Ammonium formate, Leuckart-Wallach reaction

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

In 1885, R. Leuckart reported that the reaction of ammonia and primary or secondary amines with ketones (and aldehydes) was possible with ammonium formate, to produce the corresponding primary, secondary, or tertiary amine.1 This reaction became known as the Leuckart reaction. In 1891, Wallach reported that the use of excess formic acid led to an improvement in yield, and that the reaction could be carried out at lower temperatures.2 The Leuckart-Wallach reaction was bom. Wallach went on to apply this reaction to a wide variety of carbonyl compounds, including alicyclic and terpenoid ketones.5... 

In 1931, Ingersoll et al. noted that formamide could act as an Intermediate, and consequently ammonium formate could be replaced with formamide in the Leuckart reaction,12 and in 1968, Bach carried out Leuckart-Wallach reactions on cyclic aliphatic ketones with dimethylformamide in high yields, and with reaction times of only 8-16 h.13... 

Kitamua et al. have identified a useful catalyst for the Leuckart-Wallach reaction that can be used to form primary amines at lower temperatures, and in a higher yield than the standard conditions.14 The reaction uses 0.5 mol% [RhCp Cl2]2 and a 1 5 substrate ammonium formate ratio. 

Optically active amines can also be generated directly from ketones with ammonium formate in a catalytic version of the Leuckart-Wallach reaction (Equation 15.89). The imine is derived from the ammonia generated from the ammonium formate, and the reducing equivalent is derived from the formate. In the presence of the [Ru(BINAP)Cl2]2 catalyst, the amine and formamide were formed as the major products. After hydrolysis of the formamide, the amine was isolated in high yield and ee. 

The original synthesis discovered by Leuckart was the reductive alkylation of benzaldehyde to form benzylamine using formamide or ammonium formate as the reducing agent. This was later extended by Wallach and by the Eschweiler-Glarke procedure . The scope of the Leuckart reaction has been reviewed by Moore Apart from the special case of formaldehyde, the reaction is most focile with aromatic aldehydes and water-insoluble ketones. Aliphatic... 

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