Transfer of a positively charged acyl group between substituted phenolate ion nucleophiles: the brønsted β for the calibrating equilibrium for N-methylisonicotinyl (4-carbonyl-N-methylpyridinium) transfer

Abstract

Rate constants have been measured for the reaction of substituted phenolate ions with aryl acetate esters and with aryl N-methylisonicotinate esters in aqueous solution. A new method is demonstrated for determining β_eq for group transfer from 4-nitrophenyl esters; it employs the rate constant for the reaction of 2,6-difluorophenolate ion with substituted phenyl ester as a surrogate for the reactivity of the 4-nitrophenolate ion and yields β_eq= 1.55 for the N-methylisonicotinyl transfer reaction. The Brønsted-type plot of the rate constant for phenolate ion attack on 4-nitrophenyl N-methylisonicotinate is linear over a range of pK_a values from 5.5 to 10 and provides good evidence for a concerted displacement mechanism for this reaction. The reactivity of the N-methylisonicotinate esters to phenolate ions is some 300 times larger than that of the corresponding acetate esters but the larger β_nuc value (0.90 compared with 0.74) suggests a ‘later’ transition structure. Calibration of the β values with the corresponding β_eq gives a Leffler α_nuc= 0.58 and 0.42 for N-methylisonicotinate and acetate respectively, which contrasts with the order expected from reactivity–selectivity. The tighter transition structure indicated by comparison of these α values is explained by a less favourable acylium ion in the case of the N-methylisonicotinyl transfer reaction.