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

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. An electrophilic substitution reaction, without acid and metal, of indole with ammonium tetramethylnitrate for accessing 3-nitroindole has been developed.

Automated summary

An electrophilic substitution reaction using indole and ammonium tetramethylnitrate was developed for the synthesis of 3-nitroindole. Trifluoroacetyl nitrate was produced by metathesis of ammonium tetramethyl nitrate and trifluoroacetic anhydride, and it served as an electrophilic nitrating agent for various indoles. This method has the potential to construct the skeleton structure of bioactive molecules and further derivatize 3-nitroindole into pyrrolo[2,3-b]indole.