Decarboxylation reactions 3-carboxybenzisoxazoles

Equation [10.3.29] reproduces acceptably well the sensitivity of the decarboxylation rate of 3 -carboxybenzisoxazole in pure solvents observed by Kemp and Paul. In addition, it clearly shows that such a rate increases dramatically with increasing polarity and, also, to a lesser degree, with solvent basicity. By contrast, it decreases markedly with increasing solvent acidity. This behavior is consistent with the accepted scheme for this decarboxylation reaction. 

Scheme 13 The decarboxylation reaction of 5-nitro-3-carboxybenzisoxazole studied by Shea and Kato using MIPs based on the dienamide monomeric template. ...

The decarboxylation of 3-carboxybenzisoxazole (225 R = H, NO2) gives CO2 and (226). This reaction has been studied using 13C and 15N kinetic isotope effects.201 The isotope effects were modelled theoretically at the semiempirical and ab initio levels, but comparison of experimental and theoretical results shows that die former cannot be successfidly predicted by theory at the level of calculation employed. The kinetics of decarboxylation and deamination of DL-leucine by acidic permanganate in die presence of silver ion in moderately concentrated sulfuric acid is a two-stage process.202 The... 

The predictive capabilities of results of theoretical calculations of isotope effects have again been questioned,94 following an experimental and theoretical study of the decarboxylation of 3-carboxybenzisoxazole at room temperature (Kemp s reaction). The experimentally determined 15N isotope effect in acetone is 1.0312 0.0006 and the 13C isotope effect (1.0448, 1.0445, 1.0472, and 1.0418 in 1,4-dioxane, acetonitrile, DMF, and water, respectively) is independent of solvent polarity even though the reaction rate is markedly solvent dependent. Theoretical models at die semiempirical (AMI, PM3, SAMI) and ab initio (up to B3LYP/6-31+ + G ) levels were all unable to predict die experimental results quantitatively. 

Kinetics so closely related to the solvent effect as those of the Menschutkin reaction between triethylamine and ethyl iodide [eq. (10.3.27)], the solvolysis of tert-butyl chloride [eq. (10.3.28)] or the decarboxylation of 3-carboxybenzisoxazole [eq. (10.3.29)], are acceptably described by our scales. 

The importance of substrate destabilization is illustrated by the antibody-catalyzed decarboxylation of 3-carboxybenzisoxazoles (5) to give salicylo-nitriles (7) [34]. This reaction is extraordinarily sensitive to its solvent microenvironment, with rate enhancements up to 10 -fold observed upon transfer of the reactant from aqueous buffCT to aprotic dipolar solvents [35]. De solvation of the negatively charged carboxylate group greatly destabilizes the substrate, while the charge delocalized transition state (6) may be stabilized by dispersion interactions with solvent. Similar factors are believed... 

The unimolecular decarboxylation of 3-carboxybenzisoxazoles (Figure 10, often called Kemp decarboxylation) is enormously accelerated by aprotic, polar solvents. For example, reactions of 6-nitrobenzisoxazole-3-... 

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