Catalysis, general base solvent effects

A general reaction mechanism for m-nitrobenzyl derivative is proposed (Scheme 8) which involves a non-Kekule intermediate100. The mechanism for the p-nitrobenzyl alcohol involves the highly polarized intermediate 163, which is consistent with the observed strong solvent effect and base catalysis of the reaction (equation 80). 

General base catalysis has been ascertained for reaction (28) and when combined with a solvent isotope effect of 1.67 for k 2°/k 2° it can be taken as evidence in favor of a transition state such as 190 rather than 191. A large negative entropy of activation (ASf = — 109.9 J mol 1 K. ) for this reaction also supports the hypothesis. 

The experimental evidence that these reactions do, in fact, represent general base catalysis, rather than nucleophilic catalysis of hydrolysis, is very strong. The solvent deuterium isotope effect of 2-3 (Table 39) is consistent with the breaking of a bond to hydrogen in the rate-determining step of the reaction ... 

Stoichiometry (28) is followed under neutral or in alkaline aqueous conditions and (29) in concentrated mineral acids. In acid solution reaction (28) is powerfully inhibited and in the absence of general acids or bases the rate of hydrolysis is a function of pH. At pH >5.0 the reaction is first-order in OH but below this value there is a region where the rate of hydrolysis is largely independent of pH followed by a region where the rate falls as [H30+] increases. The kinetic data at various temperatures both with pure water and buffer solutions, the solvent isotope effect and the rate increase of the 4-chloro derivative ( 2-fold) are compatible with the interpretation of the hydrolysis in terms of two mechanisms. These are a dominant bimolecular reaction between hydroxide ion and acyl cyanide at pH >5.0 and a dominant water reaction at lower pH, the latter susceptible to general base catalysis and inhibition by acids. The data at pH <5.0 can be rationalised by a carbonyl addition intermediate and are compatible with a two-step, but not one-step, cyclic mechanism for hydration. Benzoyl cyanide is more reactive towards water than benzoyl fluoride, but less reactive than benzoyl chloride and anhydride, an unexpected result since HCN has a smaller dissociation constant than HF or RC02H. There are no grounds, however, to suspect that an ionisation mechanism is involved. 

Kivinen proposes that the neutral hydrolysis of acetic anhydride is promoted by water acting as a weak base. The solvent isotope effect, kH20lkDl0 — 3, is suggestive of general base catalysis. 

Nuclear tunnelling in the aqueous iron (2+)-iron (3+) electron transfer has been investigated467 and the rate enhancement for H2O has been assessed to be 65 times the classical rate, and that for D2O 25 times the classical rate, yielding a H/D isotope effect of 2.6. The occurrence of the general base catalysis and sizable primary D KIEs indicated that the isomerization of l//-indene-l-carboxylic acid to l//-indene-3-carboxylic acid in aqueous solution takes place through an enolization-reketonization sequence468. Kinetic HH/HD/DD isotope and solvent effects have been used in a dynamic NMR study469 of the tautomerization of 15N-and 2H -labelled bicyclic oxalamidines. 

Application of the extended Grunwald-Winstein equation to solvolyses of propyl chloroformate, PrOCOCl, in a variety of pure and binary solvents indicated an addition-elimination pathway in the majority of the solvents but an ionization pathway in the solvents of highest ionizing power and lowest nucleophilicity. For methanolysis, a solvent deuterium isotope effect of 2.17 was compatible with the incorporation of general-base catalysis into the substitution process.21... 

D. G. Oakenfull, T. Riley, V. Gold, J. Chem. Soc., Chem. Comm. 385 (1966). Nucleophilic and General Base Catalysis by Acetate Ion in Hydrolysis of Aryl Acetates Substituent Effects, Solvent Isotope Effects, and Entropies of Activation. 

In several investigations of the azo coupling of arenediazonium ions with aromatic amines in organic solvents general base catalysis and consequently a primary deuterium isotope effect were observed... 

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