SYNTHESES DE LA DL-PROLINE A PARTIR DE L'α-PIPERIDONE

Abstract

By treatment of α-piperidone with sulphuryl chloride,β,β′-dichloro-α-piperidone was obtained. It was hydrolyzed to α,α′-dichloro-δ-amino-n-valeric acid, which was simultaneously reduced and cyclized to DL-proline, by low pressure hydrogenation, using Raney nickel, in alkaline solution. All the intermediate compounds were identified and characterized. The over-all yield of DL-proline is 33% calculated from α-piperidone.α-Piperidone was hydrolyzed to δ-amino-n-valeric acid, and the δ-phenylureido-n-valeric and δ-phthalimido-n-valeric acids were prepared. Halogenation of δ-phthalimido-n-valeric acid gave excellent yields of the α-bromo and α-chloro acids. These acids were hydrolyzed to the α-halogenated-δ-aminoacids. On treatment with alkali, they gave DL-proline in 56% and 50% yields respectively, from α-piperidone.Halogenation of δ-phenylureido-n-valeric acid gave the dibromo and the dichloro acids, which ring-close immediately into derivatives of α-piperidone.The different behavior of δ-benzoylamino, δ-phthalimido, and δ-phenylureido derivatives of n-valeric acid with halogens, or halogenating agents is noted.