Reductive alkylation, of amines

The reductive alkylation of amines is called the Leuckart-Wallach reaction [112-115]. The primary or secondary amine reacts with the ketone or aldehyde. The formed imine is then reduced with formic acid as hydrogen donor (Scheme 20.27). When amines are reductively methylated with formaldehyde and formic acid, the process is termed the Eschweiler-Clarke procedure [116, 117]. 

Amine synthesis from reductive amination of a ketone and an amine in the presence of excess formic acid, which serves as the reducing reagent by delivering a hydride. When the ketone is replaced by formaldehyde, it becomes Eschweiler-Clarke reductive alkylation of amines. 

A valuable application of the above-described reduction is the one-step reductive alkylation of amines with carbonyl compounds. ... 

Reductive alkylation of amines with carbonyl compounds O NHCHa... 

The reduction of nitroso compounds in the presence of ketones can be used for the reductive alkylation of amines ... 

Reductive alkylations of amines with carbonyl compounds can be also accomplished quantitatively by means of selenophenol (PhSeH) at room temperature in chloroform198 and by sodium hydrogen telluride (NaHTe) in ethanol at room temperature199. 

Formic acid is an exception among organic acids in having reducing capacity because of its combined acid/aldehyde character and the possibility for exothermic release of carbon dioxide on hydride donation. Ammonium formate, NH4CO2H, has long been used for reductive alkylation of amines. This is the Leuc-kart reaction, which has been reviewed. In this process aldehydes or ketones are used to alkylate ammonia and form a primary amine (11), as depicted in equation (11). The reductive step is the reaction of formate with an iminium ion or its equivalent (equation 12). ... 

Reductive alkylation of amines proceeds by the hydrogenation of the imine or enamine formed, in situ, by the condensation of the amine with a carbonyl compound. This reaction can give a mixture of products if the amine produced initially competes with the reactant amine in the carbonyl condensation step. The proper selection of reagent concentrations avoids this difficulty and leads to the formation of good yields of the desired product. 50 jhe use of a large excess of ammonia gives the primary amine as the predominant product (Eqn. 19.50). 51 An excess of a primary amine as the reactant leads to the preferential formation of the secondary amine product. An excess of the carbonyl compound gives the symmetrical secondary or tertiary amines (Eqn. 19.51). 50... 

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