Design, Synthesis and Nematicidal and Fungicidal Activities of 8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine Oxadiazole Thioether Derivatives

doi:10.6023/cjoc202311024

Abstract

In order to discover new compounds with high nematicidal and fungicidal activity, 22 8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine oxadiazole thioether derivatives were designed and synthesized, and the structures of all target compounds were confirmed by ¹H NMR, ¹³C NMR and high-resolution mass spectra (HRMS). The results of nematicidal activity test showed that all the target compounds possessed certain toxic activity against Caenorhabditis elegans (second-stage juveniles) at the concentration of 100 mg/L. The LC₅₀ of 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-fluoro- benzyl)thio)-1,3,4-oxadiazole (6j), 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-chlorobenzyl)thio)-1,3,4- oxadiazole (6m), 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-cyanobenzyl)thio)-1,3,4-oxadiazole (6q), 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((3-methoxybenzyl)thio)-1,3,4-oxadiazole (6s) and 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((4-methoxybenzyl)thio)-1,3,4-oxadiazole (6t) against C. elegans were 48.10, 34.94, 52.87, 48.32 and 37.62 mg/L, respectively, which were superior than that of fosthiazate (79.28 mg/L). The results of fungicidal activity test showed that 2-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)-5-((2-bromoethyl)thio)- 1,3,4-oxadiazole (6d) had good inhibitory activity against Rhizoctonia solani. The EC₅₀ value of compound 6d was 7.22 mg/L, which was superior to that of fluopyram (110.02 mg/L). At the concentration of 100 and 200 mg/L, the protective effects of compound 6d against rice sheath blight were 85.5% and 92.1%, and the curative effects were 59.2% and 79.0%. The target compounds synthesized in this study have certain nematocidal and fungicidal activities, which can provide new ideas for the design and synthesis of imidazo[1,2-a]pyridine derivatives, and have reference significance for exploring the bioactivity diversity of imidazo[1,2-a]pyridine derivatives.

Key words: imidazo[1,2-a]pyridine, oxadiazole, thioether, Caenorhabditis elegans, nematicidal activity, fungicidal activity

Cite this article

Qiannan Guo, Sen Huang, Wei Zhao, Wei Zhao, Yue Yan, Jihai Wang, Zhihong Xu. Design, Synthesis and Nematicidal and Fungicidal Activities of 8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine Oxadiazole Thioether Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(5): 1620-1629.

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References 23

[1]	AChim, M.; Hnas, R.; Stephan, D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2328.
[2]	Lahm, G. P.; Desaeger, J.; Smith, B. K.; Pahutski, T. F.; Rivera, M. A.; Meloro, T.; Kucharczyk, R.; Lett, R. M.; Daly, A.; Smith, B. T.; Cordova, D.; Thoden, T.; Wiles, J. A. Bioorg. Med. Chem. Lett. 2017, 27, 152.
[3]	Shotwell, J. B.; Baskaran, S.; Chong, P.; Creech, K. L.; Crosby, R. M.; Dickson, H.; Fang, J.; Garrido, D.; Mathis, A.; Maung, J.; Parks, D. J.; Pouliot, J. J.; Price, D. J.; Rai, R.; Seal, J. W.; Tai, V. W.; Thomson, M.; Xie, M.; Xiong, Z. Z.; Peat, J. ACS Med. Chem. Lett. 2012, 3, 565. doi: 10.1021/ml300090x pmid: 24900511
[4]	Kang, S.; Kim, R. Y.; Seo, M. J.; Lee, S.; Kim, Y. M.; Seo, M.; Seo, J. J.; Ko, Y.; Choi, I.; Jang, J.; Nam, J.; Park, S.; Kang, H.; Kim, H. J.; Kim, J.; Ahn, S.; Pethe, K.; Nam, K.; Kin, J. J. Med. Chem. 2014, 57, 5293.
[5]	Balzani, V. New J. Chem. 1996, 20, 723.
[6]	Zhang, R. Ph.D. Dissertation, Zhejiang University, Hangzhou, 2007 (in Chinese).
	( 张睿, 博士论文, 浙江大学, 杭州, 2007.)
[7]	Liu, A.-C.; Feng, J.-L.; He, X.-L.; Chen, L.; Zou, X.-D. Agrochemicals 2014, 53, 561 (in Chinese).
	( 刘安昌, 冯佳丽, 贺晓露, 陈露, 邹晓东, 农药, 2014, 53, 561.)
[8]	Gan, X.-H.; Hu, D.-Y.; Wang, Y.-J.; Song, B.-A. Sci. Sinica Chim. 2016, 46, 1204 (in Chinese).
	( 甘秀海, 胡德禹, 王艳娇, 宋宝安, 中国科学: 化学, 2016, 46, 1204.)
[9]	Du, H.-T.; Du, H.-J. Chin. J. Org. Chem. 2010, 30, 137 (in Chinese).
	( 杜海堂, 杜海军, 有机化学, 2010, 30, 137.)
[10]	Liu, J.-C.; Wang, W.-D.; He, H.-W. Chin. J. Org. Chem. 2014, 34, 1447 (in Chinese).
	( 刘建超, 王卫东, 贺红武, 有机化学, 2014, 34, 1447.) doi: 10.6023/cjoc201403013
[11]	Wang, B. L.; Zhu, H. W.; Li, Z. M.; Xiong, L. X.; Li, Y. Q.; Zhao, Y.; Zhang, J. F.; Chen, Y. W.; Zhou, S.; Li, Z. M. J. Agric. Food Chem. 2013, 61, 5483.
[12]	Mo, Q. J.; Liu, L. Z.; Duan, W. G.; Cen, B.; Lin, G. S.; Chen, N. Y.; Huang, Y.; Liu, B. M. Chem. Ind. For. Prod. 2015, 35, 8.
[13]	Shi, Y.-J.; Li, Y.; Fang, Y.; Chen, J.; Ye, L.-Y.; Ge, S.-S.; Dai, H. Chin. J. Org. Chem. 2016, 36, 2472 (in Chinese).
	( 石玉军, 李阳, 方源, 陈佳, 叶林玉, 葛书山, 戴红, 有机化学, 2016, 36, 2472.) doi: 10.6023/cjoc201605029
[14]	Fan, Z. J.; Shi, J.; Luo, N.; Ding, M. H.; Bao, X. P. J. Agric. Food Chem. 2019, 67.
[15]	Ren, Z.-L.; Fang, S.-S.; Xu, J.-W.; Ding, H.-X.; Xu, H.; Lu, M. Chin. J. Pestic. Sci. 2023 (in Chinese).
	( 任自立, 方珊珊, 徐建伟, 丁海霞, 徐晖, 吕敏, 农药学学报, 2023.)
[16]	Li, L. S.; Xu, J. Y.; Lv, B.; Kaziem, A. E.; Liu, F.; Shi, H. Y.; Wang, M. H. J. Agric. Food Chem. 2020, 68, 7609.
[17]	Jose, G.; Kumara, S. T.; Nagendrappa, G.; Sowmya, H.; Sriram, D.; Yogeeswari, P.; Sridevi, P. J.; Tayur, N.; Row, G.; Hosamani, A.; Ganapathy, S. P.; Chandrika, N.; Narendra, L. Eur. J. Med. Chem. 2015, 89.
[18]	Chen, X.-W. M.S. Thesis, Guizhou University, Guiyang, 2016 (in Chinese).
	( 陈学文, 硕士论文, 贵州大学, 贵阳, 2016.)
[19]	Chen, X.-W.; Gan, X.-H.; Chen, J.-X.; Chen, Y.-Z.; Wang, Y.-J.; Hu, D.-Y.; Song, B.-A. Chin. J. Org. Chem. 2017, 37, 2343 (in Chinese).
	( 陈学文, 甘秀海, 陈吉祥, 陈永中, 王艳娇, 胡德禹, 宋宝安, 有机化学, 2017, 37, 2343.) doi: 10.6023/cjoc201703022
[20]	Tang, X.-M. M.S. Thesis, Changchun University of Science and Technology, Shenyang, 2012 (in Chinese).
	( 唐晓明, 硕士论文, 长春理工大学, 沈阳, 2012.)
[21]	Zhou, P.; Huang, J.-J.; He, C.-W.; Guo, Q.-N.; You, J.; Liu, Y.-F.; Xu, Z.-H. Chin. J. Pestic. Sci. 2022, 24, 1367 (in Chinese).
	( 周蒲, 黄俊杰, 何昌文, 郭倩男, 游江, 刘一凡, 徐志红, 农药学学报, 2022, 24, 1367.)
[22]	Shi, J.-C. M.S. Thesis, Yangtze University, Jingzhou, 2023 (in Chinese).
	( 时锦超, 硕士论文, 长江大学, 荆州, 2023.)
[23]	Kang, Z.; Gu, B.-G. Standard Operating Procedures for Bioactivity Testing of Pesticides——Fungicide Roll, Chemical Industry Press, Shenyang, 2016, pp. 155-156 (in Chinese).
	( 康卓, 顾宝根, 农药生物活性测试标准操作规范——杀菌剂卷, 化学工作出版社, 沈阳, 2016, pp. 155-156.)

Compd.	Mortality rate/%	Compd.	Mortality rate/%
6a	27.4±2.6	6m	90.5±2.4
6b	34.5±1.7	6n	46.6±1.0
6c	17.8±2.3	6o	43.4±1.6
6d	15.2±2.2	6p	33.0±1.2
6e	38.7±2.1	6q	87.0±1.9
6f	44.4±2.8	6r	60.4±3.0
6g	38.5±1.9	6s	84.8±1.2
6h	23.0±1.4	6t	92.8±1.1
6i	43.9±0.7	6u	17.7±2.8
6j	84.9±0.9	6v	22.0±2.2
6k	31.3±2.1	噻唑磷	43.9±2.8
6l	24.0±1.7	氟吡菌酰胺	100.0

Compd.	Mortality rate/%	Compd.	Mortality rate/%
6a	27.4±2.6	6m	90.5±2.4
6b	34.5±1.7	6n	46.6±1.0
6c	17.8±2.3	6o	43.4±1.6
6d	15.2±2.2	6p	33.0±1.2
6e	38.7±2.1	6q	87.0±1.9
6f	44.4±2.8	6r	60.4±3.0
6g	38.5±1.9	6s	84.8±1.2
6h	23.0±1.4	6t	92.8±1.1
6i	43.9±0.7	6u	17.7±2.8
6j	84.9±0.9	6v	22.0±2.2
6k	31.3±2.1	噻唑磷	43.9±2.8
6l	24.0±1.7	氟吡菌酰胺	100.0

Compd.	y=ax＋b	LC₅₀/(mg•L^－1)	r
6j	y=0.9624＋2.4002x	48.10	0.9752
6m	y=0.3014＋3.0445x	34.94	0.9980
6q	y=－0.2448＋3.0436x	52.87	0.9727
6s	y=0.6381＋2.5900x	48.32	0.9804
6t	y=0.6155＋2.7831x	37.62	0.9842
噻唑磷	y=6.5220＋2.7518x	79.28	0.9935
氟吡菌酰胺	y=0.7650＋4.6132x	8.28	0.9810

Compd.	y=ax＋b	LC₅₀/(mg•L^－1)	r
6j	y=0.9624＋2.4002x	48.10	0.9752
6m	y=0.3014＋3.0445x	34.94	0.9980
6q	y=－0.2448＋3.0436x	52.87	0.9727
6s	y=0.6381＋2.5900x	48.32	0.9804
6t	y=0.6155＋2.7831x	37.62	0.9842
噻唑磷	y=6.5220＋2.7518x	79.28	0.9935
氟吡菌酰胺	y=0.7650＋4.6132x	8.28	0.9810

Compd.	Inhibition rate/%
Compd.	水稻纹枯病菌(R. solani)	油菜菌核病菌(S. sclerotiorum)	小麦赤霉病菌(F. graminearum)	茶叶炭疽病菌(C. camelliae)
6a	52.5±1.0	42.0±1.5	10.1±2.5	23.1±2.5
6b	28.6±1.5	17.1±1.2	46.8±3.1	12.7±0.6
6c	20.5±0.6	10.4±2.7	27.3±2.5	28.0±1.5
6d	74.1±2.3	70.1±1.2	39.6±1.0	53.8±2.5
6e	51.5±1.8	23.8±1.5	—	15.3±0.6
6f	20.5±2.5	42.6±3.0	—	—
6g	13.5±0.6	21.5±1.7	—	—
6h	19.2±3.5	40.9±0.6	27.6±1.5	12.7±1.1
6i	14.1±1.0	16.1±0.6	29.2±1.5	11.1±1.0
6j	13.8±1.2	46.6±3.0	25.3±2.0	16.9±2.6
6k	12.1±2.7	16.1±0.6	22.4±2.5	14.0±1.0
6l	21.9±1.5	49.0±2.9	28.3±0.6	—
6m	20.5±2.3	—	27.6±1.1	—
6n	18.2±1.0	13.4±0.0	27.0±2.6	12.1±1.0
6o	13.1±1.0	44.0±2.1	—	—
6p	27.6±1.2	14.1±0.6	27.0±0.0	—
6q	22.2±1.0	11.7±0.6	—	—
6r	30.3±2.7	—	23.1±0.0	11.4±1.5
6s	14.8±1.2	—	22.4±2.5	—
6t	22.6±2.5	—	—	10.4±0.6
6u	21.6±1.5	—	—	10.1±1.0
6v	16.5±3.3	10.1±2.5	10.1±1.5	—
多菌灵	100	100	100	100
氟吡菌酰胺	53.2±0.6	100	52.6±2.8	16.3±0.6

8-氯-6-(三氟甲基)咪唑并[1,2-a]吡啶噁二唑硫醚类衍生物的设计、合成及其杀线虫和杀菌活性