Catalysis of the beta-elimination of HF from isomeric 2-fluoroethylpyridines and 1-methyl-2-fluoroethylpyridinium salts. Proton-activating factors and methyl-activating factors as a mechanistic test to distinguish between concerted E2 and E1cb irreversible mechanisms.

Abstract

Second-order rate constants, k(OH)(N), M(-)(1) s(-)(1), for the beta-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH(-)/H(2)O, at 50 degrees C and mu = 1 M KCl, are = 0.646 x 10(-)(4) M(-)(1) s(-)(1), = 2.97 x 10(-)(6) M(-)(1) s(-)(1), and = 5.28 x 10(-)(4) M(-)(1) s(-)(1), respectively. When compared with the second-order rate constants for the same processes with the nitrogen-methylated substrates 1-methyl-2-(2-fluoroethyl)pyridinium iodide (5), 1-methyl-3-(2-fluoroethyl)pyridinium iodide (6), and 1-methyl-4-(2-fluoroethyl)pyridinium iodide (7), the methyl-activating factor (MethylAF) can be calculated from the ratio k(OH)(NCH)3/, and a value of 8.7 x 10(5) is obtained with substrates 5/2, a value of 1.6 x 10(3) with 6/3, and a value of 2.1 x 10(4) with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (A(N)D(E) + D(N)) for substrates 5 and 7 and with the high stability of the intermediate carbanion related to its enamine-type structure. In acetohydroxamate/acetohydroxamic acid buffers (pH 8.45-9.42) and acetate/acetic acid buffers (pH 4.13-5.13), the beta-elimination reactions of HF, with substrates 2 and 4, occur at NH(+), the substrates protonated at the nitrogen atom of the pyridine ring, even when the [NH(+)] is much lower than the [N], the unprotonated substrate, due to the high proton-activating factor (PAF) value observed: 3.6 x 10(5) for 2 and 6.5 x 10(4) for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (A(N)D(E)D(N)) mechanism. Finally, the rate constant for carbanion formation from NH(+) with 2 is k(B)(NH)+ = 0.35 M(-)(1) s(-)(1), which is lower than when chlorine is the leaving group ( = 1.05 M(-)(1) s(-)(1); Alunni, S.; Busti, A. J. Chem. Soc., Perkin Trans. 2 2001, 778). This is direct experimental evidence that some lengthening of the carbon-leaving group bond can occur in the intermediate carbanion. This is a point of interest for interpreting a heavy-atom isotope effect.