Synthesis of phenethylamines from phenylacetonitriles obtained by alkylation of cyanide ion with mannich bases from phenols and other benzylamines

Abstract

Benzylamines, obtained by the Mannich reaction on phenols or by reductive alkylation of aldehydes, have been used in place of benzyl chlorides to alkylate cyanide ion to obtain nitriles which may be reduced to phenethylamines. Yields of 4-hydroxy-3-methoxyphenylacetonitrile were about the same from the primary, secondary, and tertiary amines. Benzylamines not having either an ortho or para OH group did not function as alkylating agents. With such compounds it was necessary to prepare the quaternary salts before alkylation could be achieved. 6-Hydroxydopamine was prepared from 2,4,5-trimethoxybenzaldehyde utilizing the latter approach. 3,5-Dimethoxy-4-hydroxyphenethylamine was cyclized to the corresponding dihydroisoquinoline. The isoquinoline and tetrahydroisoquinoline analogs were also prepared. 4-Hydroxy-3-methoxyphenylacetonitrile was hydrolysed to homovanillic acid, the naturally occurring metabolite of dopamine.