title: Synthesis of 3-alkylbenzoxazolones from N-alkyl-N-arylhydroxylamines by contiguous O-trichloroacetylation, trichloroacetoxy ortho-shift, and cyclization sequence.
abstract: Benzoxazolone pharmacophore is present in clinical pharmaceuticals, drug candidates, and many compounds having a wide spectrum of biological activities. The methods available for the synthesis of benzoxazolones have limited diversity due to problems in accessibility and air-sensitivity of diversely substituted o-aminophenols from which they are generally prepared by cyclocarbonylation with phosgene or its equivalents. The present paper describes a mild method for the synthesis of 3-alkylbenzoxazolones from easily accessible and air-stable nitroarenes. Nitroarenes were converted to N-alkyl-N-arylhydroxylamines in two steps involving partial reduction to arylhydroxylamines followed by selective N-alkylation. Treatment of N-alkyl-N-arylhydroxylamines with trichloroacetyl chloride and triethylamine afforded 3-alkylbenzoxazolones generally in good yields through an uninterrupted three-step sequence involving O-trichloroacetylation, N→C(ortho) trichloroacetoxy shift, and cyclization in a single pot at ambient temperatures. The present method is mild, wide in scope, economical, and regioselective. Many sensitive groups like alkyl and aryl esters, amide, cyano, and the carbon-carbon double bond survive the reaction.
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Delhi, Hauz Khas, New Delhi 110016, India.
authors.forename: Ram N
authors.initials: RN
authors.lastname: Ram
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Soni
mesh_terms: D000107:Acetylation; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006898:Hydroxylamines / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D001583:Benzoxazoles; D006898:Hydroxylamines; C017057:benzoxazolone