ABSOLUTE CONFIGURATIONS OF PHENIRAMINES METHYL PHENIDATES AND PIPRADROLS

Absolute configurations of the 16 optical isomers of seven structurally related, title compounds of biological interest were determined. The pheniramines were converted to a methyl phenidate in which the relative configurationsof the two asymmetric centers was established. The endocyclic center of asymmetry introduced in the process was maintained intact while the asymmetry of the exooyclic center was destroyed in the conversion to a pipradrol derivative. This was related to pipradrol by an aufbau sequence starting with (R)-(+)-piperidine-2-carboxylic acid. The absolute configurations of desoxypipradrol and thiopipradrol were established by Birch reduction and by rotatory dispersion, respectively. The antihistaminicallv more active acid maleates of 1a and 1b are stereochemically superimposable upon 1c and all have the (S) configuration. The analeptically more active hydrochlorides (25, 19, 26) of threo-methyl phenidate, pipradrol, and thiopipradrol are stereochemically superimposable upon 22. These have the (2R:2′R), (R), (S), and (R) configurations, respectively, but are not stereochemically superimposable upon the analeptically more active (+) acid sulfate of amphetamine. © 1969, American Chemical Society. All rights reserved.