Studies On The Thio-functionalization And Construction Of N-heterocycles Catalyzed/Promoted By Halogen Species

Myriads of proofs could bear testimony to the fact that the unreasonable development of the chemical industry is one of principal contributors to the ever-increasing serious environmental pollution. Accordingly, such reason has made green chemistry a growing attention and future guideline to global governments, enterprises and academic communities, and facilitated its rapid expansion in the past decades. Within this scenario, metal-free promoters, which have a series of virtues such as inexpensive, green, and biodegradable, are generally used not only for oxidation, rearrangement, cycloaddition and direct C-H functionalization, but also for the preparation of pharmaceuticals, intermediates and natural products.Halogen-containing compounds like mass-produced NCS, iodine and TBAI, which are completely in conformity with the requirements of green chemistry providing the benefits of high activities, low costs and toxicity, eco-friendiness and stable properties, are becoming one of the optimal alternatives to transition metals in organic synthesis. Although appealingly general, there are certain limitations in halogen promoted reactions, especially in direct C-H functionalization and one-pot reaction, and such successful applications are rarely found in industrial production. Consequently, more efforts should be devoted to novel halogen promoted direct C-H functionalization or one-pot reactions, particularly for the construction of C-X bonds and N-bearing heterocyclic compounds.Based on step-, atom-, and redox-economy points of view in industrial and green chemistry, we have developed several simple and high-efficient halogen promoted processes giving a wide range of potential bioactive 3-sulfenylindoles,2,3-bis-sulfenyl indoles, 3-thiocyanatoimidazopyridines and 1H-pyrazoles via readily available materials. In addition, the possible reaction mechanisms were also investigated.(1) A simple and high-efficient system for the selective and controllable sulfenylation of indoles by means of oxidative C(sp2)-H functionalization to the corresponding mono-and bis-sulfenylindoles in the presence of catalytic amounts of iodine using thiols as sulfenylation reagent has been developed.3-sulfenylated and 2,3-bis-sulfenylated indoles with diverse substituents were obtained respectively by controlling the equivalent of iodine and thiols (up to 94% yield).(2) A versatile oxidative system for the selective thiocyanation of imidazopyridines to the corresponding thiocyanated product in the presence of NCS using NaSCN as thiocyanato-transfer reagent under mild conditions has been developed (up to 96% yield). Additionally, the functionalization the imidazo[1.2-?]pyridine moiety in a one-pot sequential condensation/C-H functionalization process between a-bromo ketones and 2-aminopyridines has been testified to be reliable, and such methodology could commendably supplements the synthetic repertoire (up to 90% yield).(3) A practical procedure for the regioselective preparation of 1H-pyrazole derivatives in the presence of only 2 mol% iodine using TsNHNH2 as nitrogen-transfer reagent under mild conditions has been demonstrated (up to 96% yield). This method not only expands the reaction type between ?,?-unsaturated carbonyl compounds and TsNHNH2, but also paves the way for the synthesis of 1H-pyrazole derivatives in an eco-friendly manner.