A QUANTUM-MECHANICAL AND STATISTICAL-MECHANICAL EXPLORATION OF THE THERMAL DECARBOXYLATION OF KEMPS OTHER ACID (BENZISOXAZOLE-3-CARBOXYLIC ACID) - THE INFLUENCE OF SOLVATION ON THE TRANSITION-STATE GEOMETRIES AND KINETIC ISOTOPE EFFECTS OF A REACTION WITH AN AWESOME SOLVENT EFFECT

The decarboxylation of benzisoxazole-3-carboxylate has been investigat ed in detail by ab initio molecular orbital calculations. The effects of solvent on transition state geometries have been investigated by in clusion of one or two water molecules in the ab initio calculations. T he decarboxylation and ring opening steps are found to be concerted. K inetic isotope effects have been calculated for the carboxylate-C-13-l abeled compound for various transition state geometries. Satisfactory agreement has been found between the experimental values for the react ion in water and ab initio HF/6-31G calculated values for systems inc luding four hydrogen bonds to the carboxylate group. The variations in free energies of solvation along the reaction path in five different solvents (water, methanol, chloroform, acetonitrile, tetrahydrofuran) have been calculated with Monte-Carlo free energy perturbation calcula tions. Solvent effects are generally overestimated, but the experiment al trends have been reproduced for four of the five solvents, The effe cts of ion pairing have been tested by inclusion of a tetramethylguani dinium cation into the Monte-Carlo simulations for acetonitrile and te trahydrofuran. With inclusion of ion pairing, the relative rates of TH F and acetonitrile are reproduced much better, but solvent effects are underestimated relative to the reaction in water.