Skip to main content
SpringerLink
Log in

Correlation between the pKa and nuclear shielding of α-hydrogen of ketones

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

The α-H acidity is an important chemical property of ketones that has attracted much research interest. Theoretical prediction of pKa for ketone α-H is significant. In this work, we theoretically studied the nuclear shielding of various α-Hs in a set of ketones and that of the corresponding enolic hydroxyl Hs in tautomeric enol forms. It has been demonstrated through linear regression analyses that the pKa values of these ketones correlate with both sets of the calculated nuclear shielding values. The correlation coefficient R2 of the linear correlation relationship is 0.90. The present work has provided a new approach to computationally evaluating the acidity of α-Hs in ketones, enabling us to semi-empirically predict the ketone α-H acidity from the calculated nuclear shielding values.

Experimental pKa values in DMSO vs predicted pKa values calculated from 1H nuclear shielding for the hydroxyl hydrogens in the enol forms and for the α-Hs in the keto forms. The surrounding solvent effects were modelled by keto/enol-DMSO clusters and SMD solvent models

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

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Guthrie JP, Cossar J, Klym A (1982) The pKa of acetone: a kinetic method for determining the pKas of ketones in aqueous solution. J Am Chem Soc 104:895–896

    Article  CAS  Google Scholar 

  2. Albro PW, Parker CA, Abusteit EO, Mester TC, Hass JR, Sheldon YS, Corbin FT (1984) Determination of the pKA values of metribuzin and three of its metabolites: a comparison of spectrophotometric and potentiometric methods. J Agric Food Chem 32:212–217

    Article  CAS  Google Scholar 

  3. Garrido G, Koort E, Ràfols C, Bosch E, Rodima T, Leito I, Rosés M (2006) Acid−base equilibria in nonpolar media. Absolute pKa scale of bases in tetrahydrofuran. J Organomet Chem 71:9062–9067

    Article  CAS  Google Scholar 

  4. Bordwell FG (1988) Equilibrium acidities in dimethyl sulfoxide solution. Acc Chem Res 21:456–463

    Article  CAS  Google Scholar 

  5. Bors DA, Kaufman MJ, Streitwieser A (1985) Carbon acidity. 67. The indicator scale of cesium ion pairs in tetrahydrofuran. J Am Chem Soc 107:6975–6982

    Article  CAS  Google Scholar 

  6. Kolling OW (1974) Empirical acidity functions for strongly basic solutions in the binary solvent: water-dimethyl sulfoxide 76:193–193

  7. Cox RA, Yates K (2011) Acidity functions: an update 61:2225–2243

  8. Nakamura S, Hirao H, Ohwada T (2004) Rationale for the acidity of Meldrum’s acid. consistent relation of C−H acidities to the properties of localized reactive orbital. J Org Chem 69:4309–4316

    Article  CAS  Google Scholar 

  9. Khursan SL, Ovchinnikov MY (2014) The pK(a) theoretical estimation of C-H, N-H, O-H and S-H acids in dimethylsulfoxide solution. J Phys Org Chem 27:926–934

    Article  CAS  Google Scholar 

  10. Lu J, Lu T, Zhao X, Chen X, Zhan C-G (2018) Correlations between the 1H NMR chemical shieldings and the pKa values of organic acids and amines. J Mol Model 24:146

    Article  Google Scholar 

  11. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter 37:785–789

    Article  CAS  Google Scholar 

  12. Becke A (1993) D., Density functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  13. Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ (1994) Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J Phys Chem 98:11623–11627

    Article  CAS  Google Scholar 

  14. Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396

    Article  CAS  Google Scholar 

  15. Cancès E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032–3041

    Article  Google Scholar 

  16. Cossi M, Barone V (1998) Analytical second derivatives of the free energy in solution by polarizable continuum models. J Chem Phys 109:6246–6254

    Article  CAS  Google Scholar 

  17. Mennucci B, Cammi R, Tomasi J (1998) Excited states and solvatochromic shifts within a nonequilibrium solvation approach: a new formulation of the integral equation formalism method at the self-consistent field, configuration interaction, and multiconfiguration self-consistent field level. J Chem Phys 109:2798–2807

    Article  CAS  Google Scholar 

  18. Szelejewska-Woźniakowska A, Chilmonczyk Z, Leś A, Cybulski J, Wawer I (1999) 13-C cross-polarization magic angle spinning NMR and gauge-independent atomic orbital, coupled Hartree–Fock calculations of buspirone analogues: Part 2. Hydrochlorides and perchlorates of 1-arylpiperazine-4-alkylimides. Solid State Nucl Magn Reson 14:59–65

    Article  Google Scholar 

  19. Frisch MJ, Schlegel GWTHB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) Gaussian(R) 09 program. Gaussian, Inc, Wallingford

    Google Scholar 

Download references

Funding

The work was supported by the National Natural Science Foundation of China (grant number 21273089), the Fundamental Research Funds for the South-Central University for Nationalities (CZW17004), the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University (grant number 2018-A01).

Author information

Authors and Affiliations

  1. College of Chemistry & Materials Science, South-Central University for Nationalities, Wuhan, 430074, People’s Republic of China

    Suting Xing, Juanfeng Lu, Xinyun Zhao & Xi Chen

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA

    Chang-Guo Zhan

Authors
  1. Suting Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juanfeng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinyun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chang-Guo Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xi Chen or Chang-Guo Zhan.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Optimized geometries and predicted 1H nuclear shieldings for the solute-DMSO clusters. Experimental pKa values for the ketones in this study. (DOCX 5164 kb)

ESM 1

(DOCX 5164 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xing, S., Lu, J., Zhao, X. et al. Correlation between the pKa and nuclear shielding of α-hydrogen of ketones. J Mol Model 25, 354 (2019). https://doi.org/10.1007/s00894-019-4244-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-019-4244-8

Keywords

Search

Navigation