EFFECT OF IMIDAZOLE GROUP ON HYDROLYSIS OF N-[2-(4-IMIDAZOLYL)ETHYL]PHTHALIMIDE

The pH dependencies (at 25°) of the pseudo-first-order rate constantsfor the hydrolysis (to phthalamic acids) of N-[2-(4-imidazoly 1 )ethyl]phthalimide (1), N-(2-trimethylaminoethyl)phthalimido bromide (2), N-(3-trimethylaminopropyl)phthalimido bromide (3), and N-methylphthalimide (4) were determined.The cationic imides 2 and 3 are most susceptible to hydroxide ion catalyzed hydrolysis. Below pH 7, however,1hydrolyzes most rapidly. This effect was ascribed to the neighboring imidazoleresidue functioning as a general base in atalyzing attack by water. A deuterium oxide solvent isotope effect of 2.1 is associated with this process. The possibility that this effect reflects the susceptibility of the protonated form of 1 to attack by hydroxide ion was deemed unlikely, since the second-order rate constant for this reaction would be 333 sec-1 M-l, while the secondorder rate constants for the hydroxide ion catalyzed hydrolysis ofcationic imides 2 and 3 with their positive charges closer to the carbonyl carbonatom are 91 and 41 sec-1 M-1 respectively. Also, cationic imides 2 and 3 are susceptible to direct attack by water, whereas the protonatedform of 1 is much less susceptibleto attack by water. It is unlikely thata neighboring imidazole residue functions asa general acid in catalyzing attack by hydroxide ion, since the calculated rate constant for this process is not significantly lowered by deuterium oxide. The first-order rate constants forintramolecular catalysis of the hydrolysis of1 by the neighboring imidazole group (2.9 ×10-5 sec-1) was found to be similar in magnitudeto the second-order rate constant for the imidazole-catalyzed hydrolysis of 4 (2.0 × 10-5 sec-1 M-1). © 1969, American Chemical Society. All rights reserved.