Studies On The Synthesis Of Polysubstituted Pyrrole Compounds Base On Iminodiacetates

Polysubstituted pyrroles and its derivatives are one of the most important heterocycles prevalent in numerous bioactive molecules.As intermediates in fine chemical products,it has a wide range of use in the fields of medicine,food,daily chemicals,printing and dyeing,etc.Due to their important bioactive and therapeutic properties,polysubstituted pyrroles have attracted much attention from the organic chemistry community,and a variety of efficient methods have been reported for their synthesis.Based on the researches of polysubstituted pyrroles and iminodiacetates,in this article,a variety of simple and efficient synthesis strategies have been developed to construct of polysubstituted pyrrole compounds.In addition,this article also has studied the synthesis of imidazole compounds.A series of 73 desired compounds had been constructed in this paper.The thesis involves could be described as following:1.A novel one-pot 1,3-dipolar cycloaddition/oxidation reaction of 1,4-quinones,aromatic aldehydes and N-substituted amino esters as starting materials to construct of polysubstituted pyrroles induced by benzoic acid has been studied.We focused on and optimized the reaction conditions,various reaction parameters were screened,including the temperature,solvents,acids,ratio of raw materials,the loading of acid and ambient conditions.The results showed that the optimal parameters were as follows:in the presence of 1.0 equivalent benzoic acid,a mixture of 1.0 equivalent1,4-naphthoquinone,1.2 equivalent benzaldehyde and 1.2 equivalent N-substituted amino esters in toluene as solvent under 100°C stirred for 10 h.A series of 21polysubstituted benzo[f]isoindole-4,9-diones were obtained in 24-95%yields and all compounds had not been reported previously.2.An efficient method for the synthesis of 2-substituted benzo[f]isoindole-4,9-dione derivatives from the raw material of N-substituted iminodiacetates and quinones via a sequential Cu?OAc?-promoted oxidation/[3+2]cycloaddition/aromatization tandem reaction has been studied.We focused on and optimized the reaction conditions.The results showed that the optimal reaction conditions were as follows:1.5 equivalent Cu?OAc?₂ as catalyst,3.0 equivalent Et₃N as a base at reflux toluene for 5 h.A series of 19 polysubstituted benzo[f]isoindole-4,9-diones were obtained in 39-95%yields,among which 12structures were new compounds.Moreover,comparing with previous reported methods,this novel method was increased the applications of derivatives,which more suitable for atom-economic principle.3.A simple and highly efficient method for the preparation of tetrasubstituted NH-pyrroles from a wide range of chalcones and iminodiacetates as the raw material via Cu?OAc?₂ and oxygen co-promoted oxidation/[3+2]cycloaddition/aromatization cascade reaction has been studied.We focused on and optimized the reaction conditions,various reaction parameters were screened,including the temperature,solvents,Cu sources,ratio of reaction materials and so on.The studies showed that1.0 equivalent chalcones,2.0 equivalent iminodiacetates with 1.0 equivalent of Et₃N and 1.0 equivalent of Cu?OAc?₂ at 100°C DMF reacted under air condition for 8 h were the optimal reaction conditions.A series of 25 tetrasubstituted NH-pyrroles were obtained in 45-94%yields,among which 23 structures were new compounds.In addition,we also investigatived the Cu?OAc?₂-catalyzed oxidation/[3+2]cycloaddition/aromatization cascade reaction combined with green oxidants,and examined the feasibility of this reaction without solvent to construct of tetrasubstituted NH-pyrroles.4.Iodine-promoted a variety of 3-acetyl coumarinands and 2-aminopyridines as the raw material to construct of imidazos has been studied.We focused on and optimized the reaction conditions,various reaction parameters were screened,including the temperature,solvents,catalysts and so on.The results indicated that 1.0equivalent 3-acetyl coumarinands,2.0 equivalent 2-aminopyridines with 1.2equivalent of iodine at 110°C were first reacted under air condition for 14 h,then residue was diluted added excess of 0.1 mL 45%aqueous sodium hydroxide,and the reaction mixture was stirred 100°C for another 30 min were the optimal reaction conditions.A series of 8 imidazo compounds which maybe have luminescence properties were obtained in 10-65%yields.