CATALYSIS AND INHIBITION OF HYDROLYSIS OF N-METHYLPHTHALIMIDE BY IMIDAZOLE

Imidazole was found to catalyze the hydrolysis of N-methylphthalimide (to N-methylphthalamic acid) at pH values of 6.4 and 7.2, and inhibit the hydrolysis of N-methylphthalimide at pH 9.7. While HPO2-4 was observed to catalyze the hydrolysis of N-methylphthalimide, it did not inhibit the hydrolysis of N-methyl-phthalimide. The second-order rate constants (k6) for the imidazole and HPO2-4-catalyzed hydrolysis of N-methylphthalimide were found to be 2 × 10-5 and 1.3 × 10-5 sec-1 M-1 respectively. These results are taken as kinetic evidence for the reversible addition of imidazole to N-methylphthalimide to form a tetrahedral addition compound which is relatively unreactive toward hydroxide ion. The dissociation constant for this addition compound estimated from the inhibition of the hydrolysis of N-methylphthalimide by imidazole (1.3 M) was in reasonable agreement with the values estimated from the perturbation of the ultraviolet spectrum of N-methylphthalimide by imidazole (1.5-1.7 M). When deuterium oxide was used in place of water, imidazole and HPO2-4 became less efficient catalysts. Isotope effects of 1.4 and 2.3 were observed for the imidazole and HPO2-4catalyzed hydrolysis of N-methylphthalimide. This result and the similar catalytic efficiencies observed for imidazole and HPO2-4 suggest that imidazole and HPO2-4 are general base catalysts for the hydrolysis of N-methylphthalimide. © 1969, American Chemical Society. All rights reserved.