• ARUN GOYAL Department of Chemistry, Govt. P.G. College Rajgarh (Alwar), Rajasthan, Alwar, India.


Objective: 4H-1,4-Benzothiazines constitute an important class of heterocycles containing 1,4-thiazine ring fused to benzene ring. They are extensively used as tranquilizer, antispasmodic, central nervous system depressant, antiulcer, antibacterial, antifungal, antioxidant, anticancer agents, fungicides, etc. Therefore, these observations prompted us to synthesize substituted 4H-1,4-benzothiazines and investigate their antimicrobial activity against selected bacterial and fungal strains.

Methods: In the present research work, 2-Amino-3,5,6-trichlorobenzenethiol condensed with β-diketones/β-ketoesters in the presence of dimethyl sulfoxide followed by oxidative cyclisation leading to the formation of 4H-1,4-benzothiazines. The spectral investigation confirmed the synthesis of these bioactive compounds. All synthesized compounds were screened for their antimicrobial activity (antibacterial and antifungal) using agar well diffusion method.

Results: The minimum inhibitory concentration values of synthesized compounds gave excellent results against bacterial as well as fungal strains (Escherichia coli [Gram negative] MTCC 2939, 58–158 μg/mL, Bacillus subtilis [Gram positive] MTCC 441, 41–124 μg/mL, Streptomyces griseus [Gram negative] MTCC 1998, 85–128 μg/mL, Fusarium oxysporum MTCC 1755, 142–151 μg/mL, Aspergillus niger MTCC 281, 59–78 μg/mL, and Rhizopus stolonifer MTCC 2591, 85–118 μg/mL).

Conclusion: Synthesized substituted benzothiazines have potential to be used as a new class of antibacterial and antifungal drugs. Further biomedical research is required to make 4H-1,4-benzothiazines related compounds as potential antibacterial and antifungal drugs.

Keywords: Benzothiazine, β-diketones/β-diketoesters, Antimicrobial properties


1. Kajino M, Mizuno K, Tawada H, Shibouta Y, Nishikawa K, Meguro K. Synthesis and biological activities of new 1, 4-benzothiazine derivatives. Chem Pharm Bull 1991;39:2888-95.
2. Grandolini G, Luana P, Ambrogi V. Synthesis of some new 1, 4-benzothiazine and 1, 5-benzothiazepine tricyclic derivatives with structural analogy with TIBO and their screening for anti-HIV activity. Eur J Med Chem 1999;34:701-9.
3. Munde SB, Bondge SP, Bhingolikar VE, Mane RA. A facile synthesis of 1, 4-benzothiazines under solvent free conditions. Green Chem 2003;5:278-9.
4. Eicher T, Hauptmann S, Speicher A. The Chemistry of Heterocycles: Structure, Reactions, Syntheses and Application. Weinheim: Wiley- VCH; 2003.
5. Deshmukh MB, Mulik AR, Desai SD. Sysnthesis of some new 2-methyl-1, 4-benzothiazin-3-(1H)-one derivatives as potential vasodilator. Eur J Chem 2004;1:206-10.
6. Dabholkar VV, Gavande RP. Synthesis of pyrazolyl 1, 4-benzothiazine derivatives. Heteroletters 2011;3:255-61.
7. Gupta K. Microwave assisted facile synthesis of some substituted 4H 1, 4-benzothiazine. Indian J Chem 2011;9:1625-8.
8. Gautam N, Ajmera N, Gupta S Gautam DC. Synthesis, spectral characterization and biological evaluation of 4H-1, 4-benzothiazines, their sulfones and ribofuranosides. Eur J Chem 2012;3:106-11.
9. Saari WS, Cochran DW, Lee YC, Cresson EL, Springer JP, Williams M. Preparation of some 10-[3-(dimethylamino)-1-propyl]-10H-pyrazino[2, 3-b] [1, 4] benzothiazines as potential neuroleptics. J Med Chem 1983;26:564-9.
10. Chikuma T, Ishii Y, Kato T, Kurihara N, Hakeda Y, Kumegawa M. Effect of chlorpromazine on PZ-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1). Biochem Pharmacol 1987;36:4319-24.
11. Gupta RR, Ojha KG. In: Gupta RR, editor. Phenothiazines and 1, 4-benzothiazines: chemical and biomedical aspects. Amsterdam: Elsevier; 1988. p. 163-269.
12. Gupta RR. Phenothiazines and 1, 4-Benzothiazines-Chemical and Biomedical Aspects. Amsterdam: Elsevier; 1988.
13. Teodori E, Dei S, Scapecchi S, Gualtieri F. The medicinal chemistry of multidrug resistance (MDR) reversing drugs. Farmaco 2002;57:385-415.
14. Khandelwal N, Abhilasha, Gautam N, Gautam DC. An efficient synthesis and biological study of substituted 8-chloro-5-methoxy/8- chloro-4H-1, 4-benzothiazines, their sulphones and ribofuranosides. J Chem Sci 2013;125:85-93.
15. Dogan HN, Duran A, Rollas S, Sener G, Uysal MK, Gulen D. Synthesis of new 2, 5-disubstituted-1, 3, 4-thiadiazoles and preliminary evaluation of anti-convulsant and antimicrobial activities. Bioorg Med Chem 2002;10:2893-8.
16. Zamani K, Faghihi K, Tofighi T, Shariatzadeh MR. Synthesis and antimicrobial activity of some pyridyl and naphthyl substituted 1, 2, 4-triazole and 1, 3, 4-thiadiazole derivatives. Turk J Chem 2004;28:95-100.
17. Dabholkar VV, Gavande RP. Synthesis and antimicrobial activities of novel 1, 4-benzothiazine derivatives. Arab J Chem 2011;9:S225-9.
18. Rathod AK. A microwave-assisted synthesis of some new benzothiazines derivatives and their antimicrobial activity. Int J Pharm Sci Rev Res 2013;18:47-9.
19. Kaneko T, Clark RS, Ohi N, Kawahara T, Akamatsu H, Ozaki F. Inhibitors of adhesion molecules expression; the synthesis and pharmacological properties of 10H-pyrazino [2, 3-b] [1, 4] benzothiazine derivatives. Chem Pharm Bull 2002;50:922-9.
20. Gautam N, Ajmera N, Gupta S, Gautam DC. Synthesis, spectral characterization and biological evaluation of 4H-1, 4-benzothiazines, their sulfones and ribofuranosides. Eur J Chem 2012;3:106-11.
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How to Cite
GOYAL, A. “SPECTRAL EVALUATION AND ANTIMICROBIAL ACTIVITY OF SYNTHESIZED 4H-1,4-BENZOTHIAZINES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 6, Apr. 2021, pp. 66-69, doi:10.22159/ajpcr.2021.v14i6.41193.
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