Skip to main content
SpringerLink
Log in

Computational study on the prototropic tautomerism between simple oxo-, thio-, carbon-, aza-hydrazones, and their respective azines

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

Abstract

Most hydrazone compounds prefer the azine tautomeric states. However, oxygen-/sulfur-substituted compounds prefer hydrazone tautomers. In this study, density functional theory at M062X level with the basis set of 6–311 +  + g(2d, 2p), with MP2/cc-pVTZ for reference, was used to investigate the different tautomeric mechanisms between hydrazone and azine forms with oxygen, sulfur, carbon, and nitrogen as negative centers. The energetic stabilities are in the order as oxygen- < sulfur- < imine- < amidino- < carbene-substituted hydrazones with respect to their azine tautomeric structures. Resonance of the molecular structures might be the geometrical basis for their energy stabilities and were estimated based on HOMED indices. Further, the increased proton affinities in the trend as hydroxyl < sulfhydryl < imine terminal groups account for their increasing azine preferences. Proton release was examined for the reversible equilibrium from azine to hydrazone by calculating the transition energy barrier of H transfer. It is favorable to form hydrazone tautomers for oxygen and sulfur containing groups, while it is less favorable for amino-substituted ones. Azine form is the most stable tautomer for methyl substituted.

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

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Xavier A, Thakur M, Marie JM (2012) Synthesis and spectral characterisation of hydrazone based 14-membered octaaza macrocyclic Ni(II) complexes. J Chem Pharm Res 4:986–990

    CAS  Google Scholar 

  2. Safari J, Gandomi-Ravandi S (2014) Structure, synthesis and application of azines: a historical perspective. RSC Adv 4:46224–46249

    Article  CAS  Google Scholar 

  3. Belskaya NP, Dehaen W, Bakulev VA (2010) Synthesis and properties of hydrazones bearing amide, thioamide and amidine functions. Arch Org Chem 1:275–332

    Google Scholar 

  4. Christie RJ, Anderson DJ, Grainger DW (2010) Comparison of hydrazone heterobifunctional cross-linking agents for reversible conjugation of thiol-containing chemistry. Bioconjugate Chem 21:1779–1787

    Article  CAS  Google Scholar 

  5. Zhou Y, Zhang S, Cai M, Wang K, Feng J, Xie D, Feng L, Peng H, He H (2021) Design, synthesis, and antifungal activity of 2,6-dimethyl-4-aminopyrimidine hydrazones as PDHc-E1 inhibitors with a novel binding mode. J Agric Food Chem 69:5804–5817

    Article  CAS  Google Scholar 

  6. Matsuzaki H, Takeda N, Yasui M, Ito Y, Konishi K, Ueda M (2020) Synthesis of pyrazoles utilizing the ambiphilic reactivity of hydrazones. Org Lett 22:9249–9252

    Article  CAS  Google Scholar 

  7. ElMetwally AE, Zeynaloo E, Shukla D, Surnar B, Dhar S, Cohn JL, Knecht MR, Bachas LG (2021) Cu2O cubes decorated with azine-based covalent organic framework spheres and Pd nanoparticles as tandem photocatalyst for light-driven degradation of chlorinated biphenyls. ACS Appl Nano Mater 4:2795–2805

    Article  CAS  Google Scholar 

  8. Bhambri H, Khullar S, Sakshi, Mandal SK (2022) Nitrogen-rich covalent organic frameworks: a promising class of sensory materials. Mater Adv 3:19–124

    Article  CAS  Google Scholar 

  9. Ye T, McKervey MA (1994) Organic synthesis with .alpha.-diazo carbonyl compounds. Chem Rev 94:1091–1160

    Article  CAS  Google Scholar 

  10. Campeau L-C, Stuart DR, Leclerc J-P, Bertrand-Laperle M, Villemure E, Sun H-Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K (2009) Palladium-catalyzed direct arylation of azine and azole N-oxides: reaction development, scope and applications in synthesis. J Am Chem Soc 131:3291–3306

    Article  CAS  Google Scholar 

  11. Cui Y, Spann AP, Couch LH, Gopee NV, Evans FE, Churchwell MI, Williams LD, Doerge DR, Howard PC (2004) Photodecomposition of pigment yellow 74, a pigment used in tattoo inks. Photochem Photobiol 80:175–184

  12. Price CP, Grzesiak AL, Kampf JW, Matzger AJ (2003) Maize 1: A Trimorphic Azo Pigment. Cryst Growth Des 3:1021–1025

    Article  CAS  Google Scholar 

  13. Phiromphu N, Suramitr S, Chotima R, Boonseng B, Songsasen A, Piyasaengthong A (2021) Azine-hydrazone tautomerism of thiazolylazo pyridine compound: synthesis, structural determination, and biological activities. J Mol Struct 1230:129658

    Article  CAS  Google Scholar 

  14. Ramakrishnan A, Chourasiya SS, Bharatam PV (2015) Azine or hydrazone? The dilemma in amidinohydrazones. RSC Adv 5:55938–55947

    Article  CAS  Google Scholar 

  15. Chourasiya SS, Kathuria D, Nikam SS, Ramakrishnan A, Khullar S, Mandal SK, Chakraborti AK, Bharatam PV (2016) Azine-hydrazone tautomerism of guanylhydrazones: evidence for the preference toward the azine tautomer. J Org Chem 81:7574–7583

    Article  CAS  Google Scholar 

  16. Mutikainen I, Elo H, Tilus P (1993) Crystal and molecular structures of the free base and the monohydrochloride salt of the antileukemic agent glyoxal bis(amidinohydrazone) [‘glyoxal bis(guanylhydrazone)’]. Naturforsch 48:1821–1827

    Article  CAS  Google Scholar 

  17. Liu G-H, Parr RG (1995) On atomic and orbital electronegativities and hardnesses. J Am Chem Soc 117:3179–3188

    Article  CAS  Google Scholar 

  18. 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 Jr JA, 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 O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09. Revision A. 01 Gaussian Inc. Wallingford

  19. Peterson KA, Shepler BC, Figgen D, Stoll H (2006) On the spectroscopic and thermochemical properties of ClO, BrO, IO, and their anions. J Phys Chem A 110:13877–13883

  20. Liptak MD, Shields GC (2005) Comparison of density functional theory predictions of gas-phase deprotonation data. Int J Quantum Chem 105:580–587

    Article  CAS  Google Scholar 

  21. Gillespie RJ (1963) The valence-shell electron-pair repulsion (VSEPR) theory of directed valency. J Chem Educ 40:295

    Article  CAS  Google Scholar 

  22. Gillespie RJ (2008) Fifty years of the VSEPR model. Coord Chem Rev 252:1315–1327

    Article  CAS  Google Scholar 

  23. Valadbeigi Y, Gal J-F (2018) On the significance of lone pair/lone pair and lone pair/bond pair repulsions in the cation affinity and Lewis acid/Lewis base interactions. ACS Omega 3:11331–11339

    Article  CAS  Google Scholar 

  24. Schreiner PR, Kim SJ, III, H. F. S., Schleyer PVR (1993) CH+5: The never-ending story or the final word? J Chem Phys 99:3716–3720

  25. Kwan T, Jordan M (2018) The proton affinity of methane and its isotopologues: a test for theory. Chem Phys Lett 708:216–221

    Article  CAS  Google Scholar 

  26. Valadbeigi Y, Gal J-F (2016) Effect of the number of methyl groups on the cation affinity of oxygen, nitrogen, and phosphorus sites of Lewis bases. J Phys Chem A 120:9109–9116

    Article  CAS  Google Scholar 

  27. Raczyńska ED, Gal J-F, Maria P-C (2016) Enhanced basicity of push–pull nitrogen bases in the gas phase. Chem Rev 116:13454–13511

    Article  Google Scholar 

  28. Aihara J (1976) A new definition of Dewar-type resonance energies. J Am Chem Soc 98:2750–2758

    Article  CAS  Google Scholar 

  29. Krygowski TM (1993) Crystallographic studies of inter- and intramolecular interactions reflected in aromatic character of .pi.-electron systems. J Chem Inf Comput Sci 33:70–78

    Article  CAS  Google Scholar 

  30. Raczyńska ED, Hallman MG, Kolczyńska K, Stępniewski TM (2010) On the harmonic oscillator model of electron delocalization (HOMED) index and its application to heteroatomic π-electron systems. Symmetry 2:1485–1509

    Article  Google Scholar 

  31. Raczyńska ED, Gal J-F, Maria P-C, Michalec P, Zalewski M (2017) Exceptionally high proton and lithium cation gas-phase basicity of the anti-diabetic drug metformin. J Phys Chem A 121:8706–8718

    Article  Google Scholar 

  32. Raczyńska E (2019) Application of the extended HOMED (harmonic oscillator model of aromaticity) index to simple and tautomeric five-membered heteroaromatic cycles with C, N, O, P, and S atoms. Symmetry 11

  33. Lu T, Chen F (2012) Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33:580–592

    Article  Google Scholar 

  34. Casals-Sainz JL, Fernández-Alarcón A, Francisco E, Costales A, Martín Pendás Á (2020) Bond Order Densities in Real Space. J Phys Chem A 124:339–352

    Article  CAS  Google Scholar 

  35. Kunz D, Johnsen EØ, Monsler B, Rominger F (2008) Highly ylidic imidazoline-based fulvenes as suitable precursors for the synthesis of imidazolium-substituted metallocenes. Chem Eur J 14:10909–10914

    Article  CAS  Google Scholar 

  36. Smith BJ, Tho NM, Bouma WJ, Radom L (1991) Unimolecular rearrangements connecting hydroxyethylidene (CH3-C-OH), acetaldehyde (CH3-CH=O) and vinyl alcohol (CH2=CH-OH). J Am Chem Soc 113:6452–6458

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We all thank professor Jianping Wang for his helpful advice.

Author information

Authors and Affiliations

  1. Department of Marine Technology, Rizhao Polytechnic, Yantai North Road 16, Rizhao, Shandong Province, 276800, People’s Republic of China

    Guixiu Wang

  2. Department of Basic Teaching, Rizhao Polytechnic, Yantai North Road 16, Rizhao, Shandong Province, 276800, People’s Republic of China

    Qing Han

  3. School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong Province, 250100, People’s Republic of China

    Rongxiu Zhu

Authors
  1. Guixiu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rongxiu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Guixiu Wang wrote the main manuscript text, Qing Han prepared Figs. 1–4. Rongxiu Zhu gave some useful suggestions on this manuscript.

Corresponding author

Correspondence to Guixiu Wang.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Office of Academic Research of Rizhao Polytech and Quantum Chemical Computing Center in Shandong University. All participants consented to publish the paper.

Consent for publication

All participants consented to publish the paper.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 71 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Han, Q. & Zhu, R. Computational study on the prototropic tautomerism between simple oxo-, thio-, carbon-, aza-hydrazones, and their respective azines. J Mol Model 28, 393 (2022). https://doi.org/10.1007/s00894-022-05387-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-022-05387-2

Keywords

Search

Navigation