3-carboxybenzisoxazole Kemp decarboxylation

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-... 

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. 

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. 

The interpretation of the large solvent effect started from the observation of Kemp and coworkers that decarboxylation of 5-hydroxy-3-carboxyben-zisoxazole was accelerated by approximately four orders of magnitude by dimethylacetamide, but this acceleration was only ninefold in case of 4-hydroxy-3-carboxybenzisoxazole (Figure 11). This result suggested that a... 

Kemp DS, Cox DD, Paul KG. Physical organic chemistry of benzisoxazoles. IV. Origins and catalytic nature of the solvent rate acceleration for the decarboxylation of 3-carboxybenzisoxazoles. /2lm Chem Soc. 1975 97 7312-7318. 

---