Studies On The Synthesis Of Spiroheterocycles By 1,3-Dipolar Cycloaddition Reaction

The paper focus on the synthesis of a number of novel spiroheterocycles by the 1,3-dipolar cycloaddition reaction.37 dipolarphiles with exo-cyclic double bond were synthesized by the conde- nsation of cycloalkanones and aryl aldehydes. 35 dipolarphiles with exo-cyclic double bond including 2-arylidene-benzo[4,5]imidazo[2,1-b]thiazol-3-one, 2-arylidene- 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-one, 2-arylidene-5,6-dihydro-imidazo[2,1-b]thiaz-ol-3-one,7-methyl-2-arylidene-3-oxo-5-phenyl-2,3- dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester, 2-arylmethylene-9-benzylidene-5-phenyl-6,7,8,9-tetrahydro-5H- thiazolo[2,3-b]quinazolin-3-one and 5-arylidene-thiazolo[3,2-b][1,2,4]tria-zol-6-one were sy- nthesized by the one-pot alkylation and condensation of chloroacetic acid , aryl aldehydes and fused thiazolidine compounds.58 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of azomethine ylide which generated in situ from sarcosine and isatin and self- synthesized dipolarphiles with exo-cyclic double bond. There are 10 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 10 new parent heterocycle were achieved by X-ray single crystal analyses. The retro-cyclo- addition reaction of cycloaddition products was discovered first times. The regioselectivity and steroselectivity of the reaction was discussed.32 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of 2,6-dichlorobenzonitrile oxide and self- synthesized dipolarphiles with exo-cyclic double bond. There are 7 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 12 new parent heterocycle were achieved by X-ray single crystal analyses. The regioselectivity of 1,3-dipole cycloaddition between 2,6-dichlorobenzon-itrile oxide and 3-(4-chlorobenzylidene)dihydrofuran-2-one was studied using ab initial RHF theory with the 6-31G* basis set. Two possible reactions approachs which lead to 3,4-disubstituted(approach 1) and 3,5-disubstituted(approach 2) isoxazoline respectively were investigated using energy analysis and frontier mol-ecular orbital analysis. Energy analysis shows that the activity energy of approach 2 is higher than approach 1. The high activity energy of approach 2 prevent the fo-rmation of 3,5-disubstituted isoxazoline and give 3,4-disubstituted isoxazoline as energy favored product. The frontier molecular orbital analysis shows the reaction was controlled by LUMOdipolar-HOMOdipolarphile interaction, and the reaction will follow approach 1 which in agree with experimental result.