Synthesis and Characterization of a Novel Biheterocyclic -amino Acid Precursor of the Triazole-Tetrazole Type, via the Copper (I) Catalyzed Alkyne-Azide Cycloaddition Reaction (CuAAC)



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Submitted Mar 5, 2021
Published Mar 26, 2021
10.24018/ejchem.2021.2.2.53

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In this paper, we describe the regioselective synthesis of a novel tri-heterocyclic compound, a biheterocyclic amino acid precursor, derived from both triazole and tetrazole. The key step of our synthesis approach was the Huigsen 1,3-dipolar cycloaddition reaction, catalyzed by the copper (I) formed in situ by reduction of Cu(II) salts (CuSO4), 5H2O) by sodium ascorbate, and using as dipole the oxazoline azide derivative 4-(azidomethyl)-4-ethyl-2-phenyl-4,5-dihydrooxazole (4) and as dipolarophile 5-(4-methoxyphenyl)-2-(prop-2-yn-1-yl)-2H-tetrazole (3).  The Cu(I) catalysis allowed us to carry out the cycloaddition at room temperature during a reaction time of only 8 hours and also to selectively obtain the 1,4-regioisomer; one of the two possible isomers, with a yield of 90% after chromatography on a silica gel column (ether/hexane: 1/2), and recrystallization in an ether/acetone mixture. The desired compound, 4-ethyl-4-((4-((5-(4-methoxyphenyl)-2H-tetrazol-2-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2-phenyl-4,5-dihydrooxazole (5) was analyzed by 1D magnetic resonance spectroscopy (1H, 13C), and characterized physico-chemically by mass spectrometry and elemental analysis.

Keywords: Tetrazole alkyne oxazoline azide triazole CuAAC

References

  1. Zhang, J. Wang, S. Ba, Y. Xu, Z. Tetrazole hybrids with potential anticancer activity. European Journal of Medicinal Chemistry, 1996, 178, pp. 341-351. https://doi.org/10.1016/j.ejmech.2019.05.071.
     Google Scholar
  2. Wang, S. Q., Wang, Y. F. and Xu, Z. (2019). Tetrazole hybrids and their antifungal activities. European Journal of Medicinal Chemistry. 2019, 170, pp. 225-234. https://doi.org/10.1016/j.ejmech.2019.03.023.
     Google Scholar
  3. Vidya S. D., Aniket P. S., Shailee V. T., Deepak K. L., Kshipra S. K., Ishwari A. K., Suneel D. Sunil S. J., Prasad V.L.S.B. Ultrasound assisted synthesis of tetrazole based pyrazolines and isoxazolines as potent anticancer agents via inhibition of tubulin polymerization. Bioorganic & Medicinal Chemistry Letters, 2020, 30, 127592. .https://doi.org/10.1016/j.bmcl.2020.127592.
     Google Scholar
  4. Roh, J. Karabanovich, G. Vlčková, H. Carazo, A. Němeček, J. Sychra, P.l Valášková, L. Pavliš, O. Stolaříková, J. Klimešová, V. Vávrová, K. Pávek, P. Hrabálek, A. Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents. Bioorganic and Medicinal Chemistry, 2017, 25(20), pp. 5468-5476. http://dx.doi.org/10.1016/j.bmc.2017.08.010
     Google Scholar
  5. Gao, C. Chang, L. Xu, Z. Yan, X. Ding, C. Zhao, F. Wu, X. Feng, L. Recent advances of tetrazole derivatives as potential anti-tubercular and anti-malarial agents. European Journal of Medicinal Chemistry, 2019, 163, pp. 404-412. https://doi.org/10.1016/j.ejmech.2018.12.001.
     Google Scholar
  6. Zhan, P. Li, Z. Liu, X. Clercq, D.E. Sulfanyltriazole/tetrazoles: A Promising Class of HIV-1 NNRTIs. Mini-Reviews in Medicinal Chemistry. 2012, 9(8), pp. 1014-1023. https://doi.org/10.2174/138955709788681618.
     Google Scholar
  7. Verma, C., Quraishi, M. A. and Singh, A. 5-Substituted 1H-tetrazoles as effective corrosion inhibitors for mild steel in 1 M hydrochloric acid. Journal of Taibah University for Science, 2016, 10(5), pp. 718-733. https://doi.org/10.1016/j.jtusci.2015.10.005.
     Google Scholar
  8. Aouine, Y. Sfaira, M. Ebn Touhami, M. Alami, A. Hammouti, B. Elbakri, M. El Hallaoui, A. Touir, R. Temperature and time investigations on the adsorption behavior of isoindoline, tetrazole and isoindoline-tetrazole on corrosion of mild steel in acidic medium. International Journal of Electrochemical Science, 2012, 7(6), pp. 5400-5419.
     Google Scholar
  9. Elkacimi, Y. Achnin, M. Aouine, Y. Ebn Touhami, M. Alami, A. Touir, R. Sfaira, M. Chebabe, D. Elachqar, A. Hammouti, B. Inhibition of mild steel corrosion by some phenyltetrazole substituted compounds in hydrochloric acid. Portugaliae Electrochimica Acta, 2011, 30(1), pp. 53-65. https://doi.org/10.4152/pea.201201053.
     Google Scholar
  10. Herr, R. J. 5-Substituted-1H-tetrazoles as carboxylic acid isosteres: Medicinal chemistry and synthetic methods. Bioorganic and Medicinal Chemistry, 2002, 10(11), pp. 3379-3393. https://doi.org/10.1016/S0968-0896(02)00239-0.
     Google Scholar
  11. Maybridge MedChem. Bioisosteres in Medicinal Chemistry, 2004, 1, 1
     Google Scholar
  12. Duncia, J. V. CHIU, A. T. CARINI, D. J. GREGORY, G. B. The Discovery of Potent Nonpeptide Angiotensin II Receptor Antagonists: A New Class of Potent Antihypertensives. Journal of Medicinal Chemistry, 1990, 33(5), pp. 1312-1329. https://doi.org/10.1021/jm00167a007.
     Google Scholar
  13. Katritzky, A. R., Cai, C. and Meher, N. K. Efficient synthesis of 1,5-disubstituted tetrazoles. Synthesis, 2007, 8, pp. 1204-1208 https://doi.org/0.1055/s-2007-966001.
     Google Scholar
  14. Demko, Z. P. and Sharpless, K. B. Jo010635W-2. 2001, 6, pp. 7945-7950. https://doi.org/10.1021/jo010635w.
     Google Scholar
  15. Alami, A., El Hallaoui, A., El Achqar, A., Roumestant, M. L., Viallefont, Ph. The use of 5-substituted tetrazoles in a Synthesis of heterocyclic α-amino esters. Bull. Soc. Chim. Belg., 1996, 105 (12), 769.
     Google Scholar
  16. Alami, A., El Hallaoui, A., El Achqar, A., El Hajji, S., Roumestant, M. L., Viallefont, Ph. Synthesis of β -Tetrazolyl DL-Alanine Derivatives. Preparative Biochemistry and Biotechnology, 1998, 28 :2, 167-173. http://dx.doi.org/10.1080/10826069808010133.
     Google Scholar
  17. Achamlale, A. Elachqar, A. El Hallaoui, A. Alami, S. El Hajji, M. L. Roumestant, Viallefont, Ph. Synthesis of biheterocyclicα-amino acids, Amino Acids, 1999, 149, 17. http://dx.doi.org/10.1080/10826069808010133.
     Google Scholar
  18. Aouine, Y., Aarab N., Alami, A., El Hallaoui, A., Ebn Touhami, M., Elachqar, A., Sfaira, M., Faraj, H. Synthesis and Characterization of novel 5-substituted tetrazoles having an inhibiting activity of corrosion for mild steel in the acidic media. Moroccan Journal of Heterocyclic Chemistry, 2011, Volume 10(1), 18. https://doi.org/10.48369/IMIST.PRSM/jmch-v10i1.2908.
     Google Scholar
  19. El Hajji, S., Ph.D. Thesis, Sidi Mohamed Ben Abdellah University, Fez, MA, 1992.
     Google Scholar
  20. Zaid, F., Thesis, Sidi Mohamed Ben Abdellah University, Fez. MA, 1996.
     Google Scholar
  21. Rostovtsev, V. V., Green, L. G., Fokin, V. V. and Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of Azides and Terminal Alkynes. Angew. Chemie. Int. Ed. 2002, 41 (14), 2596-2599. https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4.
     Google Scholar
  22. A. Atmani, A. El Hallaoui, S. El Hajji, M. L. Roumestant, P. Viallefont. From oxazolines to precursors of amino acids. Synth. Commun., vol. 21, pp. 2383-2390, 1991.
     Google Scholar
  23. Hajib, S. Ksakas, A. Aouine, Y. Alami, A. and Faraj, H. Synthesis and Structural Determination of Two New tri-Heterocyclic Regioisomeric Compounds, Precursors of Bi-Triazolic α-Amino Acids, via a Comparative Study using 1D NMR Spectroscopy. European Journal of Advanced Chemistry Research, 2020, 1(6), pp. 2-7. https://doi.org/10.24018/ejchem.2020.1.6.36.
     Google Scholar
  24. Lippmann, E., Könnecke, A., Z. Chem, 16, 90 (1976).
     Google Scholar
  25. F. R. Benson, F.R. Heterocyclic compounds; Vol 8, ed. Wiley (1967).
     Google Scholar
  26. Janda, U., Votický, Z., Jakubcová, J., Světlík, J., Grimová, J., Maturová, E. Semisynthetic cephalosporines. Synthesis of some substituted tetrazolyl acetic and propionic acids. Collect. Czech. Chem. Commun. 1984, 49, 1699-1712. https://doi.org/10.1135/cccc19841699.
     Google Scholar
  27. Padwa, A., Nahm, S. and Sato, E. Photochemical transformations of small ring heterocyclic compounds. 9. Intramolecular 1,3-dipolar cycloaddition reactions of alkenyl-subituted nitrile imines. Journal of Organic Chemistry, 1978, 43(9), pp. 1664-1671. https://doi.org/10.1021/jo00403a009.
     Google Scholar
  28. Kishore V, Parmar SS, Gildersleeve DL. Synthesis of 2,5-disubstituted tetrazoles as possible antiinflammatory agents. J. Heterocycl. Chem., 1978, 15, 1335-1338.
     Google Scholar
  29. Peet, N.P. and Sunder, S., J. Heterocycl. Chem. 1977, vol. 14, p. 561.
     Google Scholar
  30. Vereshchagin, L.I., Buzilova, S.R., Mityukova, T.K., Proidakov, A.G., Kizhnyaev, V.N., Il'ina, V.V., Sukhanov, G.T., Gareev, G.A., Bogens, A.K., Zh. Org. Khim; 22, 1979-1783 (1986).
     Google Scholar
  31. Elguero, J., Marzin, C. and Roberts, J. D. (1974) 'Carbon-13 Magnetic Resonance Studies of Azoles. Tautomerism, Shift Reagent Effects, and Solvent Effects', Journal of Organic Chemistry, 39(3), pp. 357-363. https://doi.org/10.1021/jo00917a017.
     Google Scholar
  32. Taurins, A. and Viron, S. J. (1953) 'the Tautomerism of 2-Nitraminopyridines', Canadian Journal of Chemistry, 31(11), pp. 1048-1053. https://doi.org/10.1039/P29890001903.
     Google Scholar
  33. Butler, R. N. and Fitzgerald, K. J. (1988) 'Reaction of benzonitrile N-(p-nitrophenyl) imide with 5-substituted tetrazoles: A new route to substituted 1,2,4-triazoles via N- hydrazonoyltetrazoles', Journal of the Chemical Society, Perkin Transactions 1, (6), pp. 1587-1591. https://doi.org/10.1039/p19880001587.
     Google Scholar
  34. Tornøe, C. W., Christensen, C. and Meldal, M. Peptidotriazoles on solid phase: [1,2,3]-Triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. Journal of Organic Chemistry, 2002, 67(9), pp. 3057-3064. https://doi.org/10.1021/jo011148j.
     Google Scholar
  35. Tsypin, G. I., Timofeeva, T. N., Mel'nikov, V. V., Gidaspov, B. V., Zh. Khim Org. 1977, 13, 2281.
     Google Scholar
  36. Aouine Y., Thesis, Sidi Mohamed Ben Abdellah University, Fez, MA, 2015.
     Google Scholar