Study On Nitroxyl Radical Catalyzed Oxidation Of C-h Chlorination

Chlorinated compounds are important intermediates of many fine chemicals such as drugs,dyes,pesticides,synthetic fragrances,detergents,plasticizers and synthetic resins.Chlorination plays an important role in organic synthesis.Direct chlorination of C-H is an efficient way to synthesize chlorinated compounds.For C-H direct chlorination,the inert C-H needs to be activated first.The activation of C-H usually requires noble metal catalyst and relatively stringent reaction conditions.The nitroxyl radical system is a catalytic oxidation system with high reactivity,high selectivity,strong oxidation and mild reaction conditions.It was initially used in the oxidation reaction and has been widely used in C-H direct functionalization in recent years.However,studies on nitroxyl radical system in C-H chlorination are not abundant.So far,only one report of Schreiner's group has been published.Therefore,this field needs to be further studied.In this paper,the chlorination reactions of C(sp3)-H and C(sp2)-H were developed respectively under metal and metal-free conditions based on NHPI analogue nitroxylamine.In addition,the direct amidation/esterification of aldehydes with amides/alcohols was also studied.The specific research content is as follows:(1)Using toluene chlorination as model reaction,a NHPI/THICA-cobalt catalyzed C(sp3)-H oxidation chlorination reaction system was developed.The medium yield(48%)of benzyl chloride was obtained under optimized condition.(2)In view of the excessive oxidation problem in NHPI/THICA-cobalt system,the NHPI/DDQ catalyzed toluene oxidation and chlorination reaction system was developed.The yield(80%)of benzyl chloride was obtained through the condition optimization,and the influence of substituents steric and electronic effect on the system was investigated.The reaction mechanism was proposed and verified by means of kinetic monitoring,quantum chemical calculation and chain length experiment.(3)On the basis of C(sp3)-H chlorination catalyzed by NHPI/DDQ,C(sp2)-H chlorination catalyzed by nitroxyl radical system was developed.The yield of benzoyl piperidine was 70%obtained under optimized condition.The influence of substituents steric and electronic effect on the reaction and applicability of heteroatomic substrates and primary amines were investigated.