Research On Cycloaddition Reaction Involving D-A Cyclopropane

In organic synthesis,substituted cyclopropanes and their derivatives are structural units that construct many biologically and pharmaceutically active molecules.On the one hand,it is very easy to open the ring,because of enormous ring tension of cyclopropane in thermodynamics.On the other hand,cyclopropane is easy to ring open due to the unstable C-C bond caused by different electron-withdrawing and electron-donating groups in the ring.Under most conditions,D-A cyclopropane selectively breaks the C1-C3 bond,and the 1,3-dipole formed undergoes cycloaddition reactions with various compounds to form cyclic compounds.Combined with the research of multi-substituted D-A cyclopropane ring opening and the construction and application of various heterocyclic compounds in our research group.In this paper,2-aryl-3-aryl-1,1-dicyano-cyclopropane was used as the reaction substrate to synthesize quinoxaline derivatives,2-pyridinone derivatives and thiacyclohexane derivatives by controlling the selective breaking of C1-C2 and C2-C3 bonds in the cyclopropane region.A series of six-membered heterocyclic rings containing nitrogen and sulfur were constructed.The open-ring position of substituted cyclopropane was studied and explored.The first part,a method for controlling the selective cleavage of C1-C2 bonds in D-A cyclopropane to synthesize quinoxaline derivatives was studied.Using 2-aryl-3-aryl-1,1-dicyanocyclopropane and 1,2-phenylenediamine as reaction substrates,the optimal reaction conditions were determined through screening of base,solvent,and temperature.Under the reaction conditions of CS2CO3 as a base,quinoxaline derivatives were obtained,and 20 target products were synthesized in a yield of 55-88%.All the target products were characterized by NMR,IR,and MS spectroscopies.Three of the compounds have been analyzed by single crystal X-ray diffraction to determine their structures.The second part,a method for controlling the selective cleavage of C1-C2 and C2-C3 bonds of D-A cyclopropane to synthesize 2-pyridone derivatives was studied.Using 2-aryl-3-aryl-1,1-dicyanocyclopropane as the reaction substrate,the optimal reaction conditions were determined through screening of base,solvent,and temperature.Under the coordinated action of sodium hydroxide and ethylenediamine,the reaction substrate undergoes self-ring opening to obtain 2-pyridone derivatives with configuration isomerism.A total of 21 groups of target products were synthesized,with a yield of 52-94%.All target products were characterized by NMR,IR,and MS spectroscopies.One group of compounds was analyzed by single crystal X-ray diffraction to determine their structure.The third part,a method for controlling the selective cleavage of C1-C2 bonds in D-A cyclopropane to synthesize thiocyclohexane derivatives was studied.Using 2-aryl-3-aryl-1,1-dicyanocyclopropane and 1,4-dithio-2,5-diol as reaction substrates,the optimal reaction conditions were determined through screening of acid,solvent,and temperature.Under the reaction condition of acetic acid as acid,thiocyclohexane derivatives were obtained,and 19 target products were synthesized in a yield of 61-92%.All target products were characterized by NMR,IR,and MS spectroscopies.Two of the compounds have been analyzed by single crystal X-ray diffraction to determine their structures.