3-Carboxybenzisoxazoles, decarboxylation

Famini GR, Wilson LY. Using theoretical descriptors in quantitative structure-property relationships — 3-carboxybenzisoxazole decarboxylation kinetics. J Chem Soc Perkin Trans 2. 1994 1641—1650. 

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. 

The TLSER methodology has been successfully applied to develop correlation equations for a wide variety of solvent-dependent properties and processes [350, 364-369]. Some examples are the characterization of other solvent polarity, acidity, and basicity scales [364], the acidities of substituted acetic acids in various solvents [365], the basicities of substituted dimethylamines in various solvents [366], the decarboxylation kinetics of 3-carboxybenzisoxazole [367], the C=0 stretching frequencies of substituted pyrrolidin-2-ones [368], and gas-water distribution coefficients [369]. 

Even stronger accelerations (25-fold) were obtained in the decarboxylation of 3-carboxybenzisoxazoles [10]. In this case two amino groups were placed a suitable distance apart in the cavity by means of a polymerisable di-Schiff base. 

The decarboxylation rate of 3-carboxybenzisoxazoles depends on the substituent and strongly on the solvent, which is evidenced by the use of the empirical Kamlet-Taft-Abraham solvatochromic parameter set in a multilinear correlation analysis based on LSER, along with a theoretical computational set of molecular parameters <94JCS(P2)1641>. The effect of temperature and evaluation of thermodynamic parameters for the polarographic behavior of 3-methyl-4-(2 substituted benz-eneazo)-2-isoxazol-5-ones are reported <94Mi 303-02). 

Figure 11.20 Decarboxylation catalyzed by antibody with nonpolar microenvironment In the decarboxylation of 3-carboxybenzisoxazole by a tailored antibody, the anionic substrate is destabilized relative to the charge dispersed transition state in the nonpolar microenvironment of the antibody binding site. The hapten used to elicit the antibody is shown.

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. 

In the light of the previous reasoning, describing the solvolysis of tert-butyl chloride or the decarboxylation kinetics of 3-carboxybenzisoxazole in mixed solvents in terms of SPP, SB and SA for the mixtures appeared to be rather difficult owing to the differences between the processes concerned and the solvatochromism upon which the scales were constructed. However, the results are categorical as judged by the following facts ... 

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. 

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

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... 

C. Lewis, P. Paneth, M. H, O Leary, and D. Hilvert,/. Am. Chem. Soc., 115, 1410 (1993). Carbon Kinetic Isotope Effects on the Spontaneous and Antibody-Catalyzed Decarboxylation of 5-Nitro-3-Carboxybenzisoxazole. 

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 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... 

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