Perkin reaction:
The Perkin reaction is an
organic reaction which is used for synthesis of α, β-unsaturated aromatic acid
by the condensation of an aromatic aldehyde and an acid anhydride, in the
presence of an alkali salt of the acid. The alkali salt acts as a base catalyst
and other bases can be used instead.
Perkin’s reaction mechanism
includes the reaction between aromatic aldehydes, the aliphatic acid anhydride,
and the alkali salt of the acid to give cinnamic acid derivatives. The Perkin
reaction is an organic chemical reaction named after its discoverer – William
Henry Perkin.
Example
The Perkin reaction gives an
alpha, beta-unsaturated aromatic acid via the aldol condensation of an aromatic
aldehyde and an acid anhydride. The alkali salt of the acid is also present.
This alkali salt acts as a base catalyst. Other bases can be used instead
of the alkali salt of the acid in the Perkin reaction.
Given below is an illustration of the Perkin reaction.
One of the most important
applications of the Perkin reaction is the laboratory synthesis of
phytoestrogenic stilbene resveratrol. The Perkin reaction can be considered as
a type of condensation reaction.
Perkin Reaction Mechanism
It is type of condensation
reaction, which involve the condensation of acidic anhydride and aldehyde in
the presence of weak base (i.e., Sodium and potassium salt of the acid or
trimethylamine) to give unsaturated carboxylic acid (Equation 1).
In 1968 Perkin described the
very first example of such type condensation reaction, involve the synthesis of
coumarin by condensing the sodium or potassium salt of salicylaldehyde with
acetic anhydride (Equation 2).
Generally, such type of
reaction is only applicable to aromatic aldehyde and useful for the preparation
of substituted cinnamic acid (Equation 3)
In 1883 a very important
variation is done by plÓ§chl, which involve the heating of benzaldehyde and
hippuric acid in presence of acetic anhydride. Erlenmeyer determine the
Azalactone structure of the product (Equation
4)
and extended the scope of
Perkin reaction to other aldehydes (Erlenmeyer Azalactone synthesis).
Azalactone or oxazolone acts as important intermediate for the synthesis of α-
amino acid and α- keto acid (Scheme 1).
Mechanistic Approach Of Perkin Reaction
The most accepted mechanism
of Perkin reaction is shown in Scheme
2a and Scheme 2b.
Formation of anhydride
enolates and aldol type condensation provides the alkoxide anhydride but
intermolecular acylation generates an Acetoxy carboxylate, Which form a mixed
anhydride which on elimination of acetic acid and subsequent hydrolysis gives
the unsaturated acid (Cinnamic acid). The compound 3 undergoes a minor
potential side reaction decarboxylation to form an alkene (equation 5, 6).
The reaction between aromatic
aldehyde and phenyl acetic acid give the α-phenylcinnamic acid in cis-form (equation 7).
When this product i.e.,
α-phenylcinnamic acid is heated in dilute solution of acetic anhydride-
trimethylamine gives an equilibrium mixture of 81% of the E-cinnamic acid and
19% of the Z isomer (equation 8).
According to Ahramjian and Zimmerman, the condensation between the aromatic aldehyde and phenylacetic acid is not reversible . This lack of reversibility is explained the rapid acetylation of the β-alkoxide substituent in the intermediate (Scheme 2).
The elimination of
each diasteriomeric-2, 3-diphenylpropionic acid under Perkin condensation
((MeCO)2O, Et3N, reflux,35 min) give a product having 99+2% of α-phenyl-trans-cinnamic
acid (Scheme 3).
Under the same mild
condition, the Perkin condensation between benzaldehyde and phenyl acetic acid
gives the product having 96% of eq 8.
Recently, many results have
been published showing that the initial condensation at least in presence of
trimethylamine, may not be only aldol type but also indicate a pathway
involving the formation and subsequent cycloaddition of ketene to form a
β-lactone intermediate that breaks to give the cinnamic acid (Scheme 4)
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