Acid Derivatives: Nucleophilic Substitution: Alkyl vs. Acyl

Acid Derivatives
Nucleophilic Substitution : Alkyl vs. Acyl

As we have said, nucleophlic substitution takes place much more readily at an acyl carbon than
at saturated carbon. Thus, toward nucleophilic attack acid chlorides are more reactive than alkyl
chlorides, amides are more reactive than amines and esters are more reactive than ether.
It is, of course, the carbonyl group that makes acyl compounds more reactive than alkyl
compounds. Nucleophilic attack (SN2) on a tetrahedral alkyl carbon involves a badly crowded
transition state containing pentavalent carbon ; a bond must be partly broken to permit the
attachment of the nucleophile :
Nucleophilic attack on a flat acyl compound involves a relatively unhindered transition state
leading to a tetrahedral intermediate that is actually a compound; since the carbonyl group is
unsaturated, attachment of the nucleophile requires Acyl nucleophilic substitution breaking only
of the weak and places a negative charge on an atom quite willing to accept its, oxygen.
Acyl Halide
RCONH2 do not form acid halide by PCl5 due to little reactivity for nucleophilic substitution
reaction only CO is converted into CCl2.
Properties
Acid anhydride
Properties
Esters
Preparation
Properties
(i) Hydrolysis of esters
Oil or fats are glycerides of higher fatty acid and when they undergo hydrolysis soaps are formed
in presence of alkali is known as saponification.

(ii) Trans–esterification
Esters do not undergo substitution reaction with halide ions or with carboxylate ions because
these nucleophiles are much weaker bases than the RO- leaving group of the ester. Esters react
with water to form carboxylic acids and with alcohols to form different esters. A reaction with
water is known as hydrolysis, and a reaction with an alcohol is called alcoholysis. The
hydrolysis or alcoholysis of an ester is a very slow reaction. Therefore, when these reactions are
carried out in the laboratory, they are always catalyzed. Both hydrolysis and alcoholysis of an
ester can be catalyzed by acids (H+). The rate of hydrolysis can also be increased by hydroxide
ion (HO-), and the rate of alcoholysis can be increased by presence of alkoxide ion.
When esters reacts with amines to form amides, reaction is known as aminolysis. Notice that the
aminolysis of an ester requires only one equivalent of amine, unlike the aminolysis of an acyl
halide or an acid anhydride, which we saw requires two equivalents. This is because the leaving
group of an ester (RO-) is more basic than the amine nucleophile (RNH2), so the alkoxide ion
rather than unreacted amine picks up the proton produced in the reaction.
The tetrahedral intermediate formed when an ester is hydrolyzed has both an RO- leaving group
and an HO- leaving group. Because both leaving groups have approximately the same basicity,
they are equally likely to be eliminated.
Notice that when CH3O- is eliminated, the final products are a carboxylate ion and methanol. If
only one species is protonated, it will be the more basic one (CH3O- is more basic than RCOO-).
When ester reacts with an alcohol in the presence of acid to form a new ester and a new alcohol.
This is called a transesterification reaction. Because both alcohols have approximately the
same leaving tendency in the tetrahedral intermediate, an excess of the reactant alcohol is
necessary to drive the equilibrium to the right. Or, if the boiling point of the product alcohol is
significantly lower than the boiling points of the other reaction components, the reaction can be
driven to the right by distilling off the product alcohol as it is formed. The rate of trans-
esterification can be increased by H+ or by the conjugate base (RO-) of the reactant alcohol.
Because phenols are stronger acids than alcohols, phenolate ions (ArO-) are weaker bases than
alkoxide ions (RO-). This means that phenyl esters are more reactive than alkyl esters.
The reaction of an ester with an amine is also a slow reaction. However, unlike the reaction of an
ester with water or an alcohol, the rate of the reaction of an ester with an amine cannot be
increased by H+ or by HO- or RO-. Aminolysis of an ester can be driven to completion by using
excess amine or by distilling off the alcohol as it is formed.
Reaction with hydroxyl amine to form solid which on subsequent treatment with FeCl 3, dark colored
compound is formed. This chemical reaction is used as test of ester group.
Reduction:
Esters when reduced with LiAlH4 get reduced to 2 molecules of alcohols

Alkanamides
Preparation
Properties
They are solids, soluble in water due to forming hydrogen bonds in water. They have highest boiling
points among all the acid derivatives due to strong intermolecular hydrogen bonding.
Amides are amphoteric in nature i.e. they react with both acid and bases.

They have the two resonating structures:
Through structure I, they act as lewis bases due to being electron pair donors through nitrogen, and
through structure II, they act as Arrhenius or bronstead acid, ie act as proton donor due to
electronegative nature of nitrogen to get back the electron pair to it.
(ii) Hofmann Bromamide Reaction
When an acid amide is heated with bromine and KOH it gives a primary amine with one carbon
atom less than the amide
where R may be aliphatic, aromatic or heterocyclic, reaction is used for degradation of amines in
homologous series.
Mechanism of reaction
Following mechanism has been suggested on the basis of the intermediates formed during the
course of reaction.
(iii) Reduction
When reduced with LiAlH4 they give primary amines.
(iv) Hydrolysis:
Amides undergo hydrolysis very slowly and in the presence of an alkali or an acid as shown below:
(v) Dehydration:
When heated with P2O5 it gets dehydrated to an alknae nitryl

The order of boiling points is:
Acyl chloride has minimum boiling point due to absence of intermolecular hydrogen bonding.
The boiling point of esters is higher than that of acid chlorides due to more molecular mass, more
surfacea re and stronger van-der-waals forces which continue to be stronger in acid anhydrides, so their
boiling points are still higher, while amides have stronger intermolecular H-bonding so the have highest
boiling points.
The order of acyl nucleohilic substitution reactions:
All these derivatives are resonance hyjb rid of the following structures:
More is the ease of shaing lone pair with carbonylic carbon – less is the eas of cleavage of C – X bond
- X is
- Cl in acid chlorides
- O – COR in acid anhydrides
- OR in esters
- -NH2 in amides
The ease of cleavage depends upon:
i) –I effect
ii) Resonance effect
iii) Basisity of the leaving group.
Since the order of basisity of leaving group is :
-Cl < - O – COR < -OR < -NH2
Because of strong –I of Cl and –Cl is weaker conjugate base, while –NH 2 is having maximum + R effect
and minimum – I and strongest conjugate base.

Acid Derivatives: Nucleophilic Substitution: Alkyl vs. Acyl

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Acid Derivatives: Nucleophilic Substitution: Alkyl vs. Acyl

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Acid Derivatives

Nucleophilic Substitution : Alkyl vs. Acyl

(i) Hydrolysis of esters

Esters when reduced with LiAlH4 get reduced to 2 molecules of alcohols

When reduced with LiAlH4 they give primary amines.

When heated with P2O5 it gets dehydrated to an alknae nitryl

The order of acyl nucleohilic substitution reactions:

The ease of cleavage depends upon:

Since the order of basisity of leaving group is :

-Cl < - O – COR < -OR < -NH2

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