A New Method for the Preparation of Secondary Amines. VIII

Synthesis of Phenylalkanolamines

Abstract

Synthesis of phenylalkanolamine by the saccharin method was studied and α-phenyl-β-monomethylaminoethanol, ephedrine, and α-(3, 5-dimethoxyphenyl)-β-monomethylaminoethanol (DMAE) were successfully obtained. There are two methods of preparing α-phenyl-β-monomethylaminoethanol but the one involving reduction of N-phenacylsaccharin (IIIa) to N-(α-hydroxyphenethyl)-o-carboxybenzenesulfonamide (XIa) and its treatment by the usual method gives better yield and requires simpler procedures. The other method of hydrolyzing (IIIa) with alkali is apt to afford a by-product, 3-benzoyl-4-hydroxy-1, 2-benzothiazine S-dioxide (IVa) as yellow crystals. The former method is also advantageous for the preparation of ephedrine, although the acid hydrolysis of N-methyl-N-(β-methyl-α-hydroxyphenethyl)-o-carboxybenzenesulfonamide (XXV) results in the formation of pseudoephedrine, as well as ephedrine. In the case of DMAE, alkaline hydrolysis by this method of (IIIb) did not afford the objective carboxylic acid but only 3-(3′, 5′-dimethoxybenzoyl)-4-hydroxy-1, 2-benzothiazine S-dioxide (IVb) was obtained as yellow crystals and the objective was attained by the former method.