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Reactions of 1-trifluoromethyl-prop-2-yne1-iminium salts with 2- and 3-aminopyridines

  • Bianca Seitz ORCID logo and Gerhard Maas ORCID logo EMAIL logo
Published/Copyright: May 30, 2022
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Zeitschrift für Naturforschung B
From the journal Zeitschrift für Naturforschung B Volume 77 Issue 7-8

Abstract

4-CF3-pyrido[1,2-a]pyrimidin-5-ium triflates could be prepared in fair to high yields from acetylenic iminium salts R-C≡C–C(CF3)=N+Me2·CF3SO3 − and 2-aminopyridinium triflate under thermal conditions. Their reactions with protic heteronucleophiles, leading to 4-CF3, 4-XR-substituted 1,4-dihydropyrido[1,2-a]pyrimidin-5-ium salts, have been studied and reversible addition as well as subsequent opening of the pyrimidine ring have been observed. The cyclocondensation of a 3-phenyl-propyniminium triflate and 3-aminoyridinium triflate required strong thermal activation and yielded a 4-CF3-and a 4-CF3,5-CH3-[1,7]naphthyridine. A 1-CF3-benzo[f][1,7]naphthyridine was obtained from the same propyniminium salt and 3-aminoquinolinium triflate.

Keywords: 1,7-naphthyridines; acetylenic iminium salts; aminopyridines; organofluorine chemistry; pyrido[1,2-a]pyrimidines; trifluoromethylated building blocks
Corresponding author: Gerhard Maas, Institute of Organic Chemistry I, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany, E-mail:

Acknowledgments

We thank Dr. Markus Wunderlin for recording the mass spectra and Bernhard Müller for the X-ray data collection. Elisabeth Urbanke and Nikola Majstorović have contributed experimentally during their Master studies.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported financially by Ulm University.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed.; WileyVCH: Weinheim, 2013.10.1002/9783527651351Search in Google Scholar

2. Petrov, V. H., Ed. Fluorinated Heterocyclic Compounds – Synthesis, Chemistry, and Applications; John Wiley & Sons: Hoboken, NJ, 2009.10.1002/9780470528952Search in Google Scholar

3(a). Haufe, G., Leroux, F., Eds. Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals; Academic Press: Oxford, 2019.Search in Google Scholar

(b) Ojima, I., Ed. Fluorine in Medicinal Chemistry and Chemical Biology; John Wiley & Sons: Chichester, 2009.10.1002/9781444312096Search in Google Scholar

4. Purser, S., Moore, P. R., Swallow, S., Gouverneur, V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 237–432. https://doi.org/10.1039/b610213c.Search in Google Scholar PubMed

5. Hunter, L. The C–F bond as a conformational tool in organic and biological chemistry. Beilstein J. Org. Chem. 2010, 6, 38. https://doi.org/10.3762/bjoc.6.38.Search in Google Scholar PubMed PubMed Central

6. Wang, J., Sánchez-Roselló, M., Aceña, J. L., del Pozo, C., Sorochinsky, A. E., Fustero, S., Soloshonok, V. A., Liu, H. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001−2011). Chem. Rev. 2014, 114, 2432–2506. https://doi.org/10.1021/cr4002879.Search in Google Scholar PubMed

7. Schneider, T., Seitz, B., Schiwek, M., Maas, G. 1-Fluoroalkyl-prop-2-yne 1-imines and 1-iminium salts as building blocks: a new synthesis of α-(trifluoromethyl)pyrroles. J. Fluor. Chem. 2020, 235, 109567. https://doi.org/10.1016/j.jfluchem.2020.109567.Search in Google Scholar

8. Schneider, T., Fleischmann, M., Hergesell, D., Majstorović, N., Maas, G. A convenient synthesis of 4-CF3-quinolines from 1-trifluoromethyl-prop-2-yne 1-iminium salts and arylamines. Eur. J. Org Chem. 2021, 2869–2886. https://doi.org/10.1002/ejoc.202100378.Search in Google Scholar

9. Seitz, B., Schneider, T., Majstorović, N., Fleischmann, M., Maas, G. Reactions of 1-trifluoromethyl-propyne 1-iminium salts with nitroanilines: synthesis of 4-CF3-nitroquinolines and 1,2,3-trisubstituted-5-CF3-pyrroles. Synthesis 2022, 54, 2057–2069.10.1055/a-1685-2279Search in Google Scholar

10. Seitz, B., Maas, G. A convenient synthesis of trifluoromethyl-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines. Z. Naturforsch. 2021, 76b, 495–501. https://doi.org/10.1515/znb-2021-0099.Search in Google Scholar

11. Schneider, T., Keim, M., Seitz, B., Maas, G. Reactions of 3-aryl-1-trifluoromethyl-prop-2-yne iminium salts with 1,3-dienes and styrenes. Beilstein J. Org. Chem. 2020, 16, 2064–2072. https://doi.org/10.3762/bjoc.16.173.Search in Google Scholar PubMed PubMed Central

12. Schneider, T., Heinrich, G., Koch, R., Maas, G. Reactions of a 3-Phenyl-2-trifluoromethyl-prop-2-yne iminium salt with furans, thiophenes, and pyrroles. Eur. J. Org Chem. 2021, 1011–1025. https://doi.org/10.1002/ejoc.202001577.Search in Google Scholar

13. Maas, G., Koch, R. 1-Trifluoromethyl-prop-2-yne 1-iminium salts and 1-imines: reactions with the mesoionic “Nitron”. Z. Naturforsch. 2020, 75b, 1065–1074. https://doi.org/10.1515/znb-2020-0178.Search in Google Scholar

14. Bonacorso, H. G., Andrighetto, R., Krüger, N., Zanatta, N., Martins, M. A. P. General pathway for a convenient one-pot synthesis of trifluoromethyl-containing 2-amino-7-alkyl(aryl/heteroaryl)-1,8-naphthyridines and fused cycloalkane analogues. Molecules 2011, 16, 2817–2832. https://doi.org/10.3390/molecules16042817.Search in Google Scholar

15. Fossey, J., Loupy, A., Strzelecka, H. An abinitio study of protonation and alkylation of aminopyridine. Tetrahedron 1981, 37, 1935–1941. https://doi.org/10.1016/s0040-4020(01)97943-8.Search in Google Scholar

16. Bellobono, I., Favini, G. Ultraviolet absorption and protonation equilibria of amino- and nitro-substituted pyridines. J. Chem. Soc. B 1971, 2034–2037.10.1039/j29710002034Search in Google Scholar

17. Nikitin, S. V., Smirnov, L. D. Synthesis, chemical and biological properties of pyrido[1,2-a]pyrimidines. Chem. Heterocycl. Compd. 1994, 30, 507–522. https://doi.org/10.1007/bf01169824.Search in Google Scholar

18. Hermecz, I. Recent development in the chemistry of pyrido-oxazines, pyrido-thiazines, pyrido-diazines and their benzologs. Part 2. Adv. Heterocycl. Chem. 2003, 85, 175–286. https://doi.org/10.1016/s0065-2725(03)85003-1.Search in Google Scholar

19. Alam, M. A., Alsharif, Z., Alkhattabi, H., Jones, D., Delancey, E., Gottsponer, A., Yang, T. Hexafluoroisopropyl alcohol mediated synthesis of 2,3-dihydro-4H-pyrido[1,2-a]pyrimidin-4-ones. Sci. Rep. 2016, 6, 36316. and lit. cit. https://doi.org/10.1038/srep36316.Search in Google Scholar PubMed PubMed Central

20. Hajós, G. Recent advances in the area of pyridodiazinium systems containing bridgehead-nitrogen atom. Curr. Org. Chem. 2006, 10, 319–332.10.2174/138527206775473887Search in Google Scholar

21. Sawyer, J. R. H., Wibberley, G. Pyrido[l,2-a]pyrimidinium salts. Part I. Synthesis from 2-aminopyridines and interconversion with 2-(2-acylvinylamino)pyridines. J. Chem. Soc., Perkin Trans. 1 1970, 1, 1138–1143. https://doi.org/10.1039/p19730001138.Search in Google Scholar PubMed

22. Singh, O. M., Devi, L. R., Singh, T. P., Ila, H. Intramolecular cyclocondensation of α-oxoketene N,N-, N,S-and N,O-acetals: synthesis of novel pyrido[1,2-a]pyrimidinium tetrafluoroborates. Arkivoc 2011, 297–309.10.3998/ark.5550190.0012.224Search in Google Scholar

23. Manna, S. K., Mandal, A., Mondal, S. K., Adak, A. K., Jana, A., Das, S., Chattopadhyay, S., Ro, S., Ghorai, S. K., Samanta, S., Hossain, M., Baidya, M. Pyrido[1,2-a]pyrimidinium ions – novel bridgehead nitrogen heterocycles: synthesis, characterisation, and elucidation of DNA binding and cell imaging properties. Org. Biomol. Chem. 2015, 13, 8037–8047. https://doi.org/10.1039/c5ob01082a.Search in Google Scholar

24. Fischer, G. H. Vinyloge Acylverbindungen. XII. Über die Umsetzung von 2-Chlorvinylketonen mit 2-Aminopyridin. J. Prakt. Chem. 1974, 316, 474–484. https://doi.org/10.1002/prac.19743160316.Search in Google Scholar

25. Girreser, U., Heber, D., Rostaie-Gerylow, M., Schütt, M. Reactions of 3-chloropropeniminium salts with aminopyridines. Synthesis of N-pyridylpyridinium and pyrido[1,2-a]pyrimidinium salts. Z. Naturforsch. 2004, 59b, 424–430. https://doi.org/10.1515/znb-2004-0410.Search in Google Scholar

26. Jahromi, E. B., Mehranpour, A., Nowrouzi, N. Facile synthesis of novel 3-substituted pyrido[1,2-a]pyrimidinium salts using vinamidinium salts. Synth. Commun. 2016, 46, 1833–1839. https://doi.org/10.1080/00397911.2016.1230875.Search in Google Scholar

27. Tamura, S., Ono, M. Reaction of heterocyclic compound with malonaldehyde derivatives. Chem. Pharm. Bull. 1978, 26, 3167–3177. https://doi.org/10.1248/cpb.26.3167.Search in Google Scholar

28. Miyadera, T., Tachikawa, R. Studies on quinolizinium salts-VII. The reaction of quinolizinium ion with aniline. Tetrahedron 1969, 25, 837–845. and other references in this series. https://doi.org/10.1016/0040-4020(69)85016-7.Search in Google Scholar

29. Miyadera, T., Ohki, E., Iwai, I. The studies on quinolizinium salts. II. Ring opening reactions of quinolizinium bromide by Grignard reagents. Chem. Pharm. Bull. 1964, 12, 1344–1351. https://doi.org/10.1248/cpb.12.1344.Search in Google Scholar

30. Miyadera, T. Studies on quinolizinium salts. III. Ring opening reactions of monomethylquinolizinium bromides by phenylmagnesium bromide. Chem. Pharm. Bull. 1965, 13, 503–510.https://doi.org/10.1248/cpb.13.503.Search in Google Scholar

31. Arai, S., Hida, M. Polycyclic aromatic nitrogen cations. In: Advances in Heterocyclic Chemistry, Vol. 55; Katritzky, A., Ed.; Academic Press: New York, 1992, pp. 261‒358.10.1016/S0065-2725(08)60223-8Search in Google Scholar

32. Wozniak, M., van der Plas, H. C. Advances in the chemistry of 1,7-naphthyridines. Heterocycles 1982, 61, 318–403.10.1002/chin.198232340Search in Google Scholar

33. Paudler, W. W., Sheets, R. M. Recent developments in naphthyridine chemistry. Adv. Heterocycl. Chem. 1983, 33, 147–184. https://doi.org/10.1016/s0065-2725(08)60053-7.Search in Google Scholar

34. Litvinov, V. P., Roman, S. V., Dyachenko, V. D. Naphthyridines. Structure, physicochemical properties and general methods of synthesis. Russ. Chem. Rev. 2000, 69, 201–220. https://doi.org/10.1070/rc2000v069n03abeh000553.Search in Google Scholar

35. Walraven, H. G. M., Choudry, G. G., Pandit, U. K. Synthesis of 1,5- and 1,7-naphthyridin-4(1H)-ones. Recl. Trav. Chim. Pays-Bas 1976, 95, 220–223.10.1002/recl.19760950909Search in Google Scholar

36. Chrząstek, L., Mianowska, B., Śliwa, W. Synthesis and properties of methyl-, formyl- and amino-diazaphenanthrene. Aust. J. Chem. 1994, 47, 2129–2133. https://doi.org/10.1071/ch9942129.Search in Google Scholar

37. Litvinov, V. P. Advances in the chemistry of naphthyridines. Adv. Heterocycl. Chem. 2006, 91, 65–300. https://doi.org/10.1016/s0065-2725(06)91004-6.Search in Google Scholar

38. Vázquez-Vera, Ó., Segura-Olvera, D., Rincón-Guevara, M. A., Gutiérrez-Carrillo, A., García-Sánchez, M. A., Ibarra, I. A., Lomas-Romero, L., Islas-Jácome, A., González-Zamora, E. Synthesis of new 5-aryl-benzo[f][1,7]naphthyridines via a cascade process (Ugi-3CR/intramolecular Aza-Diels-Alder cycloaddition)/aromatization. Molecules 2018, 23, 2029.10.3390/molecules23082029Search in Google Scholar PubMed PubMed Central

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/znb-2022-0018).

Received: 2022-02-22
Accepted: 2022-03-14
Published Online: 2022-05-30
Published in Print: 2022-07-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

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  2. In this issue
  3. Research Articles
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  15. Addendum to: bixbyite-type phases in the system Ta-Zr-O-N
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https://doi.org/10.1515/znb-2022-0018
Keywords for this article
1,7-naphthyridines; acetylenic iminium salts; aminopyridines; organofluorine chemistry; pyrido[1,2-a]pyrimidines; trifluoromethylated building blocks

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Electron density of a benzoylated tetrafructopyranose
  5. Die Reihe der nicht-zentrosymmetrischen tetragonalen Lanthanoid(III)-Oxidoantimonat(III)-Chloride LnSb2O4Cl (Ln = Gd–Lu)
  6. Iminium-substituted 2,3-dihydroisoxazoles: synthesis from acetylenic iminium salts and nitrones, and some transformations
  7. Reactions of 1-trifluoromethyl-prop-2-yne1-iminium salts with 2- and 3-aminopyridines
  8. 2,5-Dihydroxy-1,4-quinones appended with two phosphinyl groups: syntheses, structures, and redox properties
  9. Ordered CaCu5-type phases REPd2Zn3 (RE = Y, La–Nd, Sm, Gd–Dy)
  10. The solid solutions TbCuIn1–x M x (M = Al, Ga)
  11. Synthesis and structural characterization of a luminescent cadmium(II) complex with bis(4-(1H-imidazole-1-yl)phenyl)amine and 4,4′-sulfonyldibenzoate ligands
  12. Synthesis and structure of a zinc(II) coordination polymer assembled with 5-(3-carboxybenzyloxy)isophthalic acid and 1,2-bis(4-pyridyl)ethane
  13. Orthoamide und Iminiumsalze, CV. Umsetzungen von Orthoamiden der Alkincarbonsäuren mit Carbonsäureamiden
  14. Notes
  15. Addendum to: bixbyite-type phases in the system Ta-Zr-O-N
  16. Addendum to: Crystal structure of mechanochemically synthesized Ag2CdSnS4
  17. Addendum to: FeBiS2Cl – a new iron-containing member of the MPnQ 2 X family
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