Carboxylation medium effects

Solvolytic reactions, medium effects on the rates and mechanisms of, 14,1 Spectroscopic detection of tetrahedral intermediates derived from carboxylic acids and the investigation of their properties, 21,37... 

Other reactions in which cations other than protons are catalyti-cally effective are esterification and acetal formation, catalyzed by calcium salts,277 and the bromination of ethyl cyclopentanone-2-carboxylate, catalyzed by magnesium, calcium, cupric, and nickel, but not by sodium or potassium ions.278 One interpretative difficulty, of course, is the separation of catalysis from the less specific salt effects. The boundary line between salt effects (medium effects) and salt effects (catalysis) is not sharp either in concept or experimentally. 

These hydrophobic ammonium ions exert a medium effect on spontaneous, unimolecular reactions. Tri-n-octylmethylammonium chloride effectively speeds decarboxylation of 5-nitrobenzisoxazole carboxylate ion (24) (Kunitake et al., 1980), and tri-n-octyl ethylammonium mesylate or bromide... 

Solvolytic reactions, medium effects on the rates and mechanisms of, 14, 1 Spectroscopic detection of tetrahedral intermediates derived from carboxylic acids and the investigation of their properties, 21, 37 Spectroscopic observations ofalkylcarbonium ions in strong acid solutions, 4, 305 Spectroscopy, 13C NMR in macromolecular systems of biochemical interest, 13, 279 Spectroscopy of substituted phenylnitrenes, kinetics and, 36, 255 Spin alignment, in organic molecular assemblies, high-spin organic molecules and,... 

The efficiency of 34E4 likely derives from a combination of factors [38, 41]. Medium effects are certainly relevant. The carboxylate base is activated by placement in a relatively hydrophobic environment, as evidenced by its elevated pK, of 6 [37]. The charge delocalized transition state is probably also stabilized by dispersive interactions with... 

It should be noted at this point that there is a consistency in the pKa values measured in pure DMSO by the various techniques. However, there is some uncertainty at present relating to pKa values obtained by acidity function procedures in alcoholic and aqueous DMSO media. Thus one has the unexpected situation that theoretical analysis of the medium effect on p/ a is hampered because the values for a number of weak acids referring to the standard state in water are in doubt. Under these circumstances less than critical application of (6) to many weak acids, including some carboxylic acids, phenols as well as carbon acids, is inadvisable. Of course, (6) is strictly applicable to those cases in which the p/sfa values can be measured in the pure hydroxylic solvents and also for those weak acids which obey the criteria outlined by Cox and Stewart (1976). Despite this difficulty there is now a large body of reliable pKa data in both DMSO and water. Thus in principle it should be possible to account for variations, or reversals, in acidity order in terms of the thermodynamic transfer functions in (6). 

This relationship was found useful in accounting for medium effects on carboxylic acid ionization. For the 3-substituted compounds the best regression equation was obtained after the exclusion of the dimethylamino data point. It is ... 

There have been a number of studies of the reaction of diazoacetic ester in aprotic solvents, mainly with carboxylic acids (Bronsted and Bell, 1931 Hartman et al., 1946 and references cited). However, the information available hardly justifies conclusions about the mechanism. Addition of relatively basic phenols causes an acceleration in rate which can be interpreted in terms of nucleophilic catalysis of a rate-determining displacement of nitrogen, but the kinetic order in acid varies between one and two. Formally, a mixed order would result if proton loss from the diazonium ion was effected by carboxylate ions alone, while the less discriminating displacement of nitrogen involved competition between anions and unionized molecules. However, there are examples of high or mixed orders in other acid-catalysed reactions (Bronsted and Bell, 1931 Bell, 1941 1959) and in all probability large medium effects play a role. 

A second, related aspect of the medium effect is also likely to be important. Decarboxylation converts a polar, highly solvated -C02 group into a nonpolar, nearly unsolvated CO2. For the case of benzisoxazole-3-carboxylic acids, carboxyl desolvation has been demonstrated to be an important component of solvent catalysis of decarboxylation 113). Desolvation of the carboxyl group on binding to an enzyme may likewise be an important factor. Carbon isotope effects are consistent with this possibility (777). Oxygen isotope effects on formate dehydrogenase are also consistent with this mechanism 114). 

The most water-like of this class of solvents is methanol, for it maintains much the same nice balance of basic and acidic properties found in water. Its autoprotolysis constant is smaller than that of water (Table 3.3.4) because of its lower dielectric constant. Medium effects for transfer of ionisation equilibria from water to methanol are approximately constant for closely related acids. For six cation acids, the pyri-dinium ion and five methyl derivatives, the average medium ejffect is 0.06 0.02, small because the ionisation of these cations creates no new charge field. For phenol and thirteen of its derivatives the medium effect is 4.32 0.09 smaller values are obtained for nitrophenols, possibly because the anions are stabilised by dispersion interactions with methanol. For 23 carboxylic acids, aliphatic and aromatic, the average medium effect is 4.87 0.15. Values of the medium effect for individual acids are collected in Appendix 3.5.5. 

---