Effect of Solvent on the α-Effect:  Nucleophilic Substitution Reactions of p-Nitrophenyl Acetate with m-Chlorophenoxide and Benzohydroxamates in MeCN−H₂O Mixtures of Varying Compositions

Abstract

Second-order rate constants have been measured spectrophotometrically for the reactions of p-nitrophenyl acetate (PNPA) with three α-effect nucleophiles, benzohydroxamate (BHA-), p-methylbenzohydroxamate (MBHA-), and p-methyl-N-methylbenzohydroxamate (M2BHA-), and a corresponding normal nucleophile, m-chlorophenoxide (ClPhO-), in MeCN−H2O mixtures of varying compositions at 25.0 °C. The reactivity of ClPhO- and M2BHA- toward PNPA decreases upon additions of MeCN into the reaction medium up to near 30−40 mol % MeCN and is followed by a gradual increase upon further additions of MeCN. BHA- and MBHA- also exhibit initial rate decreases upon the addition of MeCN up to near 40 mol % MeCN. However, unlike the ClPhO- and M2BHA- systems, the rate enhancement beyond 40 mol % MeCN is negligible for the BHA- and MBHA- systems. The present benzohydroxamates exert a large α-effect in H2O. Interestingly, BHA- and MBHA- show a decreasing α-effect trend with increasing mol % MeCN, while M2BHA- exhibits an increasing α-effect trend, indicating that the magnitude of the α-effect is significantly solvent dependent. Based on the results of the kinetic study and relative basicity measurements, the decreasing α-effect trend shown by BHA- and MBHA- has been attributed to an equilibrium shift of these hydroxamates (I) toward their isomeric structures (II or III) upon the addition of MeCN. The solvent dependent α-effect has led a conclusion that the solvent effect on the α-effect is significant; however, the ground state contribution is not solely responsible for the α-effect in the present system.

The α-Effect in Benzyl Transfers from Benzylphenylmethyl Sulfonium Salts to N-Methylbenzohydroxamate Anions

“…Other factors, such as solvent effects, could modify the expression of the α-effect observed, depending on the loci where charge was found. An example of such a possible operation occurs with p -MeNMBH anion reacting with p -nitrophenylacetate in water−acetonitrile mixtures . The only α-nucleophile to show a substantial change in the size of the α-effect was p -MeNMBH anion as the mole percent of MeCN increased.…”

“…This idea of internal base catalysis is reported to be responsible for the benzohydroxamate α-effect. Although this idea is known from the early days of the α-effect 12 with this hydroxamic acid chemistry, and although [5] is considered by ref , it seems not to play a great part of the explanation for the large variation of the α-effect with solvent composition for these workers. In fact, their conclusion was that ground-state solvation was not solely responsible for the α-effect they observed, which is at least consistent with our hypothesis that an intrinsic α-effect exists with C atom transfer, and that effect is modified by changes in the type of C atom in the simple CH 3 group.…”

The role of isomerism and medium effects on stability of anions of formo- and thioformohydroxamic acid

“…The lower aggregation energy in 1ZN À ÁH 2 O relative to other anionic forms is the result of presence of intramolecular H-bond present in the anion that decreases its ability to act as H-bond acceptor. The aggregation energy in the 1ZN À ÁH 2 O, 2EO4 À ÁH 2 O, 1EO À ÁH 2 O with single hydrogen bond interaction is 15 14.74 kcal/mol in TFHA. Though 2EO4 À ÁH 2 O adduct has highest stabilization arising out of H-bond interactions but this anion is not detected experimentally as the anion adduct stability is still lower than other anion adducts.…”

“…Hydroxamate anions are regarded as a-effect nucleophiles whose reactivity is higher than predicted by relationship between nucleophilicity and basicity [13,14]. Explaining the role of HA's as matrix metalloprotease inhibitors, Yazal and Pang suggested that anionic forms of AHA have higher affinity for zinc relative to the HA molecules, thus probable binding involves anions [15].…”

Kinetic study of solvent effects on the aminolysis of O‐ethyl S‐aryl dithiocarbonates

“…For nucleophilic substitution reactions, it was shown that the solvent plays an important role in controlling the dynamics of a chemical reaction . The aminolysis of nitrophenyl acetates and dithiocarbonyl derivatives has shown interesting mechanistic changes by varying the solvent medium.…”