Skip to main content
SpringerLink
Log in

Methoxyindoles: stability and π-electron delocalization

  • Original Research
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Theoretical calculations performed on the methoxyindole isomers using the B3LYP, MP2, and MP4 methods combined with the 6-311++G(d,p) and 6-311++G(3df,3pd) basis sets reveal that the preferred conformation exhibited by all isomers has the exocyclic group co-planar to the ring plane. Moreover, certain positions of the substituent are found to be far more stable than others. In order to rationalize these results, the harmonic oscillator model of aromaticity (HOMA), together with the natural bond orbital (NBO) and natural resonance theories (NRT), have been employed to evaluate the π-electron delocalization in the different molecules. To act as a reference, the study has been extended to indole. The donor–acceptor interactions were energetically quantified by using the NBO deletion method. In general, the results given by the three approaches are in good agreement and provide complementary data about the main effects of the position/orientation of the methoxy group on the electronic structure of the indole ring. The electron redistribution resulting from the H/OCH3 substitution was also analyzed in terms of the natural hybrid compositions of the πCC orbitals given by the NBO theory and atomic charges.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sunberg RJ (1996) Indoles. Academic Press, New York

    Google Scholar 

  2. Sundberg RJ (1970) The chemistry of indoles. Organic chemistry—a series of monographs, vol 18. Academic Press, New York

    Google Scholar 

  3. Joule John A, Mills K (2012) Heterocyclic chemistry at a glance, 2nd edn. Wiley, Chichester

    Book  Google Scholar 

  4. Gribble GW (ed) (2010) Heterocyclic scaffolds II: reactions and applications of indoles. Topics in heterocyclic chemistry, vol 2. Springer, London

    Google Scholar 

  5. Sharma V, Kumar P, Pathak D (2010) J Heterocyclic Chem 47(3):491–502

    CAS  Google Scholar 

  6. Van Order RB, Lindwall HG (1942) Chem Rev 30(1):69–96

    Article  Google Scholar 

  7. Huether G, Kochen W, Simat TJ, Steinhart S (eds) (1999) Tryptophan, serotonin, and melatonin: basic aspects and applications. Advances in experimental medicine and biology, vol. 467. Kluwer Academic, New York

  8. Kaushik N, Kaushik N, Attri P, Kumar N, Kim C, Verma A, Choi E (2013) Molecules 18(6):6620–6662

    Article  CAS  Google Scholar 

  9. Kochanowska-Karamyan AJ, Hamann MT (2010) Chem Rev 110(8):4489–4497

    Article  CAS  Google Scholar 

  10. Mahboobi S, Pongratz H, Hufsky H, Hockemeyer J, Frieser M, Lyssenko A, Paper DH, Bürgermeister J, Böhmer F-D, Fiebig H-H, Burger NM, Baasner S, Beckers T (2001) J Med Chem 44(26):4535–4553

    Article  CAS  Google Scholar 

  11. Zhang F, Zhao Y, Sun L, Ding L, Gu Y, Gong P (2011) Eur J Med Chem 46(7):3149–3157

    Article  CAS  Google Scholar 

  12. Biswal S, Sahoo U, Sethy S, Kumar HKS, Banerjee M, Banerjee M (2012) Asian J Pharm Clin Res 5:1–6

    CAS  Google Scholar 

  13. Tarzia G, Diamantini G, Di Giacomo B, Spadoni G, Esposti D, Nonno R, Lucini V, Pannacci M, Fraschini F, Stankov BM (1997) J Med Chem 40(13):2003–2010

    Article  CAS  Google Scholar 

  14. Bowden K, Grubbs EJ (1996) Chem Soc Rev 25(3):171–177

    Article  CAS  Google Scholar 

  15. Taft RW, Lewis IC (1958) J Am Chem Soc 80(10):2436–2443

    Article  CAS  Google Scholar 

  16. Campanelli AR, Domenicano A, Ramondo F (2003) J Phys Chem A 107(33):6429–6440

    Article  CAS  Google Scholar 

  17. Kim CK, Han IS, Ryu WS, Lee HW, Lee B-S, Kim CK (2006) J Phys Chem A 110(7):2500–2504

    Article  CAS  Google Scholar 

  18. Krygowski TM, Ejsmont K, Stepień BT, Cyrański MK, Poater J, Solà M (2004) J Org Chem 69(20):6634–6640

    Article  CAS  Google Scholar 

  19. Krygowski TM, Stepień BT (2004) Pol J Chem 78:2213–2217

    CAS  Google Scholar 

  20. Krygowski TM, Stepień BT (2005) Chem Rev 105(10):3482–3512

    Article  CAS  Google Scholar 

  21. Krygowski TM, Dobrowolski MA, Zborowski K, Cyrański MK (2006) J Phys Org Chem 19(12):889–895

    Article  CAS  Google Scholar 

  22. Krygowski TM, Palusiak M, Płonka A, Zachara-Horeglad JE (2007) J Phys Org Chem 20(5):297–306

    Article  CAS  Google Scholar 

  23. Mohajeri A, Shahamirian M (2010) J Mol Struct (Theochem) 951(1–3):72–76

    Article  CAS  Google Scholar 

  24. Mohajeri A, Shahamirian M (2010) J Phys Org Chem 23(5):440–450

    CAS  Google Scholar 

  25. Becke AD (1988) Phys Rev A 38(6):3098–3100

    Article  CAS  Google Scholar 

  26. Becke AD (1993) J Chem Phys 98(7):5648–5652

    Article  CAS  Google Scholar 

  27. Lee CT, Yang WT, Parr RG (1988) Phys Rev B 37(2):785–789

    Article  CAS  Google Scholar 

  28. Frisch MJ, Head-Gordon M, Pople JA (1990) Chem Phys Lett 166(3):275–280

    Article  CAS  Google Scholar 

  29. Frisch MJ, Head-Gordon M, Pople JA (1990) Chem Phys Lett 166(3):281–289

    Article  CAS  Google Scholar 

  30. Head-Gordon M, Head-Gordon T (1994) Chem Phys Lett 220(1–2):122–128

  31. Krishnan R, Pople JA (1978) Int J Quantum Chem 14(1):91–100

    Article  CAS  Google Scholar 

  32. Frisch GWT MJ, 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 J A Jr, Peralta 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 Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) GAUSSIAN 09. A.02 edn. Gaussian, Inc., Wallingford

    Google Scholar 

  33. Weinhold F, Landis CR (2005) Valency and bonding: a natural bond orbital donor–acceptor perspective. Cambridge University Press, New York

    Book  Google Scholar 

  34. Weinhold F, Landis CR (2012) Discovering chemistry with natural bond orbitals. Wiley, Hoboken

    Book  Google Scholar 

  35. Glendening ED, Landis CR, Weinhold F (2012) WIREs Comput Mol Sci 2(1):1–42

    Article  CAS  Google Scholar 

  36. Glendening ED, Badenhoop JK, Weinhold F (1998) J Comput Chem 19(6):628–646

    Article  CAS  Google Scholar 

  37. Glendening ED, Weinhold F (1998) J Comput Chem 19(6):593–609

    Article  CAS  Google Scholar 

  38. Glendening ED, Weinhold F (1998) J Comput Chem 19(6):610–627

    Article  CAS  Google Scholar 

  39. Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F (2001) NBO 5.G. Theoretical Chemistry Institute, University of Wisconsin, Madison

    Google Scholar 

  40. Krygowski TM, Cyrański MK (2001) Chem Rev 101(5):1385–1420

    Article  CAS  Google Scholar 

  41. Krygowski TM, Szatylowicz H, Stasyuk OA, Dominikowska J, Palusiak M (2014) Chem Rev 114(12):6383–6422

    Article  CAS  Google Scholar 

  42. Balaban AT, Oniciu DC, Katritzky AR (2004) Chem Rev 104(5):2777–2812

    Article  CAS  Google Scholar 

  43. Cyrañski MK, Ksawery M (2005) Chem Rev 105(10):3773–3811

    Article  Google Scholar 

  44. Krygowski TM (1993) J Chem Inf Comput Sci 33(1):70–78

    Article  CAS  Google Scholar 

  45. Kruszewski J, Krygowski TM (1972) Tetrahedron Lett 13(36):3839–3842

    Article  Google Scholar 

  46. Katritzky AR, Jug K, Oniciu DC (2001) Chem Rev 101(5):1421–1450

    Article  CAS  Google Scholar 

  47. Madura ID, Krygowski TM, Cyrañski MK (1998) Tetrahedron 54(49):14913–14918

    Article  CAS  Google Scholar 

  48. Andrzejak M, Kubisiak P, Zborowski K (2013) Struct Chem 24(4):1171–1184

    Article  CAS  Google Scholar 

  49. Raczyńska ED, Hallman M, Kolczyńska K, Stępniewski TM (2010) Symmetry 2(3):1485–1509

    Article  Google Scholar 

  50. Bansal RK (1999) Heterocyclic chemistry, 3rd edn. New Age International Publishers, New Delhi

    Google Scholar 

  51. Lopes Jesus AJ, Redinha JS (2013) Comput Theor Chem 1023(0):74–82

    Article  CAS  Google Scholar 

  52. Breneman CM, Wiberg KB (1990) J Comput Chem 11(3):361–373

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, University of Coimbra, 3004-295, Coimbra, Portugal

    A. J. Lopes Jesus

  2. Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal

    A. J. Lopes Jesus & J. S. Redinha

Authors
  1. A. J. Lopes Jesus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. S. Redinha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. J. Lopes Jesus.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 100 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopes Jesus, A.J., Redinha, J.S. Methoxyindoles: stability and π-electron delocalization. Struct Chem 26, 655–666 (2015). https://doi.org/10.1007/s11224-014-0520-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-014-0520-5

Keywords

Search

Navigation