Three-component Cycloadditions Of Diester Malonate,Amidine Or Hydrazone,Alkene And Nitrosoarene

Imidazolinone and their derivatives are used for chromophores,especially for fluorescent proteins as biologically and pharmaceutically active molecules.In particular,the study of green fluorescent protein has attracted people's attention due to its application in molecular biology.Therefore,it is significant to find a simple and efficient method for synthesis of imidazolinones.Isooxazolidine derivatives are widely consisted in natural products and synthetic drugs because of their novel pharmacological and biological activities.Due to the N-O bond,isooxazolidines are widely used to be the precursors of preparation many nitrogen compounds such as?-lactams,?-amino acids,amino alcohols and alkaloids.Therefore,it is necessary to develop a concise,green and efficient way to synthesize of isooxazolidines.In this thesis,the cycloaddition of nitrosoarenes,diester malonate compounds and amidine compounds was investigated.The reaction of nitrosobenzene,diethyl malonate and N-phenylbenzimidamide was selected as the model study to optimize reaction conditions by investigating promoters and their loading,solvents and their dosage,reaction temperature and the ratio of substrates.The optimal conditions obtained were 0.5 equiv KOH as a promoter and 1.2 mL of chloroform?CHCl₃?as a solvent at 60 ^oC,and the final ratio of substrate was 1.3:1.7:1.0 to give the desined compound in 94%yield.Then,under the optimized conditions,nitrosoarenes,diester malonate compounds and amidines were explored,and 60%to 94%yields were obtained.Finally,through the control experiments,a reasonable reaction mechanism was proposed.Next,the cycloaddition of nitrosoarenes,hydrazone compounds with styrenes was explored in the thesis.The reaction of nitrosobenzene,N-tosylhydrazones and styrene was selected as the model reaction to optimize the reaction conditions by investigating promoters and their dosage,solvents and their dosage,reaction temperature and the ratio of substrates.The optimal conditions were obtained 1.3 equiv KOH as a promoter,1.0 mL of toluene as a solvent,reaction temperature 100 ^oC,the ratio of substrate for 1.1:1.1:1.0 and the yield of the product was up to 92%.Under the optimized conditions,a series of nitrosoarenes,hydrazone compounds and alkenes were then explored,and all of the reaction yields were from 80%to 98%,indicating that the methodology is of great flexibility.Finally,through control experiments,a reasonable reaction mechanism was also proposed.In conclusion,the cycloadditions of nitrosoarenes,diesters malonate with amidines,and nitrosoarenes,hydrazones with alkenes were investigated using KOH as a promoter.Through this methodology,imidazolidones and isoxazolidines with multi-functionized groups were obtained.The two cycloadditions have the following advantages:?1?the raw substrates are prepared easily and the reaction conditions are mild;?2?the promoter KOH is cheap and the use of transition-metal is avoided.