The versatile electrophilic reactivity of 4,6-dinitrobenzo[d]isoxazole-3-carbonitrile

Organic & Biomolecular Chemistry Pub Date: 2009-01-28 DOI: 10.1039/B820256G

Abstract

The interaction of 4,6-dinitrobenzo[d]isoxazole-3-carbonitrile (5a) with methoxide ion has been kinetically investigated in methanol and a 20:80 (v/v) MeOH-Me2SO mixture. In methanol, stopped-flow experiments have revealed that a monomethoxyl σ-adduct (5a-Me) is first formed, resulting from a fast MeO? addition at the unsubstituted 7-carbon. Rate and equilibrium constants for this σ-complexation process could be determined, allowing a ranking of 5a within the pKa scale established for Meisenheimer electrophiles in methanol. With a pKa value of 13.50, the electrophilicity of 5a falls in the range of 1,3,6,8-tetranitronaphthalene, 2,4-dinitrothiophene or 4-nitrobenzofuroxan. This corresponds to a two-pKa units increase in electrophilicity from that of TNB, the common reference in σ-complex chemistry but it is notably below that of so-called superelectrophilic molecules like 4,6-dinitrobenzofuroxan. In addition to its ease of σ-complexation, 5a is found to undergo a slow but thermodynamically favourable addition of MeO? to the cyano group bonded to the isoxazole ring, leading to a complete conversion of the adduct 5a-Me into a dinitroimidate 6. The reactivity of 6 could be kinetically assessed. Going to 80% Me2SO still afforded initially the adduct 5a-Me but this anionic species undergoes addition of a second molecule of MeO? to the CN group, giving a dianion whose structure is unprecedented in the literature. Combining the above results with synthetic observations showing that 5a can readily contribute to SNAr reactions under appropriate experimental conditions emphasizes the multifaceted electrophilic reactivity of this electron-deficient heterocycle.

Graphical abstract: The versatile electrophilic reactivity of 4,6-dinitrobenzo[d]isoxazole-3-carbonitrile
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