SYNTHESIS AND REGIOSELECTIVE HYDROLYSIS OF 2-IMIDAZOL-1-YLSUCCINIC ESTERS

(+/-)-2-Imidazol-1-ylsuccinic esters were synthesized by thermal addit ion of imidazole to either fumaric or maleic esters. Acceleration of t he reaction was achieved, in some cases, using microwave heating. Thes e esters underwent an easy regioselective hydrolysis, under neutral co nditions, to give the corresponding half-esters: (+/-)-3-(alkoxycarbon yl)-2-imidazol-1-ylpropionic acids, through either BAC(3) or BAL(1) me chanisms. Kinetic studies in H2O and D2O as well as O-18 and O-17 labe ling experiments supported the proposed mechanism. The results of thes e hydrolyses, which depended on the nature of the alcohol moiety, were compared with those obtained with some imidazol-1-ylacetate analogues or with (+/-)-2-pyrazol-1-yl- and benzimidazol-1-ylsuccinic esters. I n general, imidazolylsuccinic esters hydrolyzed faster than the homolo gous derivatives from pyrazole or benzimidazole.