Abstract
A kinetic study is reported for the reactions of 2-methoxy-3-nitropyridine 1a and 2-methoxy-5-nitropyridine 1b with three secondary amines 2a-c (morpholine, piperidine, and pyrrolidine) in aqueous solution at 20 degrees C. The Bronsted-type plots are linear with beta(nuc) = 0.52 and 0.55 for pyridines 1a and 1b, respectively, indicating that the reaction proceeds through a SNAr mechanism in which the first step is the rate-determining step. Additional theoretical calculations using the DFT/B3LYP method confirm that the C-2 carbon being the most electrophilic center for the both pyridines 1a and 1b. The second-order rate constants have been used to evaluate the electrophilicity parameters E of 1a and 1b according to the linear free energy relationship log k (20 degrees C) = s(N) (N + E). The E parameters thus derived are compared with the electrophilic reactivities of a large variety of anisoles. The validity of these E values has been satisfactorily verified by comparison of calculated and experimental second-order rate constants for the reactions of pyridines 1a and 1b with anion of ethyl benzylacetate.