Mannich reaction
| Mannich reaction | |
|---|---|
| Named after | Carl Mannich |
| Reaction type | Coupling reaction |
| Identifiers | |
| Organic Chemistry Portal | mannich-reaction |
| RSC ontology ID | RXNO:0000032 |
In
The Mannich reaction starts with the nucleophilic addition of an amine to a carbonyl group followed by dehydration to the Schiff base. The Schiff base is an electrophile which reacts in a second step in an electrophilic addition with an enol formed from a carbonyl compound containing an acidic alpha-proton. The Mannich reaction is a condensation reaction.[4]: 140
In the Mannich reaction, primary or secondary
The Mannich reaction can be considered to involve a mixed-
Reaction mechanism
The mechanism of the Mannich reaction starts with the formation of an iminium ion from the amine and formaldehyde.[4]: 140
The compound with the carbonyl functional group (in this case a
On methyl ketones, the enolization and the Mannich addition can occur twice, followed by an β-elimination to yield β-amino enone derivatives.[5][6]
Asymmetric Mannich reactions
Applications
The Mannich reaction is used in many areas of organic chemistry, Examples include:
- alkyl amines
- : 142 )
- agrochemicals, such as plant growth regulators[9]
- polymers
- catalysts
- Formaldehyde tissue crosslinking
- Pharmaceutical drugs (e.g. rolitetracycline (the Mannich product of tetracycline and pyrrolidine), fluoxetine (antidepressant), tramadol and tolmetin(anti-inflammatory drug).
- soap and detergents, especially with application to automotive fuel[10]
- Polyetheramines from substituted branched chain alkyl ethers.[11][12]
- α,β-unsaturated ketones by the thermal degradation of Mannich reaction products (e.g. methyl vinyl ketone from 1-diethylamino-butan-3-one)[13][14]
See also
- Betti reaction
- Kabachnik–Fields reaction
- Pictet–Spengler reaction
- Stork enamine alkylation
- Nitro-Mannich reaction
References
- ISBN 978-0-471-72091-1.
- S2CID 94217627.
- ISBN 978-0471264187.
- ^ ISBN 978-0387683546.
- .
- .
- PMID 11866595.
- PMID 16433496.
- .
- ISSN 0148-7191. 2000-01-2020. Retrieved 20 August 2023.
- ISSN 0016-2361.
- doi:10.4271/2022-01-1074.)
{{cite journal}}: CS1 maint: location (link - ISBN 978-3527306732.
- ; Collected Volumes, vol. 4, p. 281.
