Steric activation in prototropic reactions of pyrazine derivatives. II. The Brønsted relation

Abstract

The rate of deprotonation of the 2-methyl group in 1,2,3-trimethylpyrazinium ion by carboxylate, aniline, and pyridine bases has been measured in D20. Carboxylate ions containing bulky groups near the reaction centre, e.g. ortho benzoates, react faster than predicted by the Bransted equation that correlates the reactions of unhindered carboxylates. Anilines and pyridines, on the other hand, show conventional steric effects. A tentative explanation for the activation engendered by groups adjacent to the carboxylate centre is based on the known effect that high concentrations of organic electrolytes have on the strengths of carboxylic acids but not of amines. Since ortho carboxylate ions have their relative basicities increased by an alkyl-rich environment, it is argued that the reactive methyl groups of the substrate might provide such an interaction in the transition state.

General acid catalysis in the enolization of acetone

“…As to the cause of the steric activation, we simply draw attention to the following points: (1) The effect seems to be most clearly evident when cationic substrates and anionic bases are involved in the rate-controlling step. 2As has been previously noted 3 (21), it is unwise to try to explain deviations from Bransted acting as genkral'acids, not as gAeral bases or as bifunctional catalysts; see later.) It is clear that proximity of the positive charge to the catalytic site is important since the largest negative deviations occur for the three ammonioacetic acids, whereas an ammonio group at the 4-or 6-position produces virtually no effect.…”

“…Steric acceleration of proton transfer reactions has been observed in a number of other instances, both when the steric bulk is in the substrate (19) and in the catalyst. In particular, the base-catalyzed deprotonation of the 6-methyl group in the pyrazinium ion I and the methylene group of I1 (marked by asterisks), by a series of aliphatic and aromatic carboxylate bases showed the effects of marked steric activation (20,21). However, previous studies of acetone enolization by arylphosphonate anions (base catalysis) and by arylphosphonic acids (acid catalysis) showed such effects to be absent in the former and small in the latter (12).…”

Arylphosphonic acids. II. General acid and general base catalysis of acetone enolization

“…This would lead to a curved Bronsted plot if a sufficiently wide span of reactivities were produced by changing substituents. [7] and [9] Reaction Reactants for a single series although Bell, by combining several kinds of substrate and catalyst, produced a distinctly curved plot, albeit one with considerable scatter (1 9). More frequently, the inverse relationship between Bronsted coefficient and reactivity is sought by comparing Bronsted coefficients for related series whose reactivities are considerably different.…”

“…More frequently, the inverse relationship between Bronsted coefficient and reactivity is sought by comparing Bronsted coefficients for related series whose reactivities are considerably different. In the case of acetone enolization catalyzed by arylphosphonic acids, the Bronsted coefficients of the two important rate-controlling steps (reactions [7] and [9]) can be compared. They are shown in Table 2 together with the rate constants for the unsubstituted compounds.…”

“…We have shown previously that proton removal from activated methyl groups in a number of cyclic conjugated systems is catalyzed by general acids and bases and exhibits steric activation. Activation by adjacent alkyl groups in the substrate has been demonstrated in many cases (1)(2)(3)(4)(5) and in two instances (involving general base catalysis) by adjacent groups in the base (6,7). The latter reactions are the deprotonations of 1,2,3-trimethylpyrazinium ion and methylcreatininium ion by carboxylate ions (eqs.…”