Synthesis of S-(5-aryl-1,3,4-oxadiazol-2-yl) O-alkyl carbonothioate and alkyl 2-((5-aryl-1,3,4-oxadiazol-2-yl)thio) acetate, and their antimicrobial properties

Synthesis of S-(5-aryl-1,3,4-oxadiazol-2-yl) O-alkyl carbonothioate and alkyl 2-((5-aryl-1,3,4-oxadiazol-2-yl)thio) acetate, and their antimicrobial properties

The S-(5-aryl-1,3,4-oxadiazol-2-yl) O-alkyl carbonothioate (4-9) and the alkyl 2-((5-aryl-1,3,4-oxadiazol-2-yl)thio) acetate (10-15) were synthesized by interaction of 5-aryl-1,3,4-oxadiazole-2-thiones with alkyl esters of chloroformic acid and chloroacetic acid. The yields of target compounds (7-9) obtained with isobutyl chloroformate were 69-73%, compounds (4-6) with propyl chloroformate - 74-79% and compounds (10-15) with alkyl esters of chloroacetic acid - 86-92%, respectively. The structures of the synthesized compounds were confirmed by IR, UV, 1H and 13C NMR spectra. The antibacterial and antifungal activities of these compounds were investigated. The results of in vitro antimicrobial activity tests showed that S-(5-phenyl(2-chlorophenyl)-1,3,4-oxadiazol-2-yl) O-propyl carbonothioate (4-5) and S-(5-phenyl(2-chlorophenyl)-1,3,4-oxadiazol-2-yl) O-isobutyl carbonothioate (7-8) exhibited weak, but selective antibacterial activity against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus). At the same time, no activity was shown by compounds with two chlorine atoms in the aromatic ring (13-15) and alkyl 2-((5-aryl-1,3,4-oxadiazol-2-yl) thio) acetate (10-15).


  • 1. Glomb T, Świątek P. Antimicrobial Activity of 1,3,4-Oxadiazole Derivatives. Int. J. Mol. Sci. 2021;22:6979.
  • 2. Glomb T, Szymankiewicz K, Swiatek P. Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole. Molecules. 2018;23:3361.
  • 3. Rubina B, Dharam PP, Garima K, Ravi K, Manni D. Recent Developments on Pharmacological Potential of 1,3,4-Oxadiazole Scaffold. Ind. J. Pharm. Edu. Res. 2019;53(2S):1-16.
  • 4. Tantray MA, Khan I, Hamid H, Alam MS, Dhulap A, Kalam A. Synthesis of Benzimidazole-Linked-1,3,4-Oxadiazole Carboxamides as GSK-3β Inhibitors with in Vivo Antidepressant Activity. Bioorg Chem. 2018;77:393-401.
  • 5. Akram M, Rauf A, Saeed A, Ahmed F, Mubeen S, Ashraf M, Hussain S, Qureshi AM. Synthesis, biological evaluation and molecular docking studies of Mannich bases derived from 1,3,4-oxadiazole-2-thiones as potential urease inhibitors. Trop J Pharm Res. 2018;17(1):127-134.
  • 6. Kumar D, Kumar V, Marwaha R, Singh G. Oxadiazole-An Important Bioactive Scaffold for Drug Discovery and Development Process Against HIV and Cancer- A Review. Current Bioactive Compounds. 2019;15(3):271-279.
  • 7. Alam MM. 1,3,4-Oxadiazole as a Potential Anti-Cancer Scaffold: A Review. Biointerface Research in Applied Chemistry. 2022;12(4):5727-5744.
  • 8. Thakkar SS, Thakor P, Doshi H, Ray A. 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities. Bioorganic & Medicinal Chemistry. 2017;25(15):4064-4075.
  • 9. Espinosa AV, Costa DS, Tunes LG, do Monte-Neto RL, Grazul RM, de Almeida MV, Silva H. Anticancer and antileishmanial in vitro activity of gold (I) complexes with 1,3,4-oxadiazole-2(3H)-thione ligands derived from δ-D-gluconolactone. Chem Biol Drug Des. 2021;97(1):41-50.
  • 10. Verma SK, Verma R, Verma S, Vaishnav Y, Tiwari SP, Rakesh KP. Antituberculosis activity and its structure-activity relationship (SAR) studies of oxadiazole derivatives: A key review. Eur J Med Chem. 2021;209:112886.
  • 11. Ziyaev AA, Galust’yan GG. Reaction of 5-aryl-1,3,4-oxadiazole-2(3H)-thiones with chloromethyl alkyl ethers. Chem Heterocycl Compd. 1999;35:1104-1106.
  • 12. Tozhiev IF, Ziyaev AA, Shakhidoyatov KhM. Alkylation of 5-aryl-1,3,4-оxadiazol-2(3Н)-thions with allyl- and benzylhalogens. Chemistry and chemical technology. 2012;4:17-20.
  • 13. Ziyaev AA, Tozhiev IF, Shakhidoyatov KhM. 5-Aryl-1,3,4-oxadiazolin-2(3H)-thiones in reactions with alkyl haloacetates. Chem Heterocycl Compd. 2012;48:488-491.
  • 14. Ziyaev AA, Ismailova DS. Synthesis of 5-phenoxymethyl-1,3,4-oxadiazolin-2(3H)-thion and its alkylation. Uzbek Chem J. 2015;1:15-18.
  • 15. Performance Standards for Antimicrobial Disk Susceptibility Tests. CLSI document M02. 13th Edition. Wayne, PA, USA; 2018. ISBN 1-56238-834-7.
  • 16. Koparır M, Çetin A, Cansız A. 5-Furan-2yl[1,3,4]oxadiazole-2-thiol, 5-Furan-2yl-4H [1,2,4] triazole-3-thiol and Their Thiol-Thione Tautomerism. Molecules. 2005;10(2):475-480.
  • 17. Rozhkova N, Sabirov K, Seytanidi KL. Reaction of benzothiazolin-2-thione with 1-chloro-2,3-epoxypropane. Chem Heterocycl Compd. 1983;11:1170-1173.
  • 18. Eshimbetov AG, Tojiev IF, Ziyaev AA. DFT and TD-DFT study of isomeric 5-(pyridyl)-1,3,4-oxadiazol-2-thiones and 2-methylthio-5-(pyridyl)-1,3,4-oxadiazoles. Spectrochim Acta A Mol Biomol Spectrosc. 2017 Dec 5;187:191-197.
Journal of the Turkish Chemical Society Section A: Chemistry-Cover
  • Başlangıç: 2014
  • Yayıncı: Türkiye Kimya Derneği
Sayıdaki Diğer Makaleler

Production of SBS Reinforced Polyester Composite: Characterization of Physical and Chemical Properties


Novel Perylene-Based Antimicrobial PDI Chromophores

Cansu YILMAZ, Pınar GÜNER, Tülin AŞKUN, Funda YÜKRÜK

Eco-friendly dyeing of fabric and wool yarn samples with Morus nigra leaf extracts


Assessment of Total Phenolic Compounds, Antioxidant Capacity, β-Carotene Bioaccessibility, HMF Formation, and Color Degradation Kinetics in Pumpkin Pestils


Design, Synthesis and Structural Characterization of Novel Thioanthraquinone Analogues from 1,5-Dichloroanthraquinone


Development of Two Simple Spectrophotometric Methods to Assay Phenylephrine-HCl as Pure Form And in Its Drug Forms

Hanan HAMEED, Salim ALİ

Synthesis of New Azo Compounds and Their Application for a Simple Spectrophotometric Determination of Methyldopa Drug Using Anthranilic Acid and 2-Aminopyrimidine as Reagents


A Simple, Stable, and Highly Sensitive Spectrophotometric Method for the Determination of Arsenic(III) from Different Biological Media in the Presence of Nanosilica-Cysteine Composite


Differences in Heavy Metals Adsorption on Natural, Modified, and Synthetic Zeolites-A Review

Sebghatullah MUDABER, Jenaidullah BATUR

Removal Of Sumifix Yellow EXF Reactive Azo Dye By Electro-Fenton Method