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

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 pK_a scale established for Meisenheimer electrophiles in methanol. With a pK_a 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-pK_a 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 S_NAr reactions under appropriate experimental conditions emphasizes the multifaceted electrophilic reactivity of this electron-deficient heterocycle.