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Regioisomers of 2,5,6,7,8-Pentaaryl-1H-Azepino[3,2,1-ij]Quinazoline-1,3(2H)-Dione Containing Various Aryl Substituents in the Azepine Ring: Structure Determination Using NMR Methods

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Abstract

NMR spectroscopy methods were used to prove the structures of two similar regioisomers of 2,5,6,7,8-pentaaryl-1H-azepino[3,2,1-ij]quinazoline-1,3(2H)-dione containing various aryl substituents in the azepine ring which were obtained as reaction products and existed in CDCl3 as inseparable mixture of two compounds with almost equal (56:44) relation between them. Complete signal assignment in 1H and 13C spectra of each compound was made by using some homo- and heteronuclear NMR experiments. Long-range distance estimation (up to 5.0 Å) on the base of nuclear Overhauser enhancement approach (NOE) at conditions of extreme-narrow limits (ωoτc <  < 1) was used to determine the quantitative level the internuclear distances between protons H6 and H8 situated in the rigid part of molecules and the nearest ortho- and meta-protons in mobile phenyl rings Ph5 and Ph2, respectively. The distance difference between the calculated and experimental values in all cases was not more than 10%. These results allowed us to prove that a dominant regioisomer (3a) has para-methoxy-substituted rings at positions 9 and 12 of seven-membered ring C, and a minor regioisomer (3d) has these rings at positions 10 and 12. The results of an independent approach based on the comparison of the chemical shifts of the 1H and 13C nuclei of the regioisomers under study are in full agreement (or do not contradict) with the obtained conclusions based on the quantitative NOE measurements of interproton distances. The methodological approach on the basis of long-range distance estimation by NOE tested in this work can be used to establish the structure of inseparable mixtures of two or more compounds or to solve similar problems under conditions of complex mixtures of closely related organic compounds.

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References

  1. N.S. Bhacca, D.H. Williams, Application of NMR Spectroscopy in Organic Chemistry. Illustrations from the steroid field, (Holden-Day, San Francisco, 1964), 198 P

  2. J.W. Emsley, J. Feeney, Progr. NMR. Spectrosc. 50, 179–198 (2007)

    Google Scholar 

  3. R. R. Ernst, G. Bodenhausen, A. Wokaun, Principles of Nuclear Magnetic Resonance in One and Two Dimensions, (Oxford University Press, Oxford 1987), 711 P

  4. K. Pervushin, R. Riek, G. Wider, K. Wüthrich, Proc. Natl. Acad. Sci. USA 94(23), 12366–12371 (1997)

    Article  ADS  Google Scholar 

  5. J. Wist, Magn. Reson. Chem. 55(1), 22–28 (2017)

    Article  Google Scholar 

  6. O. Beckonert, H.C. Keun, T.M.D. Ebbels, J. Bundy, E. Holmes, J.C. Lindon, J.K. Nicholson, Nat. Protoc. 2(11), 2692–2703 (2007)

    Article  Google Scholar 

  7. P.A. Keifer, Ann. Report NMR Spectroscopy 62(1), 1–47 (2007)

    Google Scholar 

  8. M.P. Williamson, Progr. NMR. Spectrosc. 73, 1–16 (2013)

    Google Scholar 

  9. N. Matsumori, D. Kaneno, M. Murata, H. Nakamura, K.J. Tachibana, J. Org. Chem. 64(3), 866–876 (1999)

    Article  Google Scholar 

  10. D.C. Burns, E.P. Mazzola, W.F. Reynolds, Nat. Prod. Rep. 36(6), 919–933 (2019)

    Article  Google Scholar 

  11. A. Navarro-Vázquez, Magn. Reson. Chem. 55(1), 29–32 (2017)

    Article  Google Scholar 

  12. W.F. Reynolds, R.G. Enrı´quez , J. Nat. Prod. 65(2), 221–244 (2002)

  13. B.L. Marquez, W.H. Gerwick, R.T. Williamson, Magn. Reson. Chem. 39(9), 499–530 (2001)

    Article  Google Scholar 

  14. K. Kobzar, B. Luy, J. Magn. Reson. 186(1), 131–141 (2007)

    Article  ADS  Google Scholar 

  15. S. Braun, H.-O. Kalinowski, S. Berger, 150 and More Basic NMR Experiments. A practical Course (Willey-VCH, 2nd expanded ed. 1998), 596 P

  16. A. Garza-Garcia, G. Ponzanelli-Velazques, Federico del Rio-Portilla. J. Magn. Reson. 148(2), 214–219 (2002)

    ADS  Google Scholar 

  17. D.P. Frueh, Progr. NMR. Spectrosc. 78(2), 47–75 (2014)

    Google Scholar 

  18. S.I. Selivanov, Solov`ev A.Yu., S.N. Morozkina, A.G. Shavva, Rus. J. Bioorg. Chem. 33(3), 302–309 (2007)

  19. C.P. Butts, C.R. Jones, E.C. Towers, J.L. Flynn, L. Appleby, N.J. Barron, Org. Biomol. Chem. 9(1), 177–184 (2011)

    Article  Google Scholar 

  20. C. Zhu, R. Wang, J.R. Falck, Chem. Asian J. 7, 1502–1514 (2012)

    Article  Google Scholar 

  21. G. Song, F. Wang, X. Li, Chem. Soc. Rev. 41, 3651–3678 (2012)

    Article  Google Scholar 

  22. J.F. Hartwig, Chem. Soc. Rev. 40, 1992–2002 (2011)

    Article  Google Scholar 

  23. Z.-Z. Shi, C. Zhang, S. Li, D.-L. Pan, S.-T. Ding, Y.-X. Cui, N. Jiao, Angew. Chem. Int. Ed. 48, 4572–4576 (2009)

    Article  Google Scholar 

  24. L. Wang, J. Huang, S. Peng, H. Liu, X. Jiang, J. Wang, Angew. Chem. Int. Ed. 52, 1768–1772 (2013)

    Article  Google Scholar 

  25. N.L. Allinger, J. Am. Chem. Soc. 99(25), 8127–8134 (1977)

    Article  Google Scholar 

  26. D. Neuhaus, M.P. Williamson, The Nuclear Overhauser Effect in Structural and Conformational Analysis (2nd ed.), (Wiley-VCH, New York, 2000), 619 P

  27. A. Bax, R. Freeman, T.A. Frenkiel, J. Am. Chem. Soc. 103, 2102–2104 (1980)

    Article  Google Scholar 

  28. R.A. Bell, J.K. Saunders, Canad. J. Chem. 48(7), 1114–1122 (1970)

    Article  Google Scholar 

  29. S.I. Selivanov, S. Wang, A.S. Filatov, A.V. Stepakov, Applied Magn. Reson. 51(2), 165–182 (2020)

    Article  Google Scholar 

  30. W.P. Aue, J. Karhan, R.R. Ernst, J. Chem. Phys. 64, 4226–4227 (1976)

    Article  ADS  Google Scholar 

  31. D.J. States, R.A. Haberkorn, D.J. Ruben, J. Magn. Reson. 48(2), 286–292 (1982)

    ADS  Google Scholar 

  32. G. Bodenhausen, D.J. Ruben, Chem. Phys. Lett. 69(1), 185–189 (1980)

    Article  ADS  Google Scholar 

  33. A. Bax, M.F. Sammers, J. Am. Chem. Soc. 108, 2093–2094 (1986)

    Article  Google Scholar 

  34. B. Vögeli, Progr. NMR. Spectrosc. 78, 1–46 (2014)

    Google Scholar 

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Acknowledgements

Spectral NMR investigations were performed in the Resource Centers “Magnetic Resonance Research Center” of the Saint-Petersburg State University. This work was supported by the Ministry of Science and Higher Education of the Russian Federation (0785.00.X6019). V.M.B. is grateful to the Ministry of Education and Science of the Russian Federation (0791-2020-0006) for financial support. S.I.S. acknowledges Saint-Petersburg State University for a research grant 92425251.

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Authors and Affiliations

  1. Saint-Petersburg State Institute of Technology (Technical University), Moskovsky prospect 26, 190013, Saint-Petersburg, Russia

    Julia A. Pronina, Alexander V. Stepakov & Stanislav I. Selivanov

  2. Department of Chemistry, St. Petersburg State University, 199034, St. Petersburg, Russia

    Darya D. Komolova, Alexander V. Stepakov & Stanislav I. Selivanov

  3. Saint Petersburg National Research Academic University of the Russian Academy of Sciences, ul. Khlopina 8/3, 194021, Saint-Petersburg, Russia

    Vitali M. Boitsov

  4. Laboratory of Biomolecular NMR, St. Petersburg State University, 199034, St. Petersburg, Russia

    Stanislav I. Selivanov

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  1. Julia A. Pronina
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  2. Darya D. Komolova
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  3. Vitali M. Boitsov
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  4. Alexander V. Stepakov
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  5. Stanislav I. Selivanov
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Contributions

JAP—participated in the synthesis of the studied compounds, prepared Figs. 1 and 2, compiled Table 1 based on the data obtained, and also actively participated in the discussion of the results and made an oral report on this topic at the Spinus-2022 conference. DDK—participated in the synthesis of the studied compounds and preliminary analysis of NMR spectra, and in the discussion of the text of the manuscript. VMB—participated in the synthesis of the studied compounds and an attempt to isolate them from the reaction mixture, and actively participated in the discussion of the results and the text of the manuscript. AVS—engaged in the substantiation, preparation and implementation of the synthesis of the studied compounds, took an active part in the planning of all work and discussion of the results, and also described the synthesis of the studied regioisomers and the prospects for their practical use. SIS—performed all NMR experiments on the DPX-300 spectrometer (300 MHz) and processed the obtained spectra, wrote the main text of the manuscript, including the design of spectral drawings and quantitative analysis of data on measuring interproton distances using NOEs. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Stanislav I. Selivanov.

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Pronina, J.A., Komolova, D.D., Boitsov, V.M. et al. Regioisomers of 2,5,6,7,8-Pentaaryl-1H-Azepino[3,2,1-ij]Quinazoline-1,3(2H)-Dione Containing Various Aryl Substituents in the Azepine Ring: Structure Determination Using NMR Methods. Appl Magn Reson 53, 1677–1691 (2022). https://doi.org/10.1007/s00723-022-01496-6

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