C-H Amination Of Nitro Aza-heterocyclic Compounds By Vicarious Nucleophilic Substitution

Nitro aza-heterocycles primary amines are important chemical products and organic synthesis intermediates,and appear in a wide range of applications.Direct amination of nitro aza-heterocyclic compounds is undoubtedly the most economical and simplest method to prepare nitro aza-heterocycles primary amines.The VNS(Vicarious Nucleophilic Substitution)amination reaction is a versatile way of introducing amino groups into the nitroarenes or nitroheteroarenes,which has many advantages.Among the commonly used VNS amination reagents,4-amino-1,2,4-triazole(ATA)has the advantages of less toxicity,inexpensive price and commercially available,and it is a relatively ideal amination reagent.Herein,we explore the C–H amination of nitro aza-heterocyclic compounds via a VNS route with4-amino-1,2,4-triazole(ATA)in this paper.The main research contents are as follows:1.C–H amination of nitro five-membered aza-heterocycles compounds by vicarious nucleophilic substitutionUsing 3,4-dinitro-1H-pyrazole(1a)as a model substrate,we obtained the5-amino-3,4-dinitro-1H-pyrazole(2a)with 45% yield by directing C–H amination of compound 1a with 4-amino-1,2,4-triazole(ATA).The reaction conditions for the synthesis of compound 2a were optimized,and the substrate scope was expanded to a variety of nitro five-membered aza-heterocycles compounds 1b～1j,and the corresponding amination products 2b～2j were prepared in 45%～88% yields.The structures of compounds 2a～2j were characterized by NMR and MS,and the structures of the crystals of5-amino-3,4-dinitro-1H-pyrazole(2a)and 5-amino-3-methoxy-1-methyl-4-nitropyrazole(2d)were characterized by single crystal X-ray diffraction.2.C–H amination of nitro benzo-fused five-membered aza-heterocycles compounds by vicarious nucleophilic substitutionUnder the optimized reaction conditions for synthesis of compound 2a,the corresponding amination products 2k～2p were prepared in 30%～74% yields by directing C–H amination of nitro benzo-fused five-membered aza-heterocycles compounds 1k～1p with4-amino-1,2,4-triazole(ATA).The structures of compounds 2k～2p and byproducts 3～4 were characterized by NMR and MS.The high regioselectivity was exhibited in the VNS amination reaction of nitro benzo-fused five-membered aza-heterocycles compounds,and the amination occurs preferentially at positions ortho or para to a nitro group.Plausible reaction mechanisms for the formation of ortho/para amination products and byproducts were also discussed.