Nucleophilic Ring-Opening of 3-Chloro-1,2-benzisothiazoles to Synthesize 2-Cyanoaryl Sulfides and Antifungal Activity Studies

doi:10.6023/cjoc202606010

Chinese Journal of Organic Chemistry

ARTICLE

3-氯-1,2-苯并异噻唑亲核开环合成2-氰基芳基硫醚与抑菌活性研究

刘一霖^†,a, 马琪琛^†,a, 朱鑫鑫^a, 罗江浩^a, 王方^*,b, 李萌杨^*,a, 林潇斌^*,a,c

^a西北农林科技大学化学与药学院陕西杨凌 412100;
^b延安大学化学与化工学院陕西延安 716000;
^c西北农林科技大学陕西省植物源农药研究与开发重点实验室陕西杨凌 412100

收稿日期:2026-06-19 修回日期:2026-07-28 发布日期:2026-09-11
基金资助:
“三秦英才引进计划”青年项目资助项目.

Nucleophilic Ring-Opening of 3-Chloro-1,2-benzisothiazoles to Synthesize 2-Cyanoaryl Sulfides and Antifungal Activity Studies

Liu Yilin^†,a, Ma Qichen^†,a, Zhu Xinxin^a, Luo Jianghao^a, Wang Fang^*,b, Li Mengyang^*,a, Lin Xiaobin^*,a,c

^aCollege of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100;
^bSchool of Chemistry and Chemical Engineering, Yan'an University, Yan'an, Shaanxi 716000;
^cShaanxi Key Laboratory of Botanical Pesticide R & D, Institute of Pesticide Science, Northwest A&F University, Yangling, Shaanxi 712100

Received:2026-06-19 Revised:2026-07-28 Published:2026-09-11
Contact: *E-mail: xiaobin.lin@nwafu.edu.cn (Lin, Xiaobin); myli@nwafu.edu.cn (Li, Mengyang); wangf@yau.edu.cn (Wang, Fang).
About author:†The authors contributed equally to this work.
Supported by:
The “Sanqin Yingcai” Introduction Program for Young Talents.

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Abstract

A base-promoted nucleophilic ring-opening reaction of 3-chloro-1,2-benzisothiazole for the synthesis of 2-cyanoaryl sulfides was developed. This method proceeds under mild conditions with operational simplicity. Using Cs₂CO₃ as the base and without the need for any metal catalyst, the ring-opening reactions of 3-chloro-1,2-benzisothiazole with three types of nucleophiles—namely indoles, 2-naphthols, and nitromethane—were achieved, affording 27 examples of 2-cyanoaryl sulfides in up to 99% yield. Some of the obtained compounds exhibited good antifungal activity; notably, compound 3d displayed excellent inhibitory activity against the phytopathogenic fungus Botrytis cinerea (B. cinerea), with an EC₅₀ value of 0.445 μg/mL. These results fully demonstrate the promising application prospects of this synthetic method and the resulting products.

Key words: Base-promoted nucleophilic ring-opening, 2-Cyanoaryl sulfide, 3-Chloro-1,2-benzisothiazole, Antifungal activity

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Liu Yilin, Ma Qichen, Zhu Xinxin, Luo Jianghao, Wang Fang, Li Mengyang, Lin Xiaobin. Nucleophilic Ring-Opening of 3-Chloro-1,2-benzisothiazoles to Synthesize 2-Cyanoaryl Sulfides and Antifungal Activity Studies[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202606010.

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[1] Smith M. B.March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley, Hoboken, NJ, 2013.
[2] Beletskaya I. P.; Ananikov, V. P. Chem. Rev.2011, 111, 1596.
[3] Liu H.; Jiang, X. F. Chem. -Asian J.2013, 8, 2546.
[4] Eichman C. C.; Stambuli J. P. Molecules2011, 16, 590.
[5] Ley S. V.; Thomas A. W.Angew. Chem. Int. Ed. 2003, 42, 5400.
[6] Kondo T.; Mitsudo T.-A. Chem. Rev.2000, 100, 3205.
[7] Dong D.-Q.; Hao S.-H.; Yang D.-S.; Li L.-X.; Wang Z.-L.Eur. J. Org. Chem. 2017, 6576.
[8] Xu X. M.; Yang H. L.; Wang Z. L.Chin. J. Org. Chem. 2020, 40, 1912.
[9] Xu X. M.; Li J. Z.; Wang Z. L.Chin. J. Org. Chem. 2020, 40, 886.
[10] Saroha M.; Sindhu J.; Kumar S.; Bhasin K. K.; Khurana J. M.; Varma R. S.; Tomar D.ChemistrySelect 2021, 6, 13077.
[11] Rani P.; Chahal S.; Singh R.; Sindhu, J. Top. Curr. Chem.2024, 382, 13.
[12] Kleemann A.; Engel J.; Kutscher B.; Reichert D.,Pharmaceutical Substance: Synthesis Patents, Applications, 4th ed., Georg Thieme, Stuttgart, 2001.
[13] Miller J. S.; Manson, J. L. Acc. Chem. Res.2001, 34, 563.
[14] Fleming F. F.; Wang Q.Chem. Rev. 2003, 103, 2035.
[15] Rappoport Z.Chemistry of the Cyano Group, Wiley, London, 1970.
[16] Larock R. C.Comprehensive Organic Transformations: A Guide to Functional Group Preparations, VCH, New York, 1989.
[17] Sandmeyer, T. Ber. Dtsch. Chem. Ges.1884, 17, 1633.
[18] Galli, C. Chem. Rev.1988, 88, 765.
[19] Rosenmund K. W.; Struck, E. Ber. Dtsch. Chem. Ges.1919, 2, 1749.
[20] Lindley, J. Tetrahedron, 1984, 40, 1433.
[21] Zhou W.; Zhang L.; Jiao, N. Angew. Chem. Int. Ed.2009, 48, 7094.
[22] Oishi T.; Yamaguchi K.; Mizuno, N. Angew. Chem. Int. Ed.2009, 48, 6286.
[23] Zhou W.; Xu J.; Zhang L.; Jiao N. Org. Lett.2010, 12, 2888.
[24] He J.; Yamaguchi K.; Mizuno, N. J. Org. Chem.2011, 76, 4606.
[25] Kim J.; Kim H. J.; Chang, S. Angew. Chem. Int. Ed.2012, 51, 11948.
[26] Wang L.; Shao Y.; Cheng J.Org. Biomol. Chem. 2021, 19, 8646.
[27] Shan Y. Y.; Zhang X. H.; Liu G. L.; Li J. M.; Liu Y. W.; Wang J.; Chen, D. P. Chem. Commun.2024, 60, 1546.
[28] Nauth A. M.; Opatz, T. Org. Biomol. Chem.2019, 17, 11.
[29] Rodrigues R. M.; Thadathil D. A.; Ponmudi K.; George A.; Varghese A.ChemistrySelect 2022, 7, e202200081.
[30] Brown D. W.; Sainsbury, M. Science of Synthesis2002, 11, 573.
[31] Watanabe, S. Bull. Chem. Soc. Jpn.1969, 42, 1152.
[32] Carrington D. E.L.; Clarke, K.; Scrowston, R. M.J. Chem. Soc. C, 1971, 3903.
[33] Carrington D. E.L.; Clarke, K.; Scrowston, R. M.J. Chem. Soc. C, 1971, 3262.
[34] Ren, J. Yu T. Li Q. Wang G. L, Wang B. Y., Wu Y. G.; Liu H. M.; Yang X. P. Asian J. Org. Chem.2026; 15, e70317.
[35] CCDC number of 3a: 2537834.

3-氯-1,2-苯并异噻唑亲核开环合成2-氰基芳基硫醚与抑菌活性研究

Nucleophilic Ring-Opening of 3-Chloro-1,2-benzisothiazoles to Synthesize 2-Cyanoaryl Sulfides and Antifungal Activity Studies

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