Mannich reaction

The Mannich reaction is a reaction in the name of 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, the German chemist Carl Mannich named after its discoverer. The Mannich reaction is counted to the condensation reactions, as water is removed.

Reaction

In the Mannich reaction of ammonia or primary or secondary amines are used both for activation of the aldehyde, as well as for insertion of the desired chemical moieties in the product to be formed. Tertiary amines can not be used for the Mannich reaction, as they would prevent the formation of the intermediate. In addition, the amino alkylation of enamines and imines is possible or feasible to electron-rich aromatic compounds such as indole. Also, phenols can aminoalkylieren easily.

As α -CH -acidic compounds ( nucleophile ) carbonyl compounds, nitriles, alkynes, nitro alkanes, α - alkyl pyridine or tertiary iminium salts can be used. In the overview reaction is called α -CH -acidic compound, an aldehyde (R1 = H, R2 = H or Organylgruppe ) or a ketone (R1 = Organylgruppe, R2 = H or Organylgruppe ) shown:

The Mannich reaction may optionally be carried out under very mild conditions; so scoop, the synthesis of tropinone in aqueous solution at room temperature and pH 5 in 90 % yield. The products of the Mannich reaction are known Mannich bases and amines, which contain additional functional groups.

Mechanism

The Mannich reaction can be roughly divided into two steps:

In the first reaction step, a secondary amine of the nucleophile attacks the formaldehyde. The hydroxyl group is then protonated and cleaved as a water molecule under acidic conditions. It forms a resonance -stabilized carbenium - iminium ion.

In the second step of the reaction occurs under the action of an acid or base to give a keto -enol tautomerism. The enol then accesses the carbenium - iminium ion to nucleophilic. After final deprotonation of the hydroxy group to give a β - aminocarbonyl compound ( Mannich base ).

Application

The Mannich reaction is used in the synthesis of natural products, such as peptide - nucleoside antibiotics and alkaloids. Other applications include the plant protection as well as the paint and polymer chemistry (dyes, reaction accelerators, curing agents and curing agent).