PREPARATION OF OPTICALLY PURE 3'-METHYLSPIRO[IMIDAZOLIDINE-4,4'(1'H)-QUINAZOLINE]-2,2',5(3'H)-TRIONE BY COMBINATION OF OPTICAL RESOLUTION AND RACEMIZATION

Optically pure 3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione was prepared by optical resolution using brucine as a resolving agent. The resulting optically pure spirohydantoin was racemized by refluxing in 1,2-dichlorobenzene for 17 h, or more effectively upon heating in 10% HCl at 90-degrees-C for 2 h. In the acid-catalyzed racemization, the introduction of difluoromethyl group at the 3-nitrogen of hydantoin ring increased the racemization rate, while the introduction of methyl group at the 3-nitrogen reduced it. These results suggest that the acid-catalyzed racemization proceeds via the N-acyliminium ion generated by the cleavage of the N3-C4 bond of the spirohydantoin ring.