Copyright (c) 2025 Dr Jagadeshwar Vannada
This work is licensed under a Creative Commons Attribution 4.0 International License.
Facile One Pot Synthesis of 4,5-Disubstituted 1,2,3-Thiadiazoles using Acid Halides via Diazo Intermediate Formation
Corresponding Author(s) : Jagadeshwar Vannada
Asian Journal of Chemistry,
Vol. 38 No. 1 (2026): Vol 38 Issue 1, 2026
Abstract
In this work, a competent straightforward one-pot synthesis of 4,5-disubstituted 1,2,3-thiadiazoles was carried out using acid halides. The reaction proceeds through the conversion of acid halides into diazo carbonyl compounds, which further involve in the nucleophilic addition with CS2 and alkylation on sulphur by alkyl halides results in substituted thiadiazoles. This process is highly regioselective and operationally simple for generating various substituted thiadiazole molecules. This protocol offers several advantages for accessing the medicinally significant thiadiazole moieties with promising yields under mild reaction conditions, furthermore it involves a simple purification and also the removal of toxic reagents.
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- P. Awasthi, A. Mittal, Swati, M. Singh and S. Sharma, Curr. Top. Med. Chem., 26 (2026); https://doi.org/10.2174/0115680266394288251007083351
- A. Irfan, S. Ullah, A. Anum, N. Jabeen, A.F. Zahoor, H. Kanwal, K. Kotwica-Mojzych and M. Mojzych, Appl. Sci., 11, 5742 (2021); https://doi.org/10.3390/app11125742
- F. Hayat, A. Salahuddin, J. Zargan and A. Azam, Eur. J. Med. Chem., 45, 6127 (2010); https://doi.org/10.1016/j.ejmech.2010.09.066
- Z. Li, Z. Wu and F. Luo, J. Agric. Food Chem., 53, 3872 (2005); https://doi.org/10.1021/jf0501746
- P. Zhan, X. Liu, Y. Cao, Y. Wang, C. Pannecouque and E. De Clercq, Bioorg. Med. Chem. Lett., 18, 5368 (2008); https://doi.org/10.1016/j.bmcl.2008.09.055
- W.L. Dong, Z.X. Liu, X.H. Liu, Z.M. Li and W.G. Zhao, Eur. J. Med. Chem., 45, 1919 (2010); https://doi.org/10.1016/j.ejmech.2010.01.032
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- P. Fra̧ckowiak, U. Gawlik-Dziki, P. Sanchez-Bel and A. Obrępalska-Stęplowska, J. Agric. Food Chem., 71, 12958 (2023); https://doi.org/10.1021/acs.jafc.3c03876
- D. Quiroga, D. Rodríguez and E. Coy-Barrera, Molecules, 30, 4373 (2025); https://doi.org/10.3390/molecules30224373
- D. Kumar, N. Aggarwal, V. Kumar, H. Chopra, R.K. Marwaha and R. Sharma, Future Med. Chem., 16, 563 (2024); https://doi.org/10.4155/fmc-2023-0203
- T. Lei, Y. Zhou, Ch. Cheng, Y. Cao, Y. Peng, J. Bian and J. Pei, Org. Lett., 13, 2642 (2011); https://doi.org/10.1021/ol200748c
- M. Marinelli, A. Candini, F. Monti, A. Boschi, M. Zangoli, E. Salatelli, F. Pierini, M. Lanzi, A. Zanelli, M. Gazzano and F. Di Maria, J. Mater. Chem. C Mater. Opt. Electron. Devices, 9, 11216 (2021); https://doi.org/10.1039/D1TC02641K
- H. Pechmann and A. Nold, Ber. Dtsch. Chem. Ges., 29, 2588 (1896); https://doi.org/10.1002/cber.18960290336
- C.D. Hurd and R.I. Mori, J. Am. Chem. Soc., 77, 5359 (1955); https://doi.org/10.1021/ja01625a047
- L. Zhang, B. Sun, Q. Liu and F. Mo, J. Org. Chem., 83, 4275 (2018); https://doi.org/10.1021/acs.joc.8b00383
- M.S. Singh, A. Nagaraju, G.K. Verma, G. Shukla, R.K. Verma, A. Srivastava and K. Raghuvanshi, Green Chem., 15, 954 (2013); https://doi.org/10.1039/c3gc37047j
- L. Wolff, Justus Liebigs Ann. Chem., 333, 1 (1904); https://doi.org/10.1002/jlac.19043330102
- Q. Liu, M. Li, R. Xiong and F. Mo, Org. Lett., 19, 6756 (2017); https://doi.org/10.1021/acs.orglett.7b03573
- C. Schmitt and T. Murai, Carbon Disulfide. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, Ltd., (2001).
- Y. Tominaga, J. Heterocycl. Chem., 26, 1167 (1989); https://doi.org/10.1002/jhet.5570260501
- T. Aoyama, Y. Iwamoto and T. Shioiri, Heterocycles, 24, 589 (1986); https://doi.org/10.3987/R-1986-03-0589
References
P. Awasthi, A. Mittal, Swati, M. Singh and S. Sharma, Curr. Top. Med. Chem., 26 (2026); https://doi.org/10.2174/0115680266394288251007083351
A. Irfan, S. Ullah, A. Anum, N. Jabeen, A.F. Zahoor, H. Kanwal, K. Kotwica-Mojzych and M. Mojzych, Appl. Sci., 11, 5742 (2021); https://doi.org/10.3390/app11125742
F. Hayat, A. Salahuddin, J. Zargan and A. Azam, Eur. J. Med. Chem., 45, 6127 (2010); https://doi.org/10.1016/j.ejmech.2010.09.066
Z. Li, Z. Wu and F. Luo, J. Agric. Food Chem., 53, 3872 (2005); https://doi.org/10.1021/jf0501746
P. Zhan, X. Liu, Y. Cao, Y. Wang, C. Pannecouque and E. De Clercq, Bioorg. Med. Chem. Lett., 18, 5368 (2008); https://doi.org/10.1016/j.bmcl.2008.09.055
W.L. Dong, Z.X. Liu, X.H. Liu, Z.M. Li and W.G. Zhao, Eur. J. Med. Chem., 45, 1919 (2010); https://doi.org/10.1016/j.ejmech.2010.01.032
M. Wu, Q. Sun, C. Yang, D. Chen, J. Ding, Y. Chen, L. Lin and Y. Xie, Bioorg. Med. Chem. Lett., 17, 869 (2007); https://doi.org/10.1016/j.bmcl.2006.11.060
I. Cikotiene, E. Kazlauskas, J. Matuliene, V. Michailoviene, J. Torresan, J. Jachno and D. Matulis, Bioorg. Med. Chem. Lett., 19, 1089 (2009); https://doi.org/10.1016/j.bmcl.2009.01.003
P. Fra̧ckowiak, U. Gawlik-Dziki, P. Sanchez-Bel and A. Obrępalska-Stęplowska, J. Agric. Food Chem., 71, 12958 (2023); https://doi.org/10.1021/acs.jafc.3c03876
D. Quiroga, D. Rodríguez and E. Coy-Barrera, Molecules, 30, 4373 (2025); https://doi.org/10.3390/molecules30224373
D. Kumar, N. Aggarwal, V. Kumar, H. Chopra, R.K. Marwaha and R. Sharma, Future Med. Chem., 16, 563 (2024); https://doi.org/10.4155/fmc-2023-0203
T. Lei, Y. Zhou, Ch. Cheng, Y. Cao, Y. Peng, J. Bian and J. Pei, Org. Lett., 13, 2642 (2011); https://doi.org/10.1021/ol200748c
M. Marinelli, A. Candini, F. Monti, A. Boschi, M. Zangoli, E. Salatelli, F. Pierini, M. Lanzi, A. Zanelli, M. Gazzano and F. Di Maria, J. Mater. Chem. C Mater. Opt. Electron. Devices, 9, 11216 (2021); https://doi.org/10.1039/D1TC02641K
H. Pechmann and A. Nold, Ber. Dtsch. Chem. Ges., 29, 2588 (1896); https://doi.org/10.1002/cber.18960290336
C.D. Hurd and R.I. Mori, J. Am. Chem. Soc., 77, 5359 (1955); https://doi.org/10.1021/ja01625a047
L. Zhang, B. Sun, Q. Liu and F. Mo, J. Org. Chem., 83, 4275 (2018); https://doi.org/10.1021/acs.joc.8b00383
M.S. Singh, A. Nagaraju, G.K. Verma, G. Shukla, R.K. Verma, A. Srivastava and K. Raghuvanshi, Green Chem., 15, 954 (2013); https://doi.org/10.1039/c3gc37047j
L. Wolff, Justus Liebigs Ann. Chem., 333, 1 (1904); https://doi.org/10.1002/jlac.19043330102
Q. Liu, M. Li, R. Xiong and F. Mo, Org. Lett., 19, 6756 (2017); https://doi.org/10.1021/acs.orglett.7b03573
C. Schmitt and T. Murai, Carbon Disulfide. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, Ltd., (2001).
Y. Tominaga, J. Heterocycl. Chem., 26, 1167 (1989); https://doi.org/10.1002/jhet.5570260501
T. Aoyama, Y. Iwamoto and T. Shioiri, Heterocycles, 24, 589 (1986); https://doi.org/10.3987/R-1986-03-0589
