PORG121

Pharmaceutical Organic Chemistry

SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

The distilled products are then piped off from the

Distillation different levels of the tower. These separated products
are called fractions or distillates.
Distillation
➢ a process of separating components of a mixture, in This process mat take place along multiple distillation
which the components are evaporated and the towers.
vapors condensed
➢ used to purify organic compounds Different Types of Distillation
➢ the most volatile substance is vaporized first and
removed from the mixture first 1. Simple Distillation
➢ vapor enters a condenser, cools, and is then
Three General Steps of Distillation collected
➢ used when components have greatly different
1. Separation boiling points or to separate volatile from
2. Evaporation nonvolatile components
3. Condensation
2. Fractional Distillation
➢ used when the boiling points of the
components of a mixture are close to each
other
➢ involves the use of a fractionating column
above the distillation flask
➢ column offers more surface area, allowing for
more efficient condensation of vapor and an
improved separation

3. Steam Distillation
➢ used to separate heat-sensitive components
Crude oil contains a variety of hydrocarbons that have ➢ water is added to the distilling flask
different boiling points. To separate these compounds, ➢ this lowers the boiling point of the components
the oil is first sent to a boiler where it is heated into a so they may be separated at a temperature
super-hot mixture of liquid and vapor called the feed. below their decomposition point
➢ Example: Steam distillation of flowers to yield
The mixture us then fed into a distillation tower. In here, essential oil and a water-based distillate
the compounds with a lower boiling point rise up as
vapors, while the compounds with a higher boiling point 4. Vacuum Distillation
fall downwards as liquids. ➢ used to separate components that have high
boiling points (Claisen Flask)
The tower contains trays that allow the vapor to bubble ➢ lowering the pressure lowers boiling points
upward through the liquid, helping to exchange heat and ➢ used to separate compounds using different
resulting in more effective separation. temperature and pressure

Organic Chemistry (Lab) LESSONS 1

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

5. Short-path distillation
6. Zone distillation Physicochemical Properties of Org. Compounds
7. Reactive distillation
8. Pervaporation
Physical Properties
9. Catalytic distillation
10. Flash evaporation
➢ State
11. Freeze distillation
➢ Color & odor
12. Extractive distillation
➢ Refractive index
➢ Density
Application of Distillation
➢ Solubility
➢ Melting & boiling points
➢ used in chemistry to separate and purify liquids
➢ Rotary evaporator (Rotavap/Rotovap) - a simple Solubility
vacuum distillation used to remove solvent from a ➢ defined as the maximum mass of a substance that
sample can be dissolved in a fixed mass of a solvent at a
➢ used to make alcoholic beverages. vinegar, and given temperature.
purified water ➢ A substance will have a different solubility in
➢ one of the oldest methods of desalinating water different solvents depending on polarity of both the
used in OIL REFINERY substance and the solvent.
➢ The solubility of an organic compound can provide
evidence for the presence (or lack) of several
important functional groups, as indicated in the
following chart

Solvent Some solubility or complete

miscibility
Water Alcohols, amines, acids, esters,
ketones, aldehydes (typically
only those with C < 4)
5% NaHCO3 Carboxylic acids
5% NaOH Carboxylic acids and phenols
5% HCl Amines
Diethyl ether Most organic molecules

➢ Most of organic molecules are usually soluble in

organic solvents (e.g. diethyl ether,
dichloromethane, chloroform, petroleum ether,
hexanes etc) *like dissolves like

Organic Chemistry (Lab) LESSONS 2

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

• Both conformation & orientation also matter in

melting point

Crystalline matrix is held together by intermolecular

forces.

Melting Point
➢ Melting point is the temperature range over which
the solid melts to become a liquid • Even vs. odd chain length
➢ The transition between the solid and the liquid is so ➢ The ability of molecules to pack together
sharp for small samples of pure substance that tightly influences intermolecular interactions &
melting points can be measured to ± 1oC melting point.
➢ Characteristic of molecule can be used to determine ➢ Tighter packing increases melting point
identity & purity.

Four Factors Influencing Melting Point

➢ Pure crystalline solids have a sharp melting
1. Molecular symmetry point whereas mixtures melt with a broad
➢ Higher symmetry = stronger lattice packing and temperature range.
higher
• Melting Point & Shape
2. Molecular polarity ➢ So even chains pack tighter than odd. And
Polar molecules with dipole-dipole interactions molecules with spherical shapes have
= higher melting point. unusually high melting points.

3. H-bonding
➢ Strong hydrogen bonds require more energy to
break, resulting in higher melting points.

4. Molecular weight
➢ Larger molecules = stronger dispersion forces
and higher melting point.
• Measuring Melting Point
➢ Using electrothermal Melt-point

Organic Chemistry (Lab) LESSONS 3

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

Boiling Point
➢ Likely the melting points, boiling points are a ➢ Density can be used to examine the unknown
physical property. sample qualitatively
➢ The boiling point of liquid is affected by the forces ➢ The measurement can use PYCNOMETER
that attract one molecule to another-ionic
attraction, dipole-dipole interaction, hydrogen
bonding & van der Waals force. Optical Rotation
➢ A very liquid in a very clean vessel will superheat ➢ A substance is optically active if it rotates the plane
and not boil when subjected to a temperature of polarized light.
above its boiling point ➢ In order for a substance to exhibit optical activity, it
➢ If boiling does occur under these conditions, it must be chiral and one enantiomer must be
occurs with explosive violence. present in excess of the other.

Applications of BP in Pharmacy
➢ Such as melting point, boiling point can be used to Polarimeter
identify the unknown drugs. ➢ a scientific instrument used to measure the optical
➢ The difference in boiling point informs the rotation of polarized light as it passes through an
difference in molecule structure. optically active substance.
➢ Phenol is an antiseptic that has boiling point higher
than ether that was used as general anesthetic.
Enantiomer
➢ will rotate the plane of polarization in exactly equal
Refractive Index amounts (same magnitude) but in opposite
➢ The refractive index (or index of refraction) of a directions.
medium is a measure of how much the speed of
light (or other waves such as sound waves) is
reduced inside the medium.
➢ It is often used to identify a particular substance,
confirm its purity, or measure its concentration. Types of Optical Activity

• Dextrorotatory designated as d or (+), clockwise

Density
rotation (to the right)
➢ is a measurement that compares the amount of
• Levorotatory designated as l or (-), anticlockwise
matter an object has to its volume.
rotation (to the left)
➢ An object with much matter in a certain volume has
high density.
➢ An object with little matter in the same amount of
volume has a low density.
➢ The density of a material is defined as its mass per
unit volume

Organic Chemistry (Lab) LESSONS 4

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

Optical Purity
➢ If only one enantiomer is present, a sample is Alcohol and Phenol
considered to be optically pure.
➢ When a sample consists of a mixture of ALCOHOL
enantiomers, the effect of each enantiomer cancels ➢ organic compounds in which a hydrogen atom of an
out, molecule for molecule. aliphatic carbon is replaced with a hydroxyl group
➢ General formula: R-OH

Chemical Properties

➢ All carbon compounds show some common

characteristic properties.
➢ Three important chemical reactions are: Classification of Alcohol
A. Hydrolysis Reaction
➢ Hydrolysis is a reaction involving the ➢ According to whether one, two, or three other
breaking of a bond in a molecule using carbon atoms are bound to the carbon atom to
water. The reaction mainly occurs which the hydroxyl group is bound.
between an ion and water molecules and
often changes the pH of a solution.
➢ Acid Hydrolysis
➢ CH3COOH+H2O ⇌ H3O++CH3COO−
➢

B. Oxidation Reaction
➢ Though combustion is generally an
oxidation reaction, not all oxidation
reactions are combustion reactions.
➢ Oxidation is also carried out by using ➢ According to number of hydroxyl group attached to
oxidizing agents (Oxidants). their molecule
➢

C. Reduction Reaction
➢ Reduction means the addition of
hydrogen to a molecule or the removal of
oxygen.
➢

Organic Chemistry (Lab) LESSONS 5

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

Method of Preparation 3. By reduction

➢ Reducing agent: NaBH4 (Sodium borohydride)
1. Hydrolysis of alkyl Halide Reduction of aldehyde = Primary Alcohol
➢ RX + HOH -> ROH + HX
➢ Ex. CH3Br + H2O -> CH3OH + HBr

2. By Grignard’s (RMgX) synthesis

A. Primary Alcohol
➢ Reaction of Grignard’s reagent with
methanal ➢ Reducing agent: NaBH4 (Sodium borohydride)
➢ RCHO + RMgX -> ROMgX Reduction of ketone = Secondary Alcohol
ROMgX + HOH -> ROH + Mg (OH) X
➢ For example:

HCHO + CH3MgCl -> CH3CH2OMgCl

CH3CH2OMgCl + HOH -> CH3CH2OHMg ➢ Reducing agent: LiAlH4 (Lithium aluminum
(OH) Cl hydride)
Reduction of acid
B. Secondary Alcohol
➢ Reaction of Grignard’s reagent with
aldehyde except methanal
➢ RCHO + RMgX -> ROMgX
ROMgX + HOH -> ROH + Mg (OH) X
➢ For example: Physical Properties

A. State, Color, and Odor

➢ Lower alcohol (C1 - C4)
C. Tertiary Alcohol • Colorless and volatile liquid
➢ Reaction of Grignard’s reagent with ketone • penetrating pleasant odor
➢ For example:
➢ Middle alcohol (C5 – C11)
• colorless, odorless, waxy solids

➢ Higher alcohol
• flowery odor

➢ rest are odorless solids

➢ All alcohols are flammable, burning with a blue
flame, forming CO2 and water

Organic Chemistry (Lab) LESSONS 6

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

B. Boiling point Chemical Properties

➢ have higher boiling points in comparison to
other hydrocarbons having equal molecular 1. Oxidation
masses
• PRIMARY ALCOHOL
➢ ↑ no of Carbon = ↑ boiling pt
➢ Oxidizing agents: Periodinane, CrO3,
➢ ↑ branching = ↓ boiling pt
Na2Cr2O7
➢ Primary alcohols have a higher boiling point

C. Solubility
➢ The solubility of alcohol in water is governed by
the hydroxyl group present
➢ ↑ no. of Carbon - ↓ solubility
➢ Lower alcohol (C1-C4) - soluble in water
➢ Middle alcohol (C5-C11) - slightly soluble in
water
• SECONDARY ALCOHOL
➢ Oxidizing agents: Periodinane, CrO3,
D. Acidity
Na2Cr2O7
➢ Alcohols are acidic because of:
1. Alcohol + metal = RO- alkoxide* (acidic)
➢ conjugate base of an alcohol and
therefore consists of an organic group
bonded to a negatively charged oxygen
• TERTIARY ALCOHOL
atom
➢ No reaction
➢ No available Hydrogen
2. Due to the polarity of –OH bond
➢ Primary alcohols are generally more
acidic than secondary and tertiary
2. Elimination
alcohols are more acidic than amines
➢ Dehydration of alcohol -> alkene or ether
and alkanes but less acidic than
hydrogen halides. The pKa for most
alcohols fall in the range of 15-18.

Organic Chemistry (Lab) LESSONS 7

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

Experiment Results PHENOL

➢ AKA: carbolic acid
➢ Germicide (protoplasmic poison)
• Acetyl Chloride Test
➢ local anesthetic action but caustic
➢ Reaction tests for the presence of alcohols
➢ Joseph Lister = antiseptic
➢ (+) Evidence of reaction (heat, HCl gas),
➢ 0.1% to 1% conc. – antipruritic in phenolated
especially if accompanied by Phase separation
calamine lotion
indicates an alcohol

Aromatic Alcohol
➢ -OH is attached to the carbon of the side chain
• Chromic Acid Test
Phenol
➢ Reaction tests for the presence of primary
➢ -OH is attached directly to the benzene ring
alcohols, secondary alcohol and aldehyde
➢ (+) primary or secondary alc – 2-3 secs
formation of cloudy blue green suspension and
disappearance of orange colored reagent
Preparation

• By Diazo Reaction
➢ This reaction uses nitrobenzene which is
reduced to aniline, upon addition of HCl it is
• Iodoform Test converted to aniline hydrochloride and finally
➢ Indicates presence of –CH(OH)CH3 and – addition of water converts it to phenol,
COCH3 grouping nitrogen and free HCl
➢ (+) formation of yellow ppt

• Lucas Test • By Hydrolysis of Chlorobenzene

➢ Used to classify primary, secondary and
tertiary alcohol
➢ (+) primary alcohol – do not react under the
conditions
➢ (+) secondary alcohol – clear to cloudy solution
in 3-5 mins; layer after 15mins • By Heating Sodium Salicylate with Soda Lime
➢ (+) tertiary alcohol – should turn cloudy
immediately and quickly form layer

Organic Chemistry (Lab) LESSONS 8

 PORG121
Pharmaceutical Organic Chemistry
SECOND SEMESTER | MIDTERMS | ACADEMIC YEAR 2024-2025

Physical Properties Experiments Results

• Colorless crystalline (if pure) which melts at 43 • Bromine Water Test

degrees ➢ Test for presence of phenol and aromatic
• Turns pink to red when expose to air (Hygroscopic) amines
• Slightly soluble in water at room temperature ➢ (+) decolorization of bromine and formation of
white ppt (pH < 7)

Chemical Properties

• Reacts with metallic sodium and potassium to form

phenoxide
• Ferric Chloride Test
➢ Test for presence of phenol
➢ (+) intense red, green, blue, or PURPLE color

• Reacts with acid chloride and anhydride to form

ester
• Reduced by zinc to form benzene

• Reacts with dilute nitric acid in a cold temp to give

a mixture of ortho and paranitrophe

Organic Chemistry (Lab) LESSONS 9