497914-02-0Relevant articles and documents
Catalysis of the β-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
Alunni, Sergio,Laureti, Valeria,Ottavi, Laura,Ruzziconi, Renzo
, p. 718 - 725 (2003)
Second-order rate constants, kOHN, M-1 s-1, for the β-elimination reactions of HF with 2-(2-fluoroethyl)pyridine (2), 3-(2-fluoroethyl)pyridine (3), and 4-(2-fluoroethyl)pyridine (4) in OH-/H2O, at 50°C and μ = 1 M KCl, are kOHN = 0.646 × 10-4 M-1 s-1, kOHN = 2.97 × 10-6 M-1 s-1, and kOHN = 5.28 × 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 kOHNCH3/kOHN, and a value of 8.7 × 105 is obtained with substrates 5/2, a value of 1.6 × 103 with 6/3, and a value of 2.1 × 104 with 7/4. The high values of MethylAF are in agreement with an irreversible E1cb mechanism (ANDE* + DN) 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 β-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 × 105 for 2 and 6.5 × 104 for 4 with acetohydroxamate base. These high PAF values are indicative of an irreversible E1cb mechanism rather than a concerted E2 (ANDEDN) mechanism. Finally, the rate constant for carbanion formation from NH+ with 2 is kBNH+ = 0.35 M-1 s-1, which is lower than when chlorine is the leaving group (kBNH+ = 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.
