[3+3] Cyclization Reaction Of Imide Compounds Containing Active Methylene With Diazo Compounds

Triazine compounds represent structural motifs found in a great number of natural compounds and drugs,it has demonstrated wide range of pharmacological activities including;antihypertensive,anti-inflammatory,inhibit platelet production,inhibit bacterial growth.Therefore,the synthesis of such compounds has attracted wide attention.Several papers have been published relating their importance in organic chemistry,medical and pharmaceutical chemistry.In the previous reports of the synthesis of 1,2,4-triazine compounds,the reaction of amino hydrazine compounds and diketones in the presence of acetic acid with the addition of ammonium acetate was heated and refluxed to give 1,2,4-triazine compound.Although this method is very effective,but there are harsh conditions;the substrate is not easy to prepare,byproducts and other deficiencies.Therefore,the development of a simple and efficient,one-step synthesis of 1,2,4-triazine compounds is very appealing.Diazo compounds are very important organic synthesis intermediates which have a wide range of applications in organic chemistry,pharmaceutical chemistry,natural product chemistry and materials chemistry.From the perspective of resonance theory,diazo compounds exist in a variety of resonance forms,making these compounds not only has a unique and diverse chemical properties,and has a high reactivity.Therefore,the research on the properties and application of various diazo compounds has been one of the hotspots in organic chemistry.In the course of the development of diazonium chemistry for centuries,most of the research on these compounds has focused on using it as carbene precursor,1,3-dipole and carbon nucleophile.However,the reaction with diazo compounds as effective end-nitrogen electrophilic reagents is rare.Therefore,it is very desirable to realize the coupling reaction between the diazo compound and the nucleophile.In this work,based on the diazo compounds as an effective terminal nitrogen electrophilic reagent,a simple and efficient method for the synthesis of 1,2,4-triazine compounds was developed,The [3+3] ring-forming reaction of the active methylene imide compound with the diazo compound under the DBU catalysis was studied.The method was as follows: containing the active methylene imide compound as a nucleophile,using its continuous nucleophilic addition reaction to the nitrogen of the diazo compound and the intramolecular N-hybrid reaction,combined with the use of DBU activation and DDQ oxidation and other strategies,efficient one-step synthesis of a series of tetrahydro 1,2,4-triazine compounds,dihydro 1,2,4-triazine compounds and 1,2,4-triazine compounds.This method not only established a new method for simple and efficient synthesis of 1,2,4-triazine derivatives,but also provided a solid foundation for the application of diazo compounds as an effective terminal nitrogen in the organic synthesis.