Reaction mechanism-

Mannich reaction

Iqra Hamid
Introduction

• The Mannich reaction involves the combination of an amine, an

aldehyde or a ketone with a nucleophilic carbon.
• In the Mannich reaction an amine is coupled in the presence of an
formaldehyde to a suitable carbon atom in a wide range of organic
compounds .
• The carbon atom must possess an “active” hydrogen atom, one with
a degree of acidic character.
 Mannich reaction

• The Mannich reaction is the organic reaction in which an acidic H+ ion

(proton), which is positioned next to a carbonyl group, undergoes an
amino alkylation with the help of formaldehyde and ammonia (a
primary or secondary amine can be used instead of NH3).
• The product of this reaction is a beta-amino carbonyl compound.
Mannich reaction

• It is an organic chemical coupling reaction which is named after the

German chemist Carl Mannich.
• The beta-amino-carbonyl compound, which is the final product, is
also referred to as a Mannich base.
Chemical reaction
• It can be noted that the Mannich reaction can also be considered as a
condensation reaction.
• The reason primary/secondary amines (or NH3) are used for the
activation of the formaldehyde is that tertiary amines would lack the
N-H proton which is required for the formation of the enamine
intermediate.
Reaction mechanism
Step 1
• The reaction between formaldehyde and the amine leads to the
formation of the iminium ion.
• This formation of an iminium ion is illustrated below.
Reaction mechanism
Step 2
• The compound containing the carbonyl group (which is a ketone in
this illustration for the mechanism of the Mannich reaction)
undergoes tautomerization to give its enol form.
• This enol form of the compound with a carbonyl functional group now
proceeds to execute an attack on the iminium ion.
• This attack finally yields the required beta-amino-carbonyl compound
or Mannich base. The illustration for this step is given below.
Reaction mechanism
• Thus, the amino alkylation of an acidic proton which is placed
alongside a carbonyl group by formaldehyde and a primary or
secondary amine or ammonia is achieved, and the required beta-
amino carbonyl compound (or Mannich base) is produced.

• Mannich reaction is an example of the nucleophilic addition of an

amine to a carbonyl group.
Application
• This organic reaction has numerous applications, primarily in the
synthesis of specific organic compounds. Some of these compounds
and their applications are listed below.

• This reaction is used in the preparation of alkyl amines, which are

employed in the production of pesticides.

• Many antibiotics are Mannich bases. For example, the Mannich base
of tetracycline is Rolitetracycline, a broad-spectrum antibiotic.
Application
• Many catalysts and polymers are produced with the help of this reaction.

• The Mannich reaction is used in the synthesis of many pharmaceutical

drugs. One such example is the use of this reaction in the production of
fluoxetine, a powerful antidepressant.

• The nonsteroidal anti-inflammatory drug tolmetin is synthesized with the

help of this reaction.

• The reaction is also used in the production of some soaps and detergents.