1

ANSWERS TO PROBLEMS IN BODY OF CHAPTER 1.

1.1. The resonance structure on the right is better because every atom has its octet.

1.2.
O– O

CH 2+ CH 2 CH 2 CH2

C O C O

NMe2 NMe2 NMe2

NMe2 NMe2 NMe2

N N N N N

H3C H3C
N CH2 N CH2
H3C H3C O O
the second structure is hopelessly strained

1.3.
2 sp3
O sp O– sp3 CH3 CH3
sp2
sp2 N sp3 sp2 sp3
sp sp Ph N
O Ph H3C CH3 H3C CH3
sp2 sp3 sp3 sp3
sp2 all sp2 all sp2
 2
sp2
F H H
sp2 O sp3 sp
sp2 sp2 sp2
B H2C CH3
F F H H
1.4.

(a) No by-products. C(1–3) and C(6–9) are the keys to numbering.

3 10
1 2 O
5 12 12
4 OH 9 O
6
11 H+, H2O 1
2 4
13 8 5
9
Ph Ph
7 8 7 6 11 13
3
O10 H
(b) After numbering the major product, C6 and Br25 are left over, so make a bond between them and call it the

by-product.
13 14 24
12 15 Br 16
H 15
21 14
10 20 O 17
HN 11 13 12 21O
16 24 25 6 25
11 18
1 Br 9 19 Br Br 1 Br 9 Me Br
8 17 N 20
2 18 2 10
22 OMe 8 19
3 7 3 4
4 23 7 OMe
5 OMe6 O5
1.5. (a) Make C4–O12, C6–C11, C9–O12. Break C4–C6, C9–C11, C11–O12.

(b) Make C8–N10, C9–C13, C12–Br24. Break O5–C6, C8–C9.

1.6. PhC≡CH is much more acidic than BuC≡CH. Because the pKb of HO– is 15, PhC≡CH has a pKa ≤ 23 and

BuC≡CH has pKa > 23.

1.7. The OH is more acidic (pKa ≈ 17) than the C α to the ketone (pKa ≈ 20). Because the by-product of the

reaction is H2O, there is no need to break the O–H bond to get to product, but the C–H bond α to the ketone must

be broken.
 3

ANSWERS TO PROBLEMS IN BODY OF CHAPTER 2.

2.1. LDA is a strong base. Two E2 eliminations give an alkyne, which is deprotonated by the excess LDA to

give an alkynyl anion. This species then reacts with MeI by an SN2 process.

Cl OMe
N(i-Pr2) H
– OMe
H H H OMe
H OMe
(i-Pr2)N– H OMe –
N(i-Pr2)

Me I
MeO MeO Me

2.2(a). LDA deprotonates the C α to the ester, which adds to the aldehyde to give the aldol product after workup.

O
O O O O
H3C – H3C
N(i-Pr2) Et
H3C H H3C
O O
CH3 CH3

O O
H3C Et workup
H3C H product
O
CH3 O–

2.2(b). BuLi deprotonates the C α to the nitrile, which adds to the ketone to give the aldol product after workup.

O Et Et
H O–
Li Bu Et Et workup
N C H N C H N C H product
H H H

2.3. Make: C2–C3. Break: none. Note that because the NaCN is catalytic, its atoms are not incorporated into the

product, and hence there is no need to number them.

1 O 3 O 1 O Ph
cat. NaCN
2 H + 4 H 2 4
EtOH, H2O
Ph Ph Ph 3 OH
 4

C2 is electrophilic, and C4 is ... electrophilic! To make a bond between them, C2 must be turned into a

nucleophile (umpolung). This must be the purpose of the –CN. Aldehydes are not acidic at the carbonyl C, so the
–CN cannot simply deprotonate C2. Instead, it must add to C2. Now C2 is α to a nitrile, it is much more acidic,

and it can be deprotonated by excess –CN to give an enolate, which can add to C4. Finally, deprotonation of O1

and elimination of –CN gives the observed product.

O – O– HO – HO O
CN H OEt OEt
H H H H
Ph Ph CN Ph CN Ph CN Ph

HO O– –
O OH O OH

Ph CN Ph Ph CN Ph Ph Ph

2.4.

(a) Make: C2–C5, C2–C6. Break: C2–Br4.

1 3 5
EtO2C 2 CO2Et 6 1 4
2 6 7
5 7 8 NaOEt EtO2C 8 H Br
CHO CHO
4
Br EtO2C3

C2 is both electrophilic and particularly acidic. C5 is electrophilic, and C6 has no reactivity, so the first bond to

be made must be C2–C5. Therefore, deprotonation of C2 gives a nucleophile, which can attack electrophilic C5

to give an enolate at C6. Now C6 is nucleophilic, and intramolecular SN2 substitution at C2 gives the product.

Although C2 is a tertiary alkyl halide and is not normally expected to undergo SN2 substitution, this reaction

works because it is intramolecular.

Br
EtO2C CO2Et EtO2C CO2Et EtO2C CO2Et EtO2C CO2Et
–
OEt
H CHO
Br Br
CHO CHO

(b) Make: C7–C8, C4–C9. Break: none.

 5
3
1 O 1
O2 CH3
2 LiN(i-Pr)(c-Hex); 4 CO2Me
3 7 5 9
H3C 10
6 9 CO2Me 7
5 CH3 10 6 8 H
H3C 4 8
CH3 CH3

The thing above the arrow is a fancy version of LDA. C4 and C8 are electrophilic, C9 is unreactive, and C7 is

acidic, so first step must be to deprotonate C7 to make it nucleophilic. Conjugate addition to C8 generates a

nucleophile at C9, which adds to C4 to give a new enolate. Workup then provides the product.
CO2Me
O O O
H
– CO2Me
H NR2 H H
CH3 CH3 CH3
H3C H3C H3C
CH3 CH3 CH3

MeO2C O MeO2C O

H workup H
CH3 CH3
H3C H3C
CH3 CH3

(c) Make: C2–C21, C5–C11, C6–C22. Break: none.

8 CH O15 3 8 CH3 O15
7 14 O OMe 14
O16 16 O 9
9 23 23 7 H 13
13 Cs2CO3 6 10
6 5 17 CO2Me 17
12
O11 10 12 18 22 18 22
H
5 11
OH
3 3
19 21 19 21
2 O4 O4
20 20 2
H
1 CO2t-Bu 1 CO2t-Bu

Among the six atoms involved in bond-making, three (C6, C10, C21) are electrophilic, two (C5, C22) are

unreactive, and only C2 is acidic, so first step is deprotonation of C2. The nucleophile adds to C21, making C22

nucleophilic. It adds to C6, making C5 nucleophilic. It adds to C10, giving the product.
 6
CH3 O O CH3 O
CO2Me

H O O
CsCO3–
H O H O
CO2t-Bu CO2t-Bu
CH3 O CH3 O CH3 O
O OMe O OMe O OMe
O O O

O O O product

O O O H OCO2Cs
H H H
CO2t-Bu CO2t-Bu CO2t-Bu

2.5. Because under basic conditions carboxylic acids are deprotonated to the carboxylate ions, which are no

longer electrophilic enough that a weak nucleophile like MeO– can attack them. Upon workup the carboxylate is

neutralized to give back the carboxylic acid.

2.6.

(a) Balancing the equation shows that EtOH is a by-product. Make: C2–C11. Break: O1–C2.
3O
O10 5
6 7
H3C 4 9 11 EtO2C 4 1
8 NaOEt 2 11
CH3 + EtOH
5 H3C 9
EtO2C OEt 6 7 8 10
2 1 O
3 O

C2 is electrophilic, so first step must be to deprotonate C11 to make it nucleophilic. Addition to C2 followed by

elimination of O1 affords the product. Because the product is a very acidic 1,3-diketone, though, it is
deprotonated under the reaction conditions to give an anion. Workup then affords the neutral product.
O O
O
H3C – H 3 C
CH2 OEt CH2 H3C
EtO2C OEt H EtO2C OEt EtO2C
O O O OEt
 7
O O O
H3C H3C workup H3C
H H H
EtO2C EtO2C EtO2C
H H
O OEt O O

(b) Make: C3–C9. Break: O8–C9.

10 O
O1 O1
9 11
7 2 8 7 2 O 10
EtO OEt 8
6 3 6 3 9 + EtOH
NaOEt, EtOH
5 4 5 4 11 OEt
The mechanism is exactly the same as drawn in part (a).

2.7.

(a) Make: O1–C9. Break: S8–C9.

15 NO2 15 NO2
6 O2 3 1
14 14
7 S 9 2 O 9
5 8 13 4 13
NaOH
2 1 10 7 10
4 3 12 5 6 8 12
OH SO2–
11 11

The base deprotonates O1, which adds to C9, giving an anion that is delocalized over C10, C12, C14, and into

the NO2 group. The anion then expels SO2– to give the product.
NO2 NO2 NO2
O2 O2 O2
S S S
–
OH
product
OH O O

(b) Make: O1–P5, C2–Br4. Break: O1–C2, Br4–P5.

4 5
Br PBr2 1 5
+ HO PBr2
2 2 4
3 1 3
N O N Br
H
O1 is clearly a nucleophile, and C2 is clearly an electrophile. P5 could be either a nucleophile (lone pair) or an

electrophile (leaving group attached), but because it reacts with O1 and because the P5–Br4 bond breaks, in this
 8

reaction it must be acting as an electrophile. Attack of O1 on P5 in SN2 fashion displaces Br4, which can now
attack C2 in an addition reaction. Finally, the N3 lone pair is used to expel O1 to give the observed product.

Br PBr2 Br
Br Br products
PBr2 PBr2 PBr2
N O N O N O N O
H H H
H

2.8. E2 elimination of HI from the aryl iodide gives a benzyne, which can be attacked at either C of the triple

bond to give two different products.

OMe OMe OMe OMe
I NH2 NH2
NH2
NH2 H NH2

H H
OMe OMe OMe
H
NH2
or H NH2

NH2 NH2

2.9. E2 elimination of HBr from the alkenyl halide gives an alkyne or an allene, neither of which is electrophilic.

The only reason benzyne is electrophilic is because of the strain of having two C(sp) atoms in a six-membered

ring. Remove the six-membered ring, and the strain goes away.

2.10. The first substitution involves attack of PhS– on C6Cl6 to give C6Cl5(SPh), and the last involves attack of

PhS– on C6Cl(SPh)5 to give C6(SPh)6. The elimination–addition mechanism is ruled out in both cases because of

the absence of H atoms adjacent to Cl, so the choices are addition–elimination or SRN1. The first reaction

involves a very electron-poor arene (all those inductively withdrawing Cl atoms), so addition–elimination is

reasonable, although SRN1 is not unreasonable. The last substitution, though, is at an electron-rich arene, so only

SRN1 is a reasonable possibility.

 9
Cl Cl Cl
First: Cl
Cl Cl Cl Cl SPh
SPh
SPh

Cl Cl Cl Cl Cl Cl
Cl Cl Cl
Last: SPh SPh
Initiation: PhS Cl PhS Cl
SPh SPh
PhS SPh PhS SPh
SPh SPh

SPh SPh
Propagation: PhS Cl PhS

PhS SPh PhS SPh

SPh SPh

SPh SPh
PhS PhS SPh
SPh

PhS SPh PhS SPh

SPh SPh

SPh SPh SPh SPh

PhS SPh PhS Cl PhS SPh PhS Cl
+ +
PhS SPh PhS SPh PhS SPh PhS SPh
SPh SPh SPh SPh

2.11.

(a) An addition–elimination mechanism is reasonable.

 10

NMe3 CN CN

CN CN
N N N N
H CN
H H

(b) An addition–elimination mechanism is not reasonable. Elimination of HBr from the starting material gives an

α,β-unsaturated ketone that is now a π bond electrophile at a C different from the one that originally had the Br

attached to it. The only reasonable mechanism is SRN1.

Initiation: O O
Me Me Br
Br
+ Me Me
NC CO2Et Me Me NC CO2Et Me Me

Propagation:
O O NC CO2Et O NC Me
Br
Me Me Me Me CO2Et
Me Me Me Me Me Me

O NC Me O O NC Me O
Br Br
Me CO2Et + Me Me CO2Et + Me
Me Me Me Me Me Me Me Me

2.12.
CO2R CO2R CO2R
H H
O O
Zn O2C H+
NCO2Me NCO2Me NCO2Me product
O O
I IZn
H H
Me Me Me
 11

2.13.

(a)

H H
I Zn(Cu) ZnI
≡ “H ” Bu
I I Bu
H H H
(b)
Br
OSiR3
EtO2C EtO2C EtO2C Br
N2
RhII
Rh ≡ “ ” EtO2C OSiR3
EtO2C
EtO2C EtO2C EtO2C

2.14.
CH3
CH3 CH3
H3C C H3C C H3C
H H
R3SiO N2 R3SiO R3SiO

2.15. Numbering correctly is key to this problem. The written product is missing the fragments COCF3 and

MsN, so it is likely that they are connected to one another in a by-product. All the numbering in the product is

clear except for N8, N9, and N10. N8 is attached to Ms in the starting material and is probably still attached to it

in the product. But is N9 or N10 attached to C3 in the product? C3 is very acidic, and when it is deprotonated it

becomes nucleophilic. N9 has a formal positive charge, so N10 is electrophilic. Therefore, N10 is most likely

attached to C3 in the product. Make: C3–N10, C4–N8. Break: C3–C4, N8–N9.

1 O O5 8 1 O
H 7 N 9 10
N 8H 6
2 6 Ms N 10 2 N 9 N 4 CF3
7
4 CF 3 N Ms
3 3 +
O5

N8 deprotonates C3 to make the latter nucleophilic, and it adds to N10. The lone pair on N10 is then used to

expel N8 from N9. N8 then comes back and adds to C4, and expulsion of C3 from C4 affords the two products.
 12

O O O O
H N
Ms N
CF3 N CF3 Ms
N N NH

O O O O
NH
CF3 CF3
N N NH N N Ms
Ms
O O H O
N O
Ms H
CF3 N
+ Ms
N N N N CF3

2.16.
O O
O O O O
O O
R base R R O
O OH O O
 13

ANSWERS TO PROBLEMS IN BODY OF CHAPTER 3.

3.1. The by-product is AcOH. It is important in this problem to draw out the structure of Ac2O and label all the
atoms. Make: C7–C12, O8–C16. Break: C3–C12, C16–O18.
17 O
13 Me 15 16 8 13 Me
17 O O 20 Me O 12 Me 14
OMe
8 14
9 19 Me O 20
15 16 18 9
6 6
10
7 Me O Me 21 10
7 18 19
5 5
11 2 3 11 2 HO Me 21
OSiR3 FeCl3 3 OSiR3
R 12 4 R 4
Me
1 CO 2Me 1 CO2Me

The fact that C12–C3 breaks and C12–C7 makes is a signal that a 1,2-alkyl shift occurs. The shift requires that a

carbocation be formed at C7, which could be accomplished by cleaving the C7–O8 bond. Before the C7–O8 bond

cleaves, something else must attach to O8 to give it a formal positive charge. Because we need to make an O8–

C16 bond, that something could be C16. The role of the FeCl3 is to encourage the ionization of the O18–C16

bond by coordinating to O20. (Alternatively, the FeCl3 can coordinate to O17, and O8 can be acetylated with C16

by an addition–elimination mechanism.)
Me
FeCl3
O O O O O OMe
FeCl3
Me O Me Me O Me Me
OSiR3
R
Me
CO2Me
O
O
Me Me
Me O
Me O Me Me Me
product

OSiR3 OSiR3
R R
Me H H
CO2Me CO2Me

Why do we draw cleavage of the C7–O8 bond concerted with migration of C12? If the two steps were

nonconcerted, then a C7 carbocation would intervene, and other 1,2-shifts could occur. For example, C13 or
 14

C14 could shift from C6 to C7. In a 1,2-shift that is concerted with leaving group departure, the migrating group

must be antiperiplanar to the leaving group, and only C12 fulfills this condition.

3.2. Make: C2–C12, C4–C10. Break: O1–C2, C4–C6, O8–Si9. Neither O1 nor Si9 are incorporated into the

product.
11 CH 8 O 11
H3C 7 10 3 CH3
9 8O 12 SnCl4 7 12
Me3Si 6
H3C 6
10 2
5 4 4
1 5
Et O 2 OMe Et O3
H 3 H
The role of the Lewis acid is either to make a π bond electrophile more electrophilic or to promote the departure of

a leaving group. There is no π bond electrophile in the starting material, but O1 is a leaving group, so the first

step must be coordination of SnCl4 to O1. Cleavage of the O1–C2 bond gives a carbocation at C2 (although it is

primary, it is well-stabilized by O3), and the C2 carbocation is attacked by nucleophilic C12 to give a C10

carbocation. Now a 1,2-shift of C4 from C6 to C10 can occur to give a new carbocation at C6. Finally,

fragmentation of the O8–Si9 bond gives the product.

CH3 CH3 CH3
H3C H3C H3C
O SnCl4 Me Si O O
Me Si 3 3 Me3Si
SnCl4
Et O OMe Et O O Et O
H H Me H
CH3 CH3 CH3
H3C H3C H3C
O O O
Me3Si Me3Si

Et O Et O Et O
H H H

3.3.

(a)
CH3 CH3 CH3 CH3
H+ –
Cl
H3C OH H3C OH2 H3C H3C Cl
CH3 CH3 CH3 CH3
 15

(b)
OH HO ZnCl2
ZnCl2
Ar Ar Ar
Ar Ar Ar
HO HO OH
Ar
Ar product
Ar O
OH Ar
H

3.4. Because the carbocations derived from aryl and alkenyl halides are extremely high in energy.

3.5. The carbonyl O of esters, amides, and the like is always more nucleophilic than any other heteroatom

attached to the carbonyl C. The first protonation occurs at the carbonyl O. An SN2 attack of I– on CH3 then gives
the free carboxylic acid.
O OH OH
H I I H3C I
CH3 CH3
R O R O R O

3.6. A few things about this reaction may have caught you off guard. First, the first step is a polar reaction under

basic conditions, involving the Grignard reagent; only the second step is a polar reaction under acidic conditions.

Second, two equivalents of the Grignard are required for the product; the second equivalent explains whence

comes the terminal alkene C (labelled C6´) in the product. (Remember that Grignards react with esters by

addition–elimination–addition to give tertiary alcohols, and that it is not possible under normal circumstances to

stop the reaction after one Grignard adds.) Make: C2–C6, C2–C6´. Break: C2–O3, C2–O4, Si5´–C6´.
3 O 5 6 6´
1 1) Me3SiCH2MgBr 1
2 2
2) TsOH 5
4 OEt 6 SiMe3
O BrMg SiMe3 O SiMe3 O BrMg SiMe3

OEt OEt SiMe3

 16
O SiMe3 OH2 SiMe3 SiMe3
H+
product
SiMe3 SiMe3 SiMe3

3.7.

(a)
H
H H
O H O H O O R O O R
H HO R

H H H H
H H H
(b) This substitution reaction must proceed by an SN1 mechanism.
H
H H
O O R O O R O H
H – HO R HO Me

H H H
H H H
H
H H
O O O OMe
Me

H H
H H

3.8. The N atom so strongly stabilizes cations that a β-halocarbocation is the likely intermediate, not a halonium

ion.
H Cl Cl
H H
Cl Cl OH2 ~H+
N N N OH2

Cl Cl Cl
H

N OH O O
H H
 17

3.9. The products have in common a bromonium ion that is formed by attack of Br2 on the face of the double
bond opposite the acyloxy substituent. The two products not consistent with simple anti addition across the π

bond are obtained via neighboring group participation of the acyloxy group.
O O Br
Ar Br
Br Br Ar
O O

O Br O Br Br
Ar Br Ar
O O
48%
Ar
O
O Br O Br O Br
Ar Br Ar Br
O O Br 30%

O Br O Br O Br Br
Ar Br Ar Br Ar
O O O 12%

O Br O Br Br
Ar Br Ar
O O
9%

3.10.

(a) The role of AlCl3 is to turn the Cl of t-BuCl into a better leaving group. Ionization of the C–Cl bond gives a

carbocation, which reacts with benzene by the standard addition–fragmentation mechanism.

Me Me AlCl3 Me Me Me Me
H
AlCl3
Me Cl Me Cl Me H
 18

Me Me
Me Me

Me H Me
H H

(b) Unlike a Friedel–Crafts alkylation, which requires only a catalytic amount of AlCl3, a Friedel–Crafts acylation

requires more than a stoichiometric amount of AlCl3. The first equivalent coordinates to the carbonyl O; the

remaining catalytic amount catalyzes the ionization of the C–Cl bond. The final product is obtained after addition–

fragmentation and aqueous workup.

O
AlCl3 AlCl3 AlCl3
O O O O
AlCl3 AlCl3 H
AlCl3
Me Cl Me Cl Me Cl Me H

AlCl3 AlCl3
O O
O O aq. workup
product
Me H Me
H H

(c) The starting material loses the elements of water, but if water is the by-product, what is the role of the POCl3?

It is not a Lewis acid; it is a σ bond electrophile at P. Because P9 is electrophilic and O1 is nucleophilic, the first

step must be formation of O1–P4 bond. If this is true, the P-containing by-product has an O–P bond. Make: O1–

P9, C2–C7. Break: O1–C2, P9–Cl10.

5 Cl 10 5
8 9 11
4 O P Cl 4 1
6 6 OH
3 1 Cl12 3 8 9 11 10
HN O N O P Cl H Cl
7 7
2 2 Cl12
CH3 CH3

In the first step, O1 attacks P9 and displaces Cl10. After deprotonation of N3, a carbocation at C2 (stabilized by

resonance with N4) is formed. Addition–elimination then gives the product. An alternative and reasonable

mechanism would have C7 attack C2 before the C2–O1 bond cleaves (addition–elimination type mechanism), but

the conventional wisdom is that the reaction proceeds through the nitrlium ion intermediate.
 19
Cl
O P Cl O Cl O Cl
P P
Cl Cl Cl
HN O N O N O
H
CH3 CH3 CH3

N N N
H
H
H H CH3 H CH3
CH3

3.11. The first product is derived from a normal electrophilic aromatic substitution reaction of the kind described

in the text. The second product is derived from ipso electrophilic aromatic substitution. The mechanism is exactly

the same, but in the last step i-Pr+ is lost instead of H+.
O O
H+ O
N N N
– –
O OH O OH2+ O
H H H O–
H O –
i-Pr H i-Pr i-Pr N
O
N N O
O O
H i-Pr H i-Pr H i-Pr
H H H
H H H O–
i-Pr O –
H i-Pr H H N
O
N N O
O O
i-Pr H i-Pr H i-Pr H
H H H

3.12. Only an N–N bond is made, and one C–C bond is broken. When an amine is combined with NaNO2 and
HCl, a diazonium ion is formed. An elimination reaction then ensues with loss of CO2.
HO2C CO2H
O O H O
H+ O
N N H2N N N
OH OH2+ N
H
 20
CO2H CO2H CO2H
O OH OH
H+
N N H+ N N N N
H H
O H
CO2H O
OH2
N N N N

3.13. The mechanism is exactly the same as in 3.10(b).

H3C CH3

AlCl3 AlCl3 AlCl3

O O O O
AlCl3 AlCl3 Me3Si
AlCl3
Me Cl Me Cl Me Cl Me
H3C CH3 H3C CH3
AlCl3 AlCl3
O O aq. workup
product
Me Si Me
Me3 H H

3.14.

(a) The mechanism proceeds by addition–elimination. However, both the addition and elimination steps are

preceded by protonation and followed by deprotonation. It is very important that these proton transfer steps are

drawn properly!
O OH OH
H+ OH2 ~H+
OH2
NH2 NH2 NH2
OH O H O
OH
NH3 OH OH
 21

(b) It is unlikely that the CH2–O bond in the starting material will break under aqueous acidic conditions (can’t
form a carbocation, and SN2 is unlikely unless conditions are very harsh). Therefore the CH2–O bond is

preserved in the product, which means that both O’s of the carboxylic acid product come from H2O.
H H H2
Et N Et N Et N Et N
H+ OH2 ~H+
HO HO
HO O HO O H2O O HO O
Et H2N Et OH2 NH3 Et OH NH3
OH2 ~H+
HO HO HO
HO O H+ HO O HO O
H
Et O H NH3 Et O

HO
HO HO HO OH

3.15. Make: C1–O4, C1–O5, O2–C3. Break: C1–O2, C3–O4, C3–O5.

2O 4 OEt 4 2
cat. H+ OEt O
3 1 6
O2N + EtO H O2N H + EtO
1 5 3
H 5 OEt H
6 OEt
There are a number of ways this reaction could proceed, but the key step in any of them is attack of O2 on a
carbocation at C3.
OEt
OEt H OEt O EtO O
H+ H OEt
EtO H EtO H EtO H Ar H Ar
OEt OEt OEt H H

OEt H EtO H EtO H

EtO O OEt ~H+ EtO O OEt EtO OH EtO
H OEt

H Ar H Ar H Ar
H H H
H
EtO OEt EtO OEt
Ar Ar
H H
 22

3.16. Under these nearly neutral conditions, it is unclear whether the carbonyl O is protonated before or after

attack of N. Either way is acceptable.

O O OH CH3
~H+
NH N N N
H3C CH3 CH3 CH3
H CH3 CH3 CH3