MANNICH REACTION

1
MANNICH REACTION
ketone
formaldehyde
excess
..
pH 6-8
-
Cl
-
..
iminium salt
A variety of R groups may be used
Mannich Base Schiffs Base
Aldehydes other than formaldehyde may be used.
The reaction works best with methyl
ketones. Et2NH - HCl is generally used in excess,
hence the chloride counter ion. Other secondary
amines sometimes work in place of diethylamine.
2
Activated phenols will also give a reaction
similar to the Mannich Condensation.

-

..
Mannich Base
resonance structures
AROMATIC SUBSTITUTION

This is essentially an electrophilic aromatic
substitution reaction a hydrogen on the ring
is replaced by the Mannich Base which is an
electrophile.
Phenols with activating substituents (methoxy,
hydroxy, amino) can give this reaction.
3



_
..

..
HNEt2
Mannich Base
B
H
4
PICTET-SPENGLER REACTION
condensation occurs at biological pH values
H3O/D

a tetrahydroisoquinoline ring
Mannich Base
if cyclization does not occur sponttaneously
This is a general method for the synthesis of
tetrahydroisoquinoline rings.
5
BISCHLER-NAPIERALSKI REACTION
amide
H3PO4 or P2O5
via
- H2O
synthesis of the initial amide
Intermediate loses water
Synthesis of a dihydroisoquinoline
An acid anhydride may be used instead of an acid
chloride to synthesize the amide.
6
ester-amide (urethane)
..
..
H3PO4 or P2O5
H
H
ethyl chloroformate
synthesis of the initial urethane