SYNTHESES OF SOME 3-PHENYL-3-tert-AMINO-1,2-PROPANEDIOLS

Abstract

Although several investigators have reported the preparation of 1-phenyl-2.amino-1 ,3-propanediols by reacting 1-phenyl-2-bromo-l , 3-propanediol (I) with amines, no proof of the position of the amino group of the resulting diols was given (1, 2). Recently, Controulis, et al. showed that I gave 3-phenyl-3-amino-1,2-propanediol when treated with ammonia (3). It seemed possible that reaction of I with secondary amines may also have led to 3-phenyl-3-tert-amino-1,Zpropanediols. It was thus interesting to reinvestigate such reactions.Another possible approach to the synthesis of l-phenyl-2-tert-amin0-1,3propanediols would be through the reduction of a-amino-p-hydroxy-p-phenylpropionic acids by lithium aluminum hydride. Despite the fact that the literature had indicated that both a-amino and P-amino products were possible when a-bromo-P-hydroxy acids were treated with amines (4), the authors were interested in using a-bromo-P-hydroxy-P-phenylpropionic acid (11) (5) as a starting material in order to correlate these two schemes in their reaction mechanisms.l-Phenyl-2-bromo-l,3-propanediol (I) was prepared in its solid form by using a slightly modified procedure of the early workers (3). On treatment of I with piperidine in water 3-phenyl-3-piperidino-l , 2-propanediol (111) was obtained, associated with one mole of piperidine as solvent of crystallization. 3-Phenyl-3morpholino-l,2-propanediol (IV) was prepared by a similar procedure in low yield.a-Bromo-P-hydroxy-P-phenylpropionic acid (11) reacted with piperidine and morpholine in ether to give the corresponding amine salts (V and VI) of the starting acid. When I1 was treated with the amines in aqueous solution, the unstable piperidine salt (VII) of a-hydroxy-p-piperidino-P-phenylpropionic acid (IX) and the morpholine salt (VIII) of a-hydroxy-8-morpholino-8-phenylpropionic acid (X) were isolated. On drying at 100" VI1 lost piperidine readily to give the free acid (IX). On the other hand, salt VI11 was quite stable. Previously Fourneau ( 6 ) had reported the preparation of acid I X by reacting piperidine with phenylglycidic ester, and had assigned the position of the amino group by referring to an early work of Erlenmeyer (7) who had assigned the structure from its method of synthesis as analogous to that for phenylisoserine. It seemed to us, however, that a melting point alone could not be the conclusive structural evidence in our investigation. The melting point of I X was found to vary widely by inserting the sample at different temperatures of the melting bath. Therefore, the location of the amino group was still doubtful until the latter part of this investigation.