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* Compounds which can form enols react with imines or iminium ions derived from formaldehyde

Primary or secondary amines can be used to form the corresponding formaldehyde imines or iminium ions

Instead of formaldehyde, other aliphatic or aromatic aldehydes or ketones can be employed.

The amine used may be ammonia or 1o or 2o aliphatic amine. Mostly dimethyl amine is used. The aromatic amines do not undergo Mannish reaction.

The Eschenmoser's salt, [(CH3)2N=CH2]+I- is used as a source of formaldehyde and dimethyl amine for Mannich reactions.

The α-CH acidic compounds include carbonyl compounds, nitriles, aliphatic nitro compounds, alkynes, α-alkyl-pyridines or imines, activated phenyl groups and electron-rich heterocycles such as furan, pyrrole, thiophene, Indole etc.

The reactions are usually carried out in aqueous or alcoholic solutions.

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The Mannich ReactionMechanism:-

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MannichReaction and Anticancer Drugs

APPLICATIONS OF MANNICH REACTION

1. 4-(dimethylamino)butan-2-one is obtained when acetone reacts with formaldehyde and dimethylaminium chloride.

2. Phenol gives a trisubstituted product in the Mannich reaction.

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3. Ethylmalonic acid also undergoes aminomethylation at active -CH site as shown below.

4. Phenylacetylene readily reacts with formaldehyde and dimethylamine to give the following Mannich base.

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T.W. GRAHAM SOLOMONS, CRAIG B. FRYHLE, Organic Chemistry 10th ed. JOHN WILEY & SONS, INC.

F.A.Carey and R.J Sandberg Advanced Organic Cheistry Part B 4th ed.

A Guidebook to Mechanism in Organic Chemistry - Peter Sykes

Jonathan Clayden, Nick Greeves, Stuart Warren & Peter Wothers, Organic Chemistry

John McMurry, Organic Chemistry 8th ed.

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