Skip to main content
SpringerLink
Log in

Comparative study on the methods for predicting the reactive site of nucleophilic reaction

Science China Chemistry Aims and scope Submit manuscript

Cite this article

Abstract

Predicting the reactivity of nucleophilic reaction at different sites has important theoretical and practical significance. Many prediction methods solely based on the electronic structure of reactants have been proposed. In this paper, detailed comparative analyses on the reliability of 14 methods are carried out and three series of molecules, carbonyl compounds, aromatic hydrocarbons and pyridine derivatives are exploited as test systems. It is found that the methods reflecting local electronic softness, such as condensed dual descriptor, have satisfactory prediction ability; while the ones reflecting electrostatic effect, such as atomic charge analysis and electrostatic potential analysis, have evidently worse overall performance. For all systems of interest, condensed dual descriptor and Hirshfeld charge display the most robust predictive capacity.

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

References

  1. Wade Jr LG. Organic Chemistry. 6th Ed. New Jersey: Pearson Education International, 2006

    Google Scholar 

  2. Cao CZ, Wu YX. Recent progress in quantifying substituent effects. Sci China Chem, 2013, 56: 883–910

    Article  CAS  Google Scholar 

  3. Marx D, Hutter J. Ab Initio Molecular Dynamics-Basic Theory and Advanced Methods. Cambridge: Cambridge University Press, 2009

    Book  Google Scholar 

  4. Esteves PM, de M. Carneiro JW, Cardoso SP, Barbosa AGH, Laali KK, Rasul G, Surya Rrakash GK, Olah GA. Unified mechanistic concept of electrophilic aromatic nitration: convergence of computational results and experimental data. J Am Chem Soc, 2003, 125: 4836–4849

    Article  CAS  Google Scholar 

  5. Jensen F. Introduction to Computational Chemistry. 2nd Ed. West Sussex: John Wiley & Sons, 2007. 487–492

    Google Scholar 

  6. Parr RG, Yang W. Density functional approach to the frontier-electron theory of chemical reactivity. J Am Chem Soc, 1984, 106: 4049–4050

    Article  CAS  Google Scholar 

  7. Morell C, Grand A, Toro-Labbé A. New dual descriptor for chemical reactivity. J Phys Chem A, 2004, 109: 205–212

    Article  Google Scholar 

  8. Sjoberg P, Politzer P. Use of the electrostatic potential at the molecular surface to interpret and predict nucleophilic processes. J Phys Chem, 1990, 94: 3959–3961

    Article  CAS  Google Scholar 

  9. Lu T, Chen FW. Comparison of computational methods for atomic charges. Acta Phys Chim Sin, 2012, 28: 1–18

    Google Scholar 

  10. Roy RK. Stockholders charge partitioning technique. A reliable electron population analysis scheme to predict intramolecular reactivity sequence. J Phys Chem A, 2003, 107: 10428–10434

    Article  CAS  Google Scholar 

  11. Fu R, Lu T, Chen FW. Comparing methods for predicting the reactive site of electrophilic substitution. Acta Phys Chim Sin, 2014, 30: 628–639

    CAS  Google Scholar 

  12. Liu SB. Conceptual density functional theory and some recent developments. Acta Phys Chim Sin, 2009, 25: 590–600

    CAS  Google Scholar 

  13. Yang W, Mortier WJ. The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines. J Am Chem Soc, 1986, 108: 5708–5711

    Article  CAS  Google Scholar 

  14. Jin JL, Li HB, Lu T, Duan YA, Geng Y, Wu Y, Su ZM. Density functional studies on photophysical properties and chemical reactivities of the triarylboranes: effect of the constraint of planarity. J Mol Model, 2013, 19: 3437–3446

    Article  CAS  Google Scholar 

  15. Oláh J, van Alsenoy C, Sannigrahi AB. Condensed Fukui functions derived from stockholder charges: assessment of their performance as local reactivity descriptors. J Phys Chem A, 2002, 106: 3885–3890

    Article  Google Scholar 

  16. Fukui K. Theory of Orientation and Stereoselection. Berlin: Springer, 1970. 1–85

    Book  Google Scholar 

  17. Lu T, Chen FW. Calculation of molecular orbital composition. Acta Chim Sin, 2011, 69: 2393–2406

    CAS  Google Scholar 

  18. Roy RK, Krishnamurti S, Geerlings P, Pal S. Local softness and hardness based reactivity descriptors for predicting intra- and intermolecular reactivity sequences: carbonyl compounds. J Phys Chem A, 1998, 102: 3746–3755

    Article  CAS  Google Scholar 

  19. Mulliken RS. Electronic population analysis on LCAO-MO molecular wave functions. I. J Chem Phys, 1955, 23: 1833–1840

    Article  CAS  Google Scholar 

  20. Breneman CM, Wiberg KB. Determining atom-centered monopoles from molecular electrostatic potentials. the need for high sampling density in formamide conformational analysis. J Comput Chem, 1990, 11: 361–373

    Article  CAS  Google Scholar 

  21. Weinhold F. Natural bond orbital methods. In: Schleyer PVR. Encyclopedia of Computational Chemistry. West Sussex: John Wiley & Sons, 1998. 1792–1811

    Google Scholar 

  22. Hirshfeld FL. Bonded-atom fragments for describing molecular charge densities. Theor Chem Acc, 1977, 44: 129–138

    Article  CAS  Google Scholar 

  23. Lu T, Chen F. Atomic dipole moment corrected hirshfeld population method. J Theor Comp Chem, 2012, 11: 163–183

    Article  CAS  Google Scholar 

  24. Murray JS, Politzer P. The electrostatic potential: an overview. WIREs Comp Mol Sci, 2011, 1: 153–163

    Article  CAS  Google Scholar 

  25. Lipkowitz KB, Cundari TR, Boyd DB. Reviews in Computational Chemistry. New York: John Wiley & Sons, 1991. 273–312

    Book  Google Scholar 

  26. Geerlings P, Langenaeker W, De Proft F. Molecular electrostatic potentials vs. DFT descriptors of reactivity. In: Murray JS, Sen K, Eds. Molecular Electrostatic Potentials: Concepts and Applications. Amsterdam: Elsevier Science BV, 1996, 3: 587–617

    Article  CAS  Google Scholar 

  27. Politzer P, Murray JS. The fundamental nature and role of the electrostatic potential in atoms and molecules. Theor Chem Acc, 2002, 108: 134–142

    Article  CAS  Google Scholar 

  28. Bader RFW, Carroll MT, Cheeseman JR, Chang C. Properties of atoms in molecules: atomic volumes. J Am Chem Soc, 1987, 109: 7968–7979

    Article  CAS  Google Scholar 

  29. Lu T, Chen FW. Quantitative analysis of molecular surface based on improved marching tetrahedra algorithm. J Mol Graph Model, 2012, 38: 314–323

    Article  Google Scholar 

  30. Pearson RG. Hard and soft acids and bases. J Am Chem Soc, 1963, 85: 3533–3539

    Article  CAS  Google Scholar 

  31. Politzer P, Murray JS. The average local ionization energy: concepts and applications. In: Toro-Labbé A, Ed. Theoretical Aspects of Chemical Reactivity. Amsterdam: Elsevier, 2007. 119–137

    Chapter  Google Scholar 

  32. Domingo LR, Pérez P, Sáez JA. Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Adv, 2013, 3: 1486–1494

    Article  CAS  Google Scholar 

  33. Lu T, Chen FW. Meaning and functional form of the electron localization function. Acta Phys Chim Sin, 2011, 27: 2786–2792

    CAS  Google Scholar 

  34. Bader RFW, Chang C. Properties of atoms in molecules: electrophilic aromatic substitution. J Phys Chem, 1989, 93: 2946–2956

    Article  CAS  Google Scholar 

  35. Murray JS, Peralta-Inga Z, Politzer P, Ekanayaka K, LeBreton P. Computational characterization of nucleotide bases: molecular surface electrostatic proteins and local ionization energies, and local polarization energies. Int J Quantum Chem, 2001, 83: 245–254

    Article  CAS  Google Scholar 

  36. Ehresmann B, Martin B, Horn AHC, Clark T. Local molecular properties and their use in predicting reactivity. J Mol Model, 2003, 9: 342–347

    Article  CAS  Google Scholar 

  37. Parthasarathi R, Padmanabhan J, Elango M, Subramanian V, Chattaraj PK. Intermolecular reactivity through the generalized philicity concept. Chem Phys Lett, 2004, 394: 225–230

    Article  CAS  Google Scholar 

  38. Morell C, Grand A, Toro-Labbé A. New dual descriptor for chemical reactivity. J Phys Chem A, 2005, 109: 205–212

    Article  CAS  Google Scholar 

  39. Oláh J, van Alsenoy C, Sannigrahi AB. Condensed Fukui functions derived from stockholder charges: assessment of their performance as local reactivity descriptors. J Phys Chem A, 2002, 106: 3885–3890

    Article  Google Scholar 

  40. Politzer P, Murray JS. Molecular electrostatic potentials and chemical reactivity. In: Lipkowitz KB, Boyd DB, Eds. Reviews in Computational Chemistry. Volume 2. New York: John Wiley & Sons, 1991: 273–312

    Article  CAS  Google Scholar 

  41. Wang JT, Hu Q, Zhang B, Wang Y. Organic Chemistry. 2nd Ed. Tianjin: NanKai University Press, 1993

    Google Scholar 

  42. Morrison RT, Boyd RN. Organic Chemistry. 6th Ed. New Jersey: Prentice Hall, Inc., 1992

    Google Scholar 

  43. Smith MB, March J. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. New York: John Wiley & Sons, 2007

    Google Scholar 

  44. Chupakhin ON, Charushin VN, van der Plas HC. Nucleophilic Aromatic Substitution of Hydrogen. London: Academic Press, 2012

    Google Scholar 

  45. Terrier, François. Modern Nucleophilic Aromatic Substitution. New York: John Wiley & Sons, 2013

    Book  Google Scholar 

  46. Deuri S, Phukan P. A DFT study on nucleophilicity and site selectivity of nitrogen nucleophiles. Comput Theor Chem, 2012, 980: 49–55

    Article  CAS  Google Scholar 

  47. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vrevon T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Menucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomparts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Namayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA. Gaussian 03. Version B.02. Wallingford, CT: Gaussian, Inc., 2004

    Google Scholar 

  48. Becke AD. A new mixing of Hartree-Fock and local densityfunctional theories. J Chem Phys, 1993, 98: 1372–1377

    Article  CAS  Google Scholar 

  49. Lu T, Chen FW. Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem, 2012, 33: 580–592

    Article  Google Scholar 

  50. Multiwfn website: http://Multiwfn.codeplex.com (accessed on 2014-10-10)

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China

    Jingsi Cao, Qing Ren & Feiwu Chen

  2. Beijing Kein Research Center for Natural Sciences, Beijing, 100022, China

    Tian Lu

Authors
  1. Jingsi Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feiwu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tian Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feiwu Chen.

Additional information

Dedicated to Professor Lemin Li on the occasion of his 80th birthday.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cao, J., Ren, Q., Chen, F. et al. Comparative study on the methods for predicting the reactive site of nucleophilic reaction. Sci. China Chem. 58, 1845–1852 (2015). https://doi.org/10.1007/s11426-015-5494-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-015-5494-7

Keywords

search

Navigation