Synthesis of N-Mannich bases from 5-((4-methylpiperazin-1-yl)methyl)-1,3,4-oxadiazole-2-thiol

Abstract

Methyl (4-methylpiperazin-1-yl)acetate (2) were synthesized by the condensation of compound (1) with ethyl bromoacetate in basic media. aThe synthesis of acid hydrazide derivatives (3) was brought about as a result of the reaction between a compound (2) and hydrazine hydrate. In the absence of basic conditions, the reaction of 2-(4-methylpiperazin-1-yl)acetohydrazide (3) with carbon disulfide resulted in the formation of 5-((4-methylpiperazin-1-yl)methyl)-1,3,4-oxadiazole-2-thiol (4). aThe reactions of (4) with different primary and secondary amines in the presence of formaldehyde led to the formation of the corresponding Mannich bases (5a-f).

Keywords

• Mannich base
• synthesis
• oxadiazole

References

1. [1] S. G. Subramaniapillai, J Chem Sci 2013, 125, 467.
2. [2] G. Roman, Eur J Med Chem 2015, 89, 743.
3. [3] J. R. Dimmock, P. Kumar, Curr Med Chem 1997, 4, 1.
4. [4] A. V. Bogdanov, A. M. Vazykhova, N. R. Khasiyatullina, D. B. Krivolapov, A. B. Dobrynin, A. D. Voloshina, V. F. Mironov, V. F., Chem Heterocycl Comp 2016, 52, 25.
5. [5] S. George, R. Chkraborty, M. Parameswaran, A. Rajan, T. K. Ravi, J Heterocycl Chem 2015, 52, 211.
6. [6] H. Guo, Eur J Med Chem 2019, 164, 678.
7. [7] S. Shen, X. Sun, Y. Liu, B. Chen, R. Jin, H. Ma, J Heterocycl Chem 2015, 52, 1296.
8. [8] T. R. Bal, B. Anand, P. Yogeeswari, D. Sriram, Bioorg Med Chem Lett 2005, 15, 4451.

9. [9] T. Aboul‐Fadl, F. A. S. Bin‐Jubair, Int J Res Pharm. Sci 2010, 1,113.
10. [10] Chen, G.; Ning,Y.; Zhao, W.; Zhang,Y.; Zhang, Y.; Hao,X.; Wang, Y.; Mu, S. Lett Drug Des Discov 2016, 13, 395.
11. [11] Kushwaha,N.; Kaushik, D. J Applied Pharm Sci 2016, 6, 159.
12. [12] L. Pan, X. Li, C. Gong, H. Jin, Qin. B. Microbial Pathogenesis 2016, 95, 186.
13. [13] A. M. Alanazi, A. S. El‐Azab, I. A. Al‐Suwaidan, K. H. ElTahir, Y. A. Asiri, N. I. Abdel‐Aziz, A. Abdel‐Aziz, Eur J Med Chem 2015, 92, 115.
14. [14] S. Arti Kumar, D. Pathak, Int J Pharm Tech Res 2011, 3, 2104.
15. [15] P. S. Nayab, M. Irfan, M. Abid, M. Pulaganti, C. Nagaraju, S. K. Chitta, Luminescence 2017, 32, 298.
16. [16] R. Bamnela, S. P. Shrivastava, Indian J Chem 2014, 53B, 1128.
17. [17] D. Sachan, J. P. Singh, D. Sachan, S. Gangwar, Amer J Pharm Tech Res 2012, 2, 491.
18. [18] Y., Uygun Cebeci, Ş., Ceylan, N., Demirbaş, S., Alpay Karaoğlu, Microwave-assisted Synthesis of Novel Mannich Base and Conazole Derivatives Containing Biologically Active Pharmacological Groups, Letters in Drug Design & Discovery, 2021, 18, 1-15.
19. [19] H., Bayrak, A., Demirbas, N., Demirbas, S., Alpay-Karaoglu, Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities. Eur. J.Med. Chem. 2009, 44, 1057–1066.
20. [20] A., Demirbas, S., Ceylan, N., Demirbas, Synthesis of some new five membered heterocycles, a facile synthesis of oxazolidinones. J. Heterocycl. Chem. 2007, 44, 1271–1280.
21. [21] N., Demirbaş, R., Uğurluoğlu, Synthesis of novel 4-alkylidene- and 4-alkylamino-5-oxo-4,5- dihydro-[1,2,4]triazole derivatives and investigation of their antitumor activities. Turk. J. Chem. 2004, 28, 559–571.
22. [22] H., Bayrak, A., Demirbas, S., Alpay Karaoğlu, N., Demirbaş, Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities, European Journal of Medicinal Chemistry 44 (2009) 1057-1066