Acid derivatives

Introduction



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 ar e 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.
CH3COCl Acid halide
CH3COCl Acid halide



Preparation





Properties





(ii) Hofmann Hypobromite Reaction
The reaction involves the conversion of an amide into a primary amine with one less carbon, by the action of alkaline
hypohalite (NaOH solution + Br2 or Cl2). The overall reaction is





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.





It is important to note that there is no cross-over products are obtained when two different amides are rearranged. It is
assumed that the rearrangement is intramolecular and the migrating group never completely separates from each other
during the migration.
This is further confirmed by the fact that if R is chiral (asymmetric), it migrates with unchanged configuration. Thus,
camphoramidic acid (A) having the COOH and CONH2 groups in cis position undergoes Hofmann rearrangement to give



the amino acid (B) in which the COOH and NH2 groups are also in cis position, since it readily forms lactam by removal of
water.





Remember, in this chemical reaction rate of reaction increases when the migrating group is more electron-donating and
decreases when electron-attracting. If R is an alkyl group with more than eight carbons, low yields are obtained.
This chemical reaction is used for degradation of amines homologous series.
Applications















CH3COOC2H5 Ethylacetate
CH3COOC2H5 Ethylacetate
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) Transesterification
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.










Acid derivatives
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 transesterification 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.





(iii) Claisen Ester Condensation
Esters which contains on reaction with a strong base, e.g., C2H5ONa or (CH3)3CONa undergo self-condensation
by intermediate carbanian to produce


This reaction is called
Claisen ester condensation
although there are several closely related reactions which follow the same path.
















Applications
Mixed or crossed Claisen condensation also occurs between two different esters or between an ester and a ketone.
Applications













Reaction with hydroxyl amine to form solid which on subsequent treatment with FeCl
3
, dark coloured compound is formed. This chemical reaction is used as test of ester group.