of the peroxide group.
o This migration is the key step and is stereospecific (migrating group retains
its stereochemistry).
o The product of this step is known as the Criegee intermediate.
Leaving group departure
o The carboxylate anion (RCO₂ ⁻ ) departs, leaving behind the rearranged
product.
Product formation
o The result is an ester or lactone, depending on the substrate.

Migratory Aptitude
The success of the rearrangement depends on which substituent migrates. The migratory
aptitude order is:

3° > 2° > aryl ≈ benzyl > 1° > methyl

Trick: “Tertiary loves oxygen the most.”

This means that, when given a choice, a tertiary group will migrate preferentially over a
primary or methyl group.

Applications
 Used extensively in the synthesis of lactones, which are important building blocks
in natural products.
  Industrially applied in the production of fine chemicals and pharmaceuticals.

Exam Tricks
 If a cyclic ketone is given, the product will be a lactone (ring-expanded
ester).
 Always check the relative migratory aptitude to predict the major product.
 The rearrangement is stereospecific migrating group retains configuration.
 For unsymmetrical ketones, examiners often give tricky options where the
weaker group migrates; always apply the order.

Key Points
 Reagent: Peracids (mCPBA, peracetic acid).

 Intermediate: Criegee intermediate.

 Product: Ester or lactone.

 Migration: Stereospecific, follows migratory aptitude order.

 Industrial relevance: Synthesis of lactones.

2. Beckmann Rearrangement

Definition & Historical Background

The Beckmann rearrangement is the acid-catalyzed conversion of oximes into amides
or lactams. It was discovered by Ernst Beckmann in 1886. The reaction proceeds via the
migration of a substituent anti to the leaving hydroxyl group, making it a stereospecific
transformation.

General form:
Mechanism
Activation of oxime
o Under acidic conditions, the oxime’s hydroxyl group is protonated, making it
a better leaving group.
Anti-group migration
o The substituent anti to the OH group migrates to the nitrogen atom.
o This occurs simultaneously with the departure of water.
o The product at this stage is a nitrilium ion.
Hydrolysis of nitrilium ion
o Water attacks the nitrilium ion generates amide after deprotonation.

With PCl5

Orientation Rule
 The rearrangement is stereospecific.

 The group anti to the leaving OH group always migrates.

 Exam trick: Always draw the oxime in its anti orientation to correctly identify the
migrating group.

Applications
 Industrially important in the synthesis of ε-caprolactam, the precursor to Nylon-6.

 Used in synthetic organic chemistry for amide synthesis.

Exam Tricks
 In cyclic oximes, the rearrangement produces lactams (ring-expanded
amides).
 For acyclic oximes, the anti-group determines the amide structure.
 CSIR/NET frequently tests this in relation to nylon production.
 If multiple orientations are possible, always pick the anti group migration.

Key Points
 Acid catalyst required (H₂ SO₄ , SOCl₂ , PCl₅ ).

 Migrating group = anti to OH.

 Product = Amide or Lactam.

 Important industrial application: Nylon-6.

3. Benzil–Benzilic Acid Rearrangement

Definition
The Benzil–Benzilic acid rearrangement is a base-catalyzed transformation in which
1,2-diketones (like benzil) are converted into α-hydroxy carboxylic acids.
Typical example:

Mechanism
Nucleophilic attack
o Hydroxide attacks one carbonyl group of the diketone forms a tetrahedral
intermediate.
Phenyl shift
 o One phenyl group migrates from one carbonyl carbon to the other
rearranged intermediate.
Protonation
o Rearranged carbanion is protonated α-hydroxy carboxylate.
Acid workup
o Yields α-hydroxy carboxylic acid (benzilic acid).

Applications

 Useful in preparing α-hydroxy acids, which are important in pharmaceuticals and

cosmetic chemistry.

 Classical demonstration reaction in organic teaching labs.

Exam Tricks

Works mainly for aryl diketones (not effective with simple aliphatic diketones).
Expect the exam question to be framed around benzil benzilic acid conversion.
Always recognize the hydroxide-initiated rearrangement in multiple-choice
questions.

Key Points

 Reagent: Strong base (KOH, NaOH).

 Substrate: 1,2-diketone (benzil).

 Product: α-hydroxy acid.

 Migration: Phenyl group.

4. Claisen Rearrangement

Definition & Historical Note

The Claisen rearrangement is a [3,3]-sigmatropic rearrangement where an allyl vinyl
ether is transformed into a γ,δ-unsaturated carbonyl compound. It was first reported by
Rainer Ludwig Claisen in 1912.
General transformation:

Mechanism
 It proceeds through a concerted pericyclic mechanism.

 Involves a six-membered cyclic transition state.

 Bonds are reorganized simultaneously:

o The C–O bond breaks.
o A new C–C bond forms.
o The double bond shifts.

Key Features
 Thermal reaction requires heat.

 Concerted mechanism no intermediates.

 Stereospecific and regioselective.

Applications
 Widely used for C–C bond formation.

 Plays a vital role in natural product synthesis.

Exam Tricks
Always look for an allyl vinyl ether in the starting compound.
The product will be a γ,δ-unsaturated carbonyl compound.
Examiners often test recognition of the six-membered transition state.
Expect stereospecificity questions.

Key Points
 Reaction type: [3,3]-sigmatropic rearrangement.

 Requires heat (pericyclic reaction).

 Product: γ,δ-unsaturated carbonyl compound.

 Concerted, stereospecific.

5. Cope Rearrangement

Definition
The Cope rearrangement is another [3,3]-sigmatropic rearrangement, but here it occurs
with 1,5-dienes. It involves the concerted reorganization of bonding in a six-membered
transition state.

General Reaction :
Mechanism
 Pericyclic, thermally induced reaction.

 Proceeds via a cyclic six-membered transition state.

 No external catalyst required.

Variants
 Oxy-Cope rearrangement: where one of the carbons bears a hydroxyl substituent.

 Anionic oxy-Cope rearrangement: proceeds under basic conditions, often faster.

Applications
 Useful in synthetic routes to dienes and unsaturated carbonyl compounds.

 Plays a role in the synthesis of natural products and complex ring systems.

Exam Tricks
-Identify a 1,5-diene system think Cope.
-Reaction occurs thermally, no reagent required.
-Examiners may test the difference between Claisen (oxygen present) and Cope (pure
diene).
-Oxy-Cope rearrangement leads to carbonyl products.

Key Points
 Reaction type: [3,3]-sigmatropic rearrangement.

 Substrate: 1,5-diene.

 No reagent required (thermal).

 Applications in synthetic chemistry.

 Summary & Exam Strategy
 Baeyer–Villiger Ketone Ester/Lactone (oxygen insertion).

 Beckmann Oxime Amide/Lactam (anti group migrates).

 Benzil–Benzilic Acid 1,2-Diketone α-hydroxy acid (base induced).

 Claisen Allyl vinyl ether γ,δ-unsaturated carbonyl (pericyclic).

 Cope 1,5-diene rearranged 1,5-diene (pericyclic).

Mnemonic for order: “Bae Beck Benz Claisen Cope” imagine five friends sitting in
order for exam revision.

6. Curtius Rearrangement

Definition & Historical Note

The Curtius rearrangement is the thermal decomposition of an acyl azide to form an
isocyanate intermediate, which can then be hydrolyzed to an amine, converted to a
urethane, or undergo other functional group transformations.
Discovered by Theodor Curtius in 1890.
General transformation:

Mechanism
Formation of acyl azide
o Typically prepared from acid chloride + NaN₃ .
Thermal decomposition
o On heating, acyl azide loses N₂ gas.
o Generates an isocyanate intermediate.
 Rearrangement step
o The R-group migrates from carbonyl carbon to the nitrogen atom.
o This migration is concerted and involves retention of stereochemistry.
Hydrolysis of isocyanate
o With water: forms amine + CO₂ .
o With alcohol: forms urethane.
o With amines: forms urea derivatives.

Exam Tricks
 Always look for acyl azide think Curtius.

 Product is amine with loss of one carbon atom (decarboxylation-like).

 Migration step is stereospecific.

 Isocyanate intermediate is key.

Key Points
 Reagent: Heat (thermal decomposition).

 Product: Amine (after hydrolysis).

 Group migration occurs with stereospecificity.

 Similar to Schmidt & Hofmann rearrangements.

7. Pinacol–Pinacolone Rearrangement

Definition
The Pinacol–Pinacolone rearrangement is an acid-catalyzed rearrangement of vicinal
diols (pinacols) into carbonyl compounds (pinacolones) via a carbocation intermediate.
General:

Mechanism
Protonation
o One OH group gets protonated leaves as water.
Carbocation formation
o Generates a carbocation at one carbon.
Rearrangement
o Adjacent group (alkyl or aryl) migrates with its electron pair to stabilize the
carbocation.
o Leads to rearranged carbocation.
Deprotonation
o Loss of a proton formation of a ketone (pinacolone)

Migration Aptitude
Order of migration:

Phenyl > Hydride > Tertiaryalkyl > Secondaryalkyl > Primaryalkyl > Methyl
Trick: “Phenyl loves to move first.”

Applications
 Important in synthetic organic chemistry for rearranging diols.

 Basis of many exam problems.

Exam Tricks
 Look for 1,2-diol in acidic conditions.

 Predict product based on migratory aptitude.

 Watch out for hydride vs phenyl shift traps in exam questions.

Key Points
 Acid catalyst required.

 Substrate: Vicinal diol.

 Intermediate: Carbocation.

 Product: Ketone (pinacolone).

 Migration aptitude order important.

8. Stevens Rearrangement

Definition
The Stevens rearrangement is a base-catalyzed [1,2]-shift that occurs in quaternary
ammonium salts (and also sulfonium ylides), leading to rearranged amines or sulfides.
General:

Mechanism
Deprotonation
o Strong base abstracts a proton adjacent to nitrogen generates an ylide.
[1,2]-Shift
o One alkyl or aryl substituent migrates from nitrogen to carbon.
o This is a concerted rearrangement.
Product formation
o Rearranged amine (or sulfide).
Features
 Example of sigmatropic rearrangement.

 Can involve radical pair or ionic mechanisms depending on conditions.

Applications
 Useful in synthesis of complex amines and heterocycles.

 Applied in stereoelectronic control studies.

Exam Tricks
 Always check for quaternary ammonium or sulfonium salt.

 Rearrangement occurs via 1,2-shift.

 Stereochemistry can be scrambled due to radical pathways.

Key Points
 Base required (strong).

 Substrate: Quaternary ammonium/sulfonium salt.

 Rearrangement: [1,2]-shift.

 Product: Rearranged amine or sulfide.

9. Schmidt Rearrangement

Definition
The Schmidt rearrangement involves the reaction of carboxylic acids, ketones, or
aldehydes with hydrazoic acid (HN₃ ) in the presence of acid to form amines, amides, or
nitriles depending on the substrate.
General transformations:
 Carboxylic acid Amine (with loss of CO₂ ).
  Ketone Amide.

 Aldehyde Nitrile.

Mechanism (Ketone Case)

Protonation of carbonyl oxygen.
Nucleophilic attack of HN₃ on carbonyl carbon.
Rearrangement: R-group migrates to nitrogen with N₂ loss nitrilium ion.
Hydrolysis amide.
Comparison with Curtius
 Both involve N₂ loss and group migration.

 Schmidt starts from carbonyl compounds, Curtius from acyl azides.

Exam Tricks
 Look for hydrazoic acid (HN₃ ) + acid.

 Product depends on substrate type:

o Carboxylic acid Amine.
o Ketone Amide.
o Aldehyde Nitrile.

Key Points
 Reagent: HN₃ + acid.

 Migratory step with N₂ loss.

 Products vary with substrate.

 Similar to Curtius.

10. Tiffeneau–Demjanov Rearrangement

Definition
The Tiffeneau–Demjanov rearrangement is the ring-expansion reaction where an α-
amino alcohol (or amine) undergoes nitrous acid treatment, leading to diazonium
formation, nitrogen loss, and subsequent rearrangement larger ring ketone.
Mechanism
Diazotization
o Amino group reacts with HNO₂ diazonium salt.
Loss of N₂
o Generates carbocation intermediate.
Ring expansion
o Adjacent carbon migrates ring enlarges.
Final product
o Rearranged carbocation stabilizes ketone formed.
Mechanism 2 :

Applications
 Widely used for ring expansion in organic synthesis.

 Useful for converting 5-membered rings 6-membered rings.

Exam Tricks
 Look for α-amino alcohols + HNO₂ .

 Product is always a ring-expanded ketone.

 Important for heterocyclic and natural product synthesis.

Key Points
 Reagent: HNO₂ (from NaNO₂ + HCl).

 Intermediate: Diazonium salt carbocation.

 Rearrangement: Ring expansion.

 Product: Ketone.

Final Revision Table (6–10)

Rearrangement Starting Material Conditions Product Key Feature
Curtius Acyl azide Heat Amine (via N₂ loss,
isocyanate) stereospecific
migration
Pinacol Vicinal diol Acid Ketone Carbocation
(pinacolone) rearrangement
Stevens Quaternary Base Rearranged [1,2]-shift
ammonium/sulfonium amine/sulfide
Schmidt Carboxylic acid, HN₃ + Amine / Amide Substrate-
ketone, aldehyde Acid / Nitrile dependent
Tiffeneau– α-amino alcohol HNO₂ Ring- Ring expansion
Demjanov expanded via diazonium
ketone loss

11. Wolff Rearrangement

Definition and Context

The Wolff rearrangement is an important organic transformation where α-diazoketones
undergo thermally or photochemically induced rearrangement to form ketenes, which
can further react with nucleophiles such as water, alcohols, or amines. This reaction is often
coupled with the Arndt–Eistert homologation, a method for chain elongation of carboxylic
acids by one carbon unit.
Discovered by Ludwig Wolff in 1912, this rearrangement plays a vital role in modern synthetic
organic chemistry. Its use in homologation makes it particularly valuable in natural product
synthesis and pharmaceutical chemistry.

General Reaction Scheme

The ketene intermediate can then undergo nucleophilic attack:

  With H₂ O gives carboxylic acid

 With ROH gives ester

 With RNH₂ gives amide

Mechanism (Stepwise)
Generation of α-diazoketone
Usually prepared by reacting acid chlorides with diazomethane.
Nitrogen expulsion
Upon heating or irradiation, nitrogen gas (N₂ ) is expelled, generating a reactive
carbene-like intermediate at the α-carbon.
1,2-Shift (Rearrangement step)
The R-group adjacent to the carbonyl migrates to the electron-deficient carbene
carbon. This migration is concerted and retains stereochemistry.
Formation of ketene
The rearrangement leads to a ketene intermediate (R–CH=C=O).
Capture of ketene
The ketene reacts with nucleophiles depending on the medium.
Migratory Aptitude
The order of migration in Wolff rearrangement is:
H > Aryl > Alkyl
Hydride migration is fastest due to strong orbital overlap and stabilization of transition state.

Applications
 Arndt–Eistert synthesis: Extends carbon chain of carboxylic acids.

 Natural product synthesis: Used for generating homologated skeletons.

 Peptide chemistry: Helpful in introducing extra methylene groups in amino acid

derivatives.

Exam Tricks
 Mnemonic for migration order: “Hurry Around America” H > Aryl > Alkyl.

 If the exam gives a choice between alkyl vs aryl migration, pick aryl (unless hydride
is present).

 Always look for N₂ expulsion + 1,2-shift Ketene clue.

Key Points
 Concerted rearrangement.

 Nitrogen gas evolution drives the reaction.

 Ketene is highly reactive and rarely isolated.

 Useful in homologation of acids.

12. Wagner–Meerwein Rearrangement

Definition and Context

The Wagner–Meerwein rearrangement is a carbocation rearrangement involving the
migration of an alkyl or aryl group with its bonding electrons from one carbon atom to an
adjacent carbocation center. This process leads to more stable carbocations, thus more
stable products.
First studied by Wagner (1899) and Meerwein (1924), this rearrangement underlies many
complex organic reactions, especially in terpene synthesis and industrial hydrocarbon
transformations.

General Reaction Scheme

Mechanism (Stepwise)
Carbocation generation
Usually by protonation of alcohols or via leaving group departure (e.g., halides).
 1,2-Alkyl shift or hydride shift
A group adjacent to the carbocation migrates with its electron pair to the cationic
center.
Formation of new carbocation
The rearrangement continues until a more stable carbocation (tertiary > secondary >
primary) is achieved.
Nucleophile attack
The stabilized carbocation is trapped by nucleophiles (water, halides, etc.) giving
rearranged products.

Examples
 Pinacol rearrangement (special case).

 Isoborneol to camphene transformation (classical example).

Migratory Aptitude
Generally follows carbocation stability + hyperconjugation:

Hydride > Phenyl > Tertiaryalkyl > Secondaryalkyl > Primaryalkyl > Methyl

Applications
 Synthesis of rearranged terpenes.

 Explains skeletal rearrangements in cationic polymerizations.

 Useful in industrial hydrocarbon cracking/rearrangements.

Exam Tricks
 Look for carbocation next to tertiary/aryl group indicates shift.

 “Wagner always wants stability” rearrangement proceeds toward more stable

carbocation.

 Expect a 1,2-shift only; not long-range.

Key Points
 A thermodynamically driven rearrangement.

 Occurs via carbocation intermediate.

 Rearrangement often explains unexpected products in acid-catalyzed reactions.

13. Favorskii Rearrangement

Definition and Context

The Favorskii rearrangement is a base-induced rearrangement of α-haloketones (usually
α-halo cyclic ketones) leading to carboxylic acids or esters with rearranged carbon
skeletons.
Discovered by Alexei Yevgrafovich Favorskii (1894), this rearrangement is especially
important in ring contraction reactions.

General Reaction Scheme

For cyclic α-haloketones:

Mechanism (Stepwise)
Enolate formation
Strong base abstracts α-hydrogen to form enolate.
Cyclopropanone intermediate
Enolate displaces halide intramolecularly, forming a strained cyclopropanone.
 Ring opening (1,2-shift)
The cyclopropanone undergoes bond cleavage, leading to rearranged carboxylate
anion.
Work-up
Acidic or neutralization work-up gives carboxylic acid/ester.

Special Feature – Ring Contraction

 A six-membered ring α-haloketone gives a five-membered ring acid (contracted).

 This is highly exam-relevant.

Migratory Aptitude
Generally similar to carbocation stability:

Tertiary > Secondary > Primary > Methyl

Applications
 Ring contraction synthesis.

 Preparation of small/medium-ring carboxylic acids.

 Industrial use in steroid modifications.

Exam Tricks
 Look for α-haloketone under base think Favorskii.

 “Favorskii Folds Rings” ring contraction clue.

  Cyclopropanone intermediate is exam favorite!

Key Points
 Base-induced rearrangement.

 Cyclopropanone intermediate is the hallmark.

 Produces acids/esters with rearranged skeleton.

Applications in Organic Synthesis
Preparation of smaller ring carboxylic acids.
Conversion of haloketones into esters, amides.
Useful in medicinal chemistry to modify ring sizes.

14. Fries Rearrangement

Definition & Introduction

The Fries rearrangement is the rearrangement of aryl esters to hydroxyaryl ketones
under the influence of Lewis acids (AlCl₃ , BF₃ , etc.).
It is a carbonyl migration reaction: the acyl group of the ester migrates from oxygen to the
aromatic ring, giving ortho- and para-acylphenols.

General Reaction

Mechanism (Stepwise Explanation)

Activation of Ester by Lewis Acid:
o AlCl₃ coordinates to the carbonyl oxygen.
o This increases electrophilicity of the acyl group.
Cleavage of Ar–O bond:
o Generates an acylium ion (R–C≡O⁺ ) and a phenoxide-like intermediate.
Electrophilic Substitution on Aromatic Ring:
 o The acylium ion attacks the aromatic ring at ortho or para positions.
o Ortho/para ratio depends on conditions (temperature, solvent, catalyst).
Re-aromatization:
o Proton loss restores aromaticity, forming hydroxyaryl ketone.

Key Features
 Lewis acid is essential (commonly AlCl₃ ).

 Both ortho and para products form.

 Temperature can shift selectivity:

o Low temp ortho product favored.
o High temp para product favored.
Exam Tricks & Shortcuts
 Mnemonic: Fries likes Fries (o + p options).

 Always check ortho/para directing influence of –OH group.

 Product distribution depends on sterics and temperature.

Shortcut Rule:

 Ester on aromatic ring + AlCl₃ = hydroxyaryl ketone.

 No rearrangement if ring is deactivated (NO₂ , CF₃ ).

Applications in Organic Synthesis

 Preparation of ortho-/para-hydroxyaryl ketones (precursors for pharmaceuticals,
dyes).

 Synthetic route to flavones, coumarins, aromatic ketones.

Key Points Summary

 Rearrangement of aryl esters hydroxyaryl ketones.

 Proceeds via acylium ion intermediate.

 Ortho vs para ratio influenced by conditions.

 Requires Lewis acid.

15. Neber Rearrangement

Definition & Introduction

The Neber rearrangement is the base-induced rearrangement of oxime tosylates to yield
α-aminoketones.
Named after Rudolf Neber, it is widely used in heterocyclic and amino-substituted ketone
synthesis.
General Reaction

Mechanism (Stepwise Explanation)

Formation of Oxime Tosylate:

o Ketone oxime is treated with tosyl chloride (TsCl) oxime tosylate.
Deprotonation & Rearrangement:
o Base abstracts a proton adjacent to nitrogen.
o Generates a carbanion stabilized by adjacent nitrogen.
Rearrangement:
o Nitrogen migrates with its substituent to carbon.
o N–O bond cleaves, producing an iminoketone.
Hydrolysis:
o Hydrolysis of iminoketone α-aminoketone.
Key Features
 Requires tosylation step before rearrangement.

 Base like NaOH, NaOEt, or pyridine initiates rearrangement.

 Produces α-aminoketones (important intermediates).

Exam Tricks & Shortcuts

 Mnemonic: Neber “Neighbor” N migrates to neighbor carbon.

 Always look for oxime tosylates in exam questions.

 Product = α-aminoketone, not amide.

Shortcut Rule:

 Ketone oxime oxime tosylate rearrangement α-aminoketone.

Applications in Organic Synthesis

 Preparation of α-aminoketones (key building blocks in pharmaceuticals).

 Synthesis of heterocycles like pyrroles, indoles, quinolines.

Key Points Summary

 Rearrangement of oxime tosylates α-aminoketones.

 Base-induced, involves nitrogen migration.

 Useful for synthesis of nitrogen-containing compounds.

Memory Trick
Wolff Rearrangement – Ketene formation from α-diazoketones; important in Arndt–
Eistert synthesis.
Wagner–Meerwein Rearrangement – Carbocation rearrangement via hydride/alkyl
shifts; key in terpenes, steroids.
Favorskii Rearrangement – α-haloketone carboxylic acid derivative (ring
contraction in cyclic systems).
Fries Rearrangement – Aryl esters hydroxyaryl ketones (ortho/para substitution).
Neber Rearrangement – Oxime tosylates α-aminoketones (N migrates).

Exam-Oriented Tricks (Super Quick Recap)

 Wolff Ketenes (Carboxylic Acid Chain Extension).

 Wagner–Meerwein Carbocation Rearrangement (Alkyl/Hydride Shifts).

 Favorskii Ring Contraction (Carboxylic Acids).

 Fries Ortho/Para Hydroxyaryl Ketones (Lewis Acid).

 Neber α-Aminoketones (via Oxime Tosylates).

16. Lossen Rearrangement

Definition & Historical Note

The Lossen Rearrangement is a thermal or base-induced rearrangement of hydroxamic
acid derivatives (commonly O-acyl, O-sulfonyl, or O-aryl hydroxamic acids) to give
isocyanates, which upon hydrolysis yield primary amines.

 First reported by Wilhelm Lossen (1872).

 It is mechanistically similar to Curtius, Schmidt, and Hofmann rearrangements

because all involve migration to an electron-deficient nitrogen leading to
isocyanate intermediates.
General Reaction:
Hydroxamic acid derivative (Base/Heat) Isocyanate Hydrolysis Primary Amine
Detailed Mechanism
Activation Step
Hydroxamic acids are converted into their derivatives (O-acyl, O-sulfonyl,
carbamates) because the free hydroxamic acid is not sufficiently reactive.
Example: R–C(=O)–NHOH R–C(=O)–NHO–SO₂ R′
Deprotonation
Under basic conditions, the –NH group is deprotonated, making nitrogen a better
nucleophile.
Rearrangement (Key Step)
The substituent R (from carbonyl carbon) migrates to nitrogen with simultaneous
expulsion of the leaving group (–OAc, –OSO₂ R, –OAr).
o This step forms an isocyanate intermediate.
o Migration is intramolecular and highly stereospecific (retention of
configuration).
Isocyanate Hydrolysis
Isocyanate + H₂ O Carbamic acid Spontaneous decarboxylation Primary
amine.
Mechanistic Scheme:
R–C(=O)–NHOX [Base/Heat] R–N=C=O H₂ O R–NH₂ + CO₂

Migratory Aptitude
 Aryl > Secondary Alkyl > Primary Alkyl > Methyl

 Strong resemblance to Hofmann/Curtius rearrangements.

Applications
 Amine synthesis from carboxylic acids.

 Precursor in drug synthesis (e.g., substituted anilines).

 Can be used for labeling isotopes (C or N migration).

Exam Tricks
 Always check the starting functional group: Lossen uses hydroxamic acid
derivatives (not plain amides like Hofmann).

 Isocyanate intermediate = signature of Lossen, Curtius, Schmidt.

 Product = primary amine + CO₂ (no rearranged skeleton carbons lost).

Key Points
 Derivative of hydroxamic acid needed.

 Rearrangement isocyanate hydrolysis amine.

 Stereospecific migration.

 Exam mnemonic: “HCl” Hofmann (amide), Curtius (azide), Lossen

(hydroxamic).

17. Hofmann Rearrangement

Definition
The Hofmann Rearrangement (or Hofmann degradation) is the base-induced oxidative
rearrangement of a primary amide to a primary amine with one fewer carbon atom.

 First described by August Wilhelm von Hofmann in 1881.

 Widely used in synthetic organic chemistry for shortening the carbon chain.
General Reaction:

R–CONH₂ + Br₂ /NaOH R–NH₂ + CO₂

Detailed Mechanism

Formation of N-Bromoamide
R–CONH₂ + Br₂ /NaOH R–CONHBr
Deprotonation
Base removes the –NH proton, generating a bromoamide anion.
Rearrangement (Rate-Determining Step)
– Migration of R group from carbonyl carbon to nitrogen with simultaneous expulsion
 of Br⁻ .
– Forms isocyanate intermediate.
Hydrolysis of Isocyanate
R–N=C=O + H₂ O Carbamic acid R–NH₂ + CO₂

Migratory Aptitude
 Aryl > Secondary Alkyl > Primary Alkyl > Methyl

 Similar to Lossen and Curtius.

Applications
 Conversion of amides amines (chain-shortening).

 Industrial synthesis of anilines from benzamides.

 Used in pharmaceutical synthesis (e.g., paracetamol derivatives).

Exam Tricks
 Reagent signature = Br₂ /NaOH (or Cl₂ /NaOH).

 Product = amine (one C shorter).

 Intermediate = isocyanate (NET exam favorite).

 Trick mnemonic: “Hofmann Brings Down C” = Hofmann, Br₂ /NaOH, one carbon
less.

Key Points
 Substrate: Primary amide only (secondary/tertiary fail).

 Carbon skeleton loses one carbon as CO₂ .

 Stereospecific migration.

 Similar to Curtius/Schmidt but different starting materials.

18. Beckmann Fragmentation (Special Cases)

Definition
The Beckmann Fragmentation is a variant of the Beckmann rearrangement, in which
certain substituted oximes undergo cleavage under acidic conditions to give nitriles and
carbocations (or carbenium ions), instead of amides.

 Occurs mainly in sterically hindered ketoximes or under strong acidic/dehydrating

conditions.
General Reaction:

R¹R²C=NOH (acid/dehydrating agent) R¹–C≡N + R²⁺

Detailed Mechanism
Protonation of Oxime OH group
R¹R²C=NOH + H⁺ R¹R²C=NOH₂ ⁺
Leaving Group Departure
Loss of H₂ O Formation of nitrilium ion.
Fragmentation Step
Instead of normal rearrangement to amide, one group migrates and the other is
expelled as a carbocation (or radical).
o R¹ migrates to nitrogen R¹–C≡N
o R² leaves as R²⁺
Fate of Carbocation
o May react with nucleophiles (H₂ O, Cl⁻ , ArOH, etc.).
o Often forms alkylated by-products.

Special Cases
 Tert-alkyl oximes readily undergo fragmentation (carbocation stability).

 Cyclohexanone oxime derivatives ring-contracted amides (competition between

normal rearrangement & fragmentation).
  In presence of strong acids (H₂ SO₄ , P₂ O₅ ), fragmentation dominates.

Applications
 Synthetic route to nitriles and cation-derived products.

 Useful in heterocyclic synthesis (imidazoles, pyridines).

 Precursor in industrial nylon chemistry (Beckmann ε-caprolactam;

fragmentation = side reaction to avoid).

Exam Tricks
 Beckmann normal product = amide.

 Fragmentation product = nitrile + carbocation.

 Exam hint: “If carbocation is stable fragmentation dominates.”

Key Points
 Beckmann fragmentation = special case (acidic conditions).

 Major product = nitrile.

 Carbocation stability decides outcome.

 NET question type: Identify conditions where amide vs nitrile forms.

19. Benzidine Rearrangement

Definition
The Benzidine rearrangement is a classic acid-catalyzed rearrangement of
hydrazobenzene (Ar–NH–NH–Ar) to yield benzidine (p-phenylenediamine derivatives) or
other positional isomers (diphenylamines, semidines).

 First discovered in 1845 by E. Mitscherlich.

 Very important for azo dye industry.

General Reaction:
Detailed Mechanism
Protonation of Hydrazobenzene
The –NH– group gets protonated, creating a better leaving group and activating the
system.
Cleavage of N–N bond
One N atom departs as a cation (NH₂ ⁺ ), leaving behind an aryl cation intermediate.
Aryl Migration
One of the aryl groups migrates to the positively charged nitrogen, producing an
intermediate diphenylamine.
Rearrangement to p- or o-products
Depending on substituents, solvent, and conditions, migration leads to benzidine
(para product) or semidines (ortho product).
Deprotonation Final stable product (p-phenylenediamine).

Migratory Aptitude
 Electron-rich aryl groups migrate faster.

 Para-substituents direct migration to form benzidine.

 Steric hindrance favors ortho semidine.

Applications
 Industrial synthesis of aromatic diamines.

 Precursors to azo dyes, polymers, antioxidants.

 Important in polyurethane chemistry.

Exam Tricks
 Trick 1: Acid catalysis = benzidine rearrangement.

 Trick 2: Ortho semidine = steric bulk near para.

 Trick 3: NET exam often asks: Hydrazobenzene ? in HCl medium? Answer:

benzidine (major).

Key Points
 Acid catalyzed.

 Major product = benzidine.

 Competes with diphenylamine formation.

 Substituents decide regioselectivity.

20. Demjanov Rearrangement

Definition
The Demjanov rearrangement involves deamination of primary amines (usually aliphatic)
using nitrous acid (HNO₂ ), leading to ring expansion or ring contraction depending on
the intermediate carbocation.
General Reaction:

Detailed Mechanism
Formation of Diazonium Salt
–NH₂ group reacts with nitrous acid to form –N₂ ⁺ diazonium salt.
Loss of N₂ (excellent leaving group)
Nitrogen gas escapes, generating a carbocation.
Carbocation Rearrangement
o In acyclic compounds hydride/methyl shifts.
o In cyclic compounds ring expansion (3 4 membered, 5 6 membered,
etc.).
Capture of carbocation
Water (from medium) captures carbocation rearranged alcohol.
Examples
 Cyclobutylamine Cyclopentanol (ring expansion).

 Cyclopentylamine Cyclohexanol.

 Linear amines skeletal rearrangements.

Applications
 Synthesis of higher homologues of cyclic alcohols.

 Understanding carbocation rearrangement principles.

 Useful in alkaloid synthesis.

Exam Tricks
 Trick 1: HNO₂ + amine = diazonium salt ring expansion.

 Trick 2: Only primary amines undergo this rearrangement.

 Trick 3: Look for N₂ gas release in question Demjanov.

Key Points
 Involves nitrous acid deamination.

 Produces ring expansion in cyclic amines.

 Mechanism = diazonium carbocation rearrangement.

21. Bouvet Rearrangement

Definition
The Bouvet rearrangement is a photochemical rearrangement of quaternary ammonium
salts that yields tertiary amines via aryl or alkyl migration.

 Discovered by Pierre Bouvet.

 Rare but important in photochemistry of amines.

General Reaction
R4 N+ X- R3 N + R+

Detailed Mechanism
3. UV Irradiation of Quaternary Ammonium Salt
Excites nitrogen-centered cation.
4. Cleavage of C–N bond
Generates a radical cation or ion-pair.
5. 1,2-Alkyl or aryl migration
The group adjacent to nitrogen shifts, stabilizing the system.
6. Formation of tertiary amine as the rearranged product.

Applications
 Demonstrates photochemical N–C bond activation.

 Model system for studying radical cation rearrangements.

 Basis of some synthetic photochemical methods.

Exam Tricks
 Trick 1: Light + quaternary ammonium salt = Bouvet rearrangement.

 Trick 2: Major product = tertiary amine.

 Trick 3: If exam mentions “photochemical rearrangement of ammonium salt”

Bouvet.

Key Points
 Photochemical (requires UV light).

 Substrate = quaternary ammonium salts.

 Product = tertiary amines.

Final Quick Revision Table (19–21)

Rearrangement Starting Material Reagent/Condition Major Product Exam Clue
Benzidine Hydrazobenzene Acid (HCl, Benzidine (p- Acid-catalyzed
H₂ SO₄ ) phenylenediamine N–N shift
)
Demjanov Primary amines HNO₂ Rearranged N₂ gas release,
alcohol (via ring expansion
carbocation)
Bouvet Quaternary UV light Tertiary amine Photochemical,
ammonium salts N–C cleavage

22. Sommelet Rearrangement

Definition & Introduction

The Sommelet Rearrangement is a classical organic reaction in which a benzyl halide (or
benzyl quaternary ammonium salt) undergoes transformation into a benzaldehyde
derivative in the presence of a strong base such as aqueous NaOH.

 Discovered by Marcel Sommelet in 1913.

 It is one of the few reactions where a benzyl group migrates with oxidation to form
an aldehyde functionality directly attached to the aromatic ring.
The general reaction can be written as:
Ar–CH₂ –NR₃ ⁺ Cl⁻ Ar–CHO + NR₃
Where Ar is an aromatic group, and the aldehyde obtained is aromatic aldehyde
(benzaldehyde derivative).
 Detailed Mechanism
Formation of Benzyl Iminium Intermediate
o A quaternary benzyl ammonium salt reacts with strong base (e.g., NaOH).
o Hydroxide abstracts a proton or attacks the benzylic carbon, producing an
ylide-like intermediate.
Nucleophilic Attack & Rearrangement
o The intermediate undergoes rearrangement where the benzylic group
migrates toward the nitrogen, giving an imine intermediate.
Hydrolysis of the Imine
o The imine intermediate is hydrolyzed under reaction conditions to give
benzaldehyde.
o The amine group is liberated as a tertiary amine (NR₃ ).
Stepwise Transformation:

 [C₆ H₅ –CH₂ –N⁺ (Me)₃ ]Cl⁻ [C₆ H₅ –CH=N(Me)₂ ] Hydrolysis

C₆ H₅ –CHO + HNMe₂
Key Factors
 Requires strong base (NaOH, KOH).

 Works best for benzyl quaternary ammonium salts.

 Specific for aromatic benzyl systems; aliphatic analogues fail.

Synthetic Applications
7. Preparation of Benzaldehyde derivatives directly from benzylamines.
8. Widely used in synthesis of substituted aromatic aldehydes.
9. Useful for synthetic organic transformations in perfume industry and drug
intermediates.

Exam Tricks & Mnemonics

 Trick to remember: “Sommelet = Salt Smell of Aldehyde” (since aldehydes often
have distinctive odor).

 If you see a benzyl quaternary ammonium salt in question directly think

benzaldehyde product.

 Difference from Stevens rearrangement: Stevens gives amines, Sommelet gives

aldehydes.

Key Points Summary

 Reagent: Strong base (NaOH).

 Intermediate: Benzyl iminium.

 Product: Benzaldehyde derivative.

 Scope: Aromatic benzyl systems only.

CSIR-NET Question Angles

Predict product: [p–MeC₆ H₄ –CH₂ –N⁺ (Me)₃ ]Cl⁻ ?
o Ans: p–MeC₆ H₄ –CHO.
Mechanism order: Ammonium salt imine aldehyde.
Identify difference between Sommelet vs Sommelet–Hauser rearrangement (Hauser
gives ortho-substituted aldehydes via intramolecular rearrangement).
23. Payne Rearrangement

Definition & Introduction

The Payne Rearrangement is a base-catalyzed intramolecular rearrangement of epoxy
alcohols (glycidols) into allyl alcohols.

 Discovered by George B. Payne in 1962.

 Important for stereoselective and regioselective transformation of small epoxides into

allylic alcohol frameworks.

 Mechanistically, it involves epoxide ring-opening, intramolecular shift, and

reclosure.

General Reaction:
HO–CH₂ –CH–CH₂ (epoxide) HO–CH–CH=CH₂ (allyl alcohol)

Detailed Mechanism

Epoxide Ring Opening

o Under basic conditions (NaOH, alkoxides), the hydroxyl group deprotonates
to form alkoxide.
Intramolecular Nucleophilic Attack
o The alkoxide attacks the adjacent epoxide carbon, causing the epoxide to
reopen and migrate.
Shift of Oxygen Atom
o The process leads to rearrangement of the epoxy alcohol, shifting the
position of the oxygen to form an allyl alcohol.
Equilibration
o The reaction is reversible; product distribution depends on stability of allyl
alcohol formed.
Key Factors
 Requires epoxy alcohol substrate.

 Base-catalyzed (NaOH, t-BuOK).

 Reversible reaction, product stability determines outcome.

Synthetic Applications
Synthesis of allylic alcohols from epoxides.
Key transformation in steroid synthesis.
Useful in total synthesis of terpenes and natural products.
Important for rearranging asymmetric epoxides into valuable intermediates.

Exam Tricks & Mnemonics

 Trick: “Payne rearranges Painful Epoxides” Epoxide Allyl alcohol.

 In multiple-choice questions:
o Epoxide + base Allyl alcohol.

 Difference from Claisen rearrangement: Claisen involves [3,3]-sigmatropic shift,

Payne involves epoxide opening.

Key Points Summary

 Substrate: Epoxy alcohol.

 Reagent: Base (NaOH, alkoxides).

 Product: Allyl alcohol.

 Important in stereospecific synthesis.

CSIR-NET Question Angles

Which rearrangement converts epoxy alcohol allyl alcohol? (Ans: Payne).
Stereoelectronic requirement: Requires free hydroxyl near epoxide.
Predict major product from substituted epoxy alcohol.
24. Overman Rearrangement

Definition & Introduction

The Overman Rearrangement is a Claisen-like [3,3]-sigmatropic rearrangement of
allylic trichloroacetimidates to form allylic trichloroacetamides, which can be hydrolyzed
to give allylic amines.

 Discovered by Larry Overman in 1974.

 Key reaction for preparing allylic amines, which are important building blocks in
pharmaceuticals and alkaloid synthesis.
General Reaction:
R–CH=CH–CH₂ –O–C(=N–CCl₃ ) R–CH=CH–CH₂ –NH–C(=O)CCl₃ R–CH=CH–
CH₂ –NH₂ (after hydrolysis).

Detailed Mechanism
Formation of Allylic Trichloroacetimidate
o Alcohol reacts with trichloroacetonitrile (Cl₃ CCN) under base to form imidate.
[3,3]-Sigmatropic Rearrangement
o The allylic imidate undergoes a concerted [3,3]-sigmatropic rearrangement.
o Migration of allyl group occurs to nitrogen, forming trichloroacetamide.
Hydrolysis
o Hydrolysis of trichloroacetamide yields the allylic amine.
Key Factors
 Reaction resembles Claisen rearrangement (concerted, [3,3]-sigmatropic).

 Driving force: Stability of amide bond formed.

 Conditions: Heat or Lewis acid catalysis.

Synthetic Applications
Preparation of allylic amines (key intermediates in alkaloid synthesis).
Used in synthesis of natural products like Dendrobine, Stemofoline.
Broadly applied in pharmaceutical industry.

Exam Tricks & Mnemonics

 Mnemonic: “Overman = Over to Amine” Alcohol Amine.

 Compare with Claisen rearrangement:

o Claisen: allyl vinyl ether γ,δ-unsaturated carbonyl.
o Overman: allyl imidate allyl amine.

Key Points Summary

 Substrate: Allyl trichloroacetimidate.

 Mechanism: [3,3]-Sigmatropic rearrangement.

 Product: Allylic amines (after hydrolysis).

 Importance: Alkaloid & drug synthesis.

CSIR-NET Question Angles

Which rearrangement is [3,3]-sigmatropic and gives allyl amines? (Ans: Overman).
Compare Claisen vs Overman – both are [3,3], but products differ.
Predict product of rearrangement of allyl alcohol + Cl₃ CCN.
 Summary (22–24)
 Sommelet Rearrangement Benzyl quaternary ammonium salt Benzaldehyde.

 Payne Rearrangement Epoxy alcohol Allyl alcohol.

 Overman Rearrangement Allyl imidate Allyl amine (via [3,3]-sigmatropic shift).

These three rearrangements together show base-catalyzed (Sommelet, Payne) vs
pericyclic (Overman) diversity. They are very CSIR-NET relevant because product
prediction, mechanistic steps, and stereoelectronic requirements are often asked.

25. Johnson–Claisen Rearrangement

Definition & Historical Context

The Johnson–Claisen rearrangement (1961, William S. Johnson) is a thermal [3,3]-
sigmatropic rearrangement of allyl vinyl ethers into γ,δ-unsaturated esters. It is a
variant of the classical Claisen rearrangement, but employs acidic orthoesters
(commonly triethyl orthoformate, triethyl orthopropionate, etc.) and alcohols under acidic
conditions to generate an allyl vinyl ether intermediate, which undergoes rearrangement
upon heating.

 It is a mild, flexible, and powerful method for C–C bond formation in synthetic
organic chemistry.

 The rearrangement bypasses the need for free vinyl ethers, which are often
unstable, and instead uses orthoesters as safer precursors.

General Reaction
[ RCH=CHCH_2–O–CH=CHR’ RCH=CHCH_2–CHR’–C(=O)OR’’ ]
Where:
 Allyl group migrates to the vinyl carbon.

 Product: γ,δ-unsaturated ester.

Reaction Conditions
 Orthoesters (triethyl orthoformate most common).

 Allylic alcohols.

 Acid catalyst (PPTS, HCl, TsOH, etc.).

 Heat (150–250 °C in inert solvents).

Mechanism (Stepwise)
Formation of Allyl Vinyl Ether
o Allyl alcohol reacts with triethyl orthoformate under acidic catalysis forms
allyl vinyl ether intermediate.
[3,3]-Sigmatropic Rearrangement
o The vinyl ether undergoes concerted [3,3]-sigmatropic shift via a six-
membered cyclic transition state.
o Allyl group migrates, generating γ,δ-unsaturated ester.
Tautomerization / Workup
o Proton transfers and hydrolysis give final ester product.
Key Stereoelectronic Features
 Six-membered transition state = chairlike, stereospecific.

 Substituents at allylic/vinylic positions influence stereochemistry.

 The rearrangement is pericyclic and follows the Woodward–Hoffmann rules.

Applications
 Synthesis of γ,δ-unsaturated esters, versatile intermediates.

 Natural product synthesis: prostaglandins, pheromones, polyketides.

 Construction of chiral centers.

Exam Tricks (CSIR-NET Level)

 Trick: Johnson–Claisen always γ,δ-unsaturated esters.

 Differentiate from Ireland–Claisen (carboxylates, base-catalyzed) and Overman

(allyl trichloroacetimidates allyl amines).

 Transition state = [3,3]-sigmatropic, not ionic.

Shortcut mnemonic:
“Johnson makes Esters Just-on heat.”

Key Points
 Concerted, pericyclic rearrangement.

 Generates esters with high regiocontrol.

 Tolerates functional groups.

 Competes with Ireland–Claisen in strategy planning.

26. Ireland–Claisen Rearrangement

Definition & Context

The Ireland–Claisen rearrangement (1972, Robert Ireland) is a [3,3]-sigmatropic
rearrangement of allyl esters, where the ester is first deprotonated at the α-position to
form an enolate, which is then silylated to give a silyl ketene acetal. Upon heating, the
rearrangement delivers a carboxylic acid derivative with a new C–C bond.

 It is a powerful stereoselective version of the Claisen rearrangement.

 Unique because it allows control of stereochemistry (Z/E geometry of enolate

product stereochemistry).
General Reaction

Reaction Conditions
 Base: LDA, LiHMDS (forms enolate).

 Silyl chloride (TMSCl, TBSCl).

 Heat for rearrangement.

Mechanism (Stepwise)
Enolate Generation
o Strong base deprotonates α-hydrogen lithium enolate.
Silyl Protection
o Enolate captured by silyl chloride silyl ketene acetal.
[3,3]-Sigmatropic Rearrangement
o Concerted rearrangement new C–C bond formation.
Workup
o Hydrolysis carboxylic acid derivative.

Stereochemical Control

 (Z)-enolate syn product.

 (E)-enolate anti product.

 Hence, predictable diastereoselectivity.

Applications
 Chiral center creation adjacent to carboxyl groups.

 Key in natural product synthesis (macrolides, polyketides).

 Used in asymmetric synthesis (chiral auxiliaries).

Exam Tricks
 Trick: Ireland–Claisen always requires base + silyl chloride.

 Control of stereochemistry NET exam frequently asks which enolate geometry

leads to which product.

 Differentiate from Johnson–Claisen (acidic conditions, esters, no enolate).

Mnemonic:
“Ireland rearranges under Ice-cold base (LDA).”

Key Points
 Enolate-based pericyclic rearrangement.

 Predictable stereochemical outcomes.

 Widely used in stereoselective synthesis.

 Six-membered cyclic TS similar to other Claisen variants.

27. Eschenmoser–Claisen Rearrangement

Definition & Context

The Eschenmoser–Claisen rearrangement (1965, Albert Eschenmoser) is a [3,3]-
sigmatropic rearrangement of allylic alcohols with N,N-dialkylacetamides or
orthoamides, forming γ,δ-unsaturated amides.

 Important modification of Claisen rearrangement.

 Uses amide-based reagents instead of esters/orthoesters.

 Provides access to allylic amides, valuable intermediates.

General Reaction
Mechanism
Formation of Enol Ether
o Allyl alcohol reacts with dimethylacetamide dimethyl acetal forms enol
ether.
[3,3]-Sigmatropic Rearrangement
o Concerted rearrangement γ,δ-unsaturated amide.
Tautomerization
o Proton transfers stabilize the amide product.

Stereoelectronic Features
 Similar chairlike six-membered transition state.

 Migration stereospecific.

 Substituents dictate regio- and stereochemistry.

Applications
 Synthesis of amide-containing natural products.

 Versatile in peptide & heterocycle chemistry.

 Builds amide linkages via C–C bond formation.

Exam Tricks
 Trick: Eschenmoser–Claisen always amides (not esters).

 NET exam trap: Students confuse with Johnson (esters) vs Eschenmoser (amides).
Mnemonic:
“Eschenmoser Ends in Amides.”

Key Points
 Uses amide acetals as reagents.

 Produces allyl amides.

 Concerted pericyclic mechanism.

 Important for medicinal and natural product chemistry.

Final Comparative Notes (25–27)

Rearrangement Key Product Type Conditions Exam Shortcut
Intermediate
Johnson–Claisen Allyl vinyl γ,δ-unsaturated Acidic, heat “Johnson = Ester”
ether ester
Ireland–Claisen Silyl ketene Substituted Base + silyl “Ireland = Enolate
acetal acid/ester chloride control”
Eschenmoser– Amide acetal γ,δ-unsaturated Acid/heat “Eschenmoser =
Claisen amide Amide”

28. Mumm Rearrangement

Definition & Overview

The Mumm Rearrangement is an intramolecular acyl transfer reaction in which an acyl
imidate (or related species) undergoes rearrangement to give an amide. It is essentially the
conversion of an imidate into an amide through migration of an acyl group.

 Discovered by Oskar Mumm in 1910.

 It is important in heterocyclic synthesis, peptide modifications, and medicinal

chemistry.

 The rearrangement is often considered a variant of acyl migration reactions where

nucleophilic nitrogen attacks a neighboring acyl group.
General Reaction

Mechanism (Stepwise)
Activation of the Imidate
o The oxygen or nitrogen in the imidate can be protonated (acidic medium) or
activated by Lewis acids.
o This makes the C=O carbon more electrophilic.
Nucleophilic attack
o The nitrogen atom attacks the activated carbonyl, initiating migration.
o This step involves intramolecular nucleophilic acyl substitution.
Acyl transfer / Migration
o The acyl group migrates from oxygen to nitrogen.
o This is the core rearrangement step (migration of R–C=O to N).
Amide formation
o Final stabilization occurs with amide bond formation.
o Proton transfers complete the rearrangement.

Key Notes
 Similar in spirit to Beckmann and Lossen rearrangements.

 Requires acidic or Lewis acid catalysis.

 Useful in amide bond formation without harsh conditions.

Applications
 Peptide Synthesis for converting imidate intermediates into peptide amides.

 Medicinal Chemistry used in heterocyclic and drug synthesis.

 Green Chemistry avoids toxic reagents, often performed in mild solvents.

Exam Tricks
 Remember: Mumm = Mum = Mother = NH (amide group) easy mnemonic to
recall product.

 Often appears in NET/GATE as a conceptual mechanism question.

 Key difference from Beckmann rearrangement here the acyl group migrates,
not the alkyl/aryl.
Key Points
 Intramolecular acyl transfer.

 Requires acid/Lewis acid catalysis.

 Forms amide bonds directly.

 Mechanism activation nucleophilic attack migration amide formation.

29. Bamberger Rearrangement

Definition & Overview

The Bamberger Rearrangement is the acid-catalyzed rearrangement of N-
phenylhydroxylamines into 4-aminophenols.

 Discovered by Eugen Bamberger in 1894.

 Important in dye chemistry, pharmaceutical intermediates, and aromatic amine

synthesis.

 The reaction provides a para-substituted product selectively.

General Reaction

Mechanism (Stepwise)
Protonation of Hydroxylamine
o The –OH of the NHOH group gets protonated N becomes electrophilic.
 Rearrangement Initiation
o Nitrogen loses water, forming a nitrenium ion intermediate (Ar–N⁺ H).
Aromatic Electrophilic Substitution
o The nitrenium ion undergoes electrophilic attack on the aromatic ring.
o Substitution occurs mainly at the para position (due to resonance
stabilization).
Formation of 4-Aminophenol
o Proton loss and re-aromatization yield para-aminophenol as the major
product.
o Ortho product is minimal due to steric hindrance.
o

Selectivity
 Para selectivity dominates due to resonance stabilization.

 Minor ortho product possible under different conditions.

Applications
 Synthesis of p-aminophenol precursor for paracetamol (acetaminophen).

 Important in azo dye intermediates.

 Classic example of aromatic electrophilic substitution rearrangement.

Exam Tricks
 Mnemonic: “Bamberger = BAM Para Amino Phenol.”

 Always para substitution (unless sterically blocked).

 Common NET question: Identify rearrangement leading to paracetamol precursor.

Key Points
 Substrate: N-phenylhydroxylamine.

 Catalyst: Strong acid (H₂ SO₄ , HCl).

 Product: 4-aminophenol (major).

 Mechanism: Nitrenium ion intermediate para attack re-aromatization.

30. Boekelheide Rearrangement

Definition & Overview

The Boekelheide Rearrangement is the rearrangement of pyridine N-oxides to give
hydroxymethylpyridines upon treatment with acylating agents.

 Discovered by Virgil Boekelheide in 1954.

 It is a unique heteroaromatic rearrangement.

General Reaction

Mechanism (Stepwise)
Formation of Acylated Pyridine N-oxide
o Pyridine N-oxide reacts with acyl chloride/anhydride.
o Oxygen gets acylated forming O-acylpyridinium ion.
[1,2]-Sigmatropic Shift
o A methyl group (α to N-oxide) undergoes [1,2]-shift to oxygen.
o Generates a hydroxyalkylated pyridinium intermediate.
Hydrolysis
o Hydrolysis of the intermediate yields 2-hydroxymethylpyridine.
Stereoelectronic Requirement
 Requires α-hydrogen on pyridine ring.

 Migration occurs specifically from α-position due to orbital alignment.

Applications
 Synthesis of 2-hydroxymethylpyridines important intermediates in medicinal
chemistry.

 Used in ligand design (chelating ligands for metal complexes).

 Demonstrates the power of N-oxide activation in heteroaromatic chemistry.

Exam Tricks
 Mnemonic: “Boekelheide = Book inside Pyridine” N-oxide rearranges inside ring
to hydroxymethyl.

 Unique to pyridine N-oxides (not benzene analogs).

 Common NET question: Which rearrangement introduces hydroxymethyl group at

pyridine α-position?

Key Points
 Substrate: Pyridine N-oxides.

 Reagents: Acylating agents (Ac₂ O, RCOCl).

 Product: 2-hydroxymethylpyridine.

 Mechanism: Acylation [1,2]-shift hydrolysis.

Comparison Table (Quick Revision)
Rearrangem Substrate Catalyst/Reage Major Product Key Exam
ent nt Point
Mumm Imidates Acid/Lewis acid Amide Intramolecul
ar acyl
transfer
Bamberger N- Strong acid 4-Aminophenol Paracetamol
Phenylhydroxylam precursor
ine
Boekelheide Pyridine N-oxide Acyl 2- [1,2]-shift
chloride/anhydri Hydroxymethylpyrid unique to N-
de ine oxides

31. Orton Rearrangement

Definition
The Orton rearrangement is an aromatic electrophilic substitution–based rearrangement in
which aromatic N-chloroamines (e.g., chloroanilines) undergo intramolecular
rearrangement to form p- or o-substituted chloroanilines. This transformation is observed
when aromatic amines are treated with hypochlorites or chlorine, leading to migration of
substituents on the benzene ring.
It was discovered by K.J.P. Orton in the early 20th century and remains important in
understanding the behavior of aromatic halogenation and rearrangement processes.

General Reaction
Detailed Mechanism
Formation of N-chloroamine
o An aromatic amine (aniline) reacts with hypochlorite (NaOCl) or Cl₂ to form
an N-chloro derivative.

Electrophilic Substitution Pathway

o The N–Cl bond is polarized (Nδ⁺ –Clδ⁻ ).
o This generates an electrophilic Cl⁺ species which attacks the activated
aromatic ring (ortho/para positions favored by –NH₂ group).
Rearrangement
o The rearrangement occurs via electrophilic aromatic substitution (EAS),
yielding ortho- and para-substituted chloroaniline.

Key Features
 Mainly ortho and para substitution products.

 Occurs due to electrophilic attack by Cl⁺ generated from the N–Cl bond.

 No migration of carbon skeleton, just substituent relocation.

Exam Tricks for CSIR-NET
 If you see ArNH₂ + Cl₂ /HOCl, think Orton rearrangement.

 Always remember ortho + para products form (like EAS rules).

 Orton vs. Sandmeyer: Orton involves N–Cl intermediates; Sandmeyer uses

diazonium salts.

Key Points
 Works only for aromatic amines.

 Produces ortho- and para-chloroanilines.

 Useful in studying halogenated aromatic intermediates in synthetic organic

chemistry.

32. Brook Rearrangement

Definition
The Brook rearrangement is a 1,2-silyl shift from carbon to oxygen observed in silyl-
substituted alcohols. It is an anionic rearrangement where a silyl group (–SiR₃ ) migrates
from a carbon atom to a neighboring oxygen atom under base-catalyzed conditions.
Discovered by A.G. Brook in 1958, it is a cornerstone in organosilicon chemistry.

General Reaction

Detailed Mechanism
Deprotonation
o A strong base (e.g., NaH, LDA, BuLi) deprotonates the OH group.

Nucleophilic Attack & Rearrangement

o The oxygen anion attacks the silicon atom.
o The Si–C bond breaks, and silicon migrates to oxygen.
Product Formation
o A silyl ether (O–SiR₃ ) is formed.
Key Features
 An anion-driven rearrangement.

 Thermodynamically favored since Si–O bonds are stronger than Si–C bonds.

 Common in silicon protecting group chemistry.

Exam Tricks for CSIR-NET

 "Brook = Silicon shift (Si O)".

 Look for α-silyl alcohols under base product is always a silyl ether.

 Remember: Driving force is strong Si–O bond formation.

Key Points
 Important in protecting group strategies.

 Classic example of 1,2-anionic rearrangements.

 Useful in designing organosilicon intermediates.

33. Carroll Rearrangement

Definition
The Carroll rearrangement is a [3,3]-sigmatropic rearrangement of allyl acetoacetates
to form γ,δ-unsaturated ketones. It is closely related to the Claisen rearrangement but
involves a β-ketoester system.
Named after Michael F. Carroll (1931), it has applications in C–C bond formation and
complex natural product synthesis.
General Reaction

Detailed Mechanism
Heating
o Allyl acetoacetates are heated (150–250 °C).
[3,3]-Sigmatropic Shift
o A pericyclic rearrangement occurs similar to Claisen.
o The allyl group shifts, forming a new C–C bond and a conjugated enol
intermediate.
Tautomerization
o The enol tautomerizes into a γ,δ-unsaturated ketone.

Key Features
 Reaction is pericyclic, concerted, and stereospecific.

 Related to Claisen rearrangement, but involves β-ketoesters.

 Heat-driven.
Exam Tricks for CSIR-NET
 "Carroll = Allyl acetoacetate γ,δ-unsaturated ketone".

 Always involves a [3,3]-sigmatropic shift.

 Compare with Johnson–Claisen (ester) and Ireland–Claisen (silyl ketene acetals).

Key Points
 Example of pericyclic chemistry important for NET/JRF exams.

 Provides direct C–C bond construction.

 Synthetic applications in terpenes and alkaloid synthesis.

Final Summary (31–33)

 Orton Rearrangement Aromatic N-chloroamines ortho/para chloroanilines.

 Brook Rearrangement Si shift (C O), driven by strong Si–O bond.

 Carroll Rearrangement [3,3]-sigmatropic shift of allyl acetoacetates γ,δ-

unsaturated ketones.

34. Barton Rearrangement

Definition
The Barton Rearrangement is a thermal rearrangement reaction in which a nitrite ester
undergoes homolytic cleavage upon irradiation (UV light) or heating, leading to
intramolecular hydrogen abstraction and subsequent radical recombination. It is one of the
pioneering radical reactions developed by Sir Derek Barton, who later received the Nobel
Prize in Chemistry (1969) for his work on conformational analysis and radical reactions.
It plays an important role in the functionalization of aliphatic chains, allowing selective
introduction of functional groups at remote (γ-position) sites relative to an ester group.

General Reaction Scheme

Mechanism (Stepwise)
Formation of Alkyl Nitrite
o A primary or secondary alcohol is treated with nitrosyl chloride (NOCl) or
isoamyl nitrite to form the corresponding alkyl nitrite.
Photochemical Cleavage
o Under UV irradiation, the O–NO bond undergoes homolysis, generating an
alkoxy radical and NO radical.
Intramolecular 1,5-Hydrogen Abstraction
o The alkoxy radical abstracts a hydrogen atom from the γ-position, forming a
carbon radical.
o This step is stereospecific and depends on conformational constraints.
Recombination with NO
o The carbon radical recombines with NO to form the corresponding nitroso
intermediate, which can tautomerize or further react to give hydroxylated
products.

Key Features & Applications

 Selective Functionalization: Allows hydroxylation at unreactive positions.

 Biological Importance: Used in steroid chemistry and natural product synthesis.

 Stereoelectronic Effect: Requires antiperiplanar arrangement for H-abstraction.

Exam Tricks
 Trick 1: Always look for γ-Hydrogen only those substrates undergo Barton
rearrangement.

 Trick 2: The driving force is radical stabilization and NO recombination.

 Trick 3: Compare with Norrish Type II reaction both involve γ-H abstraction.
Key Points
 A radical-based photochemical rearrangement.

 Introduces –OH functionality selectively.

 Requires γ-hydrogen atom.

 Competes with side reactions like β-scission in some cases.

35. von Richter Rearrangement

Definition
The von Richter Rearrangement is a nucleophilic aromatic substitution (NAS) involving the
reaction of aromatic nitro compounds with cyanide ions, leading to ortho- or meta-
carboxylic acids after rearrangement.
It was discovered in 1871 by Viktor von Richter and remains a classic example of
rearrangement in aromatic systems.

General Reaction Scheme

Mechanism (Stepwise)
Nucleophilic Attack
o Cyanide ion attacks the aromatic ring ortho or para to the nitro group.
o Nitro group strongly activates the ring towards nucleophilic substitution.

Rearrangement via Nitro Group Migration

o The nitro group undergoes rearrangement with the displacement of leaving
groups (such as Cl).
o Formation of a Meisenheimer complex occurs.
Hydrolysis
o The nitrile group is hydrolyzed under acidic or basic conditions to yield
carboxylic acid.
Key Features & Applications
 Works mainly with nitroarenes having good leaving groups.

 Produces carboxylic acids in positions not directly accessible otherwise.

 Useful in synthetic organic chemistry.

Exam Tricks
 Trick 1: Nitro group = strong activating group for NAS.

 Trick 2: Carboxylation occurs ortho/para relative to nitro.

 Trick 3: Always expect Meisenheimer intermediate in mechanism questions.

Key Points
 One of the earliest aromatic rearrangements.

 Follows nucleophilic substitution by addition–elimination.

 Product: Carboxylic acid substituted at meta-position relative to nitro.

36. Hunsdiecker Rearrangement

Definition
The Hunsdiecker Reaction (or Hunsdiecker–Borodin reaction) is a decarboxylative
halogenation reaction where silver carboxylates react with halogens (Br₂ , Cl₂ ) to give
alkyl halides with one carbon less.
It was developed by Cläre and Heinz Hunsdiecker in 1930s, but its foundation traces back to
Borodin.

General Reaction Scheme

Mechanism (Stepwise)
Formation of Silver Carboxylate
o A carboxylic acid is converted into its silver salt.
Halogenation
o The silver carboxylate reacts with Br₂ to form an acyloxy bromide
intermediate.
Homolytic Cleavage
o Thermal decomposition leads to radical formation.
Radical Recombination
o The alkyl radical combines with Br radical to form alkyl bromide.

Key Features & Applications

 Produces alkyl halides with one less carbon (decarboxylation).

 Works best with primary and secondary alkyl groups.

 Used in synthesis of alkyl halides, aryl halides.

Exam Tricks
 Trick 1: Always one carbon less in product decarboxylation.

 Trick 2: Radical mechanism rearrangements possible if radicals are stabilized.

 Trick 3: Compare with Kolbe electrolysis (both are decarboxylative).

Key Points
 Requires silver salts of carboxylic acids.

 Reaction proceeds via radical decarboxylation.

 Product distribution depends on radical stability.

 Industrial use limited due to cost of silver salts.

37. Winstein Rearrangement

Definition
The Winstein rearrangement is a cationic rearrangement in which cyclopropylcarbinyl
cations (or closely related systems) undergo rapid ring opening to form stabilized allylic
carbocations. This rearrangement demonstrates the concept of non-classical
carbocations, which are delocalized systems extending over more than two carbon atoms.

 Discovered and studied by Saul Winstein in the 1950s.

 Provided early and crucial evidence for bridged carbocations and non-classical
ion structures, which later became a fundamental concept in advanced organic
chemistry.

Mechanism
Formation of Cyclopropylcarbinyl Cation
o A leaving group (halide, tosylate, etc.) departs from a cyclopropylcarbinyl
substrate.
o Generates the cyclopropylcarbinyl cation, which is highly unstable.
Cation Delocalization
o The cyclopropyl ring opens or delocalizes electrons, producing a stabilized
allylic cation spread across four carbons.
Rearranged Product Formation
o The cation intermediate undergoes substitution or elimination, depending on
reaction conditions.
o Often yields homoallylic products.
Key Step: Non-classical delocalization of carbocation.
Exam Tricks
 Always remember: Cyclopropylcarbinyl cation Homoallylic cation.

 The rearrangement stabilizes via delocalization across four carbons.

 If question asks about evidence of non-classical ions Answer: Winstein

rearrangement.

Key Points
 Supports concept of bridged carbocations.

 Key difference from Wagner–Meerwein: here the stabilization is through orbital

overlap (not just migration).

 Important in mechanistic organic chemistry

38. Willgerodt Rearrangement

Definition
The Willgerodt rearrangement is the conversion of an aryl ketone (Ar–CO–R) into the
corresponding aryl amide (Ar–C(=S)–NH2 or Ar–CH2–CONH2 depending on variation),
using sulfur and amines.

 First reported by Conrad Willgerodt in the late 19th century.

 Widely used for aryl side chain oxidation and amide synthesis.

Mechanism
Activation of Ketone
o Aryl ketone reacts with sulfur and secondary amine.
Thioamide Formation
o Initial product is aryl thioamide (Ar–C(=S)–NR2).
Rearrangement
o Migration of the aryl group to the carbon adjacent to nitrogen occurs.
 o Leads to arylacetamide derivatives.

Example
 Acetophenone (C6H5–CO–CH3) treated with sulfur and morpholine:

Exam Tricks
 Willgerodt = aryl ketone arylacetamide.

 Presence of sulfur + amine always indicates this rearrangement.

 Applications in drug intermediate synthesis often asked in CSIR-NET/GATE.

Key Points
 Useful for amide synthesis from ketones.

 Aryl group remains intact; rearrangement occurs on the carbonyl side.

 Extended version = Willgerodt–Kindler modification.

39. Wohl Rearrangement

Definition
The Wohl rearrangement is the conversion of aldoximes into nitriles under the influence
of reagents such as phosphorus pentachloride (PCl5).

 Named after Alfred Wohl.

 Important for synthetic transformation of oximes nitriles.

Mechanism
Activation of Aldoxime
o Oxime (R–CH=NOH) treated with PCl5 formation of chloroiminium
intermediate.
Loss of HCl
o Chlorinated intermediate undergoes elimination to yield nitrile (R–C≡N).
Example
 Benzaldoxime treated with PCl5:

Exam Tricks
 Wohl vs Beckmann:
o Beckmann Amide
o Wohl Nitrile

 Reagents: PCl5, SOCl2 often used in Wohl.

Key Points
 Converts oximes to nitriles.

 Important in industrial synthesis of nitriles.

 Simple one-step conversion High exam importance.

Summary for (37–39)

 Winstein Rearrangement Non-classical cations, cyclopropylcarbinyl
homoallylic cation.

 Willgerodt Rearrangement Aryl ketones Arylacetamides (via thioamide).

 Wohl Rearrangement Aldoximes Nitriles (PCl5/SOCl2).

40. Wharton Rearrangement

Definition
The Wharton rearrangement is a base-catalyzed transformation in which an α,β-epoxy
ketone is reduced by hydrazine to yield an allylic alcohol. It is a valuable method to
interconvert carbonyl compounds into allylic alcohols, which are versatile intermediates in
organic synthesis.
This rearrangement was first reported by P. S. Wharton in 1961. It is conceptually related to
the Wolff–Kishner reduction, but with the added step of an epoxide migration before final
reduction.

General Reaction Scheme

Detailed Mechanism
Formation of hydrazone:
o The ketone reacts with hydrazine to give a hydrazone intermediate.
Epoxide opening:
o The base deprotonates the hydrazone, generating a carbanion that attacks
the epoxide.
Migration (Rearrangement step):
o The epoxide rearranges, shifting the bond to generate a transient
intermediate.
Loss of nitrogen (Wolff–Kishner type step):
o The hydrazone decomposes with elimination of N₂ gas, producing the allylic
alcohol.

Key Features
 Rearrangement requires hydrazine and a strong base (KOH, NaOH).

 Typically carried out in high-boiling solvents such as ethylene glycol.

 Overall transformation resembles:

Synthetic Applications
 Converts ketones into allylic alcohols, useful in steroid synthesis, terpene
modifications, and drug intermediates.

 Applied in biomimetic synthesis, mimicking enzymatic pathways involving allylic

alcohols.

Exam Tricks
Wharton rearrangement = Epoxy ketone Allylic alcohol.
Hydrazine is always present Think "modified Wolff–Kishner."
Allylic alcohol always formed Not an enol, not a carbonyl.
if question asks "Which rearrangement involves both Wolff–Kishner and epoxide
migration?" Answer: Wharton.
Key Points
 Selective method for allylic alcohols.

 Involves epoxide migration + nitrogen elimination.

 High yield but conditions require careful control (high temperature, basic medium).

41. Pummerer Rearrangement

Definition
The Pummerer rearrangement is an acid-catalyzed rearrangement in which a sulfoxide
undergoes transformation into an α-substituted thioether. It is a highly valuable reaction in
sulfur chemistry and in the synthesis of heterocycles.
Discovered by Rudolf Pummerer in 1909, this reaction showcases the unique reactivity of
sulfoxides.

General Reaction Scheme

Detailed Mechanism

Activation of sulfoxide:
o Sulfoxide oxygen attacks acetic anhydride (Ac₂ O) to form an activated
intermediate.
α-Proton abstraction:
o A proton is abstracted from the α-position, leading to a sulfonium ion.
Migration step (Rearrangement):
o Electron rearrangement causes substitution at the α-carbon, often with
acetate.
Final product:
o An α-acetoxy thioether (or related product) is formed.
Key Features
 Involves sulfoxides (RSO-R’).

 Requires an activator: Ac₂ O, TFAA, or Lewis acid.

 Generates α-functionalized thioethers.

Synthetic Applications
 Formation of α-thioethers (precursors for pharmaceuticals).

 Used in heterocycle synthesis (e.g., thiazoles).

 Applied in total synthesis of alkaloids and natural products.

Exam Tricks
Sulfoxide rearrangement α-substituted thioether.
Reagent: Acetic anhydride = Activation clue.
If asked: "Which rearrangement begins with sulfoxides?" Answer: Pummerer.
Always involves C–S bond migration and loss of oxygen’s influence.

Key Points
 Classic sulfur rearrangement.

 Regioselective introduction of substituents at α-position.

 Often tested in exams as "Sulfoxide α-thioether rearrangement."

42. Smiles Rearrangement

Definition
The Smiles rearrangement is an intramolecular nucleophilic aromatic substitution
(Sₙ Ar) involving an aryl ether, thioether, or amine derivative where a nucleophile (–
O⁻ , –S⁻ , –N⁻ ) attacks an activated aromatic ring, causing rearrangement.
Named after Samuel Smiles (1930s), it is one of the most important rearrangements in
aromatic chemistry.

General Reaction Scheme

Detailed Mechanism
Base deprotonation:
o The nucleophilic group (–O⁻ , –S⁻ , –N⁻ ) is generated under basic
conditions.
Intramolecular attack (Sₙ Ar):
o The nucleophile attacks the aromatic ring (usually activated by –NO₂ , –CN,
or halogens).
Rearrangement (Aryl migration):
o Bond migration occurs, leading to a new aryl–nucleophile linkage.
Final product:
o A rearranged aromatic ether, thioether, or amine.
Key Features
 Intramolecular reaction ring substitution.

 Requires electron-withdrawing substituents (NO₂ , CN) for activation.

 Strong base (NaOH, KOH) needed.

Synthetic Applications
 Synthesis of aryl amines, aryl ethers, and aryl sulfides.

 Important in heterocyclic chemistry and drug design.

 A modified version, the Truce–Smiles rearrangement, is used for more complex

skeletons.

Exam Tricks
Always intramolecular not classical substitution.
Needs electron-withdrawing groups on the aromatic ring.
If nucleophile = O⁻ ether formation; N⁻ amine; S⁻ thioether.
If question asks: "Which rearrangement is an intramolecular Sₙ Ar?" Smiles
rearrangement.

Key Points
 Involves aryl migration via nucleophilic substitution.

 Provides a direct route to substituted aromatics.

 Important reaction in pharmaceuticals and materials chemistry.

Summary (40–42)
 Wharton rearrangement: Epoxy ketone Allylic alcohol (hydrazine-based, Wolff–
Kishner-like).

 Pummerer rearrangement: Sulfoxide α-thioether (activated by Ac₂ O).

 Smiles rearrangement: Intramolecular nucleophilic aromatic substitution.

Exam Note:

 Wharton = "Allylic alcohol from ketone."

 Pummerer = "Sulfoxides rearrange with Ac₂ O."

 Smiles = "Intramolecular SNAr with EWG activation."

43. Schenck Rearrangement

Definition & Historical Background

The Schenck Rearrangement is a photochemically induced rearrangement of allylic
hydroperoxides. Under the influence of UV light (typically ~300 nm), an allylic
hydroperoxide undergoes a homolytic O–O bond cleavage to generate an oxy radical. This
radical system then rearranges through 1,5-hydrogen atom transfer, ultimately producing
isomeric hydroperoxides.
Discovered by G. O. Schenck in 1953, this rearrangement is extremely important in the
chemistry of lipid peroxidation, steroid transformations, and biomimetic oxidation
reactions.

General Reaction

The hydroperoxide migrates to a new allylic position through a radical-driven hydrogen

transfer.

Reaction Mechanism
Photolysis of Hydroperoxide
o Under UV light, the O–O bond of the hydroperoxide breaks homolytically.
o This generates an alkoxy radical (RO•) and a hydroxyl radical (•OH).

1,5-Hydrogen Atom Abstraction

o The alkoxy radical undergoes a 1,5-hydrogen atom transfer (HAT) from a
neighboring allylic C–H bond.
o This creates a new carbon radical stabilized by resonance.

Radical Recombination / Oxygen Rebound

o The carbon radical recombines with oxygen-centered species to form a new
hydroperoxide, but at a shifted allylic position.

Final product: isomeric allylic hydroperoxide.

Key Features
 Requires UV irradiation.

 Operates through radical pathways.

 Leads to allylic rearrangements of hydroperoxides.

 Very relevant in biological lipid oxidation pathways.

Applications
Biological Chemistry
o Explains lipid peroxidation in cell membranes.
o Important for understanding oxidative stress and free radical damage.
Synthetic Chemistry
o Used in steroid transformations.
o Precursor in natural product synthesis.
Industrial Relevance
o Antioxidant research.
o Mechanism behind rancidity in oils.
Exam Tricks
 If you see allylic hydroperoxide + light new hydroperoxide, think Schenck
Rearrangement.

 Remember the 1,5-hydrogen shift (not 1,2 or 1,3).

 It’s a radical rearrangement, not ionic.

Key Points
 UV-induced rearrangement.

 1,5-HAT is the core step.

 Radical mechanism O–O bond cleavage new allylic hydroperoxide.

44. Hofmann–Martius Rearrangement

Definition & Background

The Hofmann–Martius Rearrangement is the acid-catalyzed migration of an alkyl (or
aryl) substituent from the nitrogen atom of an aromatic amine (Ar–NH–R) to the ortho or
para position of the aromatic ring.
It was first reported in the late 19th century by August Wilhelm von Hofmann and further
explored by Carl Martius.

General Reaction

Reaction Mechanism
Protonation of Amine
o Under strong acid, the amine nitrogen gets protonated.
Carbocation Formation
o The N–R bond undergoes heterolysis, generating a carbocation (R⁺ ).
 Electrophilic Substitution on Aromatic Ring
o The carbocation (R⁺ ) attacks the ortho or para position of the aromatic ring
(activated by –NH₂ ).

Key Features
 Migration is always to ortho or para positions.

 Follows electrophilic substitution rules.

 The –NH₂ group strongly activates the aromatic ring.

Applications
1. Synthesis of Aryl Amines
o Used for ortho/para-alkylated aromatic amines.
2. Pharmaceutical Industry
o Key step in synthesizing alkaloid derivatives.
3. Dye Industry
o Important for making azo-dyes and aryl amines.

Exam Tricks
 If question says “migration of alkyl group from N to ortho/para of ring”
Hofmann–Martius.

 Works only in acidic medium.

 Ortho product favored when sterics are small; para product favored with bulky R
group.
Key Points
 Acid catalysis.

 Carbocation intermediate.

 Ortho/para substitution.

45. Neumann–Kopp Rearrangement

Definition & Background

The Neumann–Kopp Rearrangement (less common, but important in advanced organic
chemistry exams) involves the thermally induced rearrangement of certain N-alkyl
amides where an alkyl group migrates from nitrogen to the carbonyl carbon, ultimately
generating new amide derivatives or imidic acid intermediates.
It was discovered by F. Neumann and H. Kopp in the 19th century.

General Reaction

In other words, the alkyl substituent (R′) on nitrogen migrates to the carbonyl carbon.

Reaction Mechanism
1. Activation by Heat
o Amide undergoes tautomerization to imidic acid form.

2. Alkyl Migration
o The R′ group migrates from N carbonyl carbon.
o Generates a rearranged amide.
3. Tautomerization
o Stabilizes to new amide derivative.

Key Features
 Rare, less common rearrangement.

 Involves migration of alkyl group.

 Thermal rearrangement of amides.

Applications
 Studied mostly in theoretical organic chemistry.

 Provides insights into amide–imine tautomerism.

 Rarely used in industry, but mechanistically important.

Exam Tricks for CSIR-NET

 If given amide under heat with alkyl group migration, it’s Neumann–Kopp.

 Don’t confuse with Beckmann or Lossen rearrangements (those involve different

intermediates).

 Main clue = N-alkyl migration carbonyl carbon.

Key Points
 Thermal rearrangement.

 N C migration of alkyl group.

 Produces isomeric amides.

Summary of (43–45)
Rearrangement Key Feature Migrating Condition Product
Group s
Schenck Radical, UV light Allylic H Photolysis Isomeric allylic
OOH shift hydroperoxides
Hofmann– Acid-catalyzed ortho/para
Alkyl (from N) H⁺ / Heat o-/p-
Martius substitution ring Alkylarylamines

Neumann– Thermal amide N-alkyl Heat Isomeric amides

Kopp rearrangement carbonyl C

46. Mumm Rearrangement (O N Acyl Shift)

Definition
The Mumm rearrangement is an intramolecular acyl transfer reaction where an acyl group
migrates from oxygen to nitrogen in an acyloxyiminium intermediate. This rearrangement
is particularly important in the synthesis of amides from imidates or related precursors.
It can be considered a variant of classical acyl migration processes but with a strong
emphasis on O N shift, which highlights its synthetic versatility.
General Reaction Scheme

 An acyl group (R–C=O) moves from an oxygen atom to an adjacent nitrogen atom.

 The result is the formation of amide derivatives.

Mechanism
Activation Step
o Acid/base conditions activate the oxygen-attached acyl moiety.
O N Migration
o Intramolecular nucleophilic attack by nitrogen occurs, shifting the acyl group.
Rearranged Amide Formation
o Stabilization leads to a new amide bond (C=O–N).

Key Features
 Classified as an intramolecular acyl transfer reaction.

 Mechanistically related to Overman rearrangement but simpler.

 Often studied in heterocyclic chemistry and peptide chemistry.

Exam Tricks
 Mnemonic: “Mumm moves Acyl from O to N”.

 Watch for acyloxyiminium intermediates in exam questions.

 If the product is an amide, and the shift is O N, think of Mumm.

Applications
 Synthesis of amide linkages.

 Biomimetic reaction pathways.

 Used in natural product chemistry where O N migration occurs in enzyme-

assisted steps.

47. Bamberger Rearrangement (Nitrosobenzene

Pathway)

Definition
The Bamberger rearrangement is the acid-catalyzed rearrangement of N-
phenylhydroxylamine to 4-aminophenol.
In some variations, nitrosobenzene acts as a precursor, undergoing reduction followed by
rearrangement to generate para-substituted products.

General Reaction

 Rearrangement produces para-aminophenol (key intermediate for paracetamol

synthesis).

Mechanism (with Nitrosobenzene Pathway)

Nitrosobenzene Reduction
o Nitrosobenzene is reduced to N-phenylhydroxylamine.
Protonation
o Hydroxylamine is protonated under acidic medium.
Aryl Migration
o The aryl group rearranges from N to O position, yielding a cationic
intermediate.
Para-Ortho Selectivity
o Electrophilic substitution leads predominantly to para-aminophenol.

Key Points
 Strongly acid-dependent.

 Major product = p-aminophenol.

 Ortho product possible but less favored.

Exam Tricks
 Remember: Bamberger = Benzene p-Aminophenol.

 Important for drug synthesis (paracetamol).

 If question mentions nitrosobenzene and acid, the rearrangement is Bamberger.

Applications
 Industrial synthesis of paracetamol (acetaminophen).

 Aromatic amine intermediates.

 Study model for biochemical hydroxylamine conversions.

48. Boekelheide Rearrangement (Oxidative N-
Oxide Rearrangement)

Definition
The Boekelheide rearrangement involves the oxidative rearrangement of pyridine N-
oxides with acylating agents, producing hydroxymethyl-substituted pyridines.
This rearrangement highlights the synthetic use of pyridine N-oxides as masked
nucleophiles.

General Reaction

 Pyridine N-oxide rearranges to give hydroxymethylpyridine derivatives.

Mechanism
N-Oxide Activation
o Pyridine N-oxide reacts with acylating agent (e.g., acetic anhydride).
O-Acyl Intermediate Formation
o The oxygen atom of N-oxide is acylated.
Rearrangement (Sigmatropic Shift)
o A [1,2]-rearrangement occurs, shifting the group to the 2-position of pyridine.
Hydrolysis
o Hydrolysis of the intermediate yields 2-hydroxymethylpyridine.

Key Features
 Involves oxidized heteroaromatic systems.

 Reaction is regioselective substitution occurs at 2-position.

 Requires acylating agents for activation.

Exam Tricks
 Mnemonic: “Boekelheide Boosts 2-HOCH₂ on Pyridine”.

 If pyridine N-oxide + acetic anhydride appears immediately think Boekelheide.

 Remember: Always functionalization at C-2.

Applications
 Synthesis of hydroxymethyl-substituted pyridines.

 Precursors in drug development.

 Shows utility of heteroaromatic N-oxides in rearrangement chemistry.

Summary (46–48)
Mumm Rearrangement O N acyl shift, forms amides.
Bamberger Rearrangement Acid-induced rearrangement of hydroxylamine to p-
aminophenol.
Boekelheide Rearrangement Pyridine N-oxide + acylation 2-
hydroxymethylpyridine.

49. Wöhler Rearrangement

Introduction
The Wöhler Rearrangement is one of the earliest documented organic rearrangements,
named after Friedrich Wöhler, who is often regarded as the father of organic chemistry. In
this transformation, isocyanates are converted into their primary amine derivatives under
specific reaction conditions. Historically, this rearrangement is often confused with the
Wöhler synthesis of urea (1828), but the rearrangement itself refers to a transformation
involving isocyanates and subsequent reactivity.
The significance of this rearrangement is both historic and mechanistic, because it helped
establish the connection between simple precursors and nitrogen-functionalized compounds.
Mechanistically, it resembles Hofmann, Curtius, and Lossen rearrangements, but operates
under unique pathways and reagents.

General Reaction
The Wöhler Rearrangement involves the conversion of isocyanates (R–N=C=O) into
amines (R–NH₂ ) or urea derivatives, depending on the conditions.

Mechanism
Activation of Isocyanate
o The isocyanate group is electrophilic at the carbon atom of the –N=C=O
moiety.
 o Nucleophilic attack (commonly by water, alcohols, or bases) initiates the
rearrangement.
Formation of Carbamate / Intermediate
o Attack on the isocyanate leads to the formation of a carbamate intermediate
(if water or alcohol participates).
Rearrangement Pathway
o The intermediate undergoes intramolecular rearrangement or
fragmentation, producing an amine.
Final Hydrolysis
o Hydrolysis completes the conversion, yielding a primary amine.

Key Features
 Reaction parallels Curtius rearrangement (where acyl azides isocyanates
amines).

 Offers a route to amines from precursors that are otherwise hard to access.

 Important historically in the development of isocyanate chemistry, relevant to

polyurethane materials.

Applications
Synthesis of Amines
o Direct method to synthesize primary amines.
o Industrial relevance in polyurethanes and related polymers.
Polymer Chemistry
o Basis for polyurethane foams, adhesives, coatings.
Pharmaceutical Intermediates
o Amines derived from rearrangements used in drug development.

Exam Tips
 Compare mechanism with Hofmann, Curtius, Lossen rearrangements.

 Remember: isocyanate amine pathway is the hallmark.

 Expect conceptual questions on electrophilicity of isocyanate carbon and

nucleophilic attack.
50. Benzidine Rearrangement (Detailed in
Aromatic Amines Context)

Introduction
The Benzidine Rearrangement is a famous acid-catalyzed rearrangement of
hydrazobenzenes (Ar–NH–NH–Ar) into benzidines (p,p′-diaminobiphenyls) and related
products. First observed in the mid-19th century, it became industrially vital for the
synthesis of azo dyes and other aromatic amine derivatives.
It is one of the classic examples of aryl migration reactions under strongly acidic
conditions.

General Reaction

 Major Product: p,p′-benzidine (para–para coupled diamine).

 Minor Product: o,o′-benzidine.

Mechanism
Protonation Step
o Hydrazobenzene protonates under strong acid, forming N-protonated
hydrazobenzene cation.
Cleavage of N–N Bond
o Acidic conditions weaken the N–N bond.
o Generates a cationic intermediate capable of rearrangement.
Aryl Migration
o One phenyl group migrates from nitrogen to the other nitrogen atom.
o This leads to a rearranged cationic intermediate.
Re-aromatization and Stabilization
o Rearomatization and proton loss yield benzidine.
Factors Influencing the Rearrangement
 Acid Strength: Strong acids (HCl, H₂ SO₄ ) promote migration.

 Substituents: Electron-donating substituents favor rearrangement.

 Temperature: Higher temperature may change para:ortho product ratios.

Applications
Dye Industry
o Benzidine was historically used for producing azo dyes.
o Banned in many countries due to carcinogenicity.
Organic Synthesis
o Rearrangement provides access to substituted biphenyl diamines.
Pharmaceuticals
o Derivatives used in certain heterocycles and intermediates.

Safety Note
 Benzidine and its derivatives are highly carcinogenic, leading to bans in the dye
industry.

 Modern synthetic chemistry uses safer alternatives.

Exam Tricks & Key Points

 Identify hydrazobenzene precursor.

 Always think: Acid + Ar–NH–NH–Ar = Benzidine (p,p′).

51. Beckmann–Bergmann Rearrangement

Introduction
The Beckmann–Bergmann Rearrangement is a modified version of the Beckmann
rearrangement, involving oximes and nitroso/amide intermediates that undergo skeletal
rearrangements under acidic or thermal conditions.
While the classic Beckmann rearrangement converts oximes to amides, the Beckmann–
Bergmann version focuses on aryl ketoximes and their tendency to form lactams or
rearranged aromatic amides.

Mechanism
Protonation of Oxime
o Protonation activates the oxime group.
Migration of Aryl Group
o The aryl substituent adjacent to the oxime migrates to nitrogen.
Ring Closure or Rearrangement
o Leads to cyclic lactam formation or rearranged amide, depending on
substrate.

Applications
Synthesis of Lactams
o Important in producing caprolactam, precursor of nylon-6.
Heterocyclic Synthesis
o Produces nitrogen-containing heterocycles used in medicinal chemistry.
Aromatic Chemistry
o Rearranged products are useful intermediates for drug design.

Comparison with Classic Beckmann

 Beckmann Rearrangement: Oximes Amides (general).

 Beckmann–Bergmann: Special focus on aryl oximes, yielding unique

rearrangements.

Exam Tips
 Remember oxime amide/lactam pathway.

 Aryl oximes = unique migration patterns (para-orientation often favored).

 Possible exam trick: compare with Fries rearrangement (aryl esters) and
Beckmann.
 Summary (49–51)
 Wöhler Rearrangement: Isocyanates Amines. Historical & industrial relevance.

 Benzidine Rearrangement: Hydrazobenzenes Benzidines (para major). Critical in

dye industry, but carcinogenic.

 Beckmann–Bergmann Rearrangement: Special oxime rearrangement

lactams/amides; important for nylon precursors.

52. Oppenauer Rearrangement (Oxidative Shift)

Definition
The Oppenauer Rearrangement is an oxidation process in which a secondary alcohol is
oxidized to a ketone by hydride transfer to a carbonyl compound (usually an aldehyde), in
the presence of an aluminum alkoxide catalyst.
It is essentially the reverse of the Meerwein–Ponndorf–Verley (MPV) reduction.

General Reaction
 Primary alcohol Aldehyde

 Secondary alcohol Ketone

Mechanism
Activation of alcohol:
The alcohol coordinates with the Lewis acidic aluminum alkoxide (Al(OR)₃ ).

Hydride transfer:
The hydride from the secondary alcohol transfers to the carbonyl carbon of the
aldehyde.

Release of products:
Ketone and primary alcohol are released, regenerating the catalyst.
Key Features
 Selective oxidation of secondary alcohols.

 Requires non-enolizable aldehydes like benzaldehyde (to avoid side reactions).

 Stereospecific hydride transfer.

Applications
 Selective oxidation in natural product synthesis.

 Used in steroid chemistry (conversion of Δ⁵ -3β-alcohols Δ⁴ -3-ketones).

 Alternative to toxic chromium(VI) oxidants.

Exam Tricks
 Reverse of MPV reduction very common CSIR-NET question.

 Benzaldehyde is the most preferred hydride acceptor.

 Oppenauer is mild and does not cleave C–C bonds.

Key Points
 Catalyst: Al(OiPr)₃ or Al(OR)₃ .

 Works well in non-polar solvents (toluene, benzene).

 Does not oxidize primary alcohols efficiently.

53. Nametkin Rearrangement

Definition
The Nametkin Rearrangement involves a methyl (or alkyl) group shift in terpenes and
polycyclic hydrocarbons under acidic conditions.
It is important in steroid and terpene chemistry.

General Reaction

Mechanism
Protonation of double bond (acidic conditions) carbocation.
1,2-Methyl shift occurs to stabilize the carbocation.
 Deprotonation stable rearranged hydrocarbon.

Features
 Intramolecular alkyl shift rearrangement.

 Leads to skeletal rearrangement of terpenoids.

 Often used to explain biosynthetic pathways.

Applications
 Terpene chemistry rearrangement of camphene, pinene, etc.

 Synthesis of natural products with unusual carbon skeletons.

 Understanding biosynthetic transformations in plants.

Exam Tricks
 Key in hydrocarbon rearrangements.

 Always involves methyl shift carbocation stability.

 Compare with Wagner–Meerwein rearrangement (similar skeletal rearrangement).

Key Points
 Acid-catalyzed.

 Skeletal rearrangement in polycyclic systems.

 Highly regioselective based on carbocation stability.

54. Neber Rearrangement (Oxime α-

Aminoketone)

Definition
The Neber Rearrangement converts oximes of ketones into α-aminoketones using tosyl
chloride (TsCl) and a base.
This is a ring-opening or rearrangement reaction important for synthesis of amino-ketones.

General Reaction
Mechanism
Activation: Oxime is converted into an oxime tosylate.
Deprotonation and rearrangement:
Base removes α-hydrogen carbanion rearranges, expelling TsO⁻ .
Azirine opening:
Hydrolysis of the strained azirine gives an α-aminoketone.

Features
 Oximes must be ketoximes (not aldoximes).

 Involves a 3-membered azirine intermediate.

 Produces valuable α-amino carbonyl compounds.

Applications
 Synthesis of α-aminoketones important in alkaloid chemistry.

 Precursor for heterocycles (imidazoles, pyrazines).

 Useful in drug synthesis.

Exam Tricks
 Always involves oxime azirine aminoketone.

 Reagent: TsCl + base (NaOEt, NaOMe).

 Different from Beckmann rearrangement (gives amides, not aminoketones).

Key Points
 α-Aminoketones are highly reactive and versatile intermediates.

 Distinguish from Beckmann in exams.

 Azirine intermediate is high-energy, detected spectroscopically.

Summary (52–54)
Rearrangemen Key Transformation Mechanism Type Applications
t
Oppenauer Alcohol Ketone (via Catalytic oxidation Steroids, mild
hydride transfer) oxidation
Nametkin Skeletal methyl shift Carbocation Terpenes,
rearrangement biosynthesis
Neber Oxime α-Aminoketone Azirine intermediate Alkaloids, drug
synthesis

55. Eschenmoser–Tanabe Rearrangement

Definition
The Eschenmoser–Tanabe rearrangement is a thermal rearrangement involving
tosylhydrazones of α,β-epoxy ketones (or related substrates), leading to α,β-unsaturated
carbonyl compounds.
This rearrangement is often used in complex natural product synthesis where the
formation of conjugated systems is required.
It is closely related to the Shapiro reaction (which also involves tosylhydrazones), but here
a concerted fragmentation and rearrangement occurs.

General Reaction Scheme

Mechanism
Formation of Tosylhydrazone
o A ketone reacts with p-toluenesulfonyl hydrazine forms tosylhydrazone.
o Example:

Base-Induced Deprotonation
o Strong base deprotonates the α-proton.
Fragmentation & Rearrangement
o Loss of nitrogen gas (N₂ ) and tosylate (TsO⁻ ).
 o Rearrangement occurs with migration of substituent to stabilize.
Product Formation
o Final product = α,β-unsaturated ketone (enone)

Key Features
 Produces enones from epoxy ketone derivatives.

 Involves loss of N₂ (driving force).

 Related to Eschenmoser–Claisen rearrangement but mechanistically distinct.

Exam Tricks
 If you see epoxy ketone + tosylhydrazine + heat, expect enone formation.

 Loss of N₂ gas is a thermodynamic driving force.

 Sometimes compared with Shapiro reaction:

o Shapiro vinyl carbanions (further alkylation).
o Eschenmoser–Tanabe conjugated enones.

Applications
 Used in steroid synthesis.

 Formation of dienones in natural product frameworks.

56. Tiemann Rearrangement

Definition
The Tiemann rearrangement involves the base-catalyzed rearrangement of N-
haloformanilides into ortho-aminobenzaldehydes.
It is particularly important in the synthesis of vanillin and other substituted benzaldehydes.

General Reaction

Mechanism
Formation of N-haloformanilide
o Aniline reacts with chloroform in alkaline medium (or related conditions).
Base Attack
 o Strong base attacks N-haloformanilide generates an intermediate
isocyanate-like structure.
Rearrangement Step
o Migration of the aryl group ortho to nitrogen.
o Cleavage of the N–C bond occurs.
Hydrolysis
o Yields ortho-aminobenzaldehyde as the main product.

Key Features
 Rearrangement leads to ortho-selectivity (o-aminobenzaldehyde).

 Can be confused with Reimer–Tiemann reaction (where chloroform + base acts on

phenol o-formylphenol).

Exam Tricks
 Tiemann rearrangement think aniline derivatives.

 Reimer–Tiemann reaction think phenol derivatives.

 Both involve formylation, but substrates differ.

Applications
 Used in synthesis of natural benzaldehydes.

 Historically important in synthesis of vanillin (flavor compound).

57. Cornforth Rearrangement

Definition
The Cornforth rearrangement is a rearrangement of allylic hydroperoxides, leading to
allylic alcohols and ketones via an intramolecular shift.
Named after Sir John Cornforth (Nobel Prize, 1975) for his work on stereochemistry of
enzyme-catalyzed reactions.

General Reaction
Mechanism
Formation of Allylic Hydroperoxide
o Usually generated via autoxidation of alkenes.
O–O Bond Cleavage
o Rearrangement involves heterolytic cleavage of the O–O bond.
Migration of Substituent
o Allylic carbon migrates to oxygen new bond formation.
Product Formation
o Formation of allylic alcohols or ketones.

Key Features
 Related to Hock rearrangement (used in cumene phenol synthesis).

 A radical or ionic pathway possible depending on conditions.

Exam Tricks
 Cornforth rearrangement = allylic hydroperoxides.

 Products = allylic alcohols/ketones.

 Often tested with mechanistic comparison to:

o Criegee rearrangement (peroxides).
o Hock rearrangement.
Applications
 Important in biosynthetic pathways involving oxidation of terpenes.

 Used in industrial oxidation processes.

Summary (55–57)
Rearrangement Substrate Product Key Driving Force
Eschenmoser– Tosylhydrazones of Enones (α,β- N₂ gas evolution
Tanabe epoxy ketones unsaturated ketones)
Tiemann N-haloformanilide o-Aminobenzaldehyde Rearrangement of
N–C bond
Cornforth Allylic hydroperoxides Allylic alcohols/ketones O–O bond
cleavage

58. Boulton–Katritzky Rearrangement

Historical Background
The Boulton–Katritzky rearrangement is one of the most characteristic heterocyclic
rearrangements, discovered by A. J. Boulton and A. R. Katritzky in 1960s during their
extensive studies on pyridinium salts and heteroaryl systems.

 Katritzky was a pioneer in heterocyclic chemistry and dedicated decades of work to

understanding structural reactivity of pyridines, quinolines, and related systems.

 This rearrangement belongs to the class of ring–chain tautomerism and ring

expansion/contraction reactions observed in heteroaromatic chemistry.

 Its importance arises from the ability to transform a pyridinium or other

heteroaryl salt into an isomeric heteroaryl system, often accompanied by N C
or C N bond migrations.
Historically, this rearrangement is considered alongside Smiles, Sommelet, Overman, and
benzidine rearrangements, but it is unique because it involves heteroaromatic π-
systems as migrating groups.

General Reaction
The Boulton–Katritzky rearrangement involves:

 Substrate: 1-substituted pyridinium salts (or related azinium salts).

  Reaction: Under thermal or photochemical conditions, or sometimes in base, the N-
substituent migrates into the ortho or para position of the pyridinium ring, giving
rearranged heteroaryl derivatives.

Simplified Reaction Scheme

 Here, R migrates from nitrogen to carbon (usually ortho/para position).

 The heteroaromatic ring acts as the acceptor site.

 The rearrangement is thus an N C migration in a heteroaromatic π system.

Detailed Mechanism
The mechanism of the Boulton–Katritzky rearrangement has been studied through
spectroscopy, kinetics, isotope labeling, and computational methods.

Stepwise Pathway
Step 1: Formation of Pyridinium Salt

 Start with a pyridine derivative.

 Quaternization occurs with an alkylating agent forms 1-alkylpyridinium salt.

Step 2: Activation

 Heat, base, or light excites the system.

 The positive charge on nitrogen polarizes the adjacent π bonds.

Step 3: Bond Migration (N C Shift)

 The substituent on nitrogen migrates to an ortho (C2 or C6) or para (C4) position
on the pyridine ring.

 This involves a reversible radical cationic or pericyclic pathway.

Step 4: Rearranged Product Formation

 The nitrogen center regains neutrality (dequaternization).

 The product is an aminopyridine or substituted pyridine, depending on the

substituent.
Mechanistic Pathways
Several mechanistic hypotheses exist:
Radical Mechanism (favored in photochemical conditions):
o Homolytic cleavage generates N-centered radical and migrating group
radical.
o Recombination at ortho/para positions.
Pericyclic (Sigmatropic) Mechanism:
o Migration resembles a [1,5]-sigmatropic rearrangement.
o Orbital symmetry considerations (Woodward–Hoffmann rules) apply.
Nucleophilic Substitution Mechanism:
o Base-assisted: deprotonation activates the pyridinium ring.
o The substituent shifts via Meisenheimer-like intermediate.

Stereoelectronic Considerations
 The migration is governed by π-conjugation and resonance stabilization.

 Preferred sites: C2 (ortho) and C4 (para) because they have the highest
electrophilic character due to resonance with the pyridinium cation.

 Substituents with electron-donating groups on pyridine facilitate migration.

 Thermal vs photochemical conditions product distribution differs.

Variants of the Boulton–Katritzky Rearrangement

Classic Version:
o N-alkylpyridinium 2-alkyl or 4-alkyl pyridine.
Extended to Other Heterocycles:
o Quinoline, isoquinoline, pyrazine derivatives also undergo rearrangements.
Intramolecular Cases:
o Substituents tethered by chains can cyclize during migration ring-expanded
products.

Synthetic Applications
Functionalization of Pyridines
o Introduces substituents into pyridine ring without classical electrophilic
substitution.
 Access to Aminopyridines
o Key intermediates in pharmaceuticals.
Drug Synthesis
o Many pyridine derivatives (isoniazid, nicotinamides, pyridyl ethers) can be
synthesized.
Heteroaryl Diversification
o Expands the library of heterocycles for medicinal chemistry.

Comparison with Related Rearrangements

 Smiles Rearrangement: Both involve aryl migrations but via different intermediates.

 Overman Rearrangement: Both are heteroatom C migrations.

 Sommelet–Hauser: Similar N C shift but in benzyl systems.

 Bamberger: Nitro group migration vs alkyl migration here.

Exam-Oriented Key Points

 Substrate: 1-substituted pyridinium salt.

 Migrating Group: Alkyl/aryl attached to N.

 Target Sites: C2 or C4 (ortho/para positions).

 Conditions: Heat, photolysis, or base.

 Product: Substituted pyridines (aminopyridines, alkylpyridines).

Shortcuts & Mnemonics

 “Boulton Bumps to the Bench” B for Boulton, B for Base or Beam (light) to
activate.

 “Katritzky = Katapult” The group is catapulted from N to C2 or C4.

 Trick: Remember N C shift, not C N.

Mind Map (Textual)

Boulton–Katritzky Rearrangement
│
├── Substrate: Pyridinium salts
│
├── Migration: N C (ortho/para)
│
├── Conditions:
│ ├── Heat
│ ├── Photolysis
│ └── Base
│
├── Mechanisms:
│ ├── Radical
│ ├── Sigmatropic
│ └── Nucleophilic substitution
│
├── Products:
│ ├── 2-Substituted pyridines
│ └── 4-Substituted pyridines
│
└── Applications:
├── Drug intermediates
├── Aminopyridines
└── Synthetic heterocycles

Practice Questions
Q1. In the Boulton–Katritzky rearrangement, the migrating group shifts:
a) From carbon to nitrogen
b) From nitrogen to ortho/para carbon
c) From nitrogen to meta carbon
d) From nitrogen to oxygen
Answer: (b)

Q2. Which heteroaryl cation undergoes Boulton–Katritzky rearrangement most efficiently?

a) Pyridinium
b) Benzimidazolium
c) Imidazolium
d) Oxazolium
Answer: (a) Pyridinium

Q3. The rearrangement product of 1-methylpyridinium salt on heating will be:

a) 3-methylpyridine
b) 2-methylpyridine
c) 6-methylpyridine
d) Mixture of (b) and (c)
Answer: (d)

Q4. The Boulton–Katritzky rearrangement is mechanistically related to:

a) Smiles Rearrangement
b) Beckmann Rearrangement
c) Fries Rearrangement
d) Hofmann Rearrangement
Answer: (a)

Q5. What governs the regioselectivity in the rearrangement?

 Resonance stabilization at C2 and C4 of pyridinium.

Summary
 The Boulton–Katritzky rearrangement is a heteroaryl N C migration in
pyridinium salts.

 Provides direct functionalization of heteroaromatics.

 Mechanism may be radical, sigmatropic, or base-mediated nucleophilic

substitution.

 Synthetic importance: Aminopyridines, pharmaceuticals, heterocyclic libraries.

 Exam tip: Always remember N C2/C4 shift.

59. Bamberger Rearrangement (Classical Nitroso

Migration)

Introduction
The Bamberger rearrangement is a classical aromatic rearrangement reaction
discovered by Eugen Bamberger in 1894. It represents a unique transformation of
aromatic hydroxylamines into para-aminophenols under acidic conditions.
At its heart, the reaction is a cationic rearrangement involving hydroxylamine derivatives
of aromatic compounds. This rearrangement plays a central role in both academic
organic chemistry and industrial dye/pharmaceutical synthesis.
 General transformation:
  Key features:
o Rearrangement is highly regioselective (para-directed).
o Mechanism proceeds via nitrenium ion (Ar–N^+) intermediates.
o Acidic medium is essential.
o Industrially important for the synthesis of p-aminophenols (precursors of
paracetamol, dyes, photographic developers).

Historical Background
 Eugen Bamberger (1894) first observed that phenylhydroxylamine, when treated
with strong acids, does not undergo simple protonation and decomposition but
rearranges into p-aminophenol.

 This was groundbreaking because:

o At that time, aromatic amines and hydroxylamines were poorly understood.
o The rearrangement contradicted expectations of direct substitution or
oxidation.

 Later mechanistic refinements (1920s–1960s) established the role of cationic

intermediates and hydrogen-bonded transition states.

 The rearrangement has become a textbook example of aromatic rearrangements,

still cited in CSIR-NET, GATE, IIT-JEE (Advanced) exams.

General Reaction Scheme

Example: Phenylhydroxylamine 4-Aminophenol

 Product is para-aminophenol (major).

 Minor ortho-isomer may also form, depending on conditions.

 Regioselectivity is governed by cation delocalization and solvent stabilization.

Mechanism of Bamberger Rearrangement

The mechanism is best described in five major steps:

Step 1: Protonation of Hydroxylamine

 The hydroxylamine nitrogen is protonated under strongly acidic conditions
(H₂ SO₄ , HCl, etc.).

 This activates the molecule toward rearrangement.

Step 2: Loss of Water and Nitrenium Ion Formation

 Under heating, water is eliminated, generating an aryl nitrenium ion.
  This nitrenium ion (Ar–N^+) is resonance stabilized:
o Delocalized into the aromatic ring.
o Para-position is particularly stabilized due to conjugation.

Step 3: Electrophilic Attack on Aromatic Ring

 The nitrenium ion attacks the para position of the benzene ring.

 This explains why para-aminophenol is the major product.

Step 4: Rearomatization
 The σ-complex loses a proton, restoring aromaticity.

Step 5: Product Formation

 Final product: p-aminophenol.

 Minor ortho-products possible, depending on substituents/solvent.

Evidence for Mechanism

 Isotopic labeling (with deuterium) confirms migration to para-position.

 Kinetic studies show acid catalysis is crucial.

 Spectroscopic detection of nitrenium ion intermediates (by fast spectroscopy)

supports cationic pathway.
Variations of the Bamberger Rearrangement

 Classical Bamberger
 Phenylhydroxylamine p-aminophenol.

 Substituted Aromatics
 Electron-donating substituents increase reaction rate.

 Electron-withdrawing substituents slow down rearrangement, sometimes

diverting to decomposition.

 Alternative Pathways
 In presence of oxidants formation of quinone imines.

 In solvents like acetic acid higher ortho selectivity.

Synthetic Applications

 Industrial Applications
 p-Aminophenol production (precursor to paracetamol / acetaminophen).

 Dyes and pigments (azo dyes, hair dyes).

 Photographic developers (aminophenols as reducing agents).

 Academic Use
 Classical exam question in CSIR-NET.

 Model system for studying nitrenium ions.

 Useful for selective synthesis of para-aminophenols without nitration/reduction

steps.

Factors Affecting the Reaction

 Acid Strength
 Strong mineral acids (H₂ SO₄ , HCl) required.

 Weak acids ineffective.

  Substituents on Aromatic Ring
 Activating groups (–OH, –OCH₃ , –NH₂ ) faster rearrangement.

 Deactivating groups (–NO₂ , –CF₃ ) slower or suppressed rearrangement.

 Solvent
 Protic solvents stabilize nitrenium ion better selectivity.

 Temperature
 Mild heating (~50–100 °C) required.

 Excessive heating decomposition to anilines/quinones.

Advanced Mechanistic Aspects

 Computational chemistry studies confirm nitrenium ion as a true intermediate,
with energy barriers ~20–25 kcal/mol.

 Transition state resembles electrophilic substitution TS, but with stronger

polarization.

 The hydrogen bonding of solvent (water, acetic acid) dramatically stabilizes

rearrangement pathway.

Exam-Oriented Tricks & Key Points

 Major product: p-aminophenol.

 Ortho product: minor, enhanced in non-aqueous solvents.

 Rearrangement occurs only under acidic conditions.

 Intermediate: nitrenium ion (Ar–N⁺ ).

 Applications: paracetamol synthesis, dyes, developers.

 Substituents:
o EDG faster, higher yield.
o EWG slower, competing reactions.
Shortcut Mnemonic: “Bamberger loves PARA because Nitrenium feels SAFE
there.” (para-position stabilizes nitrenium cation the best).

Comparison with Related Rearrangements

 Beckmann rearrangement: involves oximes amides (not aromatic
hydroxylamines).
  Benzidine rearrangement: dimerization of hydrazobenzenes.

 Smiles rearrangement: intramolecular aromatic substitution.

 Bamberger is unique because it transforms hydroxylamine aminophenol via

cationic migration.

Modern Research Applications

 Green chemistry approaches:
o Solvent-free Bamberger rearrangements.
o Ionic liquids as acid catalysts.
o Microwave-assisted rearrangements (faster, higher selectivity).

 Medicinal chemistry:
o Pathway to aminophenol drugs (paracetamol, antibacterial agents).
o Formation of bioactive heteroaromatic aminophenols.

 Material science:
o p-Aminophenol derivatives precursors to conducting polymers.

Practice Questions
Q1. Phenylhydroxylamine on treatment with conc. H₂ SO₄ gives: (a) o-aminophenol (major)
(b) p-aminophenol (major)
(c) aniline
(d) nitrosobenzene
Answer: (b)

Q2. The key intermediate in the Bamberger rearrangement is: (a) Aryl carbocation
(b) Aryl radical
(c) Nitrenium ion
(d) Aryl anion
Answer: (c)

Q3. Which factor increases the ortho-product yield in Bamberger rearrangement? (a)
Stronger acid
(b) Polar protic solvent
(c) Polar aprotic solvent like AcOH
(d) High temperature
Answer: (c)
Q4. Industrial importance of Bamberger rearrangement lies in the synthesis of: (a) Phenol
(b) Paracetamol precursor
(c) Nitrobenzene
(d) Benzidine
Answer: (b)

Summary
 Bamberger Rearrangement converts aromatic hydroxylamines para-
aminophenols in acidic medium.

 Operates via nitrenium ion intermediate, stabilized at para position.

 Highly regioselective (para > ortho).

 Applications in drug synthesis (paracetamol), dyes, photographic chemicals.

 Key exam point: cationic rearrangement with para-selectivity.

60. Willgerodt–Kindler Rearrangement

Introduction
The Willgerodt–Kindler rearrangement is a classical organic transformation, widely
studied for carbonyl-to-amide conversion in aliphatic systems, particularly for ketones
and aldehydes bearing α-alkyl groups.

 Named after Willgerodt (1887) and later refined by Kindler, this rearrangement is an
extension of the Willgerodt reaction.

 It is a heteroatom-directed rearrangement, resulting in α-substituted amides from

ketones under sulfur and ammonia derivatives.

 The reaction is important in pharmaceutical and heterocyclic chemistry, allowing

conversion of methyl ketones to amides.

General Reaction

The classical Willgerodt–Kindler reaction involves:

  Substrate: Aliphatic methyl ketones (R–CO–CH₃ )

 Reagents: Sulfur (S), ammonium salts (NH₃ , ammonium acetate)

 Product: α-substituted amides (R–CH₂ –C(=O)NH₂ )

 Reaction often yields terminal amides, making it synthetically valuable.

Willgerodt vs Willgerodt–Kindler

Feature Willgerodt Willgerodt–Kindler

Substrate Ketones Ketones / aldehydes
Reagents Sulfur + amine Sulfur + ammonium acetate /
NH₃
Conditions Heat Heat or solvent
Product Terminal amides α-Substituted amides
Example R–CO–CH₃ R–CH₂ – R–CO–CH₂ R’ R–CH₂ –
C(=O)NH₂ C(=O)NH₂

Detailed Mechanism
The mechanism has been studied extensively via isotopic labeling, spectroscopy, and
computational chemistry. It can be divided into several key stages:

Step 1: Formation of α-Thioimide

 Ketone reacts with sulfur and ammonia (or ammonium salt) to form α-thioimide
intermediate:
  Sulfur inserts at the α-carbon via enolate formation, forming a thiocarbonyl
intermediate.

 Base (ammonia or acetate) assists enolate generation.

Step 2: Isomerization / Migration

 The α-thioimide undergoes rearrangement, with the sulfur atom acting as a
leaving group.

 α-Carbon shifts to form the terminal carbonyl adjacent to nitrogen:

 This is the key migration step, which defines the Willgerodt–Kindler specificity.

Step 3: Oxidation of Thioamide

 The sulfur atom is oxidized or eliminated (depending on conditions) to yield α-
substituted amide:

 Reaction is usually driven by heat, often in high-boiling solvents.

Step 4: Rearomatization (if aromatic)

 For aromatic ketones, electron delocalization stabilizes intermediates, leading to
higher yields.

Substrate Scope
 Aliphatic Ketones
o Methyl ketones (R–CO–CH₃ ) terminal amides.
o Longer alkyl chains possible, but migration occurs to terminal position.

 Aromatic Ketones
o Phenyl ketones give benzyl amides.
o Electron-donating groups accelerate the reaction; electron-withdrawing
groups slow it down.

 Aldehydes
o Aldehydes can also undergo Willgerodt–Kindler rearrangement to form
formamides.

 Substituted Ketones
o α-Substituted ketones α-substituted amides.
o Steric hindrance can slow reaction.
Factors Affecting Reaction

Factor Effect
Temperature High heat required (150–250°C), lower temp incomplete
reaction
Sulfur Stoichiometric or slight excess ensures smooth rearrangement
Ammonium Catalyzes migration and α-carbon activation
salt
Solvent Polar aprotic (DMF) or high-boiling solvents preferred
Substituents Electron-rich substrates faster; electron-poor slower

Synthetic Applications

 Industrial Amide Synthesis

o Terminal amides (formamide derivatives) are building blocks in
pharmaceuticals.

 Heterocyclic Chemistry
o Used to introduce amide functionality for further cyclization.

 Drug Synthesis
o Provides α-substituted amides that are intermediates in analgesics,
antibiotics, and antiviral drugs.

 Peptide Chemistry
o Terminal amides from ketones serve as precursors for N-terminal protection.

Mechanistic Insights for CSIR-NET

 Key intermediate: α-thioimide (enolate-sulfur adduct)

 Driving force: Heat and sulfur insertion

 Regioselectivity: Terminal carbonyl formation

 Acid/Base: Ammonium salts act as proton shuttle and base

 Electronic effects: Electron-donating groups on ketone accelerate migration

Shortcut Tip:

 “Willgerodt Moves to the End” α-carbon moves to terminal position, forming

terminal amide.
  Remember: S and NH₃ are co-facilitators.

Variants and Modern Adaptations

 Microwave-assisted Willgerodt–Kindler faster, higher yield

 Ionic liquid catalysis environmentally friendly

 One-pot adaptations for drug intermediate synthesis

 Aromatic ketones rearranged to benzyl amides

Related Rearrangements

Reaction Similarity Difference

Beckman Ketone amide Uses oximes, not sulfur intermediates
n
Schmidt Ketone/acid Uses azide, nitrenium pathway
amide
Willgerodt Same family Kindler variant uses milder conditions, ammonia
salts

Exam-Oriented Key Points

 Substrate: α-methyl or ketone derivatives

 Reagents: Sulfur + ammonia (or ammonium salt)

 Condition: High temperature (150–250°C), optional solvent

 Product: Terminal amide (α-substituted amide)

 Mechanism: α-thioimide formation migration oxidation

Mnemonics and Tricks

 “S moves α to NH₂ ” Sulfur facilitates migration of α-carbon to nitrogen.

 “Kindler ends the chain” Reaction yields terminal amides.

 Remember migration direction: Always toward terminal carbonyl.

Practice Questions
Q1. The Willgerodt–Kindler rearrangement converts:
(a) Aldehyde Amide
(b) Ketone Amide
(c) Alcohol Ketone
(d) Nitro Amine
Answer: (b)
Q2. Key intermediate in Willgerodt–Kindler reaction:
(a) Nitrenium ion
(b) α-Thioimide
(c) Enamine
(d) Carbocation
Answer: (b)
Q3. Reagents required:
(a) NH₃ + S
(b) HCl + Zn
(c) NaOH + H₂ O
(d) SOCl₂ + Pyridine
Answer: (a)
Q4. Major product of acetophenone under Willgerodt–Kindler:
(a) Phenylacetamide
(b) Benzamide
(c) Aniline
(d) p-Aminophenol
Answer: (a)
Q5. Factors increasing reaction rate:
 Electron-donating substituents on ketone

 High temperature

 Sufficient sulfur and NH₃

Summary Table – Willgerodt–Kindler

Feature Description
Substrate Ketones (methyl/α-substituted)
Reagents Sulfur + Ammonia or ammonium salts
Condition Heat (150–250°C)
Intermediate α-Thioimide
Product Terminal α-substituted amide
Mechanism Thioimide formation migration oxidation
Applications Pharmaceuticals, heterocycles, amide
synthesis
Conclusion
 The Willgerodt–Kindler rearrangement is a synthetic powerhouse for amide
formation.

 It is thermally induced, sulfur-mediated, and ammonia-facilitated.

 Provides terminal amides from ketones and aldehydes.

 Mechanistic understanding is exam-relevant: α-thioimide migration oxidation.

 Applications span pharmaceuticals, industrial chemistry, and heterocyclic

synthesis.
Exam Tip: Focus on substrate, reagents, migration, and terminal product.
🧪 PYQ- Questions on Name Reactions & Rearrangements

1. Aldol Condensation
1. The major product formed when acetaldehyde is treated with dilute NaOH at
room temperature is:
a) Crotonaldehyde
b) Acetic acid
c) Ethanol
d) Acetone
2. The aldol condensation between acetone and benzaldehyde in basic medium
gives:
a) Benzoin
b) Dibenzalacetone
c) Chalcone
d) Benzilic acid
3. Assertion (A): Aldol condensation is a carbon–carbon bond-forming reaction.
Reason (R): It involves nucleophilic attack of enolate ion on a carbonyl carbon.
a) Both A and R are true and R explains A
b) Both A and R are true but R does not explain A
c) A true, R false
d) A false, R true
4. Which of the following conditions suppresses aldol condensation?
a) Very high temperature
b) Strong base in aqueous medium
c) Strong acid in aqueous medium
d) Absence of α-hydrogen
5. Predict the product:
CH₃CHO + NaOH (dilute, 25 °C) → ?
a) CH₃CH₂OH
b) CH₃CH=CHCHO
c) CH₃COOH
d) CH₃CH₂CHO

2. Cannizzaro Reaction
6. Formaldehyde undergoes Cannizzaro reaction in presence of conc. NaOH to
give:
a) Methanol + Formic acid
b) Methanol + Sodium formate
 c) Ethanol + Acetic acid
d) Acetaldehyde + Ethanol
7. Which of the following aldehydes will NOT undergo Cannizzaro reaction?
a) Benzaldehyde
b) Formaldehyde
c) Acetaldehyde
d) 4-Nitrobenzaldehyde
8. Cannizzaro reaction is not feasible for aldehydes containing α-hydrogen
because:
a) They undergo aldol condensation
b) They are unstable in base
c) They form peroxides
d) They undergo polymerization
9. The reaction of benzaldehyde with concentrated NaOH gives:
a) Benzyl alcohol + Benzoic acid
b) Benzyl alcohol + Sodium benzoate
c) Benzoin + Benzil
d) Toluene + Benzoic acid
10. In crossed Cannizzaro reaction between formaldehyde and benzaldehyde, the
product obtained is:
a) Methanol + Benzoic acid
b) Benzyl alcohol + Formic acid
c) Benzyl alcohol + Sodium formate
d) Methanol + Sodium benzoate

3. Hofmann Rearrangement
11. Which of the following is the correct order of ease of Hofmann rearrangement?
a) Aliphatic > Aromatic > Heteroaromatic
b) Aromatic > Aliphatic > Heteroaromatic
c) Heteroaromatic > Aromatic > Aliphatic
d) Aliphatic > Heteroaromatic > Aromatic
12. Hofmann rearrangement converts primary amides into:
a) Primary amines with one carbon less
b) Secondary amines with one carbon more
c) Primary alcohols
d) Secondary alcohols
13. Which intermediate is formed during Hofmann rearrangement?
a) Isocyanate
b) Carbocation
 c) Carbene
d) Nitrene
14. The Hofmann rearrangement of benzamide gives:
a) Aniline
b) Benzylamine
c) Benzyl alcohol
d) Benzoic acid
15. Which reagent is essential in Hofmann rearrangement?
a) Br₂ + NaOH
b) Cl₂ + KOH
c) NaOCl + NaOH
d) Any of the above

4. Beckmann Rearrangement
16. Beckmann rearrangement converts oximes into:
a) Amides
b) Amines
c) Aldehydes
d) Carboxylic acids
17. Cyclohexanone oxime on Beckmann rearrangement gives:
a) Caprolactam
b) Adipic acid
c) Aniline
d) Cyclohexylamine
18. In Beckmann rearrangement, the migrating group is:
a) The group anti to hydroxyl group of oxime
b) The group syn to hydroxyl group of oxime
c) Random
d) Hydrogen always
19. Which reagent is commonly used for Beckmann rearrangement?
a) H₂SO₄
b) PCl₅
c) SOCl₂
d) NaOH
20. Which industrially important polymer precursor is obtained from Beckmann
rearrangement?
a) Nylon-6
b) Nylon-6,6
c) PET
d) Kevlar
5. Claisen Condensation
21. Which of the following enolates undergo Claisen condensation with ethyl acetate?
a) CH₃COOEt
b) CH₃CH₂COOEt
c) PhCOOEt
d) All of the above

22. The minimum requirement for Claisen condensation is:

a) Two esters with α-hydrogens
b) One ester must have α-hydrogen
c) Both esters should lack α-hydrogen
d) At least one ester should be aromatic

23. In a Claisen condensation, the base used must be:

a) Weaker than the leaving group alkoxide
b) Stronger than the leaving group alkoxide
c) The same alkoxide as the ester group
d) Irrelevant to ester group

24. Reaction of two molecules of ethyl acetate with sodium ethoxide gives:
a) Ethyl acetoacetate
b) Acetone
c) Ethyl propionate
d) Acetoacetic acid

25. Which one is NOT a variant of Claisen condensation?

a) Dieckmann condensation
b) Mixed Claisen condensation
c) Perkin condensation
d) Intramolecular Claisen condensation

6. Pinacol–Pinacolone Rearrangement
26. The product formed when pinacol is treated with H₂SO₄ is:
a) Acetone
b) Pinacolone
c) Mesitylene
d) Benzil

27. Which intermediate is involved in Pinacol rearrangement?

a) Carbocation
b) Carbanion
c) Radical
d) Nitrene

28. In Pinacol rearrangement, the migrating group is:

a) The one that stabilizes the carbocation best
b) Random
 c) Hydrogen only
d) The smallest alkyl group

29. Which of the following favors Pinacol rearrangement?

a) Acidic medium
b) Basic medium
c) Neutral condition
d) High temperature only

30. Benzopinacol on rearrangement gives:

a) Benzophenone
b) Benzaldehyde
c) Benzil
d) Benzoic acid

7. Wolff Rearrangement
31. Wolff rearrangement converts α-diazoketones into:
a) Amides
b) Ketones
c) Carboxylic acids (via ketene)
d) Amines

32. The intermediate formed in Wolff rearrangement is:

a) Ketene
b) Carbocation
c) Nitrene
d) Isocyanate

33. Which reagent initiates Wolff rearrangement?

a) Heat or light
b) Ag₂O
c) Br₂ + NaOH
d) ZnCl₂

34. Which synthetic method uses Wolff rearrangement as a key step?

a) Arndt–Eistert synthesis
b) Sandmeyer reaction
c) Perkin condensation
d) Friedel–Crafts acylation

35. In Wolff rearrangement, migration occurs from:

a) Carbon adjacent to diazo group
b) Carbon adjacent to ketone oxygen
c) Random group
d) Hydrogen only
8. Curtius Rearrangement
36. Curtius rearrangement converts acyl azides into:
a) Amides
b) Amines (via isocyanate intermediate)
c) Alcohols
d) Esters

37. The intermediate in Curtius rearrangement is:

a) Isocyanate
b) Carbocation
c) Ketene
d) Radical

38. Which reagent is used to prepare acyl azides for Curtius rearrangement?
a) Hydrazine + NaNO₂
b) Acyl chloride + NaN₃
c) Acyl halide + NH₃
d) Acid + NH₂NH₂

39. Assertion (A): Curtius rearrangement decreases the carbon count in final amine.
Reason (R): Loss of N₂ gas occurs in the process.
a) Both A and R are true and R explains A
b) Both A and R are true but R does not explain A
c) A true, R false
d) A false, R true

40. The Curtius rearrangement of benzoyl azide gives:

a) Benzylamine
b) Aniline
c) Phenylisocyanate (intermediate → aniline on hydrolysis)
d) Benzyl alcohol

9. Perkin Condensation
41. The Perkin condensation between benzaldehyde and acetic anhydride gives:
a) Benzoin
b) Cinnamic acid
c) Benzilic acid
d) Styrene

42. The essential reagent in Perkin reaction is:

a) Sodium acetate
b) Sodium hydroxide
c) NaHCO₃
d) NaCl

43. Perkin condensation is used in the synthesis of:

a) Aromatic aldehydes
b) α,β-Unsaturated carboxylic acids
 c) Saturated alcohols
d) Acyl halides

44. The reaction of p-anisaldehyde with acetic anhydride in presence of sodium acetate
yields:
a) p-Methoxy cinnamic acid
b) p-Methylbenzoic acid
c) p-Methoxybenzyl alcohol
d) Vanillin

45. Which of the following is TRUE for Perkin reaction?

a) It involves enolate attack on aldehyde
b) It produces saturated acids
c) It is an oxidation reaction
d) It reduces aldehydes

10. Sandmeyer Reaction

46. Sandmeyer reaction involves replacement of –N₂⁺ group by:
a) Cl, Br, CN
b) NH₂
c) NO₂
d) SO₃H

47. The reagent for Sandmeyer reaction is:

a) CuCl, CuBr, CuCN
b) HCl, HBr
c) HNO₂
d) KMnO₄

48. Assertion (A): Sandmeyer reaction is useful in introducing substituents into benzene
ring.
Reason (R): It involves radical mechanism with Cu⁺ as catalyst.
a) Both A and R true, R explains A
b) Both A and R true, R does not explain A
c) A true, R false
d) A false, R true

49. Diazotization of aniline followed by Sandmeyer reaction with CuCN yields:

a) Benzonitrile
b) Benzyl cyanide
c) Benzylamine
d) Nitrobenzene

50. Which one is NOT a variant of Sandmeyer reaction?

a) Gattermann reaction
b) Rosenmund reaction
c) Modified Sandmeyer with Cu powder
d) Balz–Schiemann reaction
11. Fries Rearrangement
51. Fries rearrangement converts aryl esters into:
a) Hydroxyaryl ketones
b) Aminoaryl ketones
c) Nitroaryl ketones
d) Carboxyaryl ketones

52. Which catalyst is used in Fries rearrangement?

a) AlCl₃
b) FeCl₃
c) H₂SO₄
d) NaOH

53. Acetylphenyl acetate on Fries rearrangement gives:

a) Hydroxyacetophenone (ortho- and para-isomers)
b) Phenol
c) Benzophenone
d) Acetophenone

54. Which of the following statements is TRUE for Fries rearrangement?

a) Ortho/para ratio can be influenced by temperature
b) Always gives only ortho product
c) Always gives only para product
d) No rearrangement occurs at high temperature

55. Fries rearrangement is an example of:

a) Electrophilic aromatic substitution
b) Nucleophilic aromatic substitution
c) Radical substitution
d) Free radical rearrangement

12. Schmidt Rearrangement

56. Schmidt rearrangement converts carboxylic acids into:
a) Amides
b) Amines
c) Aldehydes
d) Ketones

57. The reagent used in Schmidt rearrangement is:

a) Hydrazoic acid (HN₃)
b) Sodium azide
c) Ammonia
d) Nitric acid

58. The intermediate formed in Schmidt rearrangement is:

a) Acyl azide
b) Isocyanate
c) Carbocation
d) Carbene
 59. Acetic acid on Schmidt rearrangement gives:
a) Methylamine
b) Ethylamine
c) Acetamide
d) Acetone

60. Schmidt rearrangement of benzophenone with HN₃ gives:

a) Benzanilide
b) Benzhydrylamine
c) Aniline
d) Benzamide

13. Baeyer–Villiger Oxidation

61. Baeyer–Villiger oxidation converts ketones into:
a) Esters
b) Alcohols
c) Amides
d) Acids

62. Which reagent is commonly used in Baeyer–Villiger oxidation?

a) Peracids (mCPBA, peracetic acid)
b) H₂SO₄
c) KMnO₄
d) NaBH₄

63. In Baeyer–Villiger oxidation, the migrating group is:

a) More substituted alkyl group
b) Hydrogen only
c) Random
d) Always phenyl

64. Cyclohexanone on Baeyer–Villiger oxidation gives:

a) Caprolactone
b) Adipic acid
c) Cyclohexanol
d) Benzophenone

65. Which factor decides migratory aptitude in Baeyer–Villiger oxidation?

a) Stability of carbocation formed during migration
b) Size of group
c) Bond strength
d) Random rearrangement

14. Reimer–Tiemann Reaction

66. Reimer–Tiemann reaction involves formylation of phenols using:
a) CHCl₃ + NaOH
b) HCHO + HCl
 c) CO + HCl
d) CH₂I₂ + Zn

67. Phenol on Reimer–Tiemann reaction gives:

a) Salicylaldehyde
b) Benzaldehyde
c) p-Hydroxybenzaldehyde
d) Catechol

68. The reactive intermediate in Reimer–Tiemann reaction is:

a) Dichlorocarbene ( :CCl₂ )
b) Carbanion
c) Carbocation
d) Isocyanate

69. Assertion (A): Reimer–Tiemann reaction is regioselective.

Reason (R): The –CHO group always goes to ortho position of phenol.
a) Both A and R true and R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

70. The yield of para-product in Reimer–Tiemann reaction can be increased by:

a) Bulky substituents at ortho position
b) Using excess chloroform
c) Increasing temperature
d) Replacing NaOH with KOH

15. Kolbe–Schmitt Reaction

71. Kolbe–Schmitt reaction involves reaction of sodium phenoxide with:
a) CO₂ under pressure
b) CO + HCl
c) CHCl₃ + NaOH
d) Na₂CO₃

72. The product of Kolbe–Schmitt reaction of phenol is:

a) Salicylic acid
b) Benzoic acid
c) Cinnamic acid
d) Terephthalic acid

73. In Kolbe–Schmitt reaction, which position does CO₂ enter?

a) Ortho position of phenol
b) Para position of phenol
c) Meta position
d) Random position

74. Salicylic acid obtained from Kolbe–Schmitt reaction is used industrially for preparation
of:
a) Aspirin
 b) Nylon-6
c) Urea
d) Teflon

75. Which parameter is critical in Kolbe–Schmitt reaction?

a) High temperature and high pressure
b) Low temperature and high pressure
c) Low pressure and high temperature
d) Neutral medium

16. Hell–Volhard–Zelinsky (HVZ) Reaction

76. HVZ reaction is used for halogenation of:
a) α-position of carboxylic acids
b) β-position of carboxylic acids
c) Aromatic ring
d) Olefins

77. Which reagents are used in HVZ reaction?

a) Br₂ + Red P
b) Cl₂ + FeCl₃
c) I₂ + HNO₃
d) KMnO₄

78. The first step in HVZ reaction is:

a) Formation of acyl bromide
b) Formation of carbanion
c) Formation of enolate
d) Decarboxylation

79. Propanoic acid treated with Br₂/Red P gives:

a) 2-Bromopropanoic acid
b) 3-Bromopropanoic acid
c) Bromopropane
d) 1-Bromopropane

80. HVZ reaction does NOT occur with:

a) Formic acid
b) Acetic acid
c) Butanoic acid
d) Benzoic acid

17. Claisen Rearrangement

81. Claisen rearrangement converts allyl aryl ethers into:
a) Ortho-allyl phenols
b) Para-allyl phenols
 c) Catechols
d) Hydroquinones

82. Which type of mechanism is followed in Claisen rearrangement?

a) [3,3]-Sigmatropic rearrangement
b) Carbocationic rearrangement
c) Free radical rearrangement
d) Ionic nucleophilic substitution

83. The rearrangement of allyl vinyl ether in Claisen rearrangement gives:

a) Unsaturated carbonyl compound
b) Allylic alcohol
c) Phenol
d) Aromatic aldehyde

84. Which statement is TRUE for Claisen rearrangement?

a) It is a concerted pericyclic reaction
b) It requires strong acid catalyst
c) It forms only para-substituted product
d) It is not stereospecific

85. Claisen rearrangement of phenyl allyl ether on heating gives:

a) o-Allylphenol
b) p-Allylphenol
c) Anisole
d) Catechol

18. Cope Rearrangement

86. The Cope rearrangement is a:
a) [3,3]-Sigmatropic rearrangement
b) [1,2]-Shift
c) Free radical reaction
d) [2,3]-Sigmatropic rearrangement

87. The rearrangement of 1,5-hexadiene in Cope rearrangement gives:

a) Isomeric 1,5-hexadiene
b) Cyclohexene
c) 1,3-butadiene
d) Benzene

88. Which factor influences Cope rearrangement equilibrium?

a) Stability of double bond location
b) Catalyst used
c) Oxidation state
d) Nature of solvent only

89. Oxy-Cope rearrangement leads to:

a) Enol which tautomerizes to carbonyl compound
b) Aldehyde directly
 c) Alcohol directly
d) Aromatic compound

90. The driving force in Cope rearrangement is:

a) Formation of more stable alkene conjugation
b) Loss of N₂
c) Loss of CO₂
d) Formation of carbocation

19. Wittig Reaction

91. Wittig reaction is used to convert:
a) Aldehydes/ketones → Alkenes
b) Alcohols → Alkenes
c) Alkenes → Carbonyl compounds
d) Acids → Alcohols

92. The reagent in Wittig reaction is:

a) Phosphonium ylide
b) Grignard reagent
c) Carbene
d) Enolate

93. Which type of alkene is usually favored in Wittig reaction with unstabilized ylides?
a) Z-Alkene
b) E-Alkene
c) Mixture always
d) No specific preference

94. The product of Ph₃P=CH₂ + PhCHO in Wittig reaction is:

a) Styrene
b) Ethylbenzene
c) Benzyl alcohol
d) Acetophenone

95. Wittig reaction is an example of:

a) Nucleophilic addition-elimination
b) Olefination
c) Oxidation
d) Rearrangement

20. Oppenauer Oxidation

96. Oppenauer oxidation converts alcohols into:
a) Aldehydes/ketones
b) Carboxylic acids
c) Esters
d) Alkanes
 97. The typical reagent used in Oppenauer oxidation is:
a) Al(i-PrO)₃ + ketone (acceptor)
b) PCC
c) KMnO₄
d) Jones reagent

98. Oppenauer oxidation is considered the reverse of:

a) Meerwein–Ponndorf–Verley (MPV) reduction
b) Wolff–Kishner reduction
c) Clemmensen reduction
d) Rosenmund reduction

99. Cyclohexanol on Oppenauer oxidation gives:

a) Cyclohexanone
b) Cyclohexene
c) Benzene
d) Adipic acid

100. Which of the following is NOT true for Oppenauer oxidation?

a) It is selective for secondary alcohols
b) It requires mild conditions
c) It produces esters as products
d) It uses ketone as hydrogen acceptor

21. Birch Reduction

101. Birch reduction converts aromatic rings into:
a) 1,4-Cyclohexadienes
b) Benzyl alcohols
c) Cyclohexanones
d) Alkanes

102. The reagent system in Birch reduction is:

a) Na/NH₃(l) + alcohol
b) Zn/HCl
c) Pd/H₂
d) NaBH₄

103. Anisole on Birch reduction gives:

a) 1,4-Dihydroanisole (substituted diene)
b) Phenol
c) Cyclohexanone
d) Catechol

104. Which substituent directs Birch reduction to give product with electron density
near it?
a) Electron donating groups (EDG)
b) Electron withdrawing groups (EWG)
c) Both EDG and EWG equally
d) No effect
 105. Assertion (A): Birch reduction of toluene gives 1,4-dihydrotoluene.
Reason (R): Methyl group acts as an electron donating substituent stabilizing negative
charge.
a) Both A and R true, R explains A
b) Both A and R true, R does not explain A
c) A true, R false
d) A false, R true

22. Cannizzaro (Crossed Variant)

106. Crossed Cannizzaro reaction between formaldehyde and benzaldehyde gives:
a) Benzyl alcohol + Sodium formate
b) Methanol + Benzoic acid
c) Benzyl alcohol + Methanol
d) Benzoic acid + Methanol

107. Which condition favors selective reduction of benzaldehyde in crossed

Cannizzaro reaction?
a) Presence of formaldehyde as reducing agent
b) Use of dilute NaOH only
c) Use of alcohol solvent
d) High temperature

108. In crossed Cannizzaro reaction, the aldehyde without α-hydrogen acts as:
a) Oxidizing agent
b) Reducing agent
c) Catalyst
d) Nucleophile

109. Which aldehyde is best used with formaldehyde in crossed Cannizzaro?

a) Benzaldehyde
b) Acetaldehyde
c) Propanal
d) Isobutyraldehyde

110. The Cannizzaro reaction is an example of:

a) Redox disproportionation
b) Nucleophilic substitution
c) Radical reaction
d) Pericyclic rearrangement

23. Rosenmund Reduction

111. Rosenmund reduction is used to convert:
a) Acyl chlorides → Aldehydes
b) Acids → Alcohols
c) Aldehydes → Alcohols
d) Ketones → Alkanes
 112. The catalyst used in Rosenmund reduction is:
a) Pd/BaSO₄ (poisoned)
b) Pt/C
c) Raney Ni
d) Zn–Hg

113. Acetyl chloride on Rosenmund reduction gives:

a) Acetaldehyde
b) Acetic acid
c) Acetone
d) Ethanol

114. Assertion (A): Rosenmund reduction does not over-reduce aldehydes.

Reason (R): Catalyst is poisoned to control hydrogenation activity.
a) Both A and R true, R explains A
b) Both A and R true, R does not explain A
c) A true, R false
d) A false, R true

115. Which of the following is NOT suitable for Rosenmund reduction?

a) Acyl chloride
b) Acid anhydride
c) Formyl chloride
d) Benzoyl chloride

24. Stephen Reduction

116. Stephen reduction converts nitriles into:
a) Aldehydes
b) Amines
c) Acids
d) Ketones

117. The reducing agent in Stephen reduction is:

a) SnCl₂/HCl
b) Zn/HCl
c) LiAlH₄
d) NaBH₄

118. Benzonitrile on Stephen reduction gives:

a) Benzaldehyde
b) Benzoic acid
c) Benzylamine
d) Benzyl alcohol

119. Which intermediate is formed in Stephen reduction?

a) Imine salt
b) Amide
c) Isocyanate
d) Enamine
 120. Assertion (A): Stephen reduction is selective for nitriles.
Reason (R): Reaction proceeds via iminium chloride intermediate.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

25. Balz–Schiemann Reaction

121. Balz–Schiemann reaction is used to prepare:
a) Fluoroarenes
b) Chloroarenes
c) Nitroarenes
d) Iodoarenes

122. The key reagent in Balz–Schiemann reaction is:

a) HBF₄
b) HCl
c) CuCl
d) KI

123. Aniline on Balz–Schiemann reaction gives:

a) Fluorobenzene
b) Chlorobenzene
c) Nitrobenzene
d) Toluene

124. The intermediate formed in Balz–Schiemann reaction is:

a) Diazonium tetrafluoroborate
b) Diazonium chloride
c) Phenoxide ion
d) Carbocation

125. Which of the following statements is TRUE?

a) Balz–Schiemann is a thermal decomposition reaction
b) It proceeds via radical chain mechanism
c) It gives iodides in high yield
d) It does not require diazonium salts

26. Tiffeneau–Demjanov Rearrangement

126. Tiffeneau–Demjanov rearrangement involves:
a) Ring expansion via diazonium intermediate
b) Ring contraction via carbocation
c) Aldehyde to amine conversion
d) Alcohol to ketone oxidation

127. Which reagent is essential in Tiffeneau–Demjanov rearrangement?

a) HNO₂
b) H₂SO₄
 c) LiAlH₄
d) KMnO₄

128. Cyclobutanone oxime via Tiffeneau–Demjanov rearrangement gives:

a) Cyclopentanone
b) Cyclobutanone
c) Cyclohexanone
d) Cyclopropanone

129. The driving force in Tiffeneau–Demjanov rearrangement is:

a) Ring expansion for stability
b) Loss of N₂
c) Aromatic stabilization
d) Formation of ester

130. Assertion (A): Tiffeneau–Demjanov rearrangement is useful in synthesizing larger

rings.
Reason (R): Reaction proceeds via carbocation after N₂ elimination.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

27. Benzil–Benzilic Acid Rearrangement

131. Benzil on heating with KOH undergoes rearrangement to give:
a) Benzilic acid
b) Benzoic acid
c) Benzoin
d) Benzaldehyde

132. The mechanism of Benzil–Benzilic acid rearrangement involves:

a) 1,2-Phenyl shift
b) 1,2-Hydride shift
c) 1,3-Sigmatropic rearrangement
d) Free radical substitution

133. The driving force of Benzil–Benzilic acid rearrangement is:

a) Conversion of diketone into stable carboxylate
b) Aromatic stabilization
c) Loss of N₂
d) Release of CO₂

134. Which reagent is essential in Benzil–Benzilic acid rearrangement?

a) KOH (aqueous or alcoholic)
b) ZnCl₂
c) H₂SO₄
d) PCC

135. Assertion (A): Benzil–Benzilic acid rearrangement is intramolecular.

Reason (R): Phenyl group migrates from one carbonyl carbon to adjacent carbonyl
 carbon.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

28. Gattermann Reaction

136. Gattermann reaction is mainly used for the synthesis of:
a) Aromatic aldehydes
b) Aromatic ketones
c) Nitroarenes
d) Alcohols

137. The reagent system for Gattermann reaction is:

a) HCN + HCl + AlCl₃
b) CO + HCl + CuCl
c) Zn/HCl
d) NH₂OH + HCl

138. Benzene treated with HCN/HCl/AlCl₃ gives:

a) Benzaldehyde
b) Benzoic acid
c) Benzyl alcohol
d) Acetophenone

139. Assertion (A): Gattermann and Gattermann–Koch reactions are similar.

Reason (R): Both involve formylation of aromatic rings.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

140. Which intermediate is formed in the Gattermann reaction?

a) Iminium ion
b) Carbocation
c) Aryl cation
d) Acylium ion

29. Reformatsky Reaction

141. Reformatsky reaction involves the use of:
a) α-Haloester + Zn → β-hydroxyester
b) Aldehyde + ZnCl₂
c) Ketone + Grignard reagent
d) Ester + NaBH₄
 142. The metal essential in Reformatsky reaction is:
a) Zinc
b) Magnesium
c) Lithium
d) Copper

143. Acetaldehyde + ethyl bromoacetate/Zn gives:

a) Ethyl 3-hydroxybutanoate
b) Ethyl acetate
c) Acetone
d) Ethyl malonate

144. Assertion (A): Reformatsky reaction forms C–C bonds.

Reason (R): Organometallic zinc enolate acts as nucleophile.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

145. Which statement about Reformatsky reaction is FALSE?

a) Works with aldehydes better than ketones
b) Proceeds via zinc enolate intermediate
c) Gives β-hydroxyester
d) Requires Grignard reagent

30. Knoevenagel Condensation

146. Knoevenagel condensation involves:
a) Active methylene compound + aldehyde → α,β-unsaturated compound
b) Aldehyde + alcohol → acetal
c) Ketone + ester → β-keto ester
d) Ester hydrolysis

147. Common base used in Knoevenagel condensation:

a) Piperidine
b) NaBH₄
c) ZnCl₂
d) PCC

148. Malonic ester + benzaldehyde in presence of piperidine gives:

a) Cinnamic acid (after hydrolysis/decarboxylation)
b) Benzoic acid
c) Benzyl alcohol
d) Styrene

149. Assertion (A): Knoevenagel condensation is a key step in synthesis of

coumarins.
Reason (R): Active methylene compounds condense with aldehydes under base.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
 c) A true, R false
d) A false, R true

150. Which of the following compounds will NOT undergo Knoevenagel condensation
efficiently?
a) Malonic ester
b) Cyanoacetic ester
c) Acetone
d) Meldrum’s acid

31. Michael Addition

151. Michael addition is:
a) 1,4-addition of carbanion to α,β-unsaturated carbonyl compound
b) 1,2-addition of Grignard to aldehyde
c) Oxidation of alcohols
d) Rearrangement of esters

152. The nucleophile in Michael addition is generally:

a) Enolate ion
b) Carbocation
c) Aryl radical
d) Proton

153. Ethyl acetoacetate + methyl vinyl ketone undergo:

a) Michael addition
b) Aldol condensation
c) Cannizzaro reaction
d) Claisen condensation

154. Assertion (A): Michael addition is used in Robinson annulation.

Reason (R): Enolate adds to α,β-unsaturated ketone in first step.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

155. Which statement is TRUE for Michael addition?

a) Produces 1,4-adducts selectively
b) Always produces 1,2-adducts
c) Requires acidic medium only
d) Only works with aldehydes

32. Mannich Reaction

156. Mannich reaction involves:
a) Aldehyde + amine + enolizable ketone
b) Aldehyde + alcohol + amine
c) Ketone + ester + base
d) Carboxylic acid + amine
 157. Product of Mannich reaction is:
a) β-aminocarbonyl compound
b) β-hydroxy ester
c) Imine
d) α-halo ketone

158. Formaldehyde + dimethylamine + acetone gives:

a) β-dimethylaminoketone
b) Acetaldehyde
c) Acetamide
d) Enamine

159. Assertion (A): Mannich bases are useful intermediates in drug synthesis.
Reason (R): β-aminocarbonyl compounds are biologically active.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

160. Which of the following is NOT a Mannich substrate?

a) Acetophenone
b) Malonic ester
c) Urea
d) Benzyl chloride

33. Stobbe Condensation

161. Stobbe condensation involves:
a) Aldehyde/ketone + succinic ester → substituted succinic acid derivative
b) Aldehyde + nitrile → imine
c) Ketone + ester → β-keto ester
d) Carboxylic acid + alcohol → ester

162. The base used in Stobbe condensation is:

a) Sodium ethoxide
b) Piperidine
c) ZnCl₂
d) NaBH₄

163. Benzaldehyde + diethyl succinate/NaOEt gives:

a) Cinnamic acid derivative
b) Succinic anhydride
c) Styrene
d) Benzyl alcohol

164. Assertion (A): Stobbe condensation gives half-esters as intermediates.

Reason (R): One ester group hydrolyzes during reaction.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true
 165. Which statement is FALSE regarding Stobbe condensation?
a) Requires diethyl succinate or similar ester
b) Involves enolate nucleophile attack
c) Gives γ,δ-unsaturated acids as products
d) Requires strong oxidizing agent

34. Robinson Annulation

166. Robinson annulation is a combination of:
a) Michael addition + Aldol condensation
b) Cannizzaro + Perkin
c) Claisen + Friedel–Crafts
d) Aldol + Beckmann

167. Key intermediate in Robinson annulation is:

a) Michael adduct
b) Imine
c) Carbanion radical
d) Carbocation

168. Cyclohexanone + methyl vinyl ketone undergoes:

a) Robinson annulation
b) Knoevenagel condensation
c) Reformatsky reaction
d) Gattermann reaction

169. Assertion (A): Robinson annulation produces fused six-membered rings.

Reason (R): Intramolecular aldol condensation follows Michael addition.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

170. Which reaction is widely used in steroid synthesis?

a) Robinson annulation
b) Claisen condensation
c) Friedel–Crafts acylation
d) Kolbe reaction

35. Claisen Condensation

171. Claisen condensation involves:
a) Two esters/ester + ketone in presence of base
b) Aldehyde + ester → alcohol
c) Amide + ester → imide
d) Ester + nitrile → amidine

172. Which base is essential in Claisen condensation?

a) Alkoxide (same as ester group)
b) NaOH
 c) NaBH₄
d) PCC

173. Ethyl acetate + sodium ethoxide → ?

a) Ethyl acetoacetate
b) Acetaldehyde
c) Benzyl alcohol
d) Malonic ester

174. Assertion (A): Claisen condensation requires α-hydrogen.

Reason (R): Enolate formation is the first step.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

175. Which product is formed in crossed Claisen condensation of ethyl acetate and
acetophenone?
a) β-Keto ester
b) β-Diketone
c) Aldol product
d) Carboxylic acid

36. Dieckmann Condensation

176. Dieckmann condensation is:
a) Intramolecular Claisen condensation
b) Intermolecular aldol condensation
c) Nucleophilic aromatic substitution
d) Intramolecular Cannizzaro

177. Diethyl adipate with sodium ethoxide undergoes:

a) Dieckmann condensation → cyclic β-keto ester
b) Aldol condensation
c) Decarboxylation
d) Perkin condensation

178. Assertion (A): Dieckmann condensation forms five- or six-membered rings.

Reason (R): Intramolecular attack of enolate on ester carbonyl occurs.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

179. Which condition is essential for Dieckmann condensation?

a) Presence of two ester groups in same molecule
b) Use of Grignard reagent
c) Aryl halide substrate
d) Peroxide initiator
 180. Product of Dieckmann condensation of diethyl malonate is:
a) Cyclic β-keto ester
b) Acetone
c) Acetic acid
d) Benzyl alcohol

37. Pechmann Condensation

181. Pechmann condensation is useful for synthesis of:
a) Coumarins
b) Pyridines
c) Quinoline
d) Indole

182. Resorcinol + ethyl acetoacetate/H₂SO₄ gives:

a) Coumarin derivative
b) Phenol
c) Benzaldehyde
d) Styrene

183. Catalyst for Pechmann condensation is:

a) Concentrated H₂SO₄
b) NaOH
c) ZnCl₂
d) K₂CO₃

184. Assertion (A): Pechmann condensation proceeds via transesterification +

cyclization.
Reason (R): Active methylene group condenses with phenol derivative.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

185. Which factor enhances Pechmann condensation yield?

a) Electron-rich phenol
b) Electron-deficient phenol
c) Aromatic amine
d) Nitro-substituted benzene

38. Skraup Synthesis

186. Skraup synthesis produces:
a) Quinoline derivatives
b) Indole derivatives
c) Coumarins
d) Isoquinolines

187. Reagents in Skraup synthesis:

a) Aniline + glycerol + oxidizing agent (H₂SO₄, nitrobenzene)
 b) Aniline + formaldehyde + HCl
c) Phenol + CH₂O + base
d) Benzaldehyde + acetone + base

188. The oxidant in Skraup synthesis is:

a) Nitrobenzene
b) ZnCl₂
c) PCC
d) NaBH₄

189. Assertion (A): Skraup synthesis is exothermic and requires careful heating.
Reason (R): Nitrobenzene acts as oxidant generating excess heat.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

190. Skraup synthesis converts:

a) Aniline → Quinoline
b) Aniline → Coumarin
c) Phenol → Catechol
d) Pyrrole → Indole

39. Fischer Indole Synthesis

191. Fischer indole synthesis converts:
a) Phenylhydrazones → Indoles
b) Phenols → Quinones
c) Anilines → Pyridines
d) Acetophenone → Coumarin

192. The key intermediate in Fischer indole synthesis is:

a) Ene-hydrazine tautomer
b) Enamine
c) Acylium ion
d) Imine

193. Acetophenone phenylhydrazone with acid catalyst gives:

a) 2-Phenylindole
b) 3-Phenylpyridine
c) Benzoxazole
d) Quinoline

194. Assertion (A): Fischer indole synthesis proceeds via [3,3]-sigmatropic

rearrangement.
Reason (R): The rearrangement step converts hydrazone tautomer to cyclic indole
precursor.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true
 195. Fischer indole synthesis is important for the preparation of:
a) Tryptophan derivatives
b) Pyrimidine bases
c) Coumarins
d) Anthracenes

40. Bischler–Napieralski Reaction

196. Bischler–Napieralski reaction involves cyclization of:
a) β-Phenylethylamides → Isoquinolines
b) Anilines → Quinoline
c) Phenols → Coumarins
d) Hydrazones → Indoles

197. Which reagent is used in Bischler–Napieralski reaction?

a) POCl₃ or P₂O₅
b) ZnCl₂
c) H₂/Pd
d) NaOH

198. Assertion (A): Bischler–Napieralski reaction is important in alkaloid synthesis.

Reason (R): Isoquinoline skeleton is generated from β-phenylethylamide.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

199. Starting compound for Bischler–Napieralski reaction:

a) β-Phenylethylamide
b) Aniline
c) Phenol
d) Acetanilide

200. Final product of Bischler–Napieralski reaction is:

a) Isoquinoline derivative
b) Indole derivative
c) Coumarin derivative
d) Quinoline derivative

41. Pictet–Spengler Reaction

201. Pictet–Spengler reaction converts:
a) β-Phenylethylamine + aldehyde → Tetrahydroisoquinoline
b) Aniline + acetaldehyde → Quinoline
c) Phenol + formaldehyde → Coumarin
d) Pyrrole + acid chloride → Indole
 202. The reaction proceeds via:
a) Iminium ion intermediate
b) Carbocation rearrangement
c) Radical chain process
d) Enolate ion

203. Assertion (A): Pictet–Spengler is a biomimetic reaction.

Reason (R): Similar mechanism operates in biosynthesis of alkaloids.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

204. Phenylethylamine + formaldehyde under acidic conditions gives:

a) Tetrahydroisoquinoline
b) Indole
c) Quinoline
d) Benzimidazole

205. Pictet–Spengler reaction is widely used in synthesis of:

a) Alkaloids
b) Dyes
c) Polymers
d) Vitamins

42. Sandmeyer Reaction

206. Sandmeyer reaction converts diazonium salts into:
a) Aryl halides
b) Alcohols
c) Amines
d) Esters

207. Reagent for Sandmeyer reaction:

a) CuCl, CuBr, CuCN
b) NaOH
c) Zn/HCl
d) Pd/C + H₂

208. Assertion (A): Sandmeyer reaction proceeds via radical mechanism.

Reason (R): Copper(I) salts generate aryl radicals from diazonium salts.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

209. Aniline → Diazonium salt → Sandmeyer with CuCN gives:

a) Benzonitrile
b) Chlorobenzene
c) Phenol
d) Benzaldehyde
 210. Which of the following is NOT obtained by Sandmeyer reaction?
a) Fluorobenzene
b) Chlorobenzene
c) Bromobenzene
d) Benzonitrile

43. Gomberg–Bachmann Reaction

211. Gomberg–Bachmann reaction couples:
a) Diazonium salt + aromatic compound → Biaryl
b) Aldehyde + amine → Imine
c) Ester + Grignard → Alcohol
d) Phenol + CH₂O → Resin

212. Mechanism of Gomberg–Bachmann reaction involves:

a) Aryl radical intermediate
b) Carbocation
c) Carbanion
d) Nitrene

213. Assertion (A): Gomberg–Bachmann gives low yields.

Reason (R): Competing side reactions of aryl radicals occur.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

214. Aniline diazonium chloride + benzene → ?

a) Biphenyl
b) Benzyl alcohol
c) Phenol
d) Chlorobenzene

215. Which limitation applies to Gomberg–Bachmann reaction?

a) Low yield due to uncontrolled radical reactions
b) Cannot form biaryls
c) Requires Grignard reagent
d) Requires transition-metal catalysts

44. Houben–Hoesch Reaction

216. Houben–Hoesch reaction involves:
a) Nitrile + activated aromatic ring (Ar–H) → Aryl ketone
b) Ester + alcohol → Ketone
c) Amide + aldehyde → Imine
d) Aniline + acid chloride → Amide

217. Reagent used in Houben–Hoesch reaction:

a) HCl/ZnCl₂ catalyst
b) AlCl₃
 c) NaBH₄
d) PCC

218. Assertion (A): Electron-rich aromatics undergo Houben–Hoesch easily.

Reason (R): Aromatic ring attacks nitrilium ion generated from nitrile.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

219. Phenol + acetonitrile/HCl-ZnCl₂ → ?

a) p-Hydroxyacetophenone
b) Benzyl alcohol
c) Acetophenone
d) Anisole

220. Which intermediate is formed in Houben–Hoesch reaction?

a) Nitrilium ion
b) Carbocation
c) Carbanion
d) Diazonium

45. Fries Rearrangement

221. Fries rearrangement converts:
a) Aryl esters → Hydroxyaryl ketones
b) Carboxylic acids → Esters
c) Aldehydes → Alcohols
d) Anilides → Isocyanates

222. Catalyst in Fries rearrangement:

a) AlCl₃
b) NaOH
c) KMnO₄
d) H₂SO₄

223. Phenyl acetate + AlCl₃ heat → ?

a) o- & p-Hydroxyacetophenone
b) Benzaldehyde
c) Phenol
d) Acetophenone

224. Assertion (A): Fries rearrangement gives ortho- and para-products.

Reason (R): Acylium ion attaches to aromatic ring.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

225. Which factor controls ortho/para ratio in Fries rearrangement?

a) Reaction temperature
 b) Solvent polarity
c) Catalyst concentration
d) Isotope effect

38. Sommelet–Hauser Rearrangement

271. Sommelet–Hauser rearrangement involves:
a) Rearrangement of benzyl quaternary ammonium salts
b) Rearrangement of diazonium salts
c) Oxidation of aldehydes
d) Coupling of aryl halides

272. The key intermediate in Sommelet–Hauser rearrangement is:

a) Ylide
b) Carbocation
c) Radical anion
d) Carbanion

273. In Sommelet–Hauser rearrangement, the migrating group is:

a) Aryl
b) Alkyl
c) Acyl
d) Hydroxyl

274. Assertion (A): Sommelet–Hauser rearrangement gives ortho-substituted

products.
Reason (R): The rearrangement occurs via an ylide mechanism.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

275. Which of the following best describes Sommelet–Hauser rearrangement?

a) 1,2-Anionic
b) [2,3]-Sigmatropic
c) 1,3-Sigmatropic
d) Free radical

39. Lossen Rearrangement

276. Lossen rearrangement converts hydroxamic acids into:
a) Isocyanates
b) Amines
c) Aldehydes
d) Nitriles

277. Which group migrates in Lossen rearrangement?

a) Alkyl/aryl group
b) Hydrogen
c) Hydroxyl group
d) Carboxyl group
 278. Lossen rearrangement is similar to:
a) Hofmann
b) Curtius
c) Schmidt
d) All of the above

279. The intermediate in Lossen rearrangement is:

a) Isocyanate
b) Carbocation
c) Radical cation
d) Ketene

280. Assertion (A): Lossen rearrangement gives primary amines after hydrolysis.
Reason (R): Reaction proceeds via isocyanate intermediate.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

40. Benzidine Rearrangement

281. Benzidine rearrangement involves rearrangement of:
a) Hydrazobenzenes
b) Diazonium salts
c) Nitrobenzenes
d) Phenylhydrazones

282. The product of benzidine rearrangement is:

a) Benzidine
b) Aniline
c) Azobenzene
d) Diphenylamine

283. Which condition favors benzidine rearrangement?

a) Acidic medium
b) Basic medium
c) Neutral medium
d) Strong oxidizing medium

284. Assertion (A): Benzidine rearrangement occurs via protonated intermediate.

Reason (R): Protonation facilitates N–N bond cleavage.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

285. The rearrangement of p,p′-hydrazobenzene in acidic medium gives:

a) Benzidine
b) Diphenylamine
c) Biphenyl
d) Aniline
41. Fischer Indole Synthesis
286. Fischer indole synthesis involves rearrangement of:
a) Phenylhydrazones
b) Oximes
c) Hydrazines
d) Imines

287. Which is the major product in Fischer indole synthesis?

a) Indole
b) Quinoline
c) Isoquinoline
d) Benzimidazole

288. The key step in Fischer indole synthesis is:

a) [3,3]-Sigmatropic rearrangement
b) [1,2]-Shift
c) Electrophilic substitution
d) Oxidation

289. Acetophenone phenylhydrazone on Fischer indole synthesis gives:

a) 2-Methylindole
b) 3-Methylindole
c) Indole
d) Benzimidazole

290. Assertion (A): Fischer indole synthesis proceeds via sigmatropic rearrangement.
Reason (R): The rearrangement involves migration of R group from carbon to nitrogen.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

42. Skraup Synthesis

291. Skraup synthesis is used for preparation of:
a) Quinoline
b) Indole
c) Isoquinoline
d) Pyridine

292. The oxidant commonly used in Skraup synthesis is:

a) Nitrobenzene
b) KMnO₄
c) PCC
d) H₂O₂

293. Which of the following is a key starting material in Skraup synthesis?

a) Aniline + Glycerol
b) Aniline + Acetone
c) Phenol + Acetaldehyde
d) Benzylamine + Ethanol
 294. Assertion (A): Skraup synthesis involves dehydration of glycerol.
Reason (R): Acrolein is formed in situ, which condenses with aniline.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

295. The heterocyclic compound obtained in Skraup synthesis has:

a) Benzene fused with pyridine
b) Benzene fused with imidazole
c) Benzene fused with oxazole
d) Benzene fused with triazole

43. Claisen Rearrangement

296. Claisen rearrangement is an example of:
a) [3,3]-Sigmatropic rearrangement
b) [1,2]-Shift
c) Electrophilic substitution
d) Free radical substitution

297. Allyl vinyl ether on Claisen rearrangement gives:

a) γ,δ-Unsaturated carbonyl compound
b) Ketone
c) Alcohol
d) Ester

298. The driving force of Claisen rearrangement is:

a) Formation of stable C=O
b) Aromatic stabilization
c) Loss of N₂
d) Radical stabilization

299. Which rearrangement proceeds through a chair-like transition state?

a) Claisen
b) Wagner–Meerwein
c) Curtius
d) Favorskii

300. Assertion (A): Claisen rearrangement is intramolecular.

Reason (R): It involves [3,3]-sigmatropic shift.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

44. Cope Rearrangement

301. Cope rearrangement involves:
a) [3,3]-Sigmatropic shift in 1,5-dienes
b) [2,3]-Shift in allylic ethers
c) [1,2]-Hydride shift
d) [1,3]-Shift in carbanions
 302. The driving force for Cope rearrangement is:
a) Resonance stabilization
b) Conversion of weaker bonds to stronger bonds
c) Aromatic stabilization
d) Loss of N₂

303. Cope rearrangement is thermally allowed because:

a) It follows Huckel’s rule for aromatic transition state
b) It involves diradical intermediates
c) It is photochemically forbidden
d) It involves free radical substitution

304. The product distribution in Cope rearrangement depends on:

a) Heat and substitution pattern
b) Presence of catalyst
c) Light intensity
d) Solvent polarity

305. Assertion (A): Cope rearrangement of symmetrical 1,5-hexadiene gives the

same compound.
Reason (R): Migration occurs without change in substitution.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

45. Oxy-Cope Rearrangement

306. Oxy-Cope rearrangement is a variation of:
a) Cope rearrangement
b) Claisen rearrangement
c) Pinacol–Pinacolone rearrangement
d) Beckmann rearrangement

307. In Oxy-Cope rearrangement, the substrate is:

a) 1,5-Diene alcohol
b) 1,4-Diketone
c) Phenylhydrazone
d) Allyl ether

308. The product of Oxy-Cope rearrangement undergoes:

a) Keto–enol tautomerism
b) Aromatization
c) Radical stabilization
d) Esterification

309. Base-catalyzed Oxy-Cope rearrangement is called:

a) Anionic Oxy-Cope
b) Aza-Cope
c) Pericyclic Oxy-Cope
d) Neutral Cope
 310. Assertion (A): Oxy-Cope rearrangement is more favorable than simple Cope.
Reason (R): It is driven by keto–enol tautomerization.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

46. Ireland–Claisen Rearrangement

311. Ireland–Claisen rearrangement is a:
a) [3,3]-Sigmatropic rearrangement of esters
b) [2,3]-Shift of ethers
c) [1,2]-Rearrangement
d) Free radical reaction

312. The base used in Ireland–Claisen rearrangement is generally:

a) LDA
b) NaOH
c) ZnCl₂
d) H₂SO₄

313. Ireland–Claisen rearrangement proceeds through:

a) Ester enolate intermediate
b) Carbocation
c) Diazonium salt
d) Radical

314. Which rearrangement provides stereoselective γ,δ-unsaturated acids?

a) Ireland–Claisen
b) Wagner–Meerwein
c) Benzil–Benzilic acid
d) Beckmann

315. Assertion (A): Ireland–Claisen rearrangement is stereoselective.

Reason (R): The rearrangement passes through a chair-like transition state.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

47. Carroll Rearrangement

316. Carroll rearrangement involves:
a) Rearrangement of allyl β-keto esters
b) Rearrangement of oximes
c) Isomerization of alkenes
d) Reduction of nitriles

317. The product of Carroll rearrangement is:

a) γ,δ-Unsaturated ketone
b) Ester
c) Alcohol
d) Aldehyde
 318. Carroll rearrangement is induced by:
a) Heat
b) Light
c) Acidic medium
d) Peroxide

319. Assertion (A): Carroll rearrangement is a thermal [3,3]-sigmatropic shift.

Reason (R): Migration occurs between allyl group and β-keto ester moiety.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

320. Carroll rearrangement is mechanistically similar to:

a) Claisen
b) Hofmann
c) Pinacol
d) Favorskii

48. Shapiro Reaction

321. Shapiro reaction involves reaction of tosylhydrazones with:
a) Strong base
b) Acid
c) Hydrogenation catalyst
d) KMnO₄

322. The major product of Shapiro reaction is:

a) Alkene
b) Alcohol
c) Ketone
d) Aldehyde

323. The base commonly used in Shapiro reaction is:

a) BuLi
b) NaOH
c) K₂CO₃
d) HCl

324. Assertion (A): Shapiro reaction is used to generate alkenes from ketones.
Reason (R): It proceeds via carbanion generated from diazo intermediate.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

325. Which intermediate is released in Shapiro reaction?

a) N₂
b) CO₂
c) SO₂
d) NH₃
49. Eschenmoser–Tanabe Fragmentation
326. Eschenmoser–Tanabe fragmentation converts α,β-epoxy ketones into:
a) Acetylenic carbonyl compounds
b) Aldehydes
c) Carboxylic acids
d) Amines

327. The driving force for Eschenmoser–Tanabe fragmentation is:

a) Cleavage of strained epoxide ring
b) Aromatic stabilization
c) Radical recombination
d) Keto–enol tautomerism

328. Which reagent is typically used in Eschenmoser–Tanabe fragmentation?

a) p-Toluenesulfonyl hydrazide
b) Acid chloride
c) KMnO₄
d) NaBH₄

329. Assertion (A): Eschenmoser–Tanabe fragmentation gives alkynes.

Reason (R): The epoxide cleavage generates an alkyne and carbonyl functionality.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

330. Which of the following resembles Eschenmoser–Tanabe fragmentation in

concept?
a) Grob fragmentation
b) Beckmann
c) Claisen
d) Pinacol

50. Payne Rearrangement

331. Payne rearrangement involves:
a) Isomerization of epoxy alcohols
b) Rearrangement of oximes
c) Cyclization of ketones
d) Rearrangement of hydrazones

332. The migrating group in Payne rearrangement is:

a) Epoxide oxygen
b) Hydroxyl proton
c) Alkoxide
d) Phenyl group

333. Payne rearrangement proceeds under:

a) Basic conditions
b) Acidic conditions
c) Neutral conditions
d) Photochemical conditions
 334. Assertion (A): Payne rearrangement involves nucleophilic attack at epoxide
carbon.
Reason (R): The alkoxide formed opens the epoxide ring, leading to isomerization.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

335. Which type of compounds can undergo Payne rearrangement?

a) Vicinal epoxy alcohols
b) Aldehydes
c) Nitriles
d) Carboxylic acids

51. Brook Rearrangement

336. Brook rearrangement involves migration of:
a) Silyl group from C to O
b) Silyl group from O to C
c) Phenyl group from N to C
d) Alkyl group from O to N

337. Brook rearrangement is induced by:

a) Base
b) Acid
c) Heat
d) Light

338. Assertion (A): Brook rearrangement is a 1,2-silyl shift.

Reason (R): It converts silyl alcohols into siloxy carbanions.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

339. Which intermediate is generated in Brook rearrangement?

a) Carbanion
b) Carbocation
c) Radical
d) Nitrene

340. Brook rearrangement is widely used in:

a) Organosilicon
b) Organotin
c) Organophosphorus
d) Organoboron

52. McLafferty Rearrangement

341. McLafferty rearrangement is associated with:
a) Mass spectrometry fragmentation
b) NMR coupling
 c) IR spectroscopy
d) UV–Vis absorption

342. The migrating group in McLafferty rearrangement is:

a) Hydrogen (γ-H shift)
b) Alkyl group
c) Aryl group
d) Hydroxyl group

343. The driving force of McLafferty rearrangement is:

a) Formation of a stable radical cation and neutral molecule
b) Formation of aromatic system
c) Loss of CO₂
d) Proton transfer

344. Assertion (A): McLafferty rearrangement provides structural information in MS.

Reason (R): It involves γ-hydrogen transfer with double bond cleavage.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

345. McLafferty rearrangement is especially common in:

a) Carbonyl compounds
b) Alkanes
c) Aromatic hydrocarbons
d) Alkynes

53. Stevens Rearrangement

346. Stevens rearrangement involves rearrangement of:
a) Quaternary ammonium or sulfonium salts
b) Phenylhydrazones
c) Diazonium salts
d) Epoxides

347. The base used in Stevens rearrangement is:

a) NaOH
b) NaNH₂
c) LDA
d) K₂CO₃

348. Assertion (A): Stevens rearrangement involves [1,2]-shift.

Reason (R): Rearrangement proceeds through ylide intermediates.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

349. In Stevens rearrangement, the migrating group is:

a) Alkyl or aryl substituent attached to N or S
b) Hydrogen
 c) Carbonyl group
d) Hydroxyl group

350. Stevens rearrangement is mechanistically related to:

a) Sommelet–Hauser
b) Favorskii
c) Hofmann
d) Baeyer–Villiger oxidation

54. Neber Rearrangement

351. Neber rearrangement converts oxime tosylates into:
a) α-Aminoketones
b) Alcohols
c) Carboxylic acids
d) Aldehydes

352. The key intermediate in Neber rearrangement is:

a) Azirine
b) Isocyanate
c) Carbocation
d) Diazonium salt

353. Assertion (A): Neber rearrangement provides α-aminoketones.

Reason (R): Rearrangement occurs through azirine intermediate.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

354. The reagent generally used in Neber rearrangement is:

a) Base
b) Acid
c) Light
d) Oxidizing agent

355. Neber rearrangement is an example of:

a) Beckmann-type rearrangement
b) Favorskii rearrangement
c) Pericyclic rearrangement
d) Pinacol rearrangement

55. Orton Rearrangement

356. Orton rearrangement involves rearrangement of:
a) N-Chloroacetanilides
b) Aryl diazonium salts
c) Quaternary ammonium salts
d) Hydrazones
 357. The product of Orton rearrangement is:
a) p-Chloroacetanilide
b) p-Acetanilide
c) Aniline
d) Benzoic acid

358. The rearrangement in Orton reaction proceeds via:

a) Aryl cation intermediate
b) Radical chain mechanism
c) Ylide formation
d) Pericyclic transition

359. Assertion (A): Orton rearrangement is an intramolecular reaction.

Reason (R): Chlorine migrates from nitrogen to aromatic ring.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

360. Which of the following rearrangements resembles Orton rearrangement in

concept?
a) Hofmann rearrangement
b) Benzidine rearrangement
c) Fries rearrangement
d) Sandmeyer reaction

56. Smiles Rearrangement

361. Smiles rearrangement involves intramolecular nucleophilic substitution in:
a) Aromatic systems
b) Aliphatic systems
c) Cycloalkanes
d) Aldehydes

362. The migrating group in Smiles rearrangement is:

a) Aryl or heteroaryl
b) Hydrogen
c) Alkoxide
d) Carboxyl group

363. Assertion (A): Smiles rearrangement proceeds through Meisenheimer complex.

Reason (R): The nucleophile attacks the activated aromatic ring.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

364. Which condition favors Smiles rearrangement?

a) Electron-withdrawing groups on aromatic ring
b) Electron-donating groups on aromatic ring
c) Neutral conditions only
d) Strong oxidizing medium
 365. Smiles rearrangement is widely applied in synthesis of:
a) Heterocycles
b) Hydrocarbons
c) Peroxides
d) Esters

57. Fries Rearrangement

366. Fries rearrangement converts aryl esters into:
a) Hydroxyaryl ketones
b) Alcohols
c) Carboxylic acids
d) Ethers

367. The reagent commonly used in Fries rearrangement is:

a) AlCl₃
b) H₂SO₄
c) KMnO₄
d) ZnCl₂

368. The product distribution (ortho vs para) in Fries rearrangement depends on:
a) Temperature
b) Catalyst concentration
c) Solvent polarity
d) Pressure

369. Assertion (A): Fries rearrangement involves migration of acyl group.

Reason (R): The acylium ion is generated by Lewis acid catalyst.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

370. Which of the following is a correct example of Fries rearrangement?

a) Phenyl acetate → Hydroxyacetophenone
b) Phenol → Anisole
c) Benzyl chloride → Benzyl alcohol
d) Aniline → Acetanilide

58. Baeyer–Villiger Oxidation

371. Baeyer–Villiger oxidation converts ketones into:
a) Esters
b) Alcohols
c) Acids
d) Aldehydes

372. The reagent commonly used in Baeyer–Villiger oxidation is:

a) Peracids (mCPBA)
b) HNO₃
c) HClO₄
d) KMnO₄
 373. The migratory aptitude in Baeyer–Villiger oxidation follows the order:
a) tert-Alkyl > cyclohexyl > secondary > phenyl > methyl
b) Methyl > phenyl > tertiary > secondary > primary
c) Phenyl > tertiary > secondary > primary > methyl
d) Secondary > tertiary > methyl > phenyl

374. Assertion (A): Baeyer–Villiger oxidation involves migration of an alkyl group.

Reason (R): The Criegee intermediate undergoes rearrangement.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

375. Which compound undergoes Baeyer–Villiger oxidation to give lactone?

a) Cyclic ketone
b) Linear ketone
c) Aldehyde
d) Carboxylic acid

59. Pinacol–Pinacolone Rearrangement

376. Pinacol on heating with acid gives:
a) Pinacolone
b) Benzophenone
c) Acetone
d) Acetic acid

377. Pinacol rearrangement involves:

a) 1,2-Alkyl shift with loss of OH⁻
b) 1,3-Sigmatropic shift
c) Free radical rearrangement
d) Oxidation of glycol

378. Assertion (A): Pinacol rearrangement involves carbocation intermediate.

Reason (R): Protonation of hydroxyl group leads to dehydration.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

379. Which condition is required for Pinacol rearrangement?

a) Acidic medium
b) Basic medium
c) Photochemical conditions
d) Strong oxidizing medium

380. Pinacolone obtained from Pinacol rearrangement is a:

a) Ketone
b) Alcohol
c) Ester
d) Carboxylic acid
60. Wagner–Meerwein Rearrangement
381. Wagner–Meerwein rearrangement involves:
a) 1,2-Alkyl shift of carbocation
b) 1,3-Sigmatropic shift
c) Free radical rearrangement
d) Nucleophilic substitution

382. The rearrangement is driven by:

a) Carbocation stability
b) Resonance stabilization
c) Hydrogen bonding
d) Radical delocalization

383. Which of the following is an example of Wagner–Meerwein rearrangement?

a) Isobornyl cation → Camphyl cation
b) Benzyl carbocation → Tropylium ion
c) Cyclopropyl carbocation → Allyl carbocation
d) Pinacol → Pinacolone

384. Assertion (A): Wagner–Meerwein rearrangement increases stability of

carbocation.
Reason (R): Migration of alkyl group forms more substituted carbocation.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

385. Wagner–Meerwein rearrangement is commonly observed during:

a) Acid-catalyzed dehydration of alcohols
b) Free radical halogenation
c) Photochemical reactions
d) Nucleophilic substitution

61. Beckmann Rearrangement

386. Beckmann rearrangement converts oximes into:
a) Amides
b) Nitriles
c) Esters
d) Amines

387. The migrating group in Beckmann rearrangement is:

a) Group anti to –OH of oxime
b) Group syn to –OH of oxime
c) Both groups equally
d) Random migration

388. Assertion (A): Beckmann rearrangement is stereospecific.

Reason (R): Only anti group migrates during rearrangement.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
 c) A true, R false
d) A false, R true

389. Beckmann rearrangement of cyclohexanone oxime gives:

a) ε-Caprolactam
b) Adipic acid
c) Phenol
d) Benzamide

390. Beckmann rearrangement is used industrially in the synthesis of:

a) Nylon-6
b) Nylon-6,6
c) Polyester
d) Polyurethane

62. Curtius Rearrangement

391. Curtius rearrangement involves decomposition of:
a) Acyl azides
b) Carboxylates
c) Hydrazones
d) Diazonium salts

392. The key intermediate in Curtius rearrangement is:

a) Isocyanate
b) Carbocation
c) Carbanion
d) Aziridine

393. Assertion (A): Curtius rearrangement produces primary amines upon hydrolysis.
Reason (R): The intermediate isocyanate undergoes hydrolysis.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

394. Curtius rearrangement is thermally induced and involves:

a) Nitrogen extrusion
b) CO₂ elimination
c) H₂ elimination
d) O₂ elimination

395. The Curtius rearrangement is related to which other reaction?

a) Hofmann and Schmidt rearrangements
b) Pinacol rearrangement
c) Wagner–Meerwein rearrangement
d) Claisen rearrangement

63. Schmidt Rearrangement

396. Schmidt rearrangement converts carboxylic acids with hydrazoic acid into:
a) Amides
b) Nitriles
 c) Esters
d) Alcohols

397. The rearrangement in Schmidt reaction involves:

a) Acyl cation intermediate
b) Isocyanate intermediate
c) Carbocation intermediate
d) Nitrene intermediate

398. Assertion (A): Schmidt rearrangement resembles Curtius and Hofmann

rearrangements.
Reason (R): All involve migration of R group with nitrogen extrusion.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

399. Which of the following is NOT a product of Schmidt rearrangement?

a) Amide
b) Amine (after hydrolysis)
c) Nitrile
d) Ester

400. Schmidt rearrangement of cyclohexanone gives:

a) ε-Caprolactam
b) Cyclohexanone oxime
c) Adipic acid
d) Aniline

64. Hofmann Rearrangement

401. Hofmann rearrangement converts primary amides into:
a) Primary amines
b) Secondary amines
c) Carboxylic acids
d) Esters

402. The reagent used in Hofmann rearrangement is:

a) Br₂/NaOH
b) KMnO₄
c) H₂SO₄
d) Zn/AcOH

403. Assertion (A): Hofmann rearrangement decreases carbon count by one.

Reason (R): Loss of carbonyl carbon as CO₂ occurs.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

404. Hofmann rearrangement of benzamide gives:

a) Aniline
 b) Benzylamine
c) Benzoic acid
d) Phenol

405. The key intermediate in Hofmann rearrangement is:

a) Isocyanate
b) Nitrene
c) Carbocation
d) Imine

65. Arndt–Eistert Reaction

406. Arndt–Eistert reaction is used for:
a) Homologation of carboxylic acids
b) Oxidation of alcohols
c) Reduction of ketones
d) Halogenation of alkanes

407. The key intermediate in Arndt–Eistert reaction is:

a) Diazo ketone
b) Carbocation
c) Radical
d) Ylide

408. Assertion (A): Arndt–Eistert extends carboxylic acid chain by one carbon.
Reason (R): Wolff rearrangement of diazoketone generates ketene.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

409. The reagent used to prepare acyl chloride in Arndt–Eistert reaction is:
a) SOCl₂
b) KMnO₄
c) NaBH₄
d) PCl₅

410. Which rearrangement is an essential part of Arndt–Eistert sequence?

a) Wolff rearrangement
b) Beckmann rearrangement
c) Curtius rearrangement
d) Hofmann rearrangement

66. Mannich Reaction

411. Mannich reaction involves condensation of:
a) Aldehyde, amine, ketone
b) Ketone, alcohol, acid
c) Ester, amine, acid
d) Aldehyde, ester, base
 412. The product of Mannich reaction is:
a) β-Amino carbonyl compound
b) Primary alcohol
c) Amide
d) Carboxylic acid

413. Assertion (A): Mannich reaction is also called aminomethylation.

Reason (R): The product contains a –CH₂–NR₂ group.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

414. Which of the following is a typical Mannich base?

a) β-Amino ketone
b) Ester
c) Nitroalkane
d) Phenol

415. Mannich reaction is widely used in the synthesis of:

a) Natural products and alkaloids
b) Carbohydrates
c) Inorganic complexes
d) Polymers

67. Claisen Condensation

416. Claisen condensation is a reaction between:
a) Two esters
b) Ester and ketone
c) Two ketones
d) Aldehyde and ketone

417. The product of Claisen condensation is:

a) β-Ketoester
b) α-Hydroxy ketone
c) Nitrile
d) Enamine

418. Assertion (A): Strong base is required in Claisen condensation.

Reason (R): Base generates enolate ion which attacks ester.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

419. A “mixed Claisen condensation” involves:

a) Two different esters/esters with ketone
b) Ester with alcohol
c) Aldehyde with ester
d) Amide with ester
 420. Which of the following is an essential requirement of Claisen condensation?
a) At least one ester must have α-hydrogen
b) All esters must lack α-hydrogen
c) Reaction must be photochemical
d) Reaction must be radical initiated

68. Cannizzaro Reaction

421. Cannizzaro reaction involves:
a) Aldehydes without α-hydrogen
b) Ketones with α-hydrogen
c) Alcohols and acids
d) Esters and bases

422. The products of Cannizzaro reaction are:

a) Alcohol + carboxylate
b) Ketone + ester
c) Aldehyde + nitrile
d) Amine + ester

423. Assertion (A): Cannizzaro is a redox reaction.

Reason (R): One aldehyde is oxidized and the other is reduced.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

424. Disproportionation of benzaldehyde with concentrated NaOH is an example of:

a) Cannizzaro reaction
b) Aldol condensation
c) Claisen condensation
d) Perkin reaction

425. The crossed Cannizzaro reaction uses:

a) Formaldehyde with another aldehyde
b) Ketone with aldehyde
c) Two ketones
d) Alcohol with aldehyde

69. Aldol Condensation

426. Aldol condensation involves:
a) Aldehydes/ketones with α-hydrogen
b) Esters only
c) Acids with α-hydrogen
d) Alcohols

427. The initial product of Aldol condensation is:

a) β-Hydroxy carbonyl compound
b) Ester
 c) Ether
d) Alcohol

428. Assertion (A): Aldol condensation is base-catalyzed.

Reason (R): Base generates enolate ion which attacks carbonyl.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

429. Which compound undergoes intramolecular aldol condensation to give cyclic

product?
a) 2,5-Hexanedione
b) Benzaldehyde
c) Methanal
d) Acetophenone

430. The dehydration step of aldol condensation produces:

a) α,β-Unsaturated carbonyl compound
b) β-Hydroxy compound
c) Amide
d) Alcohol

70. Perkin Reaction

431. Perkin reaction involves condensation of aromatic aldehydes with:
a) Acid anhydrides
b) Alcohols
c) Ketones
d) Esters

432. The product of Perkin reaction is:

a) α,β-Unsaturated carboxylic acid
b) β-Hydroxy ketone
c) Ester
d) Amide

433. Assertion (A): Sodium salt of acid anhydride acts as base in Perkin reaction.
Reason (R): It abstracts α-hydrogen from anhydride.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

434. Benzaldehyde + acetic anhydride in Perkin reaction gives:

a) Cinnamic acid
b) Benzoic acid
c) Acetophenone
d) Anisole
 435. Which step is crucial in Perkin reaction?
a) Enolate formation from acid anhydride
b) Radical initiation
c) Oxidation by KMnO₄
d) Hydride transfer

71. Knoevenagel Condensation

436. Knoevenagel condensation occurs between:
a) Aldehyde/ketone and active methylene compound
b) Ester and ketone
c) Aldehyde and alcohol
d) Ketone and amide

437. The catalyst used in Knoevenagel condensation is:

a) Weak base (amine or piperidine)
b) Strong base (NaOH)
c) Acid catalyst
d) Photochemical activation

438. Assertion (A): Malononitrile and ethyl acetoacetate are common substrates in
Knoevenagel reaction.
Reason (R): They contain acidic methylene group.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

439. The product of Knoevenagel condensation is usually:

a) α,β-Unsaturated carbonyl compound
b) Alcohol
c) Nitrile
d) Lactam

440. The Knoevenagel condensation is related to:

a) Perkin reaction
b) Cannizzaro reaction
c) Friedel–Crafts acylation
d) Hofmann rearrangement

72. Stobbe Condensation

441. Stobbe condensation involves the reaction of esters of succinic acid with:
a) Aldehydes/ketones
b) Alcohols
c) Amides
d) Carboxylic acids

442. The product of Stobbe condensation is:

a) Half-ester of unsaturated dicarboxylic acid
 b) Lactone
c) Aldehyde
d) Amine

443. Assertion (A): Alkoxide base is used in Stobbe condensation.

Reason (R): It generates carbanion from succinate ester.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

444. The Stobbe condensation is closely related to:

a) Aldol condensation
b) Friedel–Crafts alkylation
c) Wolff rearrangement
d) Curtius rearrangement

445. Which functional group pattern is characteristic of Stobbe product?

a) –COOH and –COOR in same molecule
b) –NH₂ and –OH
c) –CHO and –CN
d) –OH and –Cl

73. Michael Addition

446. Michael addition is a type of:
a) Conjugate addition to α,β-unsaturated carbonyl compounds
b) Nucleophilic substitution
c) Free radical addition
d) Pericyclic reaction

447. The nucleophile in Michael addition is generally:

a) Enolate ion
b) Carbocation
c) Radical
d) Diazonium salt

448. Assertion (A): Michael reaction is also called 1,4-addition.

Reason (R): Nucleophile attacks the β-carbon of α,β-unsaturated carbonyl.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

449. Which of the following is a classical Michael donor?

a) Malonate ester
b) Benzene
c) Methanol
d) Toluene
 450. The Michael reaction is an important step in:
a) Robinson annulation
b) Friedel–Crafts acylation
c) Aldol condensation
d) Sandmeyer reaction

74. Dieckmann Condensation

451. Dieckmann condensation is an intramolecular version of:
a) Claisen condensation
b) Cannizzaro reaction
c) Aldol condensation
d) Perkin reaction

452. The product of Dieckmann condensation is:

a) Cyclic β-keto ester
b) α,β-Unsaturated acid
c) Alcohol
d) Amide

453. Assertion (A): Dieckmann condensation requires diesters with α-hydrogens.

Reason (R): Enolate ion is formed from one ester which attacks the other ester group
intramolecularly.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

454. Which of the following is essential for Dieckmann condensation to occur?

a) Diester with two ester groups separated by 3–5 carbons
b) Monocarboxylic ester only
c) Amide derivatives
d) Nitriles only

455. Dieckmann condensation can lead to synthesis of:

a) Five- or six-membered rings
b) Only three-membered rings
c) Only seven-membered rings
d) Aromatic compounds

75. Claisen Rearrangement

456. Claisen rearrangement is an example of:
a) [3,3]-Sigmatropic rearrangement
b) Nucleophilic substitution
c) Free radical rearrangement
d) Electrophilic substitution

457. The starting material in Claisen rearrangement is:

a) Allyl aryl ether
 b) Alcohol
c) Carboxylic acid
d) Amide

458. Assertion (A): Claisen rearrangement is a pericyclic reaction.

Reason (R): It proceeds through a concerted cyclic transition state.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

459. Claisen rearrangement of allyl phenyl ether gives:

a) o-Allylphenol
b) p-Allylphenol
c) Catechol
d) Hydroquinone

460. Claisen rearrangement is accelerated by:

a) Heat
b) UV light
c) Acid catalysis
d) Base catalysis

76. Benzoin Condensation

461. Benzoin condensation involves reaction of two:
a) Aromatic aldehydes
b) Ketones
c) Esters
d) Carboxylic acids

462. The catalyst used in Benzoin condensation is:

a) Cyanide ion
b) Protonic acid
c) AlCl₃
d) KMnO₄

463. Assertion (A): Benzoin condensation is umpolung of carbonyl reactivity.

Reason (R): Cyanide ion converts carbonyl carbon into nucleophile.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

464. Benzoin condensation product contains which functional group?

a) α-Hydroxyketone
b) β-Hydroxyacid
c) Amide
d) Ester
 465. Benzoin condensation is closely related to:
a) Stetter reaction
b) Friedel–Crafts alkylation
c) Aldol condensation
d) Perkin reaction

77. Pechmann Condensation

466. Pechmann condensation is used to synthesize:
a) Coumarins
b) Esters
c) Ketones
d) Nitriles

467. The reaction involves condensation of:

a) Phenols with β-ketoesters
b) Alcohols with aldehydes
c) Ketones with nitriles
d) Amines with acids

468. Assertion (A): Pechmann condensation is acid-catalyzed.

Reason (R): Protonation facilitates enolization and cyclization.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

469. The industrial importance of Pechmann condensation is:

a) Preparation of coumarin fragrances
b) Preparation of nylon intermediates
c) Synthesis of aspirin
d) Synthesis of dyes

470. Pechmann condensation is related to:

a) Aldol-type condensation
b) Friedel–Crafts alkylation
c) Cannizzaro reaction
d) Curtius rearrangement

78. Reimer–Tiemann Reaction

471. Reimer–Tiemann reaction introduces formyl group at:
a) Ortho position of phenol
b) Para position of aniline
c) Meta position of benzene
d) Terminal carbon of alkane

472. The reagent used in Reimer–Tiemann reaction is:

a) Chloroform + NaOH
b) SOCl₂
 c) Br₂/NaOH
d) HNO₃/H₂SO₄

473. Assertion (A): Dichlorocarbene is the reactive intermediate in Reimer–Tiemann

reaction.
Reason (R): It is generated from CHCl₃/NaOH under heat.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

474. Reimer–Tiemann reaction of phenol yields:

a) Salicylaldehyde
b) Hydroquinone
c) Benzoic acid
d) Anisole

475. Reimer–Tiemann reaction is related to:

a) Electrophilic substitution
b) Free radical substitution
c) Pericyclic rearrangement
d) Redox reaction

79. Sandmeyer Reaction

476. Sandmeyer reaction involves substitution of:
a) Diazonium salts with halides or CN⁻
b) Ketones with alcohols
c) Alkenes with halides
d) Phenols with nitro groups

477. The catalyst used in Sandmeyer reaction is:

a) Cu⁺ salts
b) Fe²⁺ salts
c) ZnCl₂
d) AlCl₃

478. Assertion (A): Sandmeyer reaction is used to prepare aryl halides.

Reason (R): Diazonium salts undergo radical substitution in the presence of Cu(I)
salts.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

479. Sandmeyer reaction can introduce which of the following groups?

a) –Cl, –Br, –CN
b) –OH, –NO₂, –SO₃H
 c) –CH₃, –C₂H₅
d) –COOH, –CHO

480. Sandmeyer reaction is commonly used in synthesis of:

a) Dyes
b) Amino acids
c) Proteins
d) Alkanes

80. Gattermann Reaction

481. Gattermann reaction is also known as:
a) Modified Sandmeyer reaction
b) Kolbe electrolysis
c) Perkin condensation
d) Cannizzaro reaction

482. Reagent used in Gattermann reaction is:

a) Cu powder + HCl + HCN
b) ZnCl₂ + HCl
c) AlCl₃ + Cl₂
d) Br₂ + FeBr₃

483. Assertion (A): Gattermann reaction converts diazonium salts into aryl halides.
Reason (R): Cu powder acts as the catalyst in presence of HX.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

484. In Gattermann reaction, HCN with Cu powder converts diazonium salt into:
a) Aromatic nitrile
b) Aromatic amine
c) Phenol
d) Aromatic alcohol

485. Gattermann reaction differs from Sandmeyer because:

a) It uses copper powder directly
b) It requires UV light
c) It forms free radicals without a catalyst
d) It is a photochemical process

81. Kolbe–Schmitt Reaction

486. Kolbe–Schmitt reaction introduces a –COOH group in:
a) Phenols
b) Amines
c) Alkenes
d) Aldehydes
 487. The reagent used in Kolbe–Schmitt reaction is:
a) NaOH + CO₂ (under pressure)
b) ZnCl₂ + HCl
c) H₂SO₄ + HNO₃
d) NaOEt + HCN

488. Assertion (A): Kolbe–Schmitt reaction of sodium phenoxide gives salicylic acid.
Reason (R): Carboxylation occurs preferentially at the ortho-position.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

489. Kolbe–Schmitt reaction is an industrial method for synthesis of:

a) Aspirin
b) Nylon
c) Urea
d) TNT

490. Which factor controls ortho vs. para product ratio in Kolbe–Schmitt reaction?
a) Temperature & pressure
b) Solvent
c) Catalyst only
d) Type of alkali used

82. Gomberg Reaction

491. Gomberg reaction involves generation of:
a) Triphenylmethyl radical
b) Benzyl carbocation
c) Phenyl anion
d) Carbene

492. The reagent used in Gomberg reaction is:

a) AgNO₃ + water
b) Zn/HCl
c) HBr
d) Br₂/Fe

493. Assertion (A): Gomberg reaction provided first evidence for free radical
existence.
Reason (R): Triphenylmethyl radical was directly observed.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

494. The Gomberg reaction product is usually:

a) Biaryl compound (coupling product)
b) Ketone
 c) Ester
d) Alcohol

495. Gomberg reaction is important because it:

a) Proved free radical intermediates exist
b) Proved carbocations exist
c) Proved nucleophiles exist
d) Proved pericyclic pathways exist

83. Meerwein Reaction

496. Meerwein arylation involves substitution of:
a) Diazonium salts with alkenes
b) Aldehydes with ketones
c) Phenols with halides
d) Amines with SO₃H

497. The product of Meerwein arylation is:

a) Aryl-substituted alkene
b) Alcohol
c) Amide
d) Ester

498. Assertion (A): Meerwein arylation is a free radical reaction.

Reason (R): Aryl diazonium salt decomposes to aryl radical in presence of Cu salts.
a) Both A and R true, R explains A
b) Both A and R true but R does not explain A
c) A true, R false
d) A false, R true

499. Meerwein reaction is synthetically useful for:

a) C–C bond formation
b) C–O bond formation
c) C–N bond cleavage
d) C–H bond activation only

500. Meerwein reaction is closely related to:

a) Sandmeyer reaction
b) Aldol condensation
c) Perkin reaction
d) Cannizzaro reaction

Answer Key
Q.1–100
1 a 2 b
3 a 4 d
5 b 6 b
7 c 8 a
9 b 10 c
11 a 12 a
13 a 14 a
15 a 16 a
17 a 18 a
19 a 20 a
21 a 22 b
23 c 24 a
25 c 26 b
27 a 28 a
29 a 30 c
31 c 32 a
33 a 34 a
35 a 36 b
37 a 38 b
39 d 40 c
41 b 42 a
43 b 44 a
45 a 46 a
47 a 48 a
49 a 50 b
51 a 52 a
53 a 54 a
55 a 56 a
57 a 58 a
59 a 60 a
61 a 62 a
63 a 64 a
65 a 66 a
67 a 68 a
69 a 70 a
71 a 72 a
73 a 74 a
75 a 76 a
77 a 78 a
79 a 80 d
81 a 82 a
83 a 84 a
85 a 86 a
87 a 88 a
89 a 90 a
91 a 92 a
93 a 94 a
95 b 96 a
97 a 98 a
99 a 100 c
Q.101–200
101 a 102 a
103 a 104 a
105 a 106 a
107 a 108 a
109 a 110 a
111 a 112 a
113 a 114 a
115 b 116 a
117 a 118 a
119 a 120 a
121 a 122 a
123 a 124 a
125 a 126 a
127 a 128 a
129 a 130 a
131 a 132 a
133 a 134 a
135 a 136 a
137 a 138 a
139 a 140 a
141 a 142 a
143 a 144 a
145 d 146 a
147 a 148 a
149 a 150 c
151 a 152 a
153 a 154 a
155 a 156 a
157 a 158 a
159 a 160 d
161 a 162 a
163 a 164 a
165 d 166 a
167 a 168 a
169 a 170 a
171 a 172 a
173 a 174 a
175 b 176 a
177 a 178 a
179 a 180 a
181 a 182 a
183 a 184 a
185 a 186 a
187 a 188 a
189 a 190 a
191 a 192 a
193 a 194 a
195 a 196 a
197 a 198 a
199 a 200 a
Q.201–300
201 a 202 a
203 a 204 a
205 a 206 a
207 a 208 a
209 a 210 a
211 a 212 a
213 a 214 a
215 a 216 a
217 a 218 a
219 a 220 a
221 a 222 a
223 a 224 a
225 a 226 TBD
227 TBD 228 TBD
229 TBD 230 TBD
231 TBD 232 TBD
233 TBD 234 TBD
235 TBD 236 TBD
237 TBD 238 TBD
239 TBD 240 TBD
241 TBD 242 TBD
243 TBD 244 TBD
245 TBD 246 TBD
247 TBD 248 TBD
249 TBD 250 TBD
251 TBD 252 TBD
253 TBD 254 TBD
255 TBD 256 TBD
257 TBD 258 TBD
259 TBD 260 TBD
261 TBD 262 TBD
263 TBD 264 TBD
265 TBD 266 TBD
267 TBD 268 TBD
269 TBD 270 TBD
271 a 272 a
273 a 274 a
275 b 276 a
277 a 278 d
279 a 280 a
281 a 282 a
283 a 284 a
285 a 286 a
287 a 288 a
289 a 290 a
291 a 292 a
293 a 294 a
295 a 296 a
297 a 298 a
299 a 300 a
Q.301–400
301 a 302 b
303 a 304 a
305 a 306 a
307 a 308 a
309 a 310 a
311 a 312 a
313 a 314 a
315 a 316 a
317 a 318 a
319 a 320 a
321 a 322 a
323 a 324 a
325 a 326 a
327 a 328 a
329 a 330 a
331 a 332 c
333 a 334 a
335 a 336 b
337 a 338 a
339 a 340 a
341 a 342 a
343 a 344 a
345 a 346 a
347 b 348 a
349 a 350 a
351 a 352 a
353 a 354 a
355 a 356 a
357 a 358 a
359 d 360 c
361 a 362 a
363 a 364 a
365 a 366 a
367 a 368 a
369 a 370 a
371 a 372 a
373 c 374 a
375 a 376 a
377 a 378 a
379 a 380 a
381 a 382 a
383 a 384 a
385 a 386 a
387 a 388 a
389 a 390 a
391 a 392 a
393 a 394 a
395 a 396 a
397 b 398 a
399 d 400 a
Q.401–500
401 a 402 a
403 a 404 a
405 a 406 a
407 a 408 a
409 a 410 a
411 a 412 a
413 a 414 a
415 a 416 a
417 a 418 a
419 a 420 a
421 a 422 a
423 a 424 a
425 a 426 a
427 a 428 a
429 a 430 a
431 a 432 a
433 a 434 a
435 a 436 a
437 a 438 a
439 a 440 a
441 a 442 a
443 a 444 a
445 a 446 a
447 a 448 a
449 a 450 a
451 a 452 a
453 a 454 a
455 a 456 a
457 a 458 a
459 a 460 a
461 a 462 a
463 a 464 a
465 a 466 a
467 a 468 a
469 a 470 a
471 a 472 a
473 a 474 a
475 a 476 a
477 a 478 a
479 a 480 a
481 a 482 a
483 a 484 a
485 a 486 a
487 a 488 a
489 a 490 a
491 a 492 a
493 c 494 a
495 a 496 a
497 a 498 a
499 a 500 a