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General Base and General Acid Catalyzed Intramolecular Aminolysis of Esters. Cyclization of Esters of 2-Aminomethylbenzoic Acid to Phthalimidine

2000; American Chemical Society; Volume: 65; Issue: 12 Linguagem: Inglês

10.1021/jo9906835

1520-6904

Thomas H. Fife, Leroy Chauffe,

Fluorine in Organic Chemistry

Plots of log k0 vs pH for the cyclization of trifluoroethyl and phenyl 2-aminomethylbenzoate to phthalimidine at 30 °C in H2O are linear with slopes of 1.0 at pH >3. The values of the second-order rate constants kOH for apparent OH- catalysis in the cyclization reactions are 1.7 × 105 and 5.7 × 107 M-1 s-1, respectively. These rate constants are 105- and 107-fold greater than for alkaline hydrolysis of trifluoroethyl and phenyl benzoate. The kOH for cyclization of the methyl ester is 7.2 × 103 M-1 s-1. Bimolecular general base catalysis occurs in the intramolecular nucleophilic reactions of the neutral species. The value of the Bronsted coefficient β for the trifluoroethyl ester is 0.7. The rate-limiting step in the general base catalyzed reaction involves proton transfer in concert with leaving group departure. The mechanism involving rate-determining proton transfer exemplified by the methyl ester in this series (β = 1.0) can then be considered a limiting case of the concerted mechanism. General acid catalysis of the neutral species reaction or a kinetic equivalent also occurs when the leaving group is good (pKa ≤ 12.4). That the mechanism and/or rate-determining step of the intramolecular aminolysis reactions is different than in bimolecular reactions or the intramolecular reactions of other esters is attributed to the excellent steric fit of the nucleophile to the reaction center of the 2-aminomethylbenzoate esters.