Spectroscopic Investigation and Synthesis of N-Ethyl-5-Tolyloxymethyl Triazole Derivatives
DOI:
https://doi.org/10.70749/ijbr.v3i5.1234Keywords:
N-ethylated Triazoles, Structure Elucidation, Triazole Derivatives, Spectroscopic Analysis, Synthesis of Triazole Compounds.Abstract
High-nitrogen heterocycles' synthesis has attracted much interest because of their wide applicability in many different sectors. As a significant class of organic compounds, triazoles and their fused derivatives have emerged among these. A new triazole derivative, 4-ethyl-3-ethylthio-5-(p-tolyloxymethyl)-4H-1, 2, 4-triazole, is the subject of this work on synthesis and spectrum characterization. Ethyl 2-p-tolyloxy acetate is synthesized by reacting 3, 4-dimethoxyphenylacetic acid with ethanol under concentrated H2SO4, starting the process. The ester product is subsequently transformed into 2-p-tolyloxyacetohydrazide, which is further reacted with ethyl isothiocyanate to produce 2-p-tolyloxythiosemicarbazide. Cyclizing 275 in an alkaline media generates 4-ethyl-5-(p-tolyloxymethyl)-4H-1, 2, 4-triazole-3-thiol. 276 interacts with several alkyl halides in the last stage to create N-ethyl-3, 5-substituted derivatives (278a-h). Infrared (IR), nuclear magnetic resonance (NMR), electron ionization mass spectrometry (EI-MS), and high-resolution electron ionization mass spectrometry (HR-EI-MS) were used to characterize each chemical. This work adds to the expanding area of nitrogen-rich heterocycles by providing fresh triazole derivatives with possible uses in industrial and medical chemistry.
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References
Abdelrehim, E. M. (2021). Synthesis and screening of new [1,3,4]Oxadiazole, [1,2,4]Triazole, and [1,2,4]triazolo[4,3-b][1,2,4]triazole derivatives as potential antitumor agents on the colon carcinoma cell line (HCT-116). ACS Omega, 6(2), 1687-1696.
https://doi.org/10.1021/acsomega.0c05718
Almasirad, A., Shafiee, A., Abdollahi, M., Noeparast, A., Shahrokhinejad, N., Vousooghi, N., Tabatabai, S. A., & Khorasani, R. (2010). Synthesis and analgesic activity of new 1,3,4-oxadiazoles and 1,2,4-triazoles. Medicinal Chemistry Research, 20(4), 435-442.
https://doi.org/10.1007/s00044-010-9335-0
Al-Mulla, A. (2017). A review: biological importance of heterocyclic compounds. Der Pharma Chem, 9(13), 141-147.
Arora, P., Arora, V., Lamba, H. S., & Wadhwa, D. (2012). Importance of heterocyclic chemistry: A review. International Journal of Pharmaceutical Sciences and Research, 3(9), 2947.
Asif, M. (2015). Antiviral and antiparasitic activities of various substituted triazole derivatives: A mini. Chem. Int, 1(2), 71-80.
Ata, A., & Naz, S. (2022). Synthesis of Bioactive heterocyclic compounds. Greener Synthesis of Organic Compounds, Drugs and Natural Products, 137-150.
https://doi.org/10.1201/9781003089162-8
Bayrak, H., Demirbas, A., Demirbas, N., & Karaoglu, S. A. (2009). Synthesis of some new 1,2,4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities. European Journal of Medicinal Chemistry, 44(11), 4362-4366.
https://doi.org/10.1016/j.ejmech.2009.05.022
Campos, V. R., Abreu, P. A., Castro, H. C., Rodrigues, C. R., Jordão, A. K., Ferreira, V. F., De Souza, M. C., Santos, F. D., Moura, L. A., Domingos, T. S., Carvalho, C., Sanchez, E. F., Fuly, A. L., & Cunha, A. C. (2009). Synthesis, biological, and theoretical evaluations of new 1,2,3-triazoles against the hemolytic profile of the Lachesis muta snake venom. Bioorganic & Medicinal Chemistry, 17(21), 7429-7434.
https://doi.org/10.1016/j.bmc.2009.09.031
Koparır, M., Cansız, A., & Demirdağ, A. (2004). Synthesis of some new 4,5-Substituted-4H-1,2,4-triazole-3-thiol derivatives. Molecules, 9(4), 204-212.
https://doi.org/10.3390/90400204
Colanceska-Ragenovic, K., Dimova, V., Kakurinov, V., Molnar, D., & Buzarovska, A. (2001). Synthesis, antibacterial and Antifungal activity of 4-Substituted-5-Aryl-1,2,4-Triazoles. Molecules, 6(10), 815-824.
https://doi.org/10.3390/61000815
Dastjerdi, H. F., Naderi, N., Nematpour, M., Rezaee, E., Mahboubi-Rabbani, M., Ebrahimi, M., Hosseinipoor, S., Hosseini, O., & Tabatabai, S. A. (2020). Design, synthesis and anti-diabetic activity of novel 1, 2, 3-triazole-5-carboximidamide derivatives as dipeptidyl peptidase-4 inhibitors. Journal of Molecular Structure, 1221, 128745.
https://doi.org/10.1016/j.molstruc.2020.128745
Dehestani, L., Ahangar, N., Hashemi, S. M., Irannejad, H., Honarchian Masihi, P., Shakiba, A., & Emami, S. (2018). Design, synthesis, in vivo and in silico evaluation of phenacyl triazole hydrazones as new anticonvulsant agents. Bioorganic Chemistry, 78, 119-129.
https://doi.org/10.1016/j.bioorg.2018.03.001
Desai, N. C., Shihora, P. N., Rajpara, K. M., Joshi, V. V., Vaghani, H. V., Satodiya, H. M., & Dodiya, A. M. (2011). Synthesis, characterization, and antimicrobial evaluation of novel naphthalene-based 1,2,4-triazoles. Medicinal Chemistry Research, 21(10), 2981-2989.
https://doi.org/10.1007/s00044-011-9833-8
Düğdü, E., Ünver, Y., Ünlüer, D., & Sancak, K. (2014). Synthesis and biological properties of novel triazole-thiol and Thiadiazole derivatives of the 1,2,4-Triazole-3(5)-one class. Molecules, 19(2), 2199-2212.
https://doi.org/10.3390/molecules19022199
Gupta, A. K., Prachand, S., Patel, A., & Jain, S. (2012). Synthesis of some 4-amino-5-(substituted-phenyl)-4H-[1, 2, 4] triazole-3-thiol derivatives and antifungal activity. Int J Pharm Life Sci, 3(7), 1848-1857.
Hameed, A. A., & Hassan, F. (2014). Synthesis, characterization and antioxidant activity of some 4-amino-5-phenyl-4h-1, 2, 4-triazole-3-thiol derivatives. Int J Appl, 4, 202-11.
Hasan, A., Thomas, N. F., & Gapil, S. (2011). Synthesis, characterization and Antifungal evaluation of 5-Substituted-4-Amino-1,2,4-Triazole-3-Thioesters. Molecules, 16(2), 1297-1309.
https://doi.org/10.3390/molecules16021297
Hussain, S., Sharma, J., & Amir, M. (2008). Synthesis and antimicrobial activities of 1,2,4‐Triazole and 1,3,4‐Thiadiazole derivatives of 5‐Amino‐2‐Hydroxybenzoic acid. Journal of Chemistry, 5(4), 963-968.
https://doi.org/10.1155/2008/924734
Joanna, L., Talarek, S., Orzelska, J., Fidecka, S., Wujec, M., & Plech, T. (2013). The antinociceptive effect of 4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 387(4), 367-375.
https://doi.org/10.1007/s00210-013-0938-0
Kalhor, M., Shabani, M., Nikokar, I., & Banisaeed, S. R. (2015). Synthesis, characterization and antibacterial activity of some novel thiosemicarbazides, 1, 2, 4-triazol-3-thiols and their S-substituted derivatives. Iranian Journal of Pharmaceutical Research: IJPR, 14(1), 67.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4277620/
Kapri, K. P., Singar, S. B., Khanal, S., & Shakya, B. (2020). Synthesis of Schiff bases of 4-Amino-5- (2-hydroxyphenyl)-4H- 1,2,4-Triazole-3-Thiol as potent antimicrobial agents. Amrit Research Journal, 1(1), 29-36.
https://doi.org/10.3126/arj.v1i1.32450
Khanage, S. G., Raju, A., Mohite, P. B., & Pandhare, R. B. (2013). Analgesic activity of some 1, 2, 4-triazole heterocycles clubbed with pyrazole, tetrazole, isoxazole and pyrimidine. Advanced Pharmaceutical Bulletin, 3(1), 13.
https://doi.org/10.5681/apb.2013.003
Kidwai, M., Venktaramanan, R., Mohan, R., & Sapra, P. (2002). Cancer chemotherapy and heterocyclic compounds. Current Medicinal Chemistry, 9(12), 1209-1228.
https://doi.org/10.2174/0929867023370059
Kumudha, D., Leonard, J. T., Muthumani, M., Chidhambaranathan, N., & Kalavathi, T. (2013). Synthesis and evaluation of some 1, 2, 4-triazole derivatives as anticonvulsant, anti-inflammatory and antimicrobial agents. Asian Journal of Pharmaceutical and Clinical Research, 6(2), 5-8.
Li, X., Li, X., Liu, H., Zhou, X., & Shao, Z. (2012). Synthesis and evaluation of antitumor activities of novel chiral 1,2,4-triazole Schiff bases bearing γ-butenolide moiety. Organic and Medicinal Chemistry Letters, 2(1), 26.
https://doi.org/10.1186/2191-2858-2-26
Mahdi, M. F., Naser, N. H., & Hammud, N. H. (2017). Synthesis and preliminary pharmacological evaluation of new naproxen analogues having 1, 2, 4-triazole-3-thiol. International Journal of Pharmacy and Pharmaceutical Sciences, 9(7), 66.
https://doi.org/10.22159/ijpps.2017v9i7.18273
Maji, K., Abbasi, M., Podder, D., Datta, R., & Haldar, D. (2018). Potential Antileishmanial activity of a triazole‐based hybrid peptide against Leishmania major. ChemistrySelect, 3(36), 10220-10225.
https://doi.org/10.1002/slct.201802002
Nadeem, H., Mohsin, M., Afzaal, H., Riaz, S., Zahid, A., & Muhammad, S. A. (2013). Synthesis and <i>in Vitro</i> Biological activities of 4,5-Disubstituted 1,2,4-Triazole-3-Thiols. Advances in Microbiology, 03(04), 366-375.
https://doi.org/10.4236/aim.2013.34050
Nanjan, M., Mohammed, M., Prashantha Kumar, B., & Chandrasekar, M. (2018). Thiazolidinediones as antidiabetic agents: A critical review. Bioorganic Chemistry, 77, 548-567.
https://doi.org/10.1016/j.bioorg.2018.02.009
Patel, K. R., Brahmbhatt, J. G., Pandya, P. A., Daraji, D. G., Patel, H. D., Rawal, R. M., & Baran, S. K. (2021). Design, synthesis and biological evaluation of novel 5-(4-chlorophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols as an anticancer agent. Journal of Molecular Structure, 1231, 130000.
https://doi.org/10.1016/j.molstruc.2021.130000
Pertino, M., Vega, C., Rolón, M., Coronel, C., Rojas de Arias, A., & Schmeda-Hirschmann, G. (2017). Antiprotozoal activity of Triazole derivatives of Dehydroabietic acid and Oleanolic acid. Molecules, 22(3), 369.
https://doi.org/10.3390/molecules22030369
Sahoo, P. K., Sharma, R., & Pattanayak, P. (2009). Synthesis and evaluation of 4-amino-5-phenyl-4H-[1,2,4]-triazole-3-thiol derivatives as antimicrobial agents. Medicinal Chemistry Research, 19(2), 127-135.
https://doi.org/10.1007/s00044-009-9178-8
Saini, M. S., Kumar, A., Dwivedi, J., & Singh, R. (2013). A review: biological significances of heterocyclic compounds. Int. J. Pharm. Sci. Res, 4(3), 66-77.
https://www.ijpsr.info/docs/IJPSR13-04-03-005.pdf
Shukla, P. K., Soni, N., Verma, A., & Jha, A. K. (2014). Synthesis, characterization and in vitro biological evaluation of a series of 1, 2, 4-triazoles derivatives & triazole based schiff bases. Der Pharma Chemica, 6(3), 153-160.
Singh, A. K., & Kandel, K. R. (2012). Synthesis of Triazole derivative:[4-(benzylideneamino)-5-phenyl-4H-1, 2, 4–triazole-3-thiol]. Journal of Nepal Chemical Society, 30, 174-177.
https://doi.org/10.3126/jncs.v30i0.9391
SINGH, I., KAUR, H., KUMAR, S., KUMAR, A., & KUMAR, A. (2010). PYRIDINYL/QUINAZOLINYL/AZETIDINONYL/THIAZOLIDINONYL TRIAZOLES. International Journal of Pharma and Bio Sciences, 1, 1.
Singh, R. J., & Singh, D. K. (2009). Syntheses, characterization and biological activity of some 1, 2, 4‐Triazole derivatives. Journal of Chemistry, 6(3), 796-800.
https://doi.org/10.1155/2009/419214
Turan-Zitouni, G., Kaplancıklı, Z. A., Yıldız, M. T., Chevallet, P., & Kaya, D. (2005). Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives. European Journal of Medicinal Chemistry, 40(6), 607-613.
https://doi.org/10.1016/j.ejmech.2005.01.007
Zhang, S., Xu, Z., Gao, C., Ren, Q., Chang, L., Lv, Z., & Feng, L. (2017). Triazole derivatives and their anti-tubercular activity. European Journal of Medicinal Chemistry, 138, 501-513.
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