The Copper-Mediated C-H Bond Nitration Chelation-Assisted By An N,O-Bidentate Directing Group

As the important intermediates in the synthesis of dyes, spices, medicines and explosives, nitro compounds have been widely used in many fields such as chemical engineering,pharmaceutical industry and organic synthesis, making research on the preparation of nitro compounds become a real hotpot. Among the known methods to synthesize nitro compounds, the direct nitration of C-H bond from aromatic or aliphatic hydrocarbons is usually the simplest way. In this work, we have developed a new method of direct nitration of benzoic acid derivatives with Cu(II) as catalyst, assisted by the directing group 2-aminopyridine-1-oxide. The main work of the research is as follows: 1. Synthesis of compounds 1 with N,O-bidentate directing groupFirst, we get 2-aminopyridine-1-oxide from 2-aminopyridine with the help of H2O2. Then compounds 1 were prepared from 2-aminopyridine-1-oxide and benzoic acid derivatives. Using DMAP as catalyst, EDCI as condensation agent and CH2Cl2 as solvent, we have synthesized 16 kinds of 2-benzamidopyridine 1-oxides derivatives with considerable yields(Scheme 1). 2. Cu(II)-catalyzed direct nitration of benzoic acid derivativesBy using 2-benzoylaminopyridine 1-oxide 1a as the template substrate, the reaction conditions of Cu-catalyzed direct nitration on C-H were screened. And the optimum conditions were as follows: a solution of 1a in NMP was added Cu Cl2?2H2O(0.5 equiv) as the catalyst and Na NO2 as the origin of the nitro. The mixture was stirred at 110 oC for 12 h, which provided the desired product in 73% yield. With the optimum condition, we sought to probe the scope of the substrate. This method was applied to benzoylamino and thienyl substrates, providing 16 desired products in medium to good yield(Scheme 2).