Hydrolyses of 2- and 4-Fluoro N-Heterocycles. 3. Nucleophilic Catalysis by Buffer Bases in the General Acid Catalyzed Hydrolysis of 4-Fluoroquinaldine

Article abstract of DOI:10.1021/jo00262a037

Pseudo-first-order rate constants and catalytic rate constants are reported for the buffer-catalyzed hydrolysis of 4-fluoroquinaldine (1) in carboxylic acid and phosphoric acid buffers.The buffer catalysis is consistent with specific acid, general base catalysis.Hydrolyses in 99percent 18O-labeled water with 0.04 M unlabeled acetate, and complementary hydrolyses in unlabeled water with 90percent 18O-labeled acetate, indicate that the predominant catalytic mode for the acetic acid/acetate buffer system is nucleophilic catalysis by the acetate anion coupled with specific acid catalysis.The other buffers presumably react in a similar manner.A Broensted-type plot of the catalytic rate constants for hydrolysis of protonated 1 has a slope of 0.57, with formate deviating positively from the line determined by acetate, chloroacetate, monohydrogen phosphate, and water.This Broensted slope is less than that found for hydrolysis of the 2-fluoro-1-methylpyridinium ion, 2, but is still within the range expected for aromatic nucleophilic substitution.Rate constants and 18O-labeling results for hydrolysis in acetate buffer are also reported for 4-acetoxyquinaldine (3), the proposed intermediate in the acetate-catalyzed hydrolysis of 1.