Amine From amide, with homologation

Fatty amines can be synthesized by reacting alkylhalides with either ammonia or lower amines, from fatty acids and their derivatives (i.e., amides and ammonium salts), or by ammonolysis of fatty alcohols. Amines dissociate and reveal surface activity primarily under acidic conditions. Higher homologs, such as octadecylamine, are insoluble in water, but soluble in oil. 

A variant on this structure, dioxyline, has much the same activity as the natural product but shows a better therapeutic ratio. Reduction of the oxime (113) from 3,4-dimethoxyphenyl-acetone (112) affords the veratrylamine homolog bearing a methyl group on the amine carbon atom (114). Acylation of this with 4-ethoxy-3-methoxyphenyl acetyl chloride gives the corresponding amide (115). Cyclization by means of phosphorus oxychloride followed by dehydrogenation over palladium yields dioxyline (116). ... 

Thus the kava alkaloids contain either a cinnamoyl or phenylpropionyl moiety. One would expect that a homologous series of such alkaloids may exist in the P. methysticum plant, since Achenbach and Karl (1971) isolated a series of substituted cinnamic, benzoic and phenyl propionic acids. These acids would be expected to react readily with amines to form the amide alkaloids. However, such a series of alkaloids does not appear to occur in the P. methysticum plant, although several similar alkaloids have been isolated from other Piper species, such as P. longum which yields piplactine, piperlongumine and piperlongiuninine (Chatterjee and Dutta, 1967). 

Primary amines are not usually made by reduction of amides (15) but by other reductive processes which are minor variations on this scheme. For unbranched amines (16) we can reduce cyanides. This method is especially suitable for benzylic amines since aryl cyanides (17) can be made from diazonium salts (see Chapter 2), and for the homologous amines (18) since cyanide ion reacts easily with benzyl halides. 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

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