STUDIES ON PREPARATION OF BUCLIZINE HYDROCHLORIDE

1-(p-Chlorbenzhydryl)-4-(p-tert-butylbenzyl)-piperazine dihydrochloride is a new antihistaminic markered under the names of Longifene, Softran,Vibazine hydrochloride, or Buclizine hydrochloride.Since detailed description of its preparation has not been available in literature, attempts have been made in the present work to develop a suitable method for production, p-chlorodiphenylketone was readily reduced by potassium boronhydride, giving p-chlorobenzhydryl alcohol,which was converted into p-chlorobenzhydryl bromide. The latter compound was also easily prepared by the reaction of p-chlorophenylmagnesium bromide with benzaldehyde. p-tert-Butylbenzyl chloride was condensed directly with piperazine,and the desired p-tert-benzylpiperazine was afforded. The N,N'-disubstituted by-product was found to be practically insoluble in ethanol and could thus be easily removed. In this manner the protection of piperazine was not necessary. Treatment of p-tert-benzylpiperazine and p-chlorobenzhydryl bromide in the presence of anhydrous sodium carbonate gave Buclizine hvdrochloride as expected.