Studies On Functionalization Of C-H Bond Of N-(quinolin-8-yl) Benzamide Compounds With Free Radicals

Transition-metal-catalyzed or promoted C-H bond construction of C-C and C-X bonds(X = N,O,S)has become the hotspot and focus in the field of organic chemistry at present,and has made rapid progress,However,the research mainly focused on precious transition metal catalysts,and the use of inexpensive transition metal catalysts was relatively less.Free radical is very active and formed by the cleavage of covalent bond under the conditions of oxidant,catalyst,light or heat.It simultaneously has nucleophilic and electrophilic properties,so it has high reaction activity and is used as coupling agent to participate in the C-H bond functionalization.On this basis,we have carried out some C-H bond functionalizations catalyzed or promoted by nickel and copper salts involved with free radicals.In line with the concept of being environmentally friendly,we also have developed a transition-metalfree method for construction of C-C bond involved with free radicals.This thesis is divided into the following five chapters:Chapter 1 reviews the recent development of C-H bond functionalizations catalyzed or promoted by transition metal nickel,copper salts.The development of C-H bond functionalizations catalyzed or promoted by nickel and copper salts with the assistance of bidentate directing groups is emphasized.The development of C-H bonds functionalizations involving free radicals is also reviewed.Chapter 2 explores the orth methylation of N-(quinolin-8-yl)benzamides catalyzed by nickel salt and assisted by 8-aminoquinoline.After the screening of reaction conditions,the optimized reaction conditions were obtained,the scope of substrates was also examined.It was found that the substrates with electronwithdrawing groups are more reactive and are favored for the reaction.The reaction did not need to use base and ligand,which simplified the operation and saved the cost of the reaction.The mechanism studies show that the reaction may go through a free radical process.The boiling point of acetone,the by-product of the reaction,is lower,so it is easy to be removed in the vacuum distillation without affecting the purification of the product.Chapter 3 demonstrates Cu salt promoted ortho-methylthiolation of N-(quinolin-8-yl)benzamide / acrylamide.DMSO,which is used as the source of thiomethyl in this reaction,is cheap and readily available.It was found that the electron-donating groups are slightly beneficial to the reaction.The free radical capturing experiments indicate that the reaction may go through a free radical process,and the cleavage of C-H bond may be involved in the rate-determining step.Chapter 4 dicusses the dimerization of N-(8-quinoline)benzamides at C5 position promoted by copper salt.The base copper salt was used as promotor,which greatly saved the cost.After the screening of promotor,solvent and temperature,the best reaction conditions were obtained,then the substrate scope was explored.It was found that substrates with electron-donating and halogen substituents could participate in the reaction,while the substrates with strong electron-withdrawing groups,such as nitro and cyano group,did not work.The reaction may involve a radical pathway.In Chapter 5,we have developed a method for the cyanomethylation,etherification or acetonation of 8-aminoquinoline amides at the C5 position under conditions of transition-metal-free,base-free.The reaction conditions such as oxidant,base,catalyst,the amount of TBPB and acetonitrile,reaction temperature and reaction time were screened,and the optimized conditions were obtained.The reaction did not need transition metal catalyst or base,which is in line with the concept of greenness and friendliness.The free radical trapping experiments were performed under the optimized conditions,it was found that no desired product was detected,which indicates that the reaction may go through free radical process.Finally,the practicability of the reaction was investigated.