Nickel-catalyzed C(sp~2)-H Bonds Sulfuration/Annulation Of Benzamides

Benzoisothiazolones are versatile and important structural motifs in medicine agents,agriculture and the food industry with a variety of biological activities such as antibacterial,antipsychotic,antiviral and analgesic.Benzimidazoles are also frequently found in pharmaceutical molecules.In this thesis,a variety of benzamide substrates with 2-amino alkylbenzimidazole?MBIP-amine?were synthesized,and the first nickel-catalyzed sulfuration/annulation of C?sp²?-H was developed with the assistance of MBIP-amine.This reaction protocol is characterized by broad substrate scope and readily available reagents.A wide variety of potentially biologically active benzoisothiazolones with benzimidazole skeletons have been prepared in high yields.Moreover,the benzoisothiazolones can be easily transformed to many other useful compounds such as thioethers.Based on the relevant literatures and experimental results,a plausible mechanism is proposed.The main research contents are shown as follows:1.The synthesis of benzamide substrates2-Aminoalkylbenzimidazole?MBIPNH₂?was prepared according to the synthetic method reported in the literature.The benzoic acid bearing various substiuents reacted with oxalyl chloride at room temperature to synthesize the acyl chloride,and then the corresponding benzamide substrate were obtained by condensation reaction between 2-aminoalkylbenzimidazole?MBIPNH₂?and benzoyl chloride?Scheme 1?.Scheme 12.Nickel-catalyzed C?sp²?-H bonds sulfuration/annulation of benzamideThe benzamide derivative 1a and elemental sulfur were chosen as the substrate.Then the oxidant,catalyst,base,solvent,time,amount of catalyst,and temperature of the reaction were investigated.Finally,the optimized reaction conditions were determined:Ni?OTf?₂?10 mol%?,KMnO₄?1.0 equiv?,PivONa.H₂O?2.0 equiv?,TBAI?1.0 equiv?,and cyclohexane?1.0 mL?,stirred at 140°C for 9 hours.With the optimized reaction conditions in hand,the scope of benzamide substrate was examined.And these substrates all gave the desired sulfuration/annulation products in moderate to high yields?Scheme 2?.Scheme 2...