Isolation, Identification, and Chromatographic Separation of N-Methyl Derivatives of Glycoluril

Abstract

Mono-, di-, and tetramethylglycolurils were synthesized, isolated, and purified. For the first time, the cis- and the trans-isomers of N,N-dimethylglycoluril were isolated as individual substances by semi-preparative HPLC method. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, and HR–HPLCMS. The EI mass spectra of individual substances were obtained by the GC–MS. Retention and resolution of N-methyl glycolurils were investigated in the reversed-phase HPLC mode for different stationary phases: C18, SB–Aq, and Luna 5u PFP(2). The retention of N-methyl glycolurils depended on the amount of CH3 groups and distance between the CH3 groups in the structure. The stationary phases provided different selectivity for glycoluril and its N-methyl derivatives due to different shape selectivity. Complete separation of the N-methyl derivatives of glycoluril was achieved in 4.5 min on the stationary phase with pentafluorophenyl propyl ligand in a gradient mode.

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References

  1. 1.

    Ministry of Health of the Russian Federation (2017) FS000189-280911 Tetramethyltetraazabicyclooctandione. State Register of Drugs, Moscow

  2. 2.

    Novikov SS, Khmelnitsky LI, Lebedev OI (1977) 2,4,6,8-Tetra-methyl-2,4,6,8-tetraazabicyclo-[3.3.0]-octanedi-3,7-one in treating psychic disorders, Patent US 4,004,013 A, 18 Jan 1977

  3. 3.

    Kamburg R (2008) Method for neuroprotection with glycoluril derivatives, Patent US 0,227,838 A1, 18 Sep 2008

  4. 4.

    Fiala T, Sindelar V (2016) Supramolecular complexes of bambusurils with dialkyl phosphates. Supramol Chem 28:810–816

    CAS  Article  Google Scholar 

  5. 5.

    Havel V, Svec J, Wimmerova A at al (2011) Bambus[n]urils: a new family of macrocyclic anion receptors. Org Lett 13(15):4000–4003

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Havel V (2017) Bambusuril derivatives: synthesis and supramolecular properties. PhD Dissertation, Masaryk University

  7. 7.

    Stancl A, Svec J, Sindelar V (2011) Novel supramolecular hosts based on linear and cyclic oligomers of glycoluril. Isr J Chem 51:592–599

    CAS  Article  Google Scholar 

  8. 8.

    Fiala T, Ludvikova L, Heger D et al (2017) Bambusuril as a one electron donor for photoinduced electron transfer to methyl viologen in mixed crystals. J Am Chem Soc 97(7):2597–2603

    Article  CAS  Google Scholar 

  9. 9.

    Havel V, Babik M (2017) Modulation of Bambusuril anion affinity in water. Chem A Eur J 23(37):8963–8968

    CAS  Article  Google Scholar 

  10. 10.

    Solel E, Singh M, Reany O, Keinan E (2016) Enhanced anion binding by heteroatom replacement in bambusurils. Phys Chem Chem Phys 18:13180–13185

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Veniamin MP, Vakirtzi-Lemonias C (1970) Chemical basis of the carbamidodiacetyl micromethod for estimation of urea, citrulline, and carbamyl derivatives. Clin Chem 16(1):3–6

    CAS  PubMed  Google Scholar 

  12. 12.

    Grillon E, Gallo R, Pierrota M, Boileaub J, Wimmerb E (1987) Isolation and X-ray structure of the intermediate dihydroxyimidazolidine (DHI) in the synthesis of glycoluril from glyoxal and urea. Tetrahedron Lett 29(9):1015–1016

    Article  Google Scholar 

  13. 13.

    Correia HD, Cicolani RS, Moral RF, Demets GJF (2017) Easy synthesis of trans-4,5-dihydroxy-2-imidazolidinone and 2,4-dimethylglycoluril. Synthesis 48:210–212

    Google Scholar 

  14. 14.

    Ajami D, Rebek J (2013) Unexpected consequences of methyl substitutions in supramolecular chemistry. Supramol Chem 25:574–580

    CAS  Article  Google Scholar 

  15. 15.

    Kravchenko AN, Sigachev AS, Maksareva EY et al (2005) Synthesis of new chiral mono-, di-, tri-, and tetraalkylglycolurils. Rus Chem Bull Int Ed 54(3):691–704

    CAS  Article  Google Scholar 

  16. 16.

    Kravchenko AN, Strelenko YA (2013) Synthesis of 2,4,6-trialkyl-8-(2,3-epoxypropyl)glycolurils. Mendeleev Commun 23:104–105

    CAS  Article  Google Scholar 

  17. 17.

    Lyubavskaya SS, Chernov YN, Batishcheva GA, Ushakov IB, Goncharova NY (2016) Complex therapy of chronic pancreatitis complicated by anxio-depressive disorders in railroad workers. Res Result Pharmacol Clin Pharmacol 2(4):73–86

    Google Scholar 

  18. 18.

    Nematollahi J, Ketcham R (1963) The reaction of ureas with glyoxal. Tetrahydroimidazo[4,5-d]imidazole-2,5-diones. Imidazoimidazoles 28:2378–2380

    CAS  Google Scholar 

  19. 19.

    Slezak FB, Bluestone H, Magee TA et al (1962) Preparation of substituted glycolurils and their N-chlorinated derivatives. J Org Chem 27:2181–2183

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This research was supported by “The Tomsk State University competitiveness improvement programme” under Grant No. 8.2.10.2018.

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Correspondence to D. V. Novikov.

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This article does not contain any studies with human participants or animals performed by any of the authors. No compliance with ethical standards was involved.

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Kurgachev, D.A., Kotelnikov, O.A., Novikov, D.V. et al. Isolation, Identification, and Chromatographic Separation of N-Methyl Derivatives of Glycoluril. Chromatographia 81, 1431–1437 (2018). https://doi.org/10.1007/s10337-018-3599-9

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Keywords

  • Column liquid chromatography
  • Mass spectrometry
  • Nuclear magnetic resonance spectroscopy
  • Methyl glycoluril
  • Mebicar