Theoretical study on the [4+2] cycloaddition of 1,3-dimethylindole with 2,6-dimethylquinone

  • Mousa SoleymaniEmail author
Original Research


The [4+2] cycloaddition reaction of 1,3-dimethylindole and ortho-quinone methide (obtained from tautomerization of 2,6-dimethylquinone under basic conditions), experimentally studied by Wen and co-workers, was theoretically studied at the B3LYP/6-311G** and M062X/6-311G** computational levels in both gas and ethanol solution phases. Two possible reactive channels were considered between the reactants and their theoretical parameters were calculated. The results indicated that the formation of the experimentally reported product is clearly confirmed by the analysis of the calculated Fukui and Parr functions reactivity indices. Transition states analysis showed that the experimentally reported product is both kinetically and thermodynamically preferred than the other regioisomeric adduct. The intrinsic reaction coordinates analysis indicated that in contrast to the proposed stepwise mechanism by Wen and co-workers, the reaction proceeds in one step without formation of any stable intermediate. Analysis of the global electron density transfer (GEDT) showed that the corresponding transition state is relatively polar and the electron density is fluxed from 1,3-dimethylindole toward ortho-quinone methide. Because of the polar character of the transition state, the reaction accelerates in ethanol, as a polar solvent, in comparison to the gas phase. Analysis of the frontier molecular orbitals showed that the HOMO orbital of 1,3-dimethylindole as a donor is also the frontier effective-for-reaction molecular orbital (FERMO). According to the Wiberg bond indexes and atoms in molecules analysis, it was found that both reactive channels take place via an asynchronous concerted mechanism.


Polycyclic indoline 1,3-Dimethylindole ortho-Quinone methide DFT FERMO Local reactivity 


Funding information

I am thankful to the Research Council and Office of Graduate Studies of the University of Ayatollah Alozma Borujerdi for their financial support.

Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.

Supplementary material

11224_2018_1259_MOESM1_ESM.docx (162 kb)
ESM 1 (DOCX 162 kb)


  1. 1.
    Fringuelli F, Taticchi A (2002) The Diels-Alder reaction: selected practical methods. Wiley, ChichesterGoogle Scholar
  2. 2.
    Gajewski JJ, Peterson KB, Kagel JR (1987). J Am Chem Soc 109:5545–5546CrossRefGoogle Scholar
  3. 3.
    Linder M, Brinck T (2012). J Org Chem 77:6563–6573CrossRefGoogle Scholar
  4. 4.
    Houk KN, Gonzalez J, Li Y (1995). Acc Chem Res 28:81–90CrossRefGoogle Scholar
  5. 5.
    Rideout D, Breslow R (1980). J Am Chem Soc 102:7816–7817CrossRefGoogle Scholar
  6. 6.
    Breslow R, Guo T (1988). J Am Chem Soc 110:5613–5617CrossRefGoogle Scholar
  7. 7.
    Dunams T, Hoekstra W, Pentaleri M, Liotta D (1988). Tetrahedron Lett 29:3745–3748CrossRefGoogle Scholar
  8. 8.
    Otto S, Engberts JBFN (2000). Pure Appl Chem 72:1365–1372CrossRefGoogle Scholar
  9. 9.
    Breslow R, Rizzo CJ (1991). J Am Chem Soc 113:4340–4341CrossRefGoogle Scholar
  10. 10.
    Dewick PM (2002) Medicinal natural products: a biosynthetic approach2nd edn. Wiley, New YorkGoogle Scholar
  11. 11.
    Fattorusso E, Scafati OT (2008) Modern alkaloids. Wiley-VCH, WeinheimGoogle Scholar
  12. 12.
    Sanchis PR, Savina SA, Albericio F, Alvarez MA (2011). Chem Eur J 17:1388–1408CrossRefGoogle Scholar
  13. 13.
    Trost BM, Osipov M (2015). Chem Eur J 21:16318–16343CrossRefGoogle Scholar
  14. 14.
    Popov K, Hoang A, Somfai P (2016). Angew Chem Int Ed 55:1801–1804CrossRefGoogle Scholar
  15. 15.
    Yang J-M, Li P-H, Wei Y, Tang X-Y, Shi M (2016). Chem Commun 52:346–349CrossRefGoogle Scholar
  16. 16.
    Cera G, Chiarucci M, Mazzanti A, Mancinelli M, Bandini M (2012). Org Lett 14:1350–1353CrossRefGoogle Scholar
  17. 17.
    Lin Ch DH-J, Zhao H, Yan D-F, Liu N-X, Sun H, Wen X, Xu Q-L (2017). Org Biomol Chem 15:3472–3478CrossRefGoogle Scholar
  18. 18.
    Soleymani M, Dashi Khavidaki H (2017). Comp Theor Chem 1112:37–45CrossRefGoogle Scholar
  19. 19.
    Soleymani M (2018). Monatshe Chem Chem Mon 149:2183–2193CrossRefGoogle Scholar
  20. 20.
    Memarian HR, Soleymani M, Sabzyan H, Bagherzadeh M, Ahmadi H (2011). J Phys Chem A 115:8264–8270CrossRefGoogle Scholar
  21. 21.
    Memarian HR, Sabzyan H, Soleymani M, Habibi MH, Suzuki T (2011). J Mol Struc 998:91–98CrossRefGoogle Scholar
  22. 22.
    Geerlings P, De Proft F, Langenaeker W (2003). Chem Rev 103:1793–1874CrossRefGoogle Scholar
  23. 23.
    Ess DH, Jones GO, Houk KN (2006). Adv Synth Catal 348:2337–2361CrossRefGoogle Scholar
  24. 24.
    Domingo LR, Aurell MJ, Pérez P, Contreras R (2002). Tetrahedron 58:4417–4423CrossRefGoogle Scholar
  25. 25.
    Yang W, Mortier WJ (1986). J Am Chem Soc 108:5708–5711CrossRefGoogle Scholar
  26. 26.
    Domingo LR, Aurell MJ, Pêrez P, Contreras R (2002). J Phys Chem A 106:6871–6875CrossRefGoogle Scholar
  27. 27.
    Pêrez P, Domingo LR, Duque-Noreňa M, Chamorro E (2009). J Mol Struct THEOCHEM 895:86–91CrossRefGoogle Scholar
  28. 28.
    Domingo LR, Pérez P, Sáez JA (2013). RSC Adv 3:1486–1494CrossRefGoogle Scholar
  29. 29.
    Chamorro E, Pérez P, Domingo LR (2013). Chem Phys Lett 582:141–143CrossRefGoogle Scholar
  30. 30.
    Eyring H (1935). J Chem Phys 3:107–115CrossRefGoogle Scholar
  31. 31.
    Domingo LR (2014). RSC Adv 4:32415–32428CrossRefGoogle Scholar
  32. 32.
    Da Silva RR, Ramalho TC, Santos JM, Figueroa-Villar JD (2006). J Phys Chem A 110:1031–1040CrossRefGoogle Scholar
  33. 33.
    Lee C, Yang W, Parr RG (1988) Phys. Rev. B 37:785–789Google Scholar
  34. 34.
    Zhao Y, Truhlar DG (2006). J Phys Chem 110:5121–5129CrossRefGoogle Scholar
  35. 35.
    Barone V, Cossi M (1998). J Phys Chem A 102:1995–2001CrossRefGoogle Scholar
  36. 36.
    Schlegel HB (1982). J Comput Chem 3:214–218CrossRefGoogle Scholar
  37. 37.
    Peng C, Ayala PY, Schlegel HB, Frisch MJ (1996). J Comput Chem 17:49–56CrossRefGoogle Scholar
  38. 38.
    Gonzalez C, Schlegel HB (1989). J Chem Phys 90:2154–2161CrossRefGoogle Scholar
  39. 39.
    Gonzalez C, Schlegel HB (1990). J Phys Chem 94:5523–5527CrossRefGoogle Scholar
  40. 40.
    Reed AE, Curtiss LA, Weinhold F (1988). Chem Rev 88:899–926CrossRefGoogle Scholar
  41. 41.
    Carpenter JE, Weinhold FJ (1988). J Mol Struct 169:41–62CrossRefGoogle Scholar
  42. 42.
    Domingo LR, Perez P, Ortega DE (2013). J Org Chem 78:2462–2471CrossRefGoogle Scholar
  43. 43.
    Parr RG, Szentpaly LV, Liu S (1999). J Am Chem Soc 121:1922–1924CrossRefGoogle Scholar
  44. 44.
    Parr RG, Pearson RG (1983). J Am Chem Soc 105:7512–7516CrossRefGoogle Scholar
  45. 45.
    Parr RG, Yang W (1989) Density functional theory of atoms and molecules. Oxford University Press, New YorkGoogle Scholar
  46. 46.
    Lecea B, Arrieta A, Roa G, Ugalde JM, Cossio FP (1994). J Am Chem Soc 116:9613–9619CrossRefGoogle Scholar
  47. 47.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta Jr JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2010) Gaussian 09, revision E. Gaussian, Inc, Wallingford, p 01Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceUniversity of Ayatollah Alozma BorujerdiBorujerdIran

Personalised recommendations