Regioselective synthesis of 3-nitroindoles under non-acidic and non-metallic conditions†

Abstract

An electrophilic substitution reaction, without acid and metal, of indole with ammonium tetramethylnitrate for accessing 3-nitroindole has been developed. In this protocol, trifluoroacetyl nitrate (CF₃COONO₂) was produced by metathesis of ammonium tetramethyl nitrate and trifluoroacetic anhydride at sub-room temperature. Trifluoroacetyl nitrate (CF₃COONO₂) is an electrophilic nitrating agent for a variety of indoles, aromatic and heterocyclic aromaticity. Meanwhile, this strategy could be applied to construct the skeleton structure of many kinds of bioactive molecules. Interestingly, 3-nitroindole can be further derivatived as a pyrrolo[2,3-b]indole.