Chemical Papers

, Volume 68, Issue 2, pp 283–290 | Cite as

1,3-Dipolar cycloaddition between substituted phenyl azide and 2,3-dihydrofuran

  • Ahmad Reza BekhradniaEmail author
  • Sattar Arshadi
  • Seyed Amir Siadati
Original Paper


A theoretical study was performed on the 1,3-dipolar cycloaddition between 2,3-dihydrofuran and substituted phenyl azide using Density Functional Theory (DFT) in combination with a 6-311++G(d,p) basis set. The optimum geometries for reactant, transition state and product, as well as the kinetic data, rate constants and reaction constant (ρ) were investigated to rationalise the substitution effects and reaction rates of the 1,3-dipolar cycloaddition process in various solvents. The DFT calculation and Frontier Molecular Orbital (FMO) theory as well as the atomic Fukui indices show that the electron-withdrawing substituents enhance the reaction constant (ρ > 0), especially in polar aprotic solvents. Consequently, small changes in the rate constant of the reaction in various solvents and geometric similarity between reactants and transition state structures were suggested as the early transition state mechanism for electron-withdrawing substituents. In addition, the slope of the Hammett plot and susceptibility of the reaction to electron-withdrawing substituents in various solvents confirmed the mechanism.


DFT method substituted phenyl azide 2,3-dihydrofuran 1,3-dipolar cycloadditions Hammett equation atomic Fukui indices 


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  1. Argyropoulos, N. G., Mentzafos, D., & Terzis, A. (1990). 1-3-Dipolar cycloaddition reactions of 1,4-benzoquinones with nitrilimines. Journal of Heterocyclic Chemistry, 27, 1983–1988. DOI: 10.1002/jhet.5570270725.CrossRefGoogle Scholar
  2. Arshadi, S., Bekhradnia, A. R., Ahmadi, S., Karami, A. R., & Pourbeyram, S. (2011a). New insights on the mechanism of thermal cleavage of unsaturated bicyclic diaziridines: A DFT study. Chinese Journal of Chemistry, 29, 1347–1352. DOI: 10.1002/cjoc.201180253.CrossRefGoogle Scholar
  3. Arshadi, S., Bekhradnia, A. R., & Ebrahimnejad, A. (2011b). Feasibility study of hydrogen-bonded nucleic acid base pairs in gas and water phases — a theoretical study. Canadian Journal of Chemistry, 89, 1403–1409. DOI: 10.1139/v11-124.CrossRefGoogle Scholar
  4. Aso, M., Ojida, A., Yang, G., Cha, O. J., Osawa, E., & Kanematsu, K. (1993). Furannulation strategy for synthesis of the naturally occurring fused 3-methylfurans: efficient synthesis of evodone and menthofuran and regioselective synthesis of maturone via a Lewis acid catalyzed Diels-Alder reactions. Some comments for its mechanistic aspects. The Journal of Organic Chemistry, 58, 3960–3968. DOI: 10.1021/jo00067a031.Google Scholar
  5. Awad, M. K. (2001). Theoretical investigations of [4π S+2π S] cyclodimerization and stereoselectivity of phthalazin derivatives. Journal of Molecular Structure: THEOCHEM, 542, 139–147. DOI: 10.1016/s0166-1280(00)00831-9.CrossRefGoogle Scholar
  6. Becke, A. D. (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Physical Review A, 38, 3098–3100. DOI: 10.1103/physreva.38.3098.CrossRefGoogle Scholar
  7. Bekhradnia, A. R., & Arshadi, S. (2007). Conformational analysis, infrared, and fluorescence spectra of 1-phenyl-1,2-propandione 1-oxime and related tautomers: Experimental and theoretical study. Monatshefte für Chemie — Chemical Monthly, 138, 725–734. DOI: 10.1007/s00706-007-0657-7.CrossRefGoogle Scholar
  8. Bekhradnia, A. R., & Arshadi, S. (2011). Theoretical study of halogen effect in isomerization of 2-halo-[9]-annulen anion at the DFT Level. Chinese Journal of Structural Chemistry, 30, 906–912.Google Scholar
  9. Bekhradnia, A. R., & Ebrahimzadeh, M. A. (2012). Theoretical study on some non-selective beta-adrenergic antagonists and correlation to their biologically active configurations. Medicinal Chemistry Research, 21, 2571–2578. DOI: 10.1007/s00044-011-9781-3.CrossRefGoogle Scholar
  10. Bultinck, P., Carbó-Dorca, R., & Langenaeker, W. (2003). Negative Fukui functions: New insights based on electronegativity equalization. The Journal of Chemical Physics, 118, 4349–4356. DOI: 10.1063/1.1542875.CrossRefGoogle Scholar
  11. Carpenter, J. E., & Weinhold, F. (1988). Analysis of the geometry of the hydroxymethyl radical by the “different hybrids for different spins” natural bond orbital procedure. Journal of Molecular Structure: THEOCHEM, 169, 41–62. DOI: 10.1016/0166-1280(88)80248-3.CrossRefGoogle Scholar
  12. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J. A., Jr., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, N. J., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, Ö., Foresman, J. B., Ortiz, J. V., Cioslowski, J., & Fox, D. J. (1998). Gaussian 98 [computer program]. Pittsburgh, PA, USA: Gaussian.Google Scholar
  13. Gan, Y., Harwood, L. M., Richards, S. C., Smith, I. E. D., & Vinader, V. (2009). Cycloadditions of chiral carbonyl ylides with imine dipolarophiles as a route to enantiomerically pure α-amino-β-hydroxy acids. Tetrahedron: Asymmetry, 20, 723–725. DOI: 10.1016/j.tetasy.2009.02.029.CrossRefGoogle Scholar
  14. Gonzalez, C., & Schlegel, H. B. (1989). An improved algorithm for reaction path following. The Journal of Chemical Physics, 90, 2154–2161. DOI: 10.1063/1.456010.CrossRefGoogle Scholar
  15. Gonzalez, C., & Schlegel, H. B. (1990). Reaction path following in mass-weighted internal coordinates. The Journal of Physical Chemistry, 94, 5523–5527. DOI: 10.1021/j100377a021.CrossRefGoogle Scholar
  16. Huisgen, R., Grashey, R., Vernon, J. M., & Knuz, R. (1965). Umsetzungen von Δ2-Triazolinen und von Ringketon-Anilen mit Isocyanaten und Isothiocyanaten. Tetrahedron, 21, 3311–3323. DOI: 10.1016/s0040-4020(01)96953-4. (in German)CrossRefGoogle Scholar
  17. Huisgen, R., Szeimines, G., & Mobius, L. (1967). 1,3-Dipolare Cycloadditionen, XXXII. Kinetik der Additionen organischer Azide an CC-Mehrfachbindungen. Chemische Berichte, 100, 2494–2507. DOI: 10.1002/cber.19671000806. (in German)CrossRefGoogle Scholar
  18. Huisgen, R. (1980). Cycloaddition mechanism and the solvent dependence of rate. Pure and Applied Chemistry, 52, 2283–2310. DOI: 10.1351/pac198052102283.CrossRefGoogle Scholar
  19. Huisgen, R., Fisera, L., Giera, H., & Sustmann, R. (1995). Thiones as superdipolarophiles. Rates and equilibria of nitrone cycloadditions to thioketones. Journal of the American Chemical Society, 117, 9671–9678. DOI: 10.1021/ja00143a008.CrossRefGoogle Scholar
  20. Kadaba, P. K. (1969). Triazolines-IV: Solvation effects and the role of protic-dipolar aprotic solvents in 1,3-cycloaddition reactions. Tetrahedron, 25, 3053–3066. DOI: 10.1016/s0040-4020(01)82839-8.CrossRefGoogle Scholar
  21. Kadaba, P. K. (1973). Role of protic and dipolar aprotic solvents in heterocyclic syntheses via 1,3-dipolar cycloaddition reactions. Synthesis, 1973, 71–84. DOI: 10.1055/s-1973-22136.CrossRefGoogle Scholar
  22. Kanchithalaivan, S., Kumar, R. R., & Peruma, S. (2013). Synthesis of novel 16-spiro steroids: Spiro-7′-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo-trans-androsterone hybrid heterocycles. Steroids, 78, 409–417. DOI: 10.1016/j.steroids.2012.12.017.CrossRefGoogle Scholar
  23. Lee, C. T., Yang, W. T., & Parr, R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37, 785–789. DOI: 10.1103/physrevb.37.785.CrossRefGoogle Scholar
  24. Liu, Z. Z., Chen, Z. R., Yin, H., & Yuan, S. F. (2012). Mechanistic insights into the reaction of CF3CCl3 with SO3: Theory and experiment. Chemical Papers, 66, 1059–1064. DOI: 10.2478/s11696-012-0205-8.CrossRefGoogle Scholar
  25. Michalak, A., De Proft, F., Geerlings, P., & Nalewajski, R. F. (1999). Fukui functions from the relaxed Kohn-Sham orbitals. The Journal of Physical Chemistry A, 103, 762–771. DOI: 10.1021/jp982761i.CrossRefGoogle Scholar
  26. Ohgaki, E., Motoyoshiya, J., Narita, S., Kakurai, T., Hayashi, S., & Hirakawa, K. I. (1990). Effect of boron trifluoride-diethyl ether (BF3·OEt2) in the Diels-Alder reaction of quinoline- and isoquinoline-5,8-dione with unsymmetrical aliphatic dienes: Theoretical study on the orientation of cycloadditions. Journal of the Chemical Society, Perkin Transactions 1,1990, 3109–3112. DOI: 10.1039/p19900003109.CrossRefGoogle Scholar
  27. Padwa, A. (1984). 1,3-Dipolar cycloaddition chemistry. New York, NY, USA: Wiley.Google Scholar
  28. Peng, C. Y., Ayala, P. Y., Schlegel, H. B., & Frisch, M. J. (1996). Using redundant internal coordinates to optimize equilibrium geometries and transition states. Journal of Computational Chemistry, 17, 49–56. DOI: 10.1002/(sici)1096-987x(19960115)17:1<49::aid-jcc5>;2-0.CrossRefGoogle Scholar
  29. Reed, A. E., Curtiss, L. A., & Weinhold, F. (1988). Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chemical Reviews, 88, 899–926. DOI: 10.1021/cr00088a005.CrossRefGoogle Scholar
  30. Rooney, J. J. (1995). Eyring transition-state theory and kinetics in catalysis. Journal of Molecular Catalysis A: Chemical, 96, Ll–L3. DOI: 10.1016/1381-1169(94)00054-9.CrossRefGoogle Scholar
  31. Tomasi, J., & Persico, M. (1994). Molecular interactions in solution: An overview of methods based on continuous distributions of the solvent. Chemical Reviews, 94, 2027–2094. DOI: 10.1021/cr00031a013.CrossRefGoogle Scholar
  32. Wilson, C. L. (1947). Reactions of furan compounds. VII. Thermal interconversion of 2,3-dihydrofuran and cyclopropane aldehyde. Journal of the American Chemical Society, 69, 3002–3004. DOI: 10.1021/ja01204a020.CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2013

Authors and Affiliations

  • Ahmad Reza Bekhradnia
    • 1
    • 2
    Email author
  • Sattar Arshadi
    • 3
  • Seyed Amir Siadati
    • 1
  1. 1.Pharmaceutical Sciences Research Center, Department of Medicinal ChemistryMazandaran University of Medical SciencesSariIran
  2. 2.Department of Chemistry and Molecular BiologyUniversity of GothenburgGothenburgSweden
  3. 3.Department of ChemistryPayame Noor UniversityTeheranIran

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