1

UNIVERSITY OF NAIROBI

COLLEGE OF BIOLOGICAL AND PHYSICAL SCIENCES

SCHOOL OF PHYSICAL SCIENCES

SCH 206: ORGANIC ACIDS, ESTERS, PHENOLS AND AMINES

A PRACTICAL MANUAL

FOR

BACHELOR OF EDUCATION (SCIENCE) AND BACHELOR OF

SCIENCE

2

GENERAL LABORATORY GUIDELINES AND SAFETY INSTRUCTIONS

The organic chemistry laboratory is potentially one of the most dangerous of the

undergraduate laboratories. That is why, for your personal safety and those of whom you

work with, it is important that you pay close attention to the general safety regulations

that apply in the lab.

Safety in the laboratory is also an integral part of your practical training. Adherence to

good, safe laboratory practice must be observed at all times. The following guidelines,

though not exhaustive, must be observed:

(1) You must wear a white lab-coat at all times during the laboratory session. Wear

closed shoes while reporting to the lab. No student wearing sandals will be admitted

to the lab.

(2) Punctuality must be observed. Latecomers will be barred from the practical session

and no practical will be repeated for those who either absent themselves or report

late.

(3) Handle the apparatus assigned to you with care. Since the glassware are very

expensive, you will be surcharged for any losses or breakages.

(4) All students must stay in the lab until they have completed their experiment.

Permission to move out of the lab must first be sought from the instructor.

(5) All mobile phones must be switched off during the practical session. Violation will

lead to cancellation of the practical for the offending student.

(6) Drinking, eating or playing in the lab is strictly prohibited.

(7) To avoid mix-ups, clearly label any products you isolate during a practical session

and keep them safely in your locker. Any solid products must be left to dry atleast

overnight before attempting a melting point determination.

(8) Proper waste disposal must be observed. Solid waste should only be disposed in the

solid waste containers located next to your working bench and not in the sink.

(9) Leave your working area clean at the end of the experiment and thoroughly clean

your hands with soap before leaving the lab.

(10) Remember to sign the attendance register at the end of each lab session.

(11) Lab reports are due one week after the completion of the experiment.

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EXPERIMENT 1

REACTIONS OF ALDEHYDES AND KETONES I

Acetophenone

A. Reduction of Acetophenone to Ethylbenzene

Introduction:

Carbonyl compounds can be reduced by a variety of reagents to their corresponding

alcohols (primary from aldehydes, secondary from ketones).

Other reduction methods are available which convert the carbonyl group to a methylene

group.

The Wolff-Kishner reduction effectively uses hydrazine as the reducing agent. The

carbonyl compound is first converted to its hydrazone which then undergoes a

rearrangement and decomposition, with the loss of nitrogen gas, when heated strongly

with base. The reaction is conveniently carried out in diethylene glycol, which is a good

solvent for the organic material as well as KOH and can be heated to the required high

temperatures.

Experiment:

In a 100 ml flask fitted with a reflux condenser place 4.5 ml (approx 4.6g) of

acetophenone, 15 ml of diethylene glycol, 4.0 ml of 90% hydrazine hydrate and 5 g of

potassium hydroxide pellets. Warm the mixture over a very small flame with continuous

swirling until the KOH pellets dissolve to give a clear solution. Heat the flask over a free

flame under reflux for one hour.

R

R

OR

R

H

OH

2 [H]

R

R

OR

R

H

H

4 [H]

+ H2O

4

Cool the mixture and then fit the flask with a still head, thermometer (with its bulb

dipping into the liquid) and a condenser for distillation. Distill out and collect all the

volatile material in a 10 ml graduated cylinder until the temperature of the liquid rises to

175 ºC. The distillate will consist mainly of ethylbenzene and water.

To aid in the separation, top-up the liquid in the cylinder with distilled water and the

separate the upper hydrocarbon layer from the lower water layer using a dropper.

Transfer the hydrocarbon layer into a clean conical flask. Dry the hydrocarbon (organic

layer) with a little anhydrous magnesium sulphate. Carefully decant the dry hydrocarbon

in a dry 50 ml round bottomed flask and redistill. Collect the distillate in a 10 mL

graduated cylinder. Record the boiling point range (observed), the volume of

ethylbenzene obtained and calculate the percentage yield of the reaction. Determine a

more accurate boiling point using the Siwolloboffs method.

B. Addition of a Carbanion-The Preparation of Chalcone (Benzal acetophenone).

Introduction:

Carbonyl compounds undergo aldol condensation if reacted in the presence of a base

under suitable conditions. Aldehydes which contain -hydrogens undergo self

condensation in the presence of a suitable base.

R tertiary

Cross aldol products are formed between non-enolizable aldehydes and ketones.

In this experiment you will prepare a cross aldol product between benzaldehyde, a non-

enolisable aldehyde, and acetophenone.

R H

O

R H

OBase

(e.g. OH-)

R R

O

R R

ORBase

(e.g. OH-)

(2 moles)

R H

O

CH3

R'

O

+

OH-

non-enolisable

R R'

O

a cross aldolproduct

5

Experiment:

In a conical flask mix 10 ml of 10% NaOH solution, 5 ml of 95% ethanol and 1.8 g

(0.017 mole) of benzaldehyde. Cool the mixture in an ice-bath and add dropwise 2 g

(0.017 mole) of acetophenone, while swirling vigorously. Mix the liquids thoroughly by

shaking. Stopper the flask tightly and swirl vigorously for one hour, at 5-10 minute

intervals at RT. A yellow oil will separate. Cool the flask in an ice-bath and induce

crystallisation by scratching the sides of the flask with a glass rod.

When crystallisation is complete, collect the solid precipitate by suction filtration. Wash

the crystals with a little cold water and a little ice-cold 95% ethanol. Weigh the dry

crystals of the crude product. Reserve a few crystals for seeding and recrystallize* the

crude product from 95% ethanol. Let the crystals dry (atleast overnight) and then

determine the melting point of the recrystallized material.

* As you will find out, chalcone is not easy to recrystallize. Allot of patience required.

6

EXPERIMENT 2

REACTIONS OF ALDEHYDES AND KETONES II

Addition of an Amine to an Aldehyde or Ketone- The Preparation of Imines

Introduction:

Aldehydes and ketones can be detected using Brady’s reagent (2,4-dinitrophenyl hydrazine). The product, a

hydrazone, is a yellow solid which precipitates out of solution.

In general, aldehydes and ketones react with primary amines with the loss of water to form imines.

Experiment:

You are supplied with an unknown (aromatic) aldehyde, which is to be identified by

reaction with aniline (phenylamine) to give the anil (phenylimine).

Instructions

Place 1 ml (1 g if a solid) of the unknown aldehyde, 1 ml of phenylamine, 7 ml of

petroleum ether (b.p. 40-60 oC ) and one or two boiling chips in a small flask fitted with

a still head and condenser. Gently heat the flask in a water bath so that the petroleum

ether distils off slowly and collect the distillate in a small measuring cylinder. When all

the solvent has distilled off, continue heating for an additional 30 min and then cool the

flask. Dissolve the contents of the flask in a little methanol (3 ml or less), and transfer

R R

O

+

R = H, alkyl or aryl

NH2

R'N

R'

R

R+ H2O

Imine

R R

O

NNH

NO2

NO2

R

RNH

2

NH

NO2

NO2

+

a 2,4-dinitrophenylhydrazone2,4-dinitrophenylhydrazine

A carbonylcompound

R = H, alkyl or aryl

+ H2O

7

the mixture to a small conical flask or beaker. Cool the mixture in an ice-bath and stir or

carefully scratch the sides of the flask with a glass rod to induce crystallisation. Filter the

crude solid product and rinse the solid residue with a little ice-cold methanol (just a few

sprinkles only). Recrystallize the solid product from a minimum volume of boiling

methanol, but retain a few crystals as “seeds” in case recrystallization proves to be

difficult. Let the filtered crystals dry atleast overnight before attempting a melting point

determination. Compare the melting point obtained against that of anil derivatives of

various aromatic aldehydes listed in Table 1 to identify the unknown aldehyde allotted

to you.

Table 1: Melting points of “Anils” (Phenylimines) derived from Aromatic Aldehydes

Aldehyde m.p. (º C) of the Derived Anils

(Phenylimine)

Benzaldehyde 54-55

p-Methoxybenzaldehyde (Anisaldehyde) 60-62

Cinnamaldehyde 109

o-Hydroxybenzaldehyde (Salicylaldehyde) 51

4-Hydroxy-3-methoxybenzaldehyde (Vanillin) 152-3

o-Nitrobenzaldehyde 69-70

p-Nitrobenzaldehyde 93

p-Chlorobenzaldehyde 66

For your own practice, you may attempt the reactions mechanism of the reactions shown

below. Note however that you are not required to submit the answer to these questions

Questions on mechanisms

1. Work out reaction mechanisms for the following transformations

OO

OH

H

O

O

H

H

NaOH

MeOH

(a)

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2. Paraldehyde induces sleep when it is administered to animals in large doses, and

consequently it is used as a sedative or a hypnotic. Propose a mechanism for the

formation of paraldehyde.

O

O

Br

Br

O

OO

NaOH

(b)

O

O

O

NaOH(c)

CH3

H

OO

O

O

CH3

CH3

CH3

3H+

Paraldehyde

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EXPERIMENT 3

PREPARATION OF ESTERS FROM CARBOXYLIC ACIDS AND

ALCOHOLS

Introduction

The esterification reaction between carboxylic acids and alcohols is acid-catalyzed and can be

represented by the equilibrium reaction shown below.

Since carboxylic acids themselves produce a small concentration of protons, the reaction is

spontaneous (though very slow) at room temperature. For example a mixture of acetic acid and 1-

butanol, if left at room temperature for a few days, will develop a sweet smell characteristic of

butyl acetate.

For preparative purposes, the reaction can be speeded up by using higher temperatures and an

additional supply of catalytic protons. Sulphuric acid, hydrochloric acid, phosphoric acid or p-

toluenesulphonic acid are frequently used as acid catalysts. Concentrated sulphuric acid has the

additional advantage that it tends to force the equilibrium reaction to the right by reacting with the

water molecules produced in the reaction.

Other methods of increasing the yield by forcing the equilibrium position to the right include:

- The use of a large excess of either the carboxylic acid or the alcohol reactant (especially

if one happens to be cheap and readily available.)

- Conducting the reaction under distillation conditions. Removing the more volatile

product as it forms.

In the present practical you will be supplied with about 15 ml of any one of the isomers of

butanol (C4H9OH) shown in Table 1. You will be required to use a small portion of this alcohol to

identify the alcohol (qualitatively i.e. determine whether it is a primary, secondary or tertiary

alcohol) and the main portion to prepare its liquid butyrate ester. The final portion of the alcohol

will be used to prepare a solid 3,5-dinitrobenzoate ester derivative, whose melting point should be

matched with those in Table 2 to determine the unknown isomer of butanol allocated to you.

R OH

O

R OR'

O

+ R'OHH+

+ H2O

10

(a) Preparation of Butyrate Ester

Procedure

Measure 6 ml of the unknown alcohol (assume a density of 0.8 gml-1), 6 ml of butanoic (butyric)

acid (bpt 162 oC) and 0.5 ml of concentrated sulphuric acid into a 50 ml round bottom flask. Mix

well, add one or two boiling chips, attach a reflux condenser and heat under reflux for one hour.

While waiting for the reflux period to elapse, start parts b and c of the experiment.

At the end of the reflux period, cool the reaction mixture to room temperature under the tap and

pour it into a separating funnel containing 30 mL of water. Shake gently and allow the layers to

separate before running off the aqueous layer. Wash the organic ester successively with 20 ml of

water, 10 ml of 5% sodium bicarbonate and 10 ml of water. Separate the layers as completely as

possible in each successive wash and eventually pour the washed crude ester into a clean conical

flask. Add a small amount of drying agent (anhydrous magnesium or sodium sulphate) into the

flask and stir until the ester is dry as determined by loss of cloudiness in the crude ester. Carefully

decant the dry crude ester into a distillation flask and distil, recording the temperature range over

which the product is collected. Weigh the distillate (butyrate ester) and calculate the percentage

yield of the reaction. Determine a more accurate boiling point of the distillate by the Siwoloboffs

method.

(b) Determination of the Classification of the Unknown Isomer of Butanol

Meanwhile test the remaining sample of the unknown isomer of butanol by the Lucas test to

determine if it is a primary, secondary or tertiary alcohol.

Table 1

Isomers of Butanol Classification of Alcohol

1-Butanol Primary

2-Butanol Secondary

2-Methylpropan-1ol Primary

2-Methylpropan-2-ol Tertiary

Caution: The Lucas test uses the Lucas reagent (A mixture of ZnCl2 and concentrated HCl). This

mixture is very corrosive and can cause serious burns. Inhaling the vapour is also harmful. Use

gloves when using this reagent and perform the test entirely in the fume chamber.

Procedure

Add 1 mL of the unknown alcohol to a test tube containing 2 mL of the Lucas reagent and shake

well. Allow the mixture to stand for about 15 minutes, a period within which you should

periodically monitor for any evidence of reaction (cloudiness) or layer separation (two distinct

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layers that persist even after shaking). If the alcohol is tertiary, a reaction will occur immediately

(<1 minute) and distinct layer separation occurs within this period. If the alcohol is secondary, the

reaction will take place but at a slower rate; the reaction turns cloudy in about 3 to 5 minutes and

distinct layer separation occurs within 15 minutes. Primary alcohols are essentially inactive and

the mixture remains clear. No layer separation occurs even after standing for more than 15

minutes.

(c) Preparation of 3,5-Dinitrobenzoate Ester of the Unknown Isomer of Butanol

Prepare the 3,5-dinitrobenzoate ester of the unknown alcohol provided and determine its melting

point to aid identify the specific isomer of butanol allocated to you.

Procedure

Warning: Do not inhale pyridine. Caution: PCl5 is moisture sensitive; use dry test tubes only.

Mix 0.25 g of 3,5-dinitrobenzoic acid with 0.5 g of phosphorus pentachloride (PCl5) in a small

dry test tube in the fume cupboard. Warm the mixture gently until the reaction starts (as shown

by the evolution of HCl gas) and then remove it from the flame and allow it to proceed

spontaneously. When the reaction subsides, boil the mixture until all the solid dissolves. Pour the

liquid immediately onto a dry watch glass and allow the product to solidify. Transfer the pasty

mass to a pad of two filter papers, fold them over it and press it dry. This procedure absorbs the

phosphorus oxychloride formed in the reaction and leaves the 3,5-dinitrobenzoyl chloride pure

enough to use directly.

Mix the acid chloride with 0.5 ml of the unknown alcohol and 0.5 ml of pyridine in a dry boiling

tube, cork the tube loosely and heat it in a boiling water bath for ten minutes (If the isomer you

have is a primary alcohol) or for thirty minutes if a secondary or tertiary alcohol is suspected.

Cool the mixture, add 10 ml of 5% sodium bicarbonate solution (CARE! evolution of gas), stir

and filter the solid that forms. Wash the solid with a little cold water, keep a small sample for

melting point determination and recrystallise the bulk from the aqueous alcohol (ethanol).

Determine the melting points of the crude and the recrystallised derivative. Determine the identity

of the derivative you have prepared by referring to Table 2 below.

Melting points of the 3,5-dinitrobenzoate derivatives of various isomers of butanol are as shown

in Table 2.

Table 2

Isomers of Butanol Melting point C of 3,5-Dinitrobenzoate derivative

1-Butanol 64

2-Butanol 76

2-Methylpropan-1ol 36

2-Methylpropan-2-ol 142

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Questions:

1. Account for the following observations

(c) HCl cannot be used to prepare acid chlorides from carboxylic acids.

2. Work out the reaction mechanisms for the following transformations:

R

R' COOH

COOH

R

R'

COOH

COOH

R

R'COOH

O

R

R'

O

O

H+

Heat

Heat

(a)

(b)

R OH

O

R Cl

O

+ HCl + H2O

CO2Et

CO2Et

CN

CO2H

CO2H

OOO

O CO2H

Conc HCl

AlCl3

(a)

(b)

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EXPERIMENT 4

IDENTIFICATION OF ESTERS. (2 weeks)

Introduction:

Shown below are the common reaction pathways used for forming esters.

R C

O

OH + R'OH R C

O

OR' + H2OH

R C

O

Cl + R'OH R C

O

OR' + HCl

Carboxylic Acid Ester

Acid chloride Ester

A common method used for identification of esters is the hydrolysis or saponification

with alkali to give an alcohol and a carboxylic acid salt. The alcohol can then be

converted to a 3,5-dinitrobenzoate ester derivative while the carboxylic acid salt to a p-

bromophenacyl ester derivative; two compounds with characteristic melting points.

The saponification reaction can be carried out quantitatively using a standard alkali

solution to give the saponification equivalent of the ester (that weight of the ester that

reacts with one mole of the alkali). In a monofunctional ester, the weight is equal to the

molecular mass and can thereby assist in the identification of the ester. (N.B> in industry,

a different term, the saponification value, is used which is the number of milligrams of

KOH required to saponify one gram of fat or oil. Other physical properties e.g. the

refractive index also assist identification of esters.

Saponification of esters.

For simple esters saponification by aqueous alkali proceeds rapidly and completely. The

alcohol component can be obtained by distilling off a small proportion of the reaction

mixture and collecting the distillate. The alcohol will either separate from the distillate as

an oily layer, or after saturation with potassium carbonate and can be identified in the

usual way. The acid, as its salt, is left in the distillation flask and can be converted to a p-

phenacyl derivative.

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Many esters have low solubility in water and their saponification by aqueous alkali is

excessively slow. The use of an alcoholic alkali, in which the ester is more soluble,

speeds up the saponification but because of the presence of the alcoholic solvent,

identification of the alcohol component becomes difficult or impossible although the acid

component can be readily identified.

A method which enables both components of an ester to be identified employs the high

boiling point, water soluble solvent, diethylene glycol (HOCH2CH2OCH2CH2OH). The

base, potassium hydroxide, is also readily soluble in this solvent. Its high boiling point

allows the lower boiling point alcohol (obtained from the saponification) to be distilled

out and identified.

If no distillate is obtained in this experiment, either the alcohol component of the ester is

a non-volatile polyhydric alcohol or the original ester was a phenolic ester, the resultant

phenol being retained in the distillation flask as its potassium salt. Separation will then

require acidification of the whole reaction mixture, extracting with ether and then

application of the usual method for separating the mixture of acid and phenol produced

(bicarbonate method).

If a distillate is obtained, only a solution of the potassium salt of the acid component of

the ester will remain in the distillation flask. This solution can be neutralised and a

derivative of the acid prepared directly from the neutral salt.

Experimental Procedure.

You are supplied with three unknowns of which two are esters. Identify the esters among

the unknowns by the hydroxamic acid test (procedure (a) below). Do not forget to record

the serial numbers of your unknowns.

(a) Add 2 drops of the unknown to 0.5 ml of a solution of hydroxylamine hydrochloride

in methanol (5%) and follow it by a dilute solution of potassium hydroxide until the

solution is just alkaline (test with litmus paper to determine this). Boil the solution

for one minute in a water bath, cool and just acidify with dilute hydrochloric acid.

Add a few drops of ferric chloride solution and observe the colour change. A red

colour indicates the presence of a hydroxamic acid, and therefore identifies the

unknown as an ester.

15

(b) Having determined which unknowns are esters, determine the boiling points of the

unknown esters by the Siwoloboff method (if the boiling point is above 180 C, just

record this- do not try to heat the oil bath above this level!).

(c) For one of the two esters, choose the one with the lower boiling point and assume it

is an aliphatic ester, identify the alcohol component qualitatively using the exchange

reaction (transesterification) with 3,5-dinitrobenzoic acid:

To accomplish this transesterification, dissolve 2-drops of conc. Sulphuric acid in 1

ml of the unknown ester in a 5- or 10 ml flask. Add 0.75 g of 3,5-dinitrobenzoic acid

and heat the mixture under gentle reflux for thirty minutes. Caution: Do not overheat;

decomposition of the product may occur. Cool the reaction mixture and dissolve in

25 ml ether (NO FLAMES). Remove the acidic products in the reaction mixture by

washing with 5% Na2CO3, (8 mL), wash the ether layer with water (8 mL) and then

evaporate the ether on a hot water bath (Do this in the fume hood to avoid inhaling

ether vapour). Recrystallize the product from aqueous ethanol and determine its m.pt.

Deduce from this melting point, the alcohol component of the unknown ester of low

boiling point.

(d) For the other ester (high boiling ester), attempt to identify both components (acid

and alcohol) by the method of hydrolysis in the high boiling point solvent by the

procedure given below.

Place 1 g of potassium hydroxide pellets, 3 ml of diethylene glycol and 1 ml of water in a small flask.

Warm gently over a flame with swirling until the alkali dissolves, then cool the solution. Add 2 ml of the

unknown ester, mix well and fit the flask with a reflux condenser. Heat the flask in a boiling water bath

with gentle shaking until the ester has dissolved to give a clear solution (some crystalline solid, the

potassium salt of the acid, may separate) and continue to heat for fifteen minutes.

(i) The alcohol component of the high boiling ester

Cool the reaction mixture, then fit the still head and small condenser and heat over a

small flame until the alcohol derived from the ester distils over (Note that diethylene

glycol boils at 240 C and few alcohols will be encountered with boiling point as high as

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this). The distillate should be dried with a small amount of anhydrous potassium

carbonate and identified by the preparation of a 3,5-dinitrobenzoate derivative as in

experiment 3 (page 6). A boiling point determination by the Siwoboloff’s method can

also be carried out if sufficient material is available.

(ii) The acid component of the high boiling ester

If a volatile alcohol has been obtained, the residue in the distillation flask will contain

the potassium salt of the acid suspended or dissolved in diethylene glycol. Add 20 ml

of water to dissolve the salts. Take a small portion (about 5 mL) of the solution and

acidify to Congo red with dilute sulphuric acid. If an insoluble solid acid is

precipitated, filter it off, wash with water, let dry. Determine its melting point as an

additional aid in the identification of the acid component of the unknown ester.

The remainder of the solution can be used to form a derivative of the acid directly as

follows: The alkaline solution must first be neutralised by the addition of two drops of

phenolphthalein followed by dilute mineral acid (dilute hydrochloric acid) drop-wise

until the colour is just discharged. This serves to neutralize the KOH initially used for the

saponification. Do not add excess mineral acid as this would acidify the mixture and

prevent the next step from proceeding. The resultant solution of the neutral salt of the

acid can then be used to prepare a p-bromophenacyl ester as a solid derivative (see the

procedure below), whose m.pt. will assist in the identification of the acid.

R C O

O

+ R CO

O

p-Bromophenacyl ester

BrCH2 C

O

p-Bromophenacyl bromide

O

K Br

Heat

+ KBr

Br

Preparation of p-Bromophenacyl Esters of the Acid Component of High Boiling

Ester

Take about one-half of the neutralised solution from d(ii) above, add 0.5 g of p-

bromophenacyl bromide and heat the solution to boiling under reflux. If the solution is

not homogeneous, add ethanol dropwise until the reagent is in solution. Reflux for one

hour, cool and collect the precipitated derivative by filtration. Recrystallise from ethanol

or aqueous ethanol. From the m.p. of the two derivatives, and any other data you may

have, deduce the structure of the original ester.

17

Acid Component m.pt. of Acid m.pt. of p-Bromophenacyl

ester of Acid

m.pt. ºC of p-phenyl-

phenacyl ester of Acid

Acetic acid liq 85 111

Propionic acid liq 59 102

n-Butyric acid liq 63 82

Isobutyric acid liq 77 89

Benzoic acid 122 119 167

m-Toluic acid 108 108 137

o-Toluic acid 103 57 95

p-Toluic acid 180 153 165

Phthalic acid 195 153 -

Phenylacetic acid 76 89 -

Cinnamic acid 133 183 145

Valeric acid Liq 75 64

Isovaleric acid liq 68 76

Alcohol m.pt. of 3,5-dinitrobenzoate ester (ºC) of Alcohol

Methanol 109

Ethanol 94

n-Propanol (1-Propanol) 74

tert-Butanol (2-methyl-2-propanol) 142

Benzyl alcohol 112

Cinnamyl alcohol 121

Cyclohexanol 113

1-Phenylethanol 95

2-Phenylethanol 108

18

Questions

1. Suggest a suitable synthesis of the following compounds:

2. A synthesis of a lactone is shown below:

(a) Work out the structure of (I) and (II)

(b) Suggest a reaction mechanism for the formation of (III) from (II).

O

O Ph

CO2H CO

2H

CO2H

OH

Phfrom and

(a)

CO2Me

COCl CO2H

CO2H

from(b)

R

Br

CO2Et

R CN(c)

from

OOPh

Ph CO2H

Ph

Ph(d) from

H

O

CN

O

n-Oct

O

n-Oct-BrMg

Et2On-Oct-MgBr (I)

(I)OH-

H2O, heat(II)

H+

(III)n-Oct = C8H17 (straight chain)

19

EXPERIMENT 5

CHARACTERISATION AND IDENTIFICATION OF PHENOLS (2

Weeks)

Introduction

Phenols are aromatic alcohols. They have some similar reactions with aliphatic alcohols

like ester formation (rates are slower) but in most other reactions they are different and

are studied as a different group of alcohols. Acidity of phenols (pKa ~10) is intermediate

between that of carboxylic acids (pKa ~5) and that of alcohols (pKa 16-19). They can be

distinguished from the stronger carboxylic acids by dissolving in aqueous sodium

hydroxide to form phenoxides but not reacting with potassium bicarbonate with the

formation of CO2 (i.e. they are weaker than carbonic acid (pKa 6.4).

O H OH O

H2O

_

pKa 10 Phenoxide

_

+

RC

O

O

H C

O

OHO RC

O

O

C

O

OHOH

O C OR

CO

O

_

unstable

H2O+(CO2)

_

+

Carboxylic acid bicarbonate

carboxylate

_

O H

C

O

OHOO__

Phenoxide

20

Note: Simple phenols are fairly soluble in water to give a weakly acidic solution. These

are best recognized by their ferric chloride colours. Polynitrophenols are more acidic than

simple phenols and may be stronger than carbonic acid (pKa < 6.4). They are usually

yellow in colour.

Other tests for phenols are:

(1) Ferric chloride colours. Most phenols in aqueous or alcoholic solution give bright

colours with neutral FeCl3. The colour may fade rapidly.

(2) Rapid bromination. Most phenols decolourize bromine water almost

instantaneously.

(3) Phenols form brightly coloured azo-dyes on coupling with diazotized aniline.

Warning: All Phenols are liable to burn skin and should not be handled with bare hands.

Derivatives of Phenols:

The most suitable derivatives of phenols are benzoates and p-toluene-suphonates. These

are made by reacting phenol, in the presence of base, with the appropriate acid chloride.

Examine each of the six unknowns as follows and determine which ones are phenols:

1. Test for solubility in cold water, cold or hot aqueous NaOH and cold aqueous

bicarbonate. Record your observations and conclusions in tabular form.

2. If a phenol is suspected, test an aqueous (or aqueous alcoholic) solution with

neutral FeCl3. Record your observation and conclusion.

OH

NN

R

NN

R

OH

(a diazonium compound)

diazolised aniline

+

an azo compound(highly conjugated)

phenol

+

21

Having recognised the phenols among the unknowns, identify each by forming a derivative. Make at least

one benzoyl derivative and one p-toluene-suphonyl derivative. Note that for some of the simpler phenols

benzoyl derivatives are rather low melting and therefore unsuitable as derivatives for identification.

Benzoyl Derivative (The Schotten-Baumann Procedure).

Dissolve (by warming and cooling again, if necessary) 0.5 g (or 0.5 ml) of the phenol and

5 ml of 3N NaOH in a well corked boiling tube. Add 1 ml of benzoyl chloride (fume

cupboard) and shake vigorously for 10 minutes. Check that the solution is still alkaline

(benzoyl chloride if present, would be hydrolysed by water to carboxylic acid!), cool in

ice and filter the solid derivative, wash the solid with water and recrystallise from dilute

alcohol (use only a minimum of boiling alcohol to dissolve the derivative, then add water

dropwise to lower the solubility).

p-Toluenesuphonyl Derivatives.

Warning: Pyridine causes sterility in men (you have been warned!)

Reflux 0.5 g (or 0.5 ml) of the phenol with 1 g of p-toluenesulphonyl chloride and 3 ml of

pyridine for 15 minutes. Cool, pour into the 10 ml ice-cold water, stir vigorously and

filter the solid derivative. Wash and recrystallize as for the benzoyl derivative.

Some Common Phenols and their Derivatives

Phenol m.p.

( C)

m.p. of

benzoate

( C)

m.p. of

p-toluenesulphonate

( C)

FeCl3

Colour

Phenol 42 69 95 Violet

o-Cresol 30 Liquid 55 Violet

m-Cresol 11 54 50 Blue

p-Cresol 35 71 69 Violet

o-Chlorophenol 7 Liquid 74 Violet

m-Chlorophenol 33 72 - -

p-Chlorophenol 43 87 79 Violet

o-Nitrophenol 45 59 83 -

m-Nitrophenol 96 95 112 Red-violet

p-Nitrophenol 114 142 97 Violet

2,4-Dinitrophenol 113 132 121 -

2-Naphthol 123 106 125 Green

Catechol 105 84 Green

Resorcinol 110 117 80 Violet

Hydroquinone 172 199 159 brown

22

Draw full structural formulae of your phenols and their derivatives.

Questions

1. Write the reaction mechanisms for the benzoate and p-toluene-sulphonyl derivatives

that you prepared.

2. Suggest how chemical reaction can be used to separate a mixture of 2,4,6-

trinitrophenol and 2,4,6-trimethoxyphenol.

3. Explain each of the following observations:

(a) 4-Iodophenol is a stronger acid than 4-fluorophenol

(b) o-Hydroxyacetophenone has a lower boiling point than p-hydroxyacetophenone.

(c) Addition of a few drops of phenol to a coloured solution of bromine water gives a

yellow precipitate and a decolourised solution, while addition of a few drops of

toluene to the same solution has no effect.

4. Phenols form esters on reaction with acid chlorides. They do not react directly with

acids (contrast with alcohols). Why?

5. Show by a series of chemical reactions how benzene can be converted to the

following:

(a) 2,4-dihydroxybenzoic acid

(b) 3-hydroxybenzylamine

(c) 4-(N,N-dimethylamino)-phenyl benzoate

6. Ambucaine (J) is used as a local anaesthetic.

23

What reagents would you use to convert:

(i) (A) to (B)

(ii) (C) to (D)

(iii) (F) to (G)

(iv) (G) to (H)

Write down the structure of all the intermediates.

CO2Me CO

2H

NO2

NH2

CO2H

OH

CO2H

OH

CO2H

NO2

OH

NO2

CO2Et

O

CO2Et

NO2

O

NO2

O Cl

O

O ONEt

2

NO2

O

NH2

O ONEt

2

OHNEt

2

(A) (B) (C)(D)

(E) (F) (G)

(H) (I)

(J)

H2/Nickel

?

?EtOH

HCl

HNO3

?H2/Pd?