Studies on the Steric Inversion of Alkamines. I

On the Reciprocal Inversion between dl-Ephedrine and dl-Ψ-Ephedrine. (Part 1)

Abstract

In order to obtain dl-ephedrine possessing therapeutic value from dl-Ψ-ephedrine which is obtained as a by-product in synthetic procedure, experiments were carried out by the author. Application of PCl₅ to dl-ephedrine and dl-Ψ-ephedrine results in Walden conversion in both cases and dl-Ψ-1-phenyl-1-chloro-2-methylaminopropane hydrochloride (I) and dl-1-phenyl-1-chloro-2-methylaminopropane hydrochloride (II), respectively, are formed. However, application of SOCl₂ to dl-Ψ-ephedrine results in the formation of (I). Application of AgNO₃ solution to (I) and (II) gives, in both cases, a mixture of dl- and dl-Ψ-ephedrine where the amount of the latter is always larger than the former. Heating (I) with NaOH solution gives N-methyl-1-phenyl-2-methylethylene-imine (III) which, when heated with 60% H₂SO₄, undergoes hydration and ring-cleavage, and gives about an equal mixture of dl- and dl-Ψ-ephedrine. Application of benzoyl or acetyl chloride to (III) results in their addition with concurrent ring-cleavage to give dl-Ψ-1-phenyl-1-chloro-2-benzoyl (or-acetyl)-methylaminopropane (IV and V).