Mannich reaction

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Scheme of the Mannich reaction

The Mannich reaction is a name reaction in organic chemistry in which an aminoalkylation of CH-acidic compounds with an aldehyde and ammonia or a primary or secondary amine takes place. The reaction is named after its discoverer, the German chemist Carl Mannich . The Mannich reaction is counted among the condensation reactions , since water is split off .

reaction

In the Mannich reaction, ammonia or primary or secondary amines are used both to activate the aldehyde and to introduce the desired chemical residues into the product to be formed. Tertiary amines cannot be used for the Mannich reaction because they would prevent the formation of the intermediate. In addition, the aminoalkylation of enamines and imines , as well as of electron-rich aromatics such as indole, is possible. Phenols can also be easily aminoalkylated.

Carbonyl compounds , nitriles , alkynes , nitroalkanes , α- alkylpyridines or tertiary iminium salts can serve as α-CH-acidic compounds ( nucleophile ) . In the overview reaction, an aldehyde (R 1 = H, R 2 = H or organyl group ) or a ketone (R 1 = organyl group, R 2 = H or organyl group) is shown as the α-CH-acidic compound :

Overview of the Mannich reaction

The Mannich reaction can optionally be carried out under very mild conditions; so successful pumping the synthesis of tropinone in aqueous solution at room temperature and pH 5% in 90 yield. The products of the Mannich reaction are called Mannich bases and are amines that contain other functional groups.

mechanism

The Mannich reaction takes place in several steps, including the formation of the compound for aminoalkylation and the aminoalkylation of the CH-acidic compound.

In the first reaction step, a secondary amine attacks the formaldehyde nucleophilically. The hydroxyl group is then protonated under acidic conditions and split off as a water molecule . A mesomerism- stabilized carbenium - iminium ion is formed.

Mechanism of the Mannich reaction, part 1

In the second step of the reaction, the action of an acid or base leads to keto-enol tautomerism . The enol then attacks the carbenium iminium ion nucleophilically. After subsequent deprotonation of the hydroxyl group, a β- aminocarbonyl compound (Mannich base) is obtained.

Mechanism of the Mannich reaction, part 2

application

The Mannich reaction is used in the synthesis of natural substances such as peptide - nucleoside - antibiotics and alkaloids . Further areas of application are the manufacture of pharmaceuticals , crop protection, and paint and polymer chemistry ( dyes , reaction accelerators, hardeners and crosslinkers).

Individual evidence

  1. ^ Siegfried Hauptmann : Organic Chemistry , 2nd edition, VEB Deutscher Verlag für Grundstoffindindustrie, Leipzig, 1985, p. 365, ISBN 3-342-00280-8 .
  2. ^ Siegfried Hauptmann : Organic Chemistry , 2nd Edition, VEB Deutscher Verlag für Grundstoffindindustrie, Leipzig, 1985, p. 261, ISBN 3-342-00280-8 .
  3. ↑ Louis Frederick Fieser and Mary Fieser: Organische Chemie , Verlag Chemie, 2nd edition, 1972, ISBN 3-527-25075-1 .
  4. ^ Hans Beyer and Wolfgang Walter : Organische Chemie , S. Hirzel Verlag, Stuttgart, 1984, pp. 508-509, ISBN 3-7776-0406-2 .
  5. ↑ László Kürti and Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis: Background and Detailed Mechanisms , Elsevier Academic Press, 2005, pp. 274-275, ISBN 978-0-12-429785-2 .
  6. ^ Brockhaus ABC Chemie , VEB FA Brockhaus Verlag Leipzig 1965, pp. 842-843.

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