Functionalization Of Carbazole And Quinoline Compounds Based On Directing Strategy

Carbazole and quinoline are important nitrogen-containing heterocyclic compounds,widely existed in natural products,pharmaceuticals,and functional materials.The development of efficient methods for synthesis and transformation of such nitrogen-containing heterocyclic compounds is of great significance.The conventional method for synthesizing such heterocyclic compounds is ma inly through the intermolecular or intramolecular cyclization of aniline precursor or alkyne precursor.However,there are some disadvantages in this type of reaction,such as poor selectivity and harsh reaction conditions.The construction of nitrogen-containing heterocyclic derivatives by selective functionalization of established nitrogen-containing heterocycles is a convenient and efficient method.In recent years,the site-selective functionalization of nitrogen-containing heterocyclic compounds through the C-H bond activation strategy has become a hot spot.Based on the C-H functionazation strategy,we developed a series of methods for site-selective functionalization of carbazole and quinoline rings in this thesis.Through C-H functionazation strategy,this thesis developed a series of methods for modifying carbazole and quinoline derivatives.Using directing strategy to regulate and control the selectivity of the reaction,we realized the construction of C-S bond or a new C-C bond via selectively cleaving C-H or C-C bonds.A series of useful nitrogen-containing heterocyclic compounds were synthesized.The main innovative research results and conclusions are as follows:(1)The reaction of nitrogen-containing compounds such as carbazole with diaryl disulfide was studied by an ortho-directing strategy.By using pyrimidinyl as the directing group,we achieved the copper-promoted thioetherification of the carbazole at C1/C8 position for the first time.After the reaction is completed,the directing group can be removed smoothly.The reaction uses disulfide as a source of thioether,avoiding the use of thiol or thiophenol with strong unpleasant smell.In addition to carbazole,the method can be extended to other nitrogen-containing heterocyclic compounds such as indoles,benzoquinoline and 2-phenylquinoline,with the thioether group introduced in the ortho position.In addition to the activation of the ortho C-H bond,this strategy can be further extended to the ortho C-F bond activation.The C-F bond functionalization at the ortho position of pentafluorophenylpyridine was successfully achieved by coordination of the Grignard reagent with the pyridyl group.(2)The thioetherification of the 8-amidoquinoline at the C5 position was achieved for the first time by means of a remote directing strategy,and a series of thioether groups were introduced at the C5 position of the quinoline with high regioselectivity and high yield.The reaction has good substrate tolerance for various diaryl disulfides and dialkyl disulfides.In addition,the thioetherification reaction can be extended to the selenoetherification,with the selenide functional group successfully introduced at the C5 position of the 8-amidoquinoline.By hydrolyzing the amide bond of the thioether product,a series of C5-substituted 8-aminoquinoline derivatives can be obtained in high yield.Preliminary studies on the reaction mechanism showes that the reaction is likely to undergo a single electron transfer free radical process.(3)Based on the substrate coordination directing strategy,we successfully realized the reaction of nickel-catalyzed primary amine with large-block bromides to synthesize triarylamines in one-pot manner.During the reaction of synthesizing triarylamines from primary amines,the rate of the second amination is generally slower than that of the first amination because the energy barrier of the second amination is higher.Thus,what is usually obtained after the reaction is a mixture of diarylamines and a triarylamines.By selecting 8-aminoquinoline which can form a highly efficient complex with nickel as a reaction substrate,t he activation energy of the second amination is lowered.Thereby,the process of re-arylating diarylamines to form triarylamines is accelerated,and the selectivity of the one-pot synthesis of triarylamines from primary amines is improved.This reaction avoids the use of noble metal catalysts or proceeding in two steps,which increases the possibility of practical application.(4)Based on the electrical directing strategy,the selective cleavage of CF3-C(O)bond of trifluoroacetamide and its conversion were successfully achieved.The electron density and bond strength of CF3-C(O)were changed by the strong electron-withdrawing trifluoromethyl group,and the CF3-C(O)bond of trifluoroacetamide was successfully broken and coupled with Grignard reagent to form a new amide.Preliminary mechanism studies indicate that the reaction undergoes an isocyanate mechanism or a dication intermediate process.