General catalysis kinetic equivalency

Finally we should note that the demonstration of a Br nsted relationship does not constitute proof that general acid or general base catalysis is occurring. Because of the problem of kinetic equivalence of rate terms, we may not be able unequivocally to distinguish between these possibilities ... 

Belke et al. (1971) reported general base and general acid catalysis in cyclization of 2-hydroxymethylbenzamide [equation (18)]. However, with 2-hydroxymethyl-6-aminobenzamide strict general base catalysis by buffer bases is observed with a Bronsted coefficient of O 39 (Fife and Benjamin, unpublished data). In contrast with the unsubstituted amide, the Bronsted plot is nicely linear. An amino-group in the 6-position might assist decomposition of a tetrahedral intermediate as in [37a, b] or a kinetic equivalent. The pH-rate constant profile for spontaneous cyclization at zero buffer concentra-... 

Neighbouring phenoxide ion will act as an intramolecular general base in situations where nucleophilic attack is precluded. Bender et al. (1963) found such catalysis in the hydrolysis of p-nitrophenyl 5-nitrosalicylate. Mechanism [40] was favoured over the kinetically equivalent hydroxide ion attack on the neutral species, the reason... 

We see here that the mechanism with a pre-equilibrium proton transfer leads to a specific acid catalysis rate law whereas that with a rate-determining proton transfer leads to general acid catalysis. It follows that, according to which catalytic rate law is observed, one of these two mechanisms maybe excluded from further consideration. Occasionally, however, different mechanisms lead to the same rate law and are described as kinetically equivalent (see Chapters 4 and 11) and cannot be distinguished quite so easily. 

General base catalysis of the reaction of a nucleophile (HNu) is kinetically equivalent to general acid catalysis of the reaction of the deprotonated nucleophile (Nu ). A distinction can be made employing cross-correlation effects where the value of the Bronsted a is measured as a function of another parameter such as the nucleophilicity of the attacking nucleophile. 

Intramolecular carboxyl group catalysis has been found in a number of salicyl acetals. Capon et al. (1969) preferred intramolecular general acid catalysis as the mechanism of carboxyl group participation in the hydrolysis of o-carboxyphenyl 3-D-glucoside and o-methoxymethoxybenzoic acid although the kinetically equivalent possibilities were not convincingly eliminated in the case of the glucoside. 

The mechanistic significance of the terms in Eq. (27) for pseudobase decomposition must, of course, be the microscopic reverse of the interpretations given for the pseudobase formation reactions. Thus, k,[H+] is the microscopic reverse of the kHl0 term, and may be formally interpreted as either the spontaneous loss of a molecule of water from the O-protonated pseudobase (i.e., specific-acid catalysis transition state C) or alternatively as elimination of hydroxide ion from the neutral pseudobase molecule with the aid of H30+ as a general-acid catalyst (transition state D). The k2 term is the microscopic reverse of fc0H[OH ], and so formally represents either the spontaneous decomposition of the pseudobase to heterocyclic cation and hydroxide ion (transition state A) or the kinetically equivalent general-acid catalysis of this reaction by a water molecule (transition state B). 

Both a- and p-NeuNAcOPNP hydrolyse through four processes the spontaneous departure of the phenolate from the substrate anion, an acid-catalysed process of the neutral molecule, a base-catalysed process of the anion and an apparently spontaneous process of the neutral molecule. This last process was shown to be the kinetically equivalent acid-catalysed hydrolysis of the anion of p-NeuNAcOAr by a jSig value of 0.14, and of the anion of a-NeuNAcOAr by a jSig value of 0.00 and a solvent deuterium kinetic isotope effect of 0.96, when any intramolecular general acid catalysis would give rise to negative jSig values and direct solvent isotope effects. 

That the rate acceleration due to the carboxyhc acid was intramolecular general acid catalysis, and was not the kinetically equivalent A, reaction of the anion, in which the transition state was stabilised by electrostatic catalysis (or syn nucleophilic attack) was established by the following pieces of evidence. 

Sawyer, C. B. Kirsch, J. F. /. Am. Chem. Soc. 1973, 95, 7375. Other reaction pathways can be kinetically equivalent to general base catalysis for a discussion, see reference 188. 

As with intermoleculariy general-acid and general-base catalysed reactions, it is frequently difficult to distinguish between kinetically equivalent mechanisms and eliminate all but one. Mechanisms which involve intramolecular nucleophilic catalysis are often kinetically equivalent to those which involve intramolecular general-acid or base catalysis. As these do not involve a proton transfer they will not be discussed in this chapter unless the evidence is fairly evenly balanced between them and the latter. 

A kinetic expression which is equivalent to that for general acid catalysis also occurs if a prior equilibrium between reactant and the acids is followed by rate-controlling proton transfer. Each individual conjugate base will appear in the overall rate expression ... 

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