Kemp elimination

What is Kemp elimination?

In 1973, Kemp first reported a reaction that involves a general base-catalyzed ring-opening of benzisoxazole. This reaction cleaves a N-O bond while simultaneously deprotonating carbon (C-3), resulting in o-cyano phenol derivatives.

The reaction is commonly known as the Kemp elimination, and it is an exothermic concerted reaction that follows an E2 mechanism.

Kemp elimination - general reaction scheme
Kemp elimination

When a carboxyl group is present on carbon-3, the reaction occurs through N-O cleavage accompanied by decarboxylation, which is referred to as Kemp decarboxylation.

Kemp decarboxylation - general reaction scheme
Kemp decarboxylation

The Kemp elimination is highly sensitive to medium effects. For instance, the decarboxylation of 3-carboxy benzisoxazole is over 108 times faster in an aprotic dipolar solvent, such as CH3CN, than in an aqueous solution. The rate enhancement is due to the destabilization of the carboxylate ion in microenvironments that lack hydrogen bond donors. Catalysts that mimic the microenvironment to facilitate the deprotonation, such as serum albumins, amino-cyclodextrins, antibody 38C2, commercially available coals, and vesicles formed from dimethyldioctadecylammonium chloride, can be used in the Kemp elimination.

The Kemp elimination is a simple one-step transformation without intermediates and is sensitive to the medium. Therefore, it is a model for studying enzyme-catalyzed proton transfer reactions. In enzyme-catalyzed reactions, the carboxylate, amino, and imidazole group of amino acid residues (histidine) on enzymes can function as general bases, while carboxyl, sulfurhydryl, and hydroxyl groups can function as general acids.

Enzymes can catalyze many reactions that are not possible under pure chemical conditions because of the effect of the microenvironment. For example, the enolization of ketones, in which the α-proton has a pKa of 16-24 and would not be deprotonated under neutral conditions, can occur in the presence of an enzyme. This phenomenon is known as the hard-soft acid-base theory (HSAB) and has become an interesting and extensively debated topic.

References

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