Rapid and High‐Yield Electrosynthesis of Benzisoxazole and Some Derivatives

Abstract

Cyclic voltammetry and controlled‐potential (bulk) electrolysis have been used to explore the electrochemical reduction of o‐nitrobenzaldehyde (o‐NBA) and 8 other aldehydes and ketones at glassy carbon cathodes in dimethylformamide containing various tetraalkylammonium tetrafluoroborate salts along with a proton donor (4‐chlorophenol). Cyclic voltammograms for reduction of o‐NBA exhibit three cathodic peaks attributable in succession to (a) one‐electron generation of the nitro radical‐anion, (b) three‐electron formation of the hydroxylamine, and (c) two‐electron production of benzisoxazole (anthranil). These findings have been employed to develop efficient controlled‐potential (bulk) electrosyntheses of the following compounds: benzisoxazole, methylbenzo[c]isoxazole, [1,3]dioxolo[4′,5′,4,5]benzo[1,2‐c]isoxazole, naphtho[2,3‐c]isoxazole, 6‐chlorobenzo[c]isoxazole, 6‐methoxybenzo[c]isoxazole, 3‐methyl‐benzo[c]isoxazole, 3‐isopropylbenzo[c]isoxazole, and 3‐phenylbenzo[c]isoxazole. In addition, we have examined the use of a variety of proton donors to optimize the production of the desired product, and we have been able to recover the proton donor at the conclusion of the electrosynthesis. In each case, the synthesized product was separated by means of normal phase chromatography and identified with the aid of NMR spectros‐copy, gas chromatography (GC), and gas chromatography‐mass spectrometry (GC‐MS). Isolated yields of the desired products range from 63 to 92 %. Moreover, our electrosyntheses are catalyst‐free, environmentally green, and rapid (∼30 min).

Recent Advances in the Electrochemical Reduction of Substrates Involving N−O Bonds

“…Referring to the report of Peters, the reaction is performed under potentiostatic conditions and in a divided cell, using 4‐chlorophenol (10 equiv.) as an additive (Scheme , left side ) . No scale for this electrosynthesis was reported.…”

Electrifying green synthesis: recent advances in electrochemical annulation reactions

“…Other electrosynthetic methodologies for obtaining 2,1-benzisoxazoles have been reported. [158][159][160] etc. 165 It is free of catalysts via the use of elemental sulfur with amidines 166 and hydrazones, 167 and dimerization of thioamides 168 or thiobenzamides with methyl bromocyanoacetate.…”

Subnanometric Pt clusters supported on MgO-incorporated porous carbon as efficient metal–base bifunctional catalysts for reductive heterocyclization reactions

“…2,1-Benzisoxazoles and related N-heterocyclic compounds (also known as anthranils) are important starting materials for the synthesis of pharmaceutical intermediates, organic functional materials, and industrial surfactants. [1][2][3][4][5][6] For instance, anthranil derivatives are applied to treat several central nervous system abnormalities, 7,8 act as anti-inflammatory drugs, 9,10 and can be used to produce antiplatelet inhibitors, quinolinones, and acridone. [11][12][13][14] Due to fundamental significance and practical values of these compounds, several protocols have been developed for their synthesis.…”