Nomenclature, preparation and properties of i. Acid halides ii. Acid amides iii. Acid anhydrides and iv. Esters

Introduction of carboxylic acid derivatives

Carbon compounds containing a carboxyl functional group -COOH are called carboxylic acids. A carboxyl group is constituted of two groups - a carbonyl group

functional formula of carbonyl group

and a hydroxyl group -OH. Carboxylic acids may be aliphatic (R-COOH) or aromatic (Ar-COOH) depending on whether -COOH group is attached to aliphatic alkyl chain or aryl groups respectively.

Aliphatic monocarboxylic acids (containing one carboxyl group) are known as fatty acids because some of their higher members

(C12 - C18) like palmitic acid and stearic acid are found in natural fats as esters of glycerol.

Functional derivatives of acid refer to series of closely related organic compounds which can be structurally obtained by the replacement of -OH part of carboxyl group of the acids by -X, -NH2, -OR' or -OCOR respectively.

functional group of carboxylic acid


functional group of acyl halides


functional group of acid anhydride


functional group of ester


functional group of amide

Acid chlorides
These are derivatives of carboxylic acids in which hydroxyl (-OH) part of carboxyl group in which hydroxyl (-OH) part of carboxyl group is replaced by halo group. The most reactive compounds among acyl halides are chloro compounds.
Acyl halides (sometimes also called acid halides) are named by identifying the acyl group (RCO) and then the halide. The name of the acyl group is derived from the name of the corresponding -ic acid by replacing the ending -ic acid by -yl or carboxylic acid by -carbonyl.

IUPAC and common name of acyl halide

IUPAC and common name of carboxylic acid

The most important acyl halides are acyl chlorides because they are more easily prepared, more stable and less expensive.

Preparation

The hydroxyl group of carboxylic acid like that of alcohols are easily replaced by chlorine atom on heating with PCl5, PCl3 or SOCl2.

preparation of acyl halides

action of carboxylic acid with PCl5

action of carboxylic acid with SOCl2

Of the three, thionyl chloride is preferred because the other products are gaseous and excess from the reaction mixture, which makes the purification of the acyl chloride easier. Aqueous halogen acids are not used with carboxylic acids because the acyl chloride is easily hydrolyzed by water.

Reaction of acyl halides

Acyl halides undergo nucleophilic acyl substitution with several nucleophiles.

i) They react with water to give carboxylic acids. This is called hydrolysis.

formation of carboxylic acid

ii) They react with ammonia and amines to give amides. The reaction involving cleavage of a bond with ammonia is called ammonolysis.

ammonolysis reaction

formation of N ethyl acylamide from primary amide

action of acyl chlorides with secondary amine

Tertiary amines do not react with acyl chlorides.

iii) Acyl chlorides react with alcohols and phenols to give esters. The cleavage of a bond with alcohol is called alcoholysis.

action of acyl chlorides with alcohols

iv) Acyl chlorides react with salts of carboxylic to form acid anhydrides.

formation of acid anhydrides from acyl chlorides

In these reactions, an acyl group is transferred to the nucleophiles. These reactions are known as acylation reactions. Acylation is generally done in the presence of a base in order to neutralise the HX formed.

Aliphatic acyl chloride are very reactive acylating agents. Aromatic acyl chlorides like benzoyl chloride are less reactive.

Schotten - Baumann reaction is the acylation of alcohols, phenol and amines by shaking with aromatic acyl chloride in the presence of a base usually aqueous NaOH. For eg.,

acylation of alcohols phenol

These are also called benzoylation reaction.

v) Acid chlorides acylate aromatic hydrocarbons in the presence of anhydrous in the presence of anhydrous aluminium chloride to yield aromatic ketones. This is called Friedel - Craft's acylation reaction.

formation of aromatic ketones

This is a good method for preparation of aromatic ketones. This reaction however fails when electron withdrawing group is present on the aromatic ring.

Reduction of acyl halides

Acyl halides are reduced to primary alcohols with LiAlH4 and NaBH4.

Partial reduction of acyl chloride to aldehydes can also be done by catalytic hydrogenation over palladium catalyst supported on barium sulphate. Small accounts of quinoline and sulphur are added to the reaction which does not allow further reduction to alcohol. This reaction is known as Rosen Mund reduction.

Rosen Mund reduction


Acid amides
Acid amides may be regarded as the derivatives of carboxylic acids in which -OH part of the carboxylic group is replaced by the -NH2 group.

Esters are derivatives of the carboxylic acids in which the -OH part of the carboxylic group has been replaced by -OR group where R may be alkyl or aryl group.

Acid anhydrides are considered to be derived from carboxylic acids by the removal of a molecule of water from the two molecules of the acid.

Acid anhydrides
Acid anhydrides are called symmetrical when the two acyl groups are identical when the two acyl groups are identical and if the two acyl groups are different it is said to be unsymmetrical.

Symmetrical anhydrides of unsubstituted carboxylic acids are derived from the names of the carboxylic acids by replacing the word acid with anhydride.

IUPAC name and structure of acetic anhydride

Symmetrical anhydrides of substituted carboxylic acids are named by adding the prefix bis to the name to indicate that two identical acyl groups are present.

IUPAC name and structure of chloro acetic anhydride

Unsymmetrical anhydrides are named by writing the names of the two acids alphabetically before the word anhydride.

IUPAC name and structure of acetic benzoic anhydride

Preparation

Acid anhydrides are considered to be derived from carboxylic acids by the removal of a molecule of water from two molecules of acid. So acid anhydrides can be prepared by heating carboxylic acid in the presence of P2O5 in dehydrating agent.

formation of acid anhydride

Industrially, acetic anhydride is prepared by heating acetic acid to 1073 K.

formation of acetic anhydride from acetic acid

Acetic anhydride is a dehydrating agent

Symmetrical anhydrides are prepared from acids using a dehydrating agent like P2O5.

Asymmetrical and symmetrical anhydrides can be prepared by the reaction of acyl chlorides with sodium salts of carboxylic acids in the presence of pyridine.

formation of asymmetrical and symmetrical anhydrides

Reactions

Acid anhydrides undergo reactions similar to acyl chlorides. They are good acylating agents.

They are hydrolyzed by water.

formation of carboxylic acid

Alcoholysis

They form esters with alcohols and phenols.

Alcoholysis

They form amides with ammonia and amines.

formation of amides

formation of amides from ammonia

Friedel Craft's acylation reaction

preparation of ketones by Friedel Craft s acylation

preparation of alcohols by Friedel Craft s acylation

Anhydrides are on the whole less reactive than acyl chlorides.


Esters
RCOOR' are named after the corresponding carboxylic acids by replacing the ending -ic acid with -ate and preceding this with the name of the alkyl or aryl group attached to the oxygen atom.

common and IUPAC name of esters

IUPAC name of P toly acetate

structure of ethyl 4 chloro benzoate
Preparation
Esters are prepared by the acylation of alcohols or phenols.

Esters are prepared by the acylation of alcohols

preparation of esters

formation of esters

The formation of esters is known as esterification.

Esterification of carboxylic acids with alcohols requires a mineral acid such as concentrated H2SO4 or HCl gas a catalyst.

(Fischer Esterification)

Fischer Esterification

Mechanism of esterification of carboxylic acids

The esterification of carboxylic acids with alcohols is a kind of nucleophilic acyl substitution.

The first step is the protonation of the carbonyl oxygen, which activates the carbonyl group towards nucleophilic addition of the alcohol.

The tetrahedral intermediate, which is formed transfers a proton converting the hydroxyl group into H2 group. This species H2 is a better leaving group and is eliminated at a neutral water molecule.

The protonated ester finally losses a proton to give the ester.

The above mechanism is supported by the using isotopically labeled methanol (CH3O18H) with acetic acid to give methyl acetate (having labeled oxygen) and water not containing any isotopic oxygen.

Mechanism of esterification of carboxylic acids

Esters of phenols are prepared by reversible acylation of phenols with acyl chloride or anhydrides rather than the reaction with carboxylic acid in which all the steps are reversible.

Reactions

Esters undergo typical nucleophilic acyl substitution reactions but are less reactive than acyl chlorides and anhydrides.

i) Hydrolysis

Esters hydrolyzed by boiling water slowly to carboxylic acids and phenols. The hydrolysis is accelerated in the presence of mineral acid on alkali.

ester on hydrolysis

action of esters with NaOH

The alkaline hydrolysis is known as saponification. This is because esters with high molecular mass (C12 - C17) give soap on hydrolysis with a base. Soap on hydrolysis with a base. Soaps are sodium or potassium salts of Carboxylic acids with high molecular mass (C12 - C17). The carboxylic acid is obtained by acidification of the salt with mineral acid (H2SO4 or HCl).

formation of carboxylic acid

ii) Alcoholysis

Esters react with alcohols in the presence of an acid catalyst to undergo exchange of alcohol resides i.e., alkoxy parts. The equilibrium mixture consists of the reactants and a new ester and a new alcohol. The reaction involves nucleophilic acyl substitution of the alkoxy group of the ester with the alkoxy group of the alcohol and is known as trans esterification.

trans esterification

iii) Esters react with ammonia and amines to form amides

action of esters with ammonia

amines to amides

iv) Reactions of esters with Grignard's reagent gives tertiary alcohols.

First a ketone is formed which reacts further with Grignard reagent to give the tertiary alcohol.

Reactions of esters with Grignard s reagent gives tertiary alcohols

(v) The acyl group of the ester is reduced with LiAlH4 (but not with NaBH4) to a primary alcohol.

ester to primary alcohol

Catalytic hydrogenation of esters to alcohols is not easy unlike that of aldehydes and ketones. The reaction requires high temperature and pressure. The catalyst used is a mixture of oxides known as copper chromite. The alkoxy part of the ester gives the corresponding alcohol as by product.

Amides
RCONH2 are named in the trivial system by replacing the ending -ic acid from the name of the corresponding acid with - amide. The IUPAC names are derived by replacing the ending -oic acid with -amide or carboxylic acid with carboxamide. The position of the substituent at the nitrogen atom, if any, is indicated by the letter N.

common and IUPAC name of amides

Amides are classified as primary, secondary and tertiary amides depending on whether none, one or two alkyl or aryl groups at attached to the nitrogen atom

RCONH2 - Primary

RCONHR' - Secondary

RCONR'R'' - Tertiary

Preparation

Amides are generally prepared by the reaction of acyl chlorides or anhydrides with ammonia or amines.

preparation of amides

Carboxylic amines give ammonium carboxylates, which need to heated to high temperatures gives amides. Thus this method is not useful for laboratory preparation of amides. It is however used in the industrial preparation of amides.

Carboxylic amines give amides
Reactions

(i) Amphoteric character

Amides are feeble bases. The lone pair of electrons on the nitrogen atom is responsible for the basic character. This lone pair of electrons on nitrogen atom is involved in resonance with the carbonyl group (structure II). Thus the electron pair of nitrogen is not easily available for protonation. Consequently the basic character is considerably decreased.

resonance structures of amides

The basic character of the amide is illustrated in the following reaction with hydrochloric acid (an acid) to form a salt.

illustration of basic character of the amide

However, under suitable conditions, amides can also exhibit feeble acidic character. The amide (acting in the capacity of a acid) reacts with mercuric oxide (a base) to form mercury salt and water.

formation of mercury salt from amide

Thus amides are said to be amphoteric in nature as they exhibit both acidic and basic character.

(ii) Amides are hydrolyzed by aqueous solutions of mineral acids or alkalis to give carboxylic acids.

hydrolysis of amides

action of amides with alkali

(iii) Primary amides get dehydrated with phosphorous pentoxide to give nitriles.

formation of nitrile

(iv) On treatment with nitrous acid, primary amides give carboxylic acid and nitrogen gas. The volume of nitrogen can be measured to determine the amide quantitatively.

action of amines with nitrous acid

(v) When primary amides are treated with bromine in the presence of an alkali, a primary amine containing one carbon less than the amide is formed.

action of primary amides with bromine

The reaction involves molecular management in which alkyl or aryl group migrates from the acyl carbon to nitrogen. This reaction is known as Hofmann Bromamide reaction and is useful for descending of series i.e., preparing a lower homologue from a higher one.

vi) Amides are reduced to amines with LiAlH4.

 Amides are reduced to amines

Structure of functional group in carboxylic acid derivatives

The structure of the functional groups in acyl halide, acid anhydride, ester and amide are similar to that of the carboxyl group. Due to the presence of lone pairs of electrons at the halogen, oxygen and nitrogen atoms, resonance is possible in these derivatives just like that in carboxylic acids.

structure of carboxylic acid derivatives

The nature of the L group determines the relative electrophilic nature of the carbonyl carbon and thus the relative reactivity of the acyl derivatives.

All acid derivatives are polar molecules.

Physical properties

Being polar in nature, the acid derivatives have higher boiling points than hydrocarbons of comparable molecular masses.

Acid chlorides, anhydrides and esters have nearly the same boiling points as the aldehydes and ketones of comparable molecular masses. Their boiling points are lower than that of carboxylic acids of comparable molecular masses, due to the absence of hydrogen bonding in acid derivatives.

Primary amides have quite high melting points and boiling points because they form strong intermolecular hydrogen bonds.

intermolecular hydrogen bonds of primary amides

Esters and amides of low molecular masses are fairly soluble in water due to formation of hydrogen bonds with water. The solubility in water decreases with increasing molecular mass and is negligible for compounds containing more than six carbon atoms.

All acid derivatives are soluble in usual organic solvents. Volatile esters have pleasant fruity smell. Acyl halides and anhydrides have sharp irritating odors and are lachrymatory (tear producing).

Reactivity of acid derivatives

The reactions of carboxylic acids and their derivatives involve substitution of the group L with nucleophiles and are known as nucleophilic acyl substitution reaction.

substitution of the group L with nucleophiles

Order of reactivity of the acid derivatives is

Order of reactivity of the acid derivatives

Carboxylic acids and their derivatives can be interconverted by nucleophilic acyl substitution reactions.


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