Separation of the organic bases by Craig partition. VII. Acyl migration in the stereoisomeric N-(N,N-dimethylphenylalanyl)ephedrines

Abstract

cf. CA 66: 49281u. The compds. studied were N-(L-N,N-dimethylphenylalanyl)-L-ephedrine (I), N-(D-N,N-dimethylphenylalanyl)-L-ephedrine (II), N-(L-N,N-dimethylphenylalanyl)-L-pseudoephedrine (III), and N-(D-N,N-dimethylphenylalanyl)-L-pseudoephedrine (IV). In every case, only the ester of L-pseudoephedrine resulted, even under mild conditions (room temp., acetone-HCl). Complete inversion of the erythro derivs. occurred. In 2N HCl at 80 Deg, the ester from I formed quant. in 10 min. while that from III (retention of configuration) required 25 hrs. With II, 5 hrs. and with IV, 22 hrs. were required. The 4 amides pass through either of 2 cyclic intermediates during the migration, L,L-(V) or D,L-pseudooxazolidine (VI). The rates are explained by steric considerations of the mechanism, V resulting from I via inversion and from III with retention, and VI, from II via inversion and IV with retention. Craig partition as described previously (loc. cit.) was used to sep. and det. the reaction products. Twenty-four partition steps using a solvent mixt. of 0.5M citrate buffer (pH 4/5)-MeOH-CHCl3 (9:1:10 parts by vol.) were required for sepn. into N- and O-aminoacylephedrines. The O-(L-N,N-dimethylphenylalanyl)-L-pseudoephedrine m. 170-2 Deg, [alpha ]20D + 114 Deg (c = 0.0055 g./ml., 5N HCl) and the O-(D-N,N-dimethyl-) ester melts at 174-6 Deg, [alpha ]20D 48 Deg (c 0.0055 g./ml., 5N HCl).