1,2,3-苯并三嗪-4-酮噁二唑硫醚(砜)甲基衍生物的设计、合成及杀菌和杀线虫活性

doi:10.6023/cjoc202403019

摘要/Abstract

为了寻找高活性的新化合物, 设计并合成了20个含噁二唑片段的1,2,3-苯并三嗪-4-酮硫醚(砜)类衍生物. 离体抑菌活性测定结果显示, 6-氯-3-(5-乙砜基)-1,3,4-噁二唑-2-基甲基)苯并[d][1,2,3]三嗪-4(3H)-酮(7c)对油菜菌核病菌Sclerotinia scleotiorum具有较好抑制效果, EC₅₀值为3.84 mg/L, 与对照药剂噁霉灵(5.43 mg/L)相当. 7c (1.81 mg/L)对水稻纹枯病菌Rhizoctonia solani的毒力与对照药剂多菌灵(1.09 mg/L)相当, 显著高于对照药剂噁霉灵(45.70 mg/L). 在100和200 mg/L浓度下, 化合物7c对水稻纹枯病菌保护防效分别为78.51%和84.48%, 治疗防效分别为60.34%和78.91%, 低浓度时的治疗防效与多菌灵(61.53%)相当. 离体杀线虫活性测定结果显示, 浓度为100 mg/L时, 部分化合物对秀丽隐杆线虫和松材线虫有一定的活性, 3-(5-乙硫基)-1,3,4-噁二唑-2-基甲基)苯并[d][1,2,3]三嗪-4(3H)酮(6a)对秀丽隐杆线虫二龄幼虫的LC₅₀值为3.96 mg/L, 优于对照药剂噻唑磷(57.39 mg/L), 与氟吡菌酰胺(4.68 mg/L)相当; 化合物6a (50.28 mg/L)对松材线虫的毒力低于噻唑磷(24.68 mg/L)和氟吡菌酰胺(0.57 mg/L). 本研究所合成的目标化合物具有较高杀菌活性和一定的杀线虫活性, 为新型1,2,3-苯并三嗪-4-酮类衍生物活性研究提供参考.

关键词: 1,2,3-苯并三嗪-4-酮, 噁二唑, 硫醚, 砜, 抑菌活性, 杀线虫活性

In order to find new compounds with high activity, 20 1,2,3-benzotriazin-4-one thioether (sulfone) derivatives containing oxadiazole fragments were designed and synthesized. The results of in vitro antibacterial activity assay showed that 6-chloro-3-(5-ethylsulfonyl)-1,3,4-oxadiazo-2-ylmethyl)benzo[d][1,2,3]triazin-4(3H)-one (7c) had a good inhibitory effect on Sclerotinia sclerotiorum with an EC₅₀ value of 3.84 mg/L, which was comparable to that of the control agent hymexazol (5.43 mg/L). The toxicity of 7c (1.81 mg/L) against Rhizoctonia solani was comparable to that of carbendazim (1.09 mg/L), and significantly higher than that of the control agent hymexazol (45.70 mg/L). At the concentrations of 100 and 200 mg/L, the protective effects of compound 7c against Rhizoctonia solani were 78.51% and 84.48%, and the curative effects of compound 7c were 60.34% and 78.91%, respectively. At low concentrations, the curative effect was comparable to that of carbendazim (61.53%). At a concentration of 100 mg/L, some compounds had certain in vitro activities against Caenorhabditis elegans and Bursaphelenchus xylophilus, and the LC₅₀ value of 3-(5-ethylthio)-1,3,4-oxadiazo-2-ylmethyl)benzo[d][1,2,3]triazin-4(3H)one (6a) against C. elegans was 3.96 mg/L, which was better than that of fosthiazate (57.39 mg/L) and comparable to that of fluopyram (4.68 mg/L). However, the virulence of compound 6a (50.28 mg/L) against B. xylophilus was lower than that of fosthiazate (24.68 mg/L) and fluopyram (0.57 mg/L). The target compounds synthesized have high fungicidal activity and certain nematicidal activity, which can provide a reference for the study of new 1,2,3-benzotriazine-4-one derivatives.

Key words: 1,2,3-benzotriazin-4-one, oxadiazole, thioether, sulfone, fungicidal activity, nematocidal activity

引用此文

赵薇, 李凤宇, 赵伟, 查润, 史彩华, 徐志红. 1,2,3-苯并三嗪-4-酮噁二唑硫醚(砜)甲基衍生物的设计、合成及杀菌和杀线虫活性[J]. 有机化学, 2024, 44(11): 3446-3455.

Wei Zhao, Fengyu Li, Wei Zhao, Run Zha, Caihua Shi, Zhihong Xu. Design, Synthesis and Fungicidal and Nematocidal Activity of 1,2,3-Benzotriazine-4-one Oxadiazole Thioether (Sulfone) Methyl Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3446-3455.

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参考文献 23

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Compd.	R. solani	F. graminearm	M.oryzae	S. sclerotiorm	S. rolfsii	C. camelliae
5a	54.5±2.9	12.6±1.1	—	65.5±2.2	74.9±0.8	33.8±1.9
5b	38.1±1.3	11.0±0.9	—	31.3±3.2	72.7±2.4	40.5±2.9
6a	68.9±2.2	13.6±1.4	31.0±0.8	60.1±1.2	37.8±3.7	33.2±1.8
6b	56.6±2.2	24.6±1.4	51.9±3.3	19.6±1.4	44.2±3.3	38.2±1.1
6c	54.1±3.1	25.6±2.3	72.5±2.6	22.9±0.4	76.7±3.0	44.5±0.8
6d	38.8±1.6	17.3±1.4	14.3±2.0	40.2±1.6	21.2±3.6	47.0±1.1
6e	52.9±1.9	13.9±1.6	—	59.8±1.3	47.0±1.6	19.4±1.5
6f	64.6±0.7	26.9±2.4	36.9±2.9	57.4±2.2	54.8±2.9	49.5±0.9
6g	47.4±2.2	21.6±0.7	21.3±0.3	28.9±3.0	39.6±1.6	40.3±0.9
6h	43.0±3.3	25.6±1.0	41.5±0.7	17.3±2.2	39.2±1.6	21.6±1.7
6i	81.5±0.6	23.3±0.9	25.4±2.0	37.5±1.9	76.7±3.0	46.7±2.0
6j	36.0±3.2	13.0±0.9	28.2±1.1	36.9±1.7	40.3±3.4	41.4±0.9
6k	77.5±0.9	25.6±2.3	16.7±2.1	40.7±0.9	48.1±1.2	29.7±0.9
6l	40.9±2.4	13.9±1.6	20.5±1.9	20.5±3.2	43.8±2.4	39.6±0.8
6m	22.7±2.9	15.3±1.3	13.3±3.3	27.7±1.0	—	20.9±0.6
6n	43.1±3.2	45.5±1.0	—	23.8±0.6	28.6±1.1	14.5±2.1
6o	41.9±1.0	11.3±1.5	—	19.9±2.4	40.3±1.2	30.0±1.2
7a	77.8±2.1	45.8±1.6	49.8±1.2	77.4±3.1	92.9±0.5	28.3±1.5
7b	56.6±0.9	36.9±2.0	32.1±2.3	97.3±1.5	30.7±1.8	54.1±2.5
7c	75.4±1.1	51.8±2.3	38.0±3.8	92.9±3.2	58.0±1.9	71.8±1.6
Hymexazol	56.0±1.7	44.2±0.7	49.1±2.2	94.4±0.5	85.9±0.5	26.1±1.5

Compd.	R. solani	F. graminearm	M.oryzae	S. sclerotiorm	S. rolfsii	C. camelliae
5a	54.5±2.9	12.6±1.1	—	65.5±2.2	74.9±0.8	33.8±1.9
5b	38.1±1.3	11.0±0.9	—	31.3±3.2	72.7±2.4	40.5±2.9
6a	68.9±2.2	13.6±1.4	31.0±0.8	60.1±1.2	37.8±3.7	33.2±1.8
6b	56.6±2.2	24.6±1.4	51.9±3.3	19.6±1.4	44.2±3.3	38.2±1.1
6c	54.1±3.1	25.6±2.3	72.5±2.6	22.9±0.4	76.7±3.0	44.5±0.8
6d	38.8±1.6	17.3±1.4	14.3±2.0	40.2±1.6	21.2±3.6	47.0±1.1
6e	52.9±1.9	13.9±1.6	—	59.8±1.3	47.0±1.6	19.4±1.5
6f	64.6±0.7	26.9±2.4	36.9±2.9	57.4±2.2	54.8±2.9	49.5±0.9
6g	47.4±2.2	21.6±0.7	21.3±0.3	28.9±3.0	39.6±1.6	40.3±0.9
6h	43.0±3.3	25.6±1.0	41.5±0.7	17.3±2.2	39.2±1.6	21.6±1.7
6i	81.5±0.6	23.3±0.9	25.4±2.0	37.5±1.9	76.7±3.0	46.7±2.0
6j	36.0±3.2	13.0±0.9	28.2±1.1	36.9±1.7	40.3±3.4	41.4±0.9
6k	77.5±0.9	25.6±2.3	16.7±2.1	40.7±0.9	48.1±1.2	29.7±0.9
6l	40.9±2.4	13.9±1.6	20.5±1.9	20.5±3.2	43.8±2.4	39.6±0.8
6m	22.7±2.9	15.3±1.3	13.3±3.3	27.7±1.0	—	20.9±0.6
6n	43.1±3.2	45.5±1.0	—	23.8±0.6	28.6±1.1	14.5±2.1
6o	41.9±1.0	11.3±1.5	—	19.9±2.4	40.3±1.2	30.0±1.2
7a	77.8±2.1	45.8±1.6	49.8±1.2	77.4±3.1	92.9±0.5	28.3±1.5
7b	56.6±0.9	36.9±2.0	32.1±2.3	97.3±1.5	30.7±1.8	54.1±2.5
7c	75.4±1.1	51.8±2.3	38.0±3.8	92.9±3.2	58.0±1.9	71.8±1.6
Hymexazol	56.0±1.7	44.2±0.7	49.1±2.2	94.4±0.5	85.9±0.5	26.1±1.5

Pathogenic fungi	Compd.	y=ax＋b	EC₅₀/(mg•L^－1)	r
R. solani	6i	y=2.6891＋1.7718x	20.15	0.9921
	6k	y=2.2707＋1.8132x	32.01	0.9879
	7a	y=3.4966＋1.3076x	14.11	0.9910
	7c	y=4.8064＋0.7520x	1.81	0.9931
	Hymexazol	y=2.7947＋1.3286x	45.70	0.9862
	Carbendazim	y=3.1039＋4.8877x	1.09	0.9925
S. sclerotiorm	7a	y=3.5630＋1.5302x	8.69	0.9938
	7b	y=4.1653＋1.1322x	5.46	0.9954
	7c	y=4.1114＋1.5213x	3.84	0.9909
	Hymexazol	y=3.7335＋1.7243x	5.43	0.9974
S.rolfsii	6c	y=2.9569＋1.4651x	24.80	0.9966
	6i	y=2.9250＋1.6167x	19.21	0.9824
	7a	y=2.3327＋1.9787x	22.29	0.9989
	Hymexazol	y=4.0154＋1.2877x	5.82	0.9928

Pathogenic fungi	Compd.	y=ax＋b	EC₅₀/(mg•L^－1)	r
R. solani	6i	y=2.6891＋1.7718x	20.15	0.9921
	6k	y=2.2707＋1.8132x	32.01	0.9879
	7a	y=3.4966＋1.3076x	14.11	0.9910
	7c	y=4.8064＋0.7520x	1.81	0.9931
	Hymexazol	y=2.7947＋1.3286x	45.70	0.9862
	Carbendazim	y=3.1039＋4.8877x	1.09	0.9925
S. sclerotiorm	7a	y=3.5630＋1.5302x	8.69	0.9938
	7b	y=4.1653＋1.1322x	5.46	0.9954
	7c	y=4.1114＋1.5213x	3.84	0.9909
	Hymexazol	y=3.7335＋1.7243x	5.43	0.9974
S.rolfsii	6c	y=2.9569＋1.4651x	24.80	0.9966
	6i	y=2.9250＋1.6167x	19.21	0.9824
	7a	y=2.3327＋1.9787x	22.29	0.9989
	Hymexazol	y=4.0154＋1.2877x	5.82	0.9928

Compd.	C. elegans	B. xylophilus	Compd.	C. elegans	B. xylophilus
5a	41.8±2.6	—	6j	25.5±3.2	—
5b	44.4±2.8	—	6k	41.5±2.7	—
6a	95.2±1.8	93.6±0.9	6l	38.1±3.2	—
6b	25.9±3.0	—	6m	20.3±3.8	—
6c	97.0±2.7	—	6n	—	—
6d	27.3±1.4	—	6o	—	—
6e	—	—	7a	27.5±1.8	—
6f	16.8±1.4	—	7b	13.2±2.7	—
6g	41.8±2.4	—	7c	—	—
6h	86.6±2.3	—	Fosthiazate	56.1±2.8	74.4±2.1
6i	43.9±2.2	38.7±2.4	Fluopyram	100.0±0.0	91.5±1.1