Study On The Copper(Ⅰ)-Catalyzed Ullmann Reaction For The Construction Of C(sp2~)-X Bonds

Cu-catalyzed Ullmann coupling reaction is one of the key methods to construct C-C and C-X（X=N,O and S）bonds in organic synthesis.Such reactions can build the ubiquitous heterocycle skeletons in bioscience and materials science.In this thesis,four series of fused polycyclic heterocycles were synthesized through Ullmann coupling reaction for the construction of C-C,C-N,C-O and C-S bonds under milder conditions.These procedures all follow the idea of green chemistry using as few steps as possible and inexpensive copper（Ⅰ）catalyst.In the first chapter,the development of Ullmann reaction is described,and the research status of Ullmann reaction is also introduced briefly.In the second chapter,the construction of carbon-nitrogen bond was realized under mild reaction conditions via copper（Ⅰ）-catalyzed Ullmann coupling reaction.The reaction between N-（benzimidazolyl）anthranilamide and 4-haloisatin was promoted with CuI in the presence of Cs₂CO₃ to build quinazoline moiety first.And then it was C-N bond Ullmann coupling reaction.The last step was the ring-opening reaction of isatin to construct of quinazolinobenzimidazoquinazoline derivatives.This reaction is related to the steric hindrance.The Ullmann coupling reaction was prevented but only to give ring-opening products of 3-（1H-benzo[d]imidazol-2-yl）quinazolin-4（3H）-ones when 4-bromo-5-methylisatin was used as a reactant.Finally,the possible reaction mechanism was put forward according to the different products.In the following chapter,CuI-catalyzed Ullmann C（sp²）-C（sp³）coupling reaction was studied.The diethyl 2-（2-aminobenzamido）malonate and 2-halobenzaldehydes were used as the starting materials to synthesize a series of isoindoloquinazoline derivatives catalyzed by CuI.All the products were characterized by ¹H NMR,¹³C NMR,IR and HRMS,and the structure of 7g was further confirmed by X-ray diffraction analysis.This reaction mainly included a construction of quinazoline moiety,dehydroaromatization and C（sp²）-C（sp³）bond Ullmann coupling reactionIn chapter 4,the coupling of C-O bond was achieved successfully to afford a series of dibenzooxazepinoquinazoline derivatives in high yields by a reaction of2-amino-N-（2-hydroxyphenyl）benzamide and o-haloaldehyde catalyzed by Cu I.Of which,the structure of product 9c was confirmed by single crystal X-ray diffraction analysis.The desired benzoisoxazoloquinazolines were not obtained when2-amino-N-hydroxybenzamide was submitted to react with 2-halogenated benzaldehydes.In fact,it was a domino type reaction to give final benzonitriles.In the last chapter,we realized the twice constructions of C（sp²）-S successfully using2-（2-bromophenyl）-4,5-diphenyl-1H-imidazoleandpotassiumO-ethyl carbonodithioate as the reactants catalyzed by CuI.In the presence of CuI and Cs₂CO₃,the first is C-S bond Ullmann coupling reaction in this procedure,and the subsequent cyclization did not take place as expected but to give a new sulfur anion.The second C-S bond Ullmann coupling reaction occurred to provide a series of bis（2-（4,5-diphenyl-1H-imidazol-2-yl）phenyl）sulfanes in high yields.The structures of all products were characterized by ¹H NMR and IR,some of them were characterized by ¹³C NMR and HRMS.The structures of 7g,9c and 12f were further confirmed by X-ray diffraction analysis.