Cerium Ammonium Nitrate-Mediated Nitration Of Benzyl C(sp~3)-H Bond

Nitro compounds have an central role in the fields of medicine,pesticides,dyes and chemicals.Because the nitro group can be easily converted into many other functional groups,nitro compound also serves as important synthetic intermediate.Therefore,the preparation of nitro compounds has been a prolonged topic in organic chemistry,and the nitration reaction is a popular strategy to synthesize nitro compounds.Compared with the C(sp2)-H bond nitration of the aromatic compounds,the nitration of the C(sp3)-H bond is rare reported but considering challenged.Inspired by our previous work,in this thesis,we have developed a new benzyl C(sp3)-H nitration,using cerium ammonium nitrate as a nitrating agent.As a synthetic application of this transformation,(±)-Rivastigmine,which is widely used in clinical,has been efficiently synthesized by this new nitration reaction.This thesis is divided into three chapters:Chapter 1:The progress of C(sp3)-H nitration is briefly introduced.Chapter 2:The C(sp3)-H nitration at benzyl position has been successfully achieved by using the environmentally friendly cerium ammonium nitrate(CAN)as a nitrating agent,N-hydroxyphthalimide(NHPI)as a initiator,and Vitamin C(VC)as an additive.The present nitration reaction features broad substrate scope and high functional group tolerance.Chapter 3:The concise synthesis of(±)-Rivastigmine widely used for the treatment Alzheimer’s disease in clinical has been achieved,in which the developed nitration reaction was used as a key step.