Some Extensions of von Braun (BrCN) Reaction on Organic Bases: Part II

In an earlier communication Siddiqui and Bina [1] reported some extensions of von Braun BrCN reaction on the conessine series of alkaloids, which appeared to provide a novel route for the synthesis of therapeutically active nitrogenous compounds including substituted ureas, diamines, carbinol amines and guanidine derivatives. However, it was noted by them that dimethyl a-napthylamine and diethyl amine do not form guanidine derivatives. Further limitations were observed in the case of harmala and Rauwolfia alkaloids [2, 3]. Tetrahydroharmine yielded only urea derivative, while the Rauwolfia bases sandwicine and isosandwicine failed to yield any of the above mentioned derivatives. In view of these observations it was considered of interest to ascertain the applicability, limitations and variations of these reactions with cyanamides of Ephedra alkaloids and other simpler aliphatic and aromatic amines. The present work deals with the cyanamides of ephedrine (1), O-acetyl ephedrine (2) and desoxyephedrine (3) which were obtained as oily liquids through the action of BrCN. Attempts were made to obtain from ephedrine cyanamide an N-amide, introducing a urea moiety in the molecule, through careful partial hydrolysis with 20% hydrochloric acid. However, the resulting uniform oily product did not show the presence of amide group in the IR and NMR spectra. Ir could be identified through physical and chemical characterization, and spectral studies as 2-imino-3,4-dimethyl-5-phenyl oxazolidine (4) (yield 1 g ; 100%). The protonation of the nitrile nitrogen promotes nucleophilic attack from the hydroxyl group resulting in a cyclized product. This constituted a better method of preparation than that described by Fodor et al. [4] which involves a