INTRAMOLECULAR GENERAL-BASE-CATALYZED HYDROLYSIS AND AMINOLYSIS OF ESTER BOND BY IMIDAZOLE AND QUINOLINE BASES

Kinetic studies of the hydrolysis and hydrazinolysis of the esters 4-(2′-acetoxyphenyl)imidazole (II), phenyl picolinate (Ilia), phenyl isonicotinate (Illb), 8-acetoxyquinoline (IVa), and 6-acetoxyquinoline (IVb), as well as the reactions of a series of amines with IVa and IVb, are described. Esters II and IVa (but not Ilia, Illb, and IVb) were found to be hydrolyzed via intramolecular general-base catalysis by the neighboring imidazolyl and quinoline nitrogens. Thus, the values of the deuterium solvent isotope effects (kH/kD) and entropies of activation (TΔS‡ kcal mol−1) were determined to be 3.23 and – 8.90 for II, and 2.35 and – 8.70 for IVa. The enhancements of the spontaneous rates due to intramolecular general-base catalysis have been estimated to be 103 for II and 5 × 102for IVa. The reaction of II with hydrazine and the reactions of IVa and IVb with a series of eleven primary, secondary, and tertiary amines were investigated. With the conjugate acids of pyridine, imidazole, and glycylglycine, IVa and IVb exhibited marked complex formation. For primary and secondary amines the aminolysis reactions were found to occur via simple nucleophilic attack (kn) as well as by amine general-base-catalyzed (kgb) and protonated amine general-acid-catalyzed (kga) nucleophilic attack. From the larger than anticipated value of kn for reaction of hydrazine with II it is suggested that the neighboring imidazolyl group assists the reaction as an intramolecular general-base catalyst. In comparing the reactions of IVa and IVb it is found that HO− and tertiary amines are more reactive toward IVb while H2O, primary, and secondary amines (kn) are more reactive toward IVa. Brφnsted plots constructed from values for primary and secondary amines not exhibiting the a effect are found to have slope 1.0 for IVb and 0.70 for IVa, indicating a difference in mechanism. The Brφnsted equation and the point scatter (due to α effect, steric effects, electronic effects, etc.) for IVb are strikingly similar to those found for nucleophilic attack upon phenyl acetate. When the log of the second-order rate constants for reaction of H2O, HO−, and all amines with IVa is plotted vs. the same constants for IVb it is found that the bases are clearly separated into two groups: (a) HO− and tertiary amines fit well a line of slope 1.0; and (b) H20, primary, and secondary amines provide a line of slope 0.70. The experimental data are best attributed to intramolecular general-base catalysis for the 8 isomer in reaction with primary and secondary amines and simple nucleophilic attack for the reaction of all nucleophiles with the 6 isomer and the tertiary amines (and HO−) with the 8 isomer. These results provide the first general case of intramolecular general-base-catalyzed aminolysis of an ester. The pyridine esters (IlIa and Illb) were found not to exhibit either intramolecular assistance to water hydrolysis or aminolysis by primary and secondary amines. A detailed discussion of the intramolecular reaction is provided. © 1969, American Chemical Society. All rights reserved.