Study On Iron-catalyzed Cyclization Of O-Alkynyl Benzamide Derivatives

Alkyne bond is one of the most basic and important functional groups in organic chemistry.As a multifunctional chemical synthon,alkyne bonds can be used to efficiently construct a variety of compounds with practical value.For example,oxygen-containing heterocycles or nitrogen-containing heterocycles can be selectively constructed using difunctional synthesizers containing amide and acetylene bonds.However,regional-selective control remains a major challenge in alkyne bond chemistry.For example,in the above regional-selective cyclization of difunctional syntheses containing amide and acetylene bonds,the regional-selective N-attack cyclization of amide nitrogen atoms attacking acetylene bonds has been less studied.Therefore,in this paper,based on o-acetylbenzamide as a bifunctional synthesizer,through the design of different reaction processes,the region-selective 6-endo-dig cyclization of the amide O-attacking alkyne bond and the region-selective 5-exo-dig cyclization of the amide N-attacking alkyne bond were achieved,respectively,to construct the oxa-six-member ring and aza-five-member ring.The main contents are as follows:1.Intramolecular O-cyclization-selenization of o-acetylbenzamide catalyzed by ironA visible light mediated iron-catalyzed intramolecular O-cycloselenation reaction of o-acetylbenzamide was developed.By means of solvent,catalyst,temperature,the reaction conditions such as the selection,get the optimal reaction conditions:adjacent alkynyl benzamide and diphenyldiselenide under 30 W blue LED light mediated,10%iron bromide as a catalyst,ethyl acetate as solvent,room temperature for 24 h reaction,get intramolecular O-attack 6-endo-dig cyclic organic selenium ether product.The cheap metal ferric salt was used as catalyst for the reaction,the substrate was widely applicable and the yield was good.2.Intramolecular N-cyclization-chlorination of o-acetylbenzamide with ferric chlorideAn intramolecular N-cyclization-chlorination reaction of o-alkynyl benzoamide with ferric chloride was developed.Through the selection of solvent,catalyst,temperature and other reaction conditions,the optimal reaction conditions were obtained:50%ferric chloride as the chlorine source,DCE as reaction solvent,o-acetylbenzamide stirred at 80?for 8 h to obtain N-attack chloramidated 5-exo-dig product.A series of isindolones were obtained by using cheap metal ferric salts instead of precious metals to form iron-nitrene intermediates,and then amide N-cyclization and chlorination of alkynes occurred.3.Iron-Catalyzed Intramolecular Acyl Nitrene/Alkyne Metalation for Synthesis of Pyrrolo[2,1-a]isoindol-5-onesA new method for the synthesis of pyrrole and[2,1-a]iso-indole by o-alkynyl benzoamide catalyzed by iron was developed.Through the selection of solvent,catalyst,temperature and other reaction conditions,the optimal reaction conditions were obtained:20%Fe(OAc)₂ as catalyst,20%HOAc as additive,Ph Me/DCE(v:v,1:1,2 m L)mixed solvent as reaction solvent,o-acetylbenzamide and 1.5 equiv acetylacetone reacted at 80?for 8 h to obtain N-attack chloramides 5-exo-dig product.Through the study of mechanism,the possible process of nitrene and synergistic addition of the reaction was proposed,and the existence of iron complex intermediate was verified.The synthetic pyrrolio[2,1-a]isindole-5-one has good fluorescence properties and a long Stokes shift(>100 nm),and has been successfully used in the fluorescence detection of heavy metal ions Hg²⁺,hydrazine and cysteine.