B.Sc (Hons) IV Semester

Organic Chemistry (CHB 453)

Dr. Shafiullah Department of Chemistry, AMU

Email: shafiullah1966@ gmail.com

Unit: 3 : Carboxylic Acid Derivatives

1. ACID CHLORIDES

Preparation

Reactions

1. Nucleophilic acyl substitution reactions

(a) Hydrolysis ( Conversions into acids)

(b) Alcoholysis ( Conversion into esters)

It involves the conversion of acid chloride into ester by reaction with

alcohol and hence called as alcoholysis.

For Example

(c) Ammonolysis/ Aminolysis (Conversion into amides or substituted

amides)

It involves the reaction of acyl chloride by ammonia/ amines and hence named

as ammonolysis/ Aminolysis

Amides or mono or disubstituted amides can be obtained by using ammonia or primary amine

or secondary amine in the above reaction.

Related reactions will takes when ammonia derivatives are used

(d) Conversion into acid anhydrides

Acid chlorides reacts with acids in presence of base to form anhydrides

For Example

The above reaction may also be regarded as acylation reaction as they all involve replacement

of Hydrogen in water, alcohol, phenol, ammonia, amines, carboxylic acids etc by acyl group.

Acid chlorides are thus important acylating agents.

2. Reduction

(a) Using LiAlH4

Acid chloride can be reduced to primary alcohol using LiAlH4

(b) Rosenmund Reduction

On Treatment with hydrogen in presence of palladised barium sulphate which has been

poisoned partly with quinoline, acid chlorides get reduced to aldehydes.

Lithium aluminium tri- ter-butoxy hydride LiAlH(t-BuO)3 can also be used.

3. Reaction with organometalic compound

Reaction between Grignard reagent and acid chloride leads to the formation of tertiary

alcohol via the formation of ketone. However if this reaction is carried out at low temperature

of -650C in the presence of ferric chloride as catalyst intermediate ketone is formed in good

yield

Reaction with less reactive organo cadmium compounds is however more suitable for the

preparation of ketones.

(4) Friedel Crafts acylation ( Conversion into aromatic ketones )

(5) Hell Volhard Zelinsky Reaction

Acid chloride containing alpha hydrogen atom undergo halogenation at the alpha carbon

atom

(6) Arndt- Eistert reaction

This is an important reaction of homologation of acids via acid chloride.In this reaction acid

chloride is treated with diazomethane followed by treatment with colloidal silver

(7) Reaction with ether

Acid chloride reacts with ether in presence of anhydrous ZnCl2 to form ester

(8) Reaction with Potassium cyanide

Acid chloride is converted to alpha keto acids

2. Acid Anhydride

Preparation

1. From acid chloride

2. Dehydration

Simple monocarboxylic acid donot dehydrate easily but when heated in presence of acetic

anhydride yields anhydride.

Dicarboxylic acids yields cyclic anhydride

Reactions

1. Nucleophilic acyl substitution

(A)

(B)

In case of cyclic anhydride, the acyl compound and the carboxylic acid will

necessarily be part of same molecule

Acid anhydride act as acylating agent. The lower acylating activity of acid anhydride than

acid chloride is understandable from the electronic structure of acid anhydrides and acid

chlorides.

2. Friedel Craft acylation reaction

3. Reduction

Like acid halides, acid anhydride are also reduced by LiAlH4 to primary alcohols

4. Reaction with hydrogen sulphide

Acid anhydride react with hydrogen sulphide to form thioacids

3. Amides

Preparation

1. Ammonolysis of acid derivatives

2. Pyrolysis of ammonium salts of acids

When ammonium salt of carboxylic are heated in presence of some acids, amides are formed.

The presence of acid helps to suppress the dissociation of the ammonium salt into the free

acid and ammonia

3. Partial hydrolysis of cyanides or nitriles

This is achieved by heating alkyl or aryl cyanide with phosphoric acid and then diluting the

solution with water.

Reactions

1. Nucleophilic acyl substitution

2. Neutral Character

Amides are expected to show basic character but they are neutral because the electron pair on

nitrogen atom is not available for protonation due to resonance

3. Reduction

4. Dehydration

On heating with thionyl chloride or phosphorous pentaoxide amides lose a molecule of water

forming cyanide or nitrile

5. Hofmann degradation of amide

Amides when heated with bromine and sodium or potassium hydroxide give primary amine

having one carbon atom less than tha parent atom

6. Action of Nitrous acid

This reaction forms the basis of estimation of amides

4. Esters

Preparation

1. Fischer Esterification

Other method

2. From ester by transesterification

The alcoholysis of ester is called transesterification

Reactions

1. Nucleophilic acyl substitution

(a) Hydrolysis

(b) Ammonolysis

2 (a) Reduction with LiAlH4

(b) Bouveault Blanc reduction

3 Reaction with Grignard Reagent

4 Reaction with Hydroxylamine

Formation of coloured compound is the test of hydroxamic acid

5. Claisen condensation

This reaction is given by ester containing atleast one alpha hydrogen. Such a base catalysed

condensation of ester to form beta keto ester is called claisen condensation

INGOLD’S MECHANISM OF ESTERIFICATION

AND HYDROLYSIS OF ESTERS

INTERCONVERSION OF ACID DERIVATIVES