MECHANISM OF THE ACID catalyzed HYDROLYSIS
An acid/base reaction. Since we only have a weak nucleophile and a poor
electrophile we need to activate the ester. Protonation of the amide carbonyl
makes it more electrophilic.
The water O functions as the nucleophile attacking the electrophilic C
in the C=O, with the electrons moving towards the oxonium ion, creating
the tetrahedral intermediate.
An acid/base reaction. Deprotonate the oxygen that came from the water
An acid/base reaction. Need to make the -NH2 leave, but need
to convert it into a good leaving group first by protonation.
Use the electrons of an adjacent oxygen to help "push out" the leaving
group, a neutral ammonia molecule.
An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl
in the carboxylic acid product and regenerates the acid catalyst.
(for more detail see Chapter 22)
Reactions usually in Et2O or THF followed by H3O+
Reaction type: Nucleophilic
Acyl Substitution then Nucleophilic Addition
can be reduced to the amine, RCH2NR'2 by conversion
of the C=O to -CH2-
Amides can be reduced
by LiAlH4 but NOT the less reactive NaBH4
Typical reagents :
LiAlH4 / ether solvent followed by aqueous work-up.
Note that this reaction
is different to that of other C=O compounds which reduce to alcohols
The nature of the amine
obtained depends on the substituents present on the original amide.
look at the N substituents in the following examples (those bonds don't change
or R" may be either alkyl or aryl substituents.
In the potential mechanism
note that it is an O system that leaves. This is consistent with O systems
being better leaving groups that the less electronegative N systems.
REACTION OF LiAlH4
WITH AN AMIDE
The nucleophilic H from the hydride reagent adds to the electrophilic
C in the polar carbonyl group of the ester. Electrons from the C=O move
to the electronegative O creating an intermediate metal alkoxide complex.
The tetrahedral intermediate collapses and displaces the O as part of
a metal alkoxide leaving group, this produces a highly reactive iminium
ion an intermediate.
Rapid reduction by the nucleophilic H from the hydride reagent as it adds
to the electrophilic C in the iminium system. p
electrons from the C=N move to the cationic N neutralizing the charge
creating the amine product.