Preparation of some new benzo[d]thiazole derivatives

Duong Quoc Hoan, Vu Thi Anh Tuyet, Le Thanh Duong, Nguyen Hien


In this work, four new benzo[d]thiazole derivatives were synthesized successfully from vanillin. Nitration of vanillin gave nitrovanillin followed by cyclization reaction with o-aminothiophenol under microwave irradiation in 4 minutes to give nitroaromatic compound 3. The reduction to convert the nitro group to amino group was optimized. It was found that Fe/ con. HCl in ethanol was the best condition for this case about both yield (~95 %) and simple procedure to give compound 4 as a salt. Acetylation occurs at both phenolic hydroxyl group and amino group of the salt 4 to form N,O-acetyl compound 5. Under mild hydrolysis 5 produces N-acetyl compound 6. The structures of these compounds were established by IR, 1H and 13C NMR and mass spectral analyses.

Keywords. benzo[d]thiazole, vanillin, reduction, microwave.


Benzo[d]thiazole, vanillin, reduction, microwave

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Hofmann A. W. Uebereine Reihe aromatischer, den Senfölen und Sulfocyanaten isomerer Basen, Chemische Berichte, 13, 8-22 (1880).

Caleta I., Kralj M., Branimir Bertosa B., Sanja Tomic S., Pavlovic G., Pavelic K., Karminski-Zamola G. Novel Cyano- and Amidinobenzothiazole Derivatives: Synthesis, Antitumor Evaluation, and X-ray and Quantitative Structure, Activity Relationship (QSAR) Analysis, J. Med. Chem., 52, 1744 (2009).

Chung Y., Shin Y.-K., Zhan C.-G., Lee S., Cho H. Synthesis and evaluation of antitumor activity of 2- and 6-[(1,3-benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone derivatives, Arch. Pharmacol. Res., 27, 893 (2004).

Yoshida M., Hayakawa I., Hayashi N., Agatsuma T., Oda Y., Tanzawa F., Iwasaki S., Koyama K., Furukawa H., Kurakata S. Synthesis and biological evaluation of benzothiazole derivatives as potent antitumor agents, Bioorg. Med. Chem. Lett., 15,


Bradshaw T. D., Stevens M. F. G., Westwell A. D. The Discovery of the Potent and Selective Antitumour Agent 2-(4-Amino-3-methylphenyl) benzothiazole (DF 203) and Related Compounds, Curr. Med. Chem., 8, 203 (2001).

Hutchinson I., Chua M.-S., Browne H. L., Trapani, V., Bradshaw T. D., Westwell A. D., Stevens, M. F. G. Antitumor Benzothiazoles: Synthesis and in Vitro Biological Properties of Fluorinated 2-(4-Aminophenyl)benzothiazoles, J. Med. Chem., 44, 1446 (2001).

Mortimer C. G., Wells G., Crochard J.-P., Stone E. L., Bradshaw T. D., Stevens M. F. G., Westwell A. D, Antitumor Benzothiazoles: 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a Simple Fluorinated 2-Arylbenzothiazole, Shows Potent and Selective Inhibitory Activity against Lung, Colon, and Breast Cancer Cell Lines, J. Med. Chem., 49, 179 (2006).

Kou-San Ju and Rebecca E. Parales. Nitroaromatic Compounds, from Synthesis to Biodegradation, Microbiol. Mol. Biol. Rev., 74(2), 250 (2010).

Thorata B. R., Mustapha Mandewalea, Sharda Shelke, Prasad Kamat, R. G. Atrama, Mahesh Bhalerao and R. Yamgara. Synthesis of novel Schiff bases of 4-hydroxy-3-methoxy-5-nitrobenzaldehyde and Development of HPLC Chromatographic Method for their analysis, J. Chem. Pharm. Res., 4(1), 14-17 (2012).

Karl B. and Eng W. T. Synthesis and evaluation of bifunctional nitrocatechol inhibitors of pig liver catechol-O-methyltransferase, Bioorg. Med. Chem., 13, 5740-5749 (2005).

Hoang Thi Tuyet Lan, Nguyen Hien, Nguyen Huu Dinh, Synthesis and structures of some azomethins from 2-methoxy-4-(3-methylfuroxan-4-yl)-5-nitrophenoxy acetic acid, Vietnam Journal of Chemistry, 51(6 ABC), 141-145 (2013).

Zahradník P. Quantum-chemical study of electronic structure and transmission of substituent effect in benzothiazole derivatives, Chem. Papers, 44 (2), 145-150 (1990).

Furniss B. S., Hannaford A. J., Smith P. W. G., Tatchell, A. R. Vogel’s textbook of practical organic chemistry, 5th ed., Pearson education limited (1989).

Sahoo S. S., Shukla S., Nandy S., Sahoo H. B. Synthesis of novel coumarin derivatives and its biological evaluations, European Journal of Experimental Biology, 2, 899-908 (2012).

Silverstein R. M., Webster F. X., Kiemle, D. J. Spectrometric identification of organic compounds, John Wiley  Sons, Inc (2005).