Skip to main content
SpringerLink
Log in

Synthesis of 3-(Piperidin-4-yl)-6,7-dihydro-5H-pyrrolo-[2,1-c][1,2,4]triazole and Theoretical Study of the Hydrazone-Hydrazine Tautomerism of the Intermediate Hydrazonation Product

  • Published:
Russian Journal of Organic Chemistry Aims and scope Submit manuscript

Abstract

3-(Piperidin-4-yl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole was synthesized through a four-step process including etherification, hydrazonation, cyclization, and reduction with an overall yield of 39%. The final product was characterized by 1H NMR and ESI-MS/MS. The molecular structures of benzyl (Z)-4-(2-(pyrrolidin-2-ylidene)hydrazine-1-carbonyl)piperidine-1-carboxylate and related compounds were analyzed using DFT calculations at the B3LYP/6-311+G(d,p) level of theory. The results indicated a higher stability of the hydrazone tautomers.

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

Similar content being viewed by others

References

  1. Cronin, K.A., Lake, A.J., Scott, S., Sherman, R.L., Noone, A.M., Howlader, N., Henley, S.J., Anderson, R.N., Firth, A.U., Ma, J., Kohler, B.A., and Jemal, A., Cancer, 2018, vol. 124, p. 2785. doi https://doi.org/10.1002/cncr.31551

    Article  Google Scholar 

  2. Boffa, D.J., Rosen, J.E., Mallin, K., Loomis, A., Gay, G., Palis, B., Thoburn, K., Gress, D., McKellar, D.P., Shulman, L.N., Facktor, M.A., and Winchester, D.P., JAMA Oncol., 2017, vol. 3, p. 1722. doi https://doi.org/10.1001/jamaoncol.2016.6905

    Article  Google Scholar 

  3. Coussens, N.P., Braisted, J.C., Peryea, T., Sittampalam, G.S., Simeonov, A., and Hall, M.D., Pharmacol. Rev., 2017, vol. 69, p. 479. doi https://doi.org/10.1124/pr.117.013755

    Article  CAS  Google Scholar 

  4. Verwilst, P., Han, J., Lee, J., Mun, S., Kang, H.G., and Kim, J.S., Biomaterials, 2017, vol. 115, p. 104. doi https://doi.org/10.1016/j.biomaterials.2016.11.023

    Article  CAS  Google Scholar 

  5. Maddila, S., Pagadala, R., and Jonnalagadda, S.B., Lett. Org. Chem., 2013, vol. 10, p. 693. doi https://doi.org/10.2174/157017861010131126115448

    Article  CAS  Google Scholar 

  6. Kaur, R., Ranjan Dwivedi, A., Kumar, B., and Kumar, V., Anti-Cancer Agents Med. Chem., 2016, vol. 16, p. 465. doi https://doi.org/10.2174/1871520615666150819121106

    Article  CAS  Google Scholar 

  7. Paprocka, R., Wiese, M., Eljaszewicz, A., Helmin-Basa, A., Gzella, A., Modzelewska-Banachiewicz, B., and Michalkiewicz, J., Bioorg. Med. Chem. Lett., 2015, vol. 25, p. 2664. doi https://doi.org/10.1016/j.bmcl.2015.04.079

    Article  CAS  Google Scholar 

  8. Kulabaş, N., Tatar, E., Özakpinar, Ö.B., Özsavcı, D., Pannecouque, C., Clercq, E., and Küçükgüzel, İ., Eur. J. Med. Chem., 2016, vol. 121, p. 58. doi https://doi.org/10.1016/j.ejmech.2016.05.017

    Article  Google Scholar 

  9. Van den Bos, B., Rec. des Trav. Chim. des Pays-Bas, 1960, vol. 79, p. 836. doi https://doi.org/10.1002/recl.19600790809

    Article  CAS  Google Scholar 

  10. Bourdin, J., Berthier, G., Daurade, P., and Garin, P., Phytiatr. Phytopharm, 1976, vol. 25, p. 19.

    CAS  Google Scholar 

  11. Hanna, N.B., Dimitrijevich, S.D., Larson, S.B., Robins, R.K., and Revankar, G.R., J. Heterocycl. Chem., 1988, vol. 25, p. 1857. doi https://doi.org/10.1002/jhet.5570250649

    Article  CAS  Google Scholar 

  12. Wuest, F., Tang, X., Kniess, T., Pietzsch, J., and Suresh, M., Bioorg. Med. Chem., 2009, vol. 17, p. 1146. doi https://doi.org/10.1016/j.bmc.2008.12.032

    Article  CAS  Google Scholar 

  13. Zhang, N., Ayral-Kaloustian, S., Nguyen, T., Afragola, J., Hernandez, R., Lucas, J., Gibbons, J., and Beyer, C., J. Med. Chem., 2007, vol. 50, p. 319. doi https://doi.org/10.1021/jm060717i

    Article  CAS  Google Scholar 

  14. Olah, E., Kokeny, S., Papp, J., Bozsik, A., and Keszei, M., Adv. Enzyme Regul., 2006, vol. 46, p. 176. doi https://doi.org/10.1016/j.advenzreg.2006.01.002

    Article  CAS  Google Scholar 

  15. Laurenzana, A., Cellai, C., Vannucchi, A.M., Pancrazzi, A., Romanelli, M.N., and Paoletti, F., Leukemia, 2005, vol. 19, p. 390. doi https://doi.org/10.1038/sj.leu.2403618

    Article  CAS  Google Scholar 

  16. Bulut, N., Kocyigit, U.M., Gecibesler, I.H., Dastan, T., Karci, H., Taslimi, P., Durna Dastan, S., Gulcin, I., and Cetin, A., J. Biochem. Mol. Toxicol., 2018, vol. 32, p. e22006. doi https://doi.org/10.1002/jbt.22006

    Article  Google Scholar 

  17. Dombernowsky, P., Smith, I., Falkson, G., Leonard, R., Panasci, L., Bellmunt, J., Bezwoda, W., Gardin, G., Gudgeon, A., and Morgan, M., J. Clin. Oncol., 1998, vol. 16, p. 453. doi https://doi.org/10.1200/JCO.1998.16.2.453

    Article  CAS  Google Scholar 

  18. Buzdar, A., Jonat, W., Howell, A., Jones, S.E., Blomqvist, C., Vogel, C.L., Eiermann, W., Wolter, J.M., Azab, M., and Webster, A., J. Clin. Oncol., 1996, vol. 14, p. 2000. doi https://doi.org/10.1200/JCO.1996.14.7.2000

    Article  CAS  Google Scholar 

  19. Yin, P., Ma, W.B., Chen, Y., Huang, W.C., Deng, Y., and He, L., Org. Lett., 2009, vol. 11, p. 5482. doi https://doi.org/10.1021/ol902207h

    Article  CAS  Google Scholar 

  20. Dreikorn, B.A. and Unger, P., J. Heterocycl. Chem., 1989, vol. 26, p. 1735. doi https://doi.org/10.1002/jhet.5570260640

    Article  CAS  Google Scholar 

  21. Kurzer, F., and Seeker, J.L., J. Heterocycl. Chem., 1989, vol. 26, p. 355. doi https://doi.org/10.1002/jhet.5570260216

    Article  CAS  Google Scholar 

  22. Ray, P.C., Bandari, M., Qadeeruddin, M., and Gorantla, S.R., WO Patent no. WO2007054979, 2007.

  23. Belletire, J.L., Bills, R.A., and Shackelford, S.A. Synth. Commun., 2008, vol. 38, p. 738. doi https://doi.org/10.1080/00397910701820319

    Article  CAS  Google Scholar 

  24. Haycock-Lewandowski, S.J., Wilder, A., and Åhman, J., Org. Process Res. Dev., 2008, vol. 12, p. 1094.doi https://doi.org/10.1021/op8000614

    Article  CAS  Google Scholar 

  25. Kerr, M.S., Read de Alaniz, J., and T. Rovis, J. Org. Chem., 2005, vol. 70, p. 5725. doi https://doi.org/10.1021/jo050645n

    Article  CAS  Google Scholar 

  26. Balsells, J., DiMichele, L., Liu, J., Kubryk, M., Hansen, K., and Armstrong, J.D., Org. Lett., 2005, vol. 7, 1039. doi https://doi.org/10.1021/ol0474406

    Article  CAS  Google Scholar 

  27. Shah, T.A., Ahmad, Z., Mir, N.A., Muneer, M., Rath, N.P., and Ahmad, M., RSC Adv., 2015, vol. 5, p. 107931. doi https://doi.org/10.1039/C5RA21270G

    Article  CAS  Google Scholar 

  28. Siegfried, P. and Wolfgang, W., US Patent no. 2913454, 1959.

  29. Rigo, B., Gouni, I., Ghammarti, S., Gautret, P., and Couturier, D., Synth. Commun., 1994, vol. 24, p. 3055. doi https://doi.org/10.1080/00397919408011318

    Article  CAS  Google Scholar 

  30. Frisch, J., Trucks, G., Schlegel, H., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Mennucci, B., and Petersson, A., Gaussian 09 Program, Revision C. 01, 2010. http://gaussian.com/glossary/g09/

  31. Mezey, P.G., Ladik, J.J., and Barry, M., Theor. Chim. Acta, 1979, vol. 54, p. 251. doi https://doi.org/10.1007/bf00578344

    Article  Google Scholar 

  32. Gehret, J.-C. and Traber, W., US Patent no. 4567190, 1986.

  33. Nilov, D. and Granik, V., Russ. Chem. Bull., 2006, vol. 55, p. 1636. doi https://doi.org/10.1007/s11172-006-0466-x

    Article  CAS  Google Scholar 

  34. Botta, A., US Patent no. 3936444, 1976.

  35. Barlaam, B., De Savi, C., Hawkins, A.H., Lamb, M., Pike, K., and Vasbinder, M., US Patent no. 20160376287, 2016.

Download references

Acknowledgments

This work was supported by the Key Research and Development Program of Shaanxi (2018ZDXM-GY-159), the Graduate Innovation and Practice Skills Foundation of Xi’an Shiyou University (grant no. YCS17211015), and College Students’ Innovation and Entrepreneurship Training Program of Shaanxi Province.

The authors gratefully acknowledge the support from the High Performance Computing Center, Northwestern Polytechnical University, for the computational work.

Author information

Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Xi’an Shiyou University, Xi’an, 710065, China

    Q.-Z. Zhang, C.-F. Wan, Yu Ma, N.-N. Qin, C.-Y. Ke & X.-L. Zhang

  2. Department of Pharmacy, School of Medicine, Xi’an Jiaotong University, Xi’an, 710061, China

    Q. Pan

Authors
  1. Q.-Z. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C.-F. Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N.-N. Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C.-Y. Ke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Q. Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. X.-L. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Q.-Z. Zhang or X.-L. Zhang.

Additional information

Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 8, pp. 1312.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, QZ., Wan, CF., Ma, Y. et al. Synthesis of 3-(Piperidin-4-yl)-6,7-dihydro-5H-pyrrolo-[2,1-c][1,2,4]triazole and Theoretical Study of the Hydrazone-Hydrazine Tautomerism of the Intermediate Hydrazonation Product. Russ J Org Chem 55, 1223–1230 (2019). https://doi.org/10.1134/S1070428019080232

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070428019080232

Keywords

Search

Navigation