2-甲基-6-硝基苯磺酰脲衍生物的合成及生物活性

doi:10.7503/cjcu20141121

摘要/Abstract

摘要：

设计合成了一系列2-甲基-6-硝基苯磺酰脲衍生物(4a~4p), 通过核磁共振氢谱(¹H NMR)和高分辨质谱(HRMS)对其结构进行了确认. 盆栽法除草测试结果表明, 在300 g/ha剂量下, 目标化合物具有优异的芽前或芽后除草活性. 进一步筛选发现, 在75 g/ha剂量下, 化合物4b, 4g, 4h, 4l和4p对油菜、反枝苋和稗草具有98%以上的除草活性, 与对照药单嘧磺隆(100%)和氯磺隆(≥96.3%)相当. 另外, 部分化合物对真菌也表现出一定的抑制效果, 其中化合物4l对油菜菌核病菌的半最大效应浓度EC₅₀=9.20 mg/L(对照药多菌灵的EC₅₀=5.79 mg/L).

关键词: 磺酰脲, 重氮化, 除草活性, 抑菌活性

Abstract:

In order to search for new compounds with high efficacy herbicidal activity, a series of novel sulfonylurea derivatives was designed and synthesized referring to the commercialization sulfonylurea skeletons: Monosulfuron and Triflulsulfuron-methyl. The title compounds were prepared by multistep synthetic procedures starting from 2-methyl-6-nitroaniline, and their chemical structures were characterized by ¹H NMR and HRMS. The bioassay results indicate that some of the title compounds show excellent herbicidal activities at the dosage of 300 g/ha. Further study found that compounds 4b, 4g, 4h, 4l and 4p are as effective as Monosulfuron(100%) and Chlorsulfuron(≥96.3%) against Brassica napus, Amaranthus retroflexus L. and Echinochloa Crusgalli at the dosage of 75 g/ha. Preliminary fungicidal test showed some target compounds also hold good antifungal activity in vitro. Particularly, the EC₅₀ of compound 4l against Sclerotinia sclerotiorum was 9.20 mg/L(Carbendazim, EC₅₀=5.79 mg/L).

Key words: Sulfonylurea, Diazotization, Herbicidal activity, Fungicidal activity

中图分类号:

O625.7

TrendMD:

陈伟, 魏巍, 李玉新, 万莹莹, 刘巧霞, 李永红, 于淑晶, 李正名. 2-甲基-6-硝基苯磺酰脲衍生物的合成及生物活性. 高等学校化学学报, 2015, 36(5): 907.

CHEN Wei, WEI Wei, LI Yuxin, WAN Yingying, LIU Qiaoxia, LI Yonghong, YU Shujing, LI Zhengming. Synthesis and Biological Activity of 2-Methyl-6-nitrobenzenesulfonylurea Derivatives^†. Chem. J. Chinese Universities, 2015, 36(5): 907.

图/表 7

参考文献 21

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Compd.	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺	Compd.	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺
4a	64.0	228—230	372.0166(372.0169)	4i	84.7	191—193	398.0589(398.0593)
4b	76.2	212—214	352.0712(352.0716)	4j	63.4	211—212	386.0326(386.0326)
4c	73.2	198—199	368.0663(368.0665)	4k	49.6	209—210	402.0275(402.0275)
4d	80.1	203—205	382.0817(382.0821)	4l	68.4	221—223	398.0768(398.0770)
4e	58.4	220—221	384.0433(384.0436)	4m	74.4	179—180	414.0538(414.0542)
4f	63.2	226—227	406.0432(406.0433)	4n	63.2	208—209	368.0656(368.0665)
4g	73.0	216—218	366.0870(366.0872)	4o	71.3	191—193	383.0763(383.0774)
4h	74.3	183—184	380.0820(380.0821)	4p	67.5	195—197	412.1031(412.1039)

Compd.	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺	Compd.	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺
4a	64.0	228—230	372.0166(372.0169)	4i	84.7	191—193	398.0589(398.0593)
4b	76.2	212—214	352.0712(352.0716)	4j	63.4	211—212	386.0326(386.0326)
4c	73.2	198—199	368.0663(368.0665)	4k	49.6	209—210	402.0275(402.0275)
4d	80.1	203—205	382.0817(382.0821)	4l	68.4	221—223	398.0768(398.0770)
4e	58.4	220—221	384.0433(384.0436)	4m	74.4	179—180	414.0538(414.0542)
4f	63.2	226—227	406.0432(406.0433)	4n	63.2	208—209	368.0656(368.0665)
4g	73.0	216—218	366.0870(366.0872)	4o	71.3	191—193	383.0763(383.0774)
4h	74.3	183—184	380.0820(380.0821)	4p	67.5	195—197	412.1031(412.1039)

Compd.	¹H NMR(400 MHz), δ
4a^a	12.42(br, 1H, SO₂NH),10.97(s, 1H, CONH-Pyrim), 8.69(d, J=5.4 Hz, 1H, Pyrim-H), 7.82—7.75(m, 2H, Ph-H), 7.71(dd, J=6.6, 2.1 Hz, 1H, Ph-H), 7.41(d, J=5.4 Hz, 1H, Pyrim-H), 2.76(s, 3H, Ph-CH₃)
4b^b	13.40(s, 1H, SO₂NH), 9.58(s, 1H, CONH-Pyrim), 8.57(d, J=5.1 Hz, 1H, Pyrim-H), 7.78(d, J=7.8 Hz, 1H, Ph-H), 7.73—7.62(m, 2H, Ph-H), 7.15(d, J=5.1 Hz, 1H, Pyrim-H), 2.91(s, 3H, Ph-CH₃), 2.54(s, 3H, Pyrim-CH₃)
4c^b	13.40(br, 1H, SO₂NH), 9.60(br, 1H, CONH-Pyrim), 8.43(d, J=6.0 Hz, 1H, Pyrim-H), 7.77(d, J=7.9 Hz, 1H, Ph-H), 7.70—7.64(m, 2H, Ph-H), 6.64(d, J=6.0 Hz, 1H, Pyrim-H), 3.99(s, 3H, Pyrim-OCH₃), 2.89(s, 3H, Ph-CH₃)
4d^b	13.44(br, 1H, SO₂NH), 9.57(br, 1H, CONH-Pyrim), 8.42(d, J=6.0 Hz, 1H, Pyrim-H), 7.77(t, J=7.8 Hz, 1H, Ph-H), 7.63—7.69(m, 2H, Ph-H), 6.61(d, J=6.0 Hz, 1H, Pyrim-H), 4.43(q, J=7.0 Hz, 2H, OCH₂CH₃), 2.89(s, 3H, Ph-CH₃), 1.38(t, J=7.0 Hz, 3H, OCH₂CH₃)
4e^b	13.15(br, 1H, SO₂NH), 9.67(br, 1H, CONH-Pyrim), 8.35(d, J=5.6 Hz, 1H, Pyrim-H), 7.78(d, J=7.8 Hz, 1H, Ph-H), 7.72—7.66(m, 2H, Ph-H), 7.15(d, J=5.6 Hz, 1H, Pyrim-H), 2.90(s, 3H, Ph-CH₃), 2.60(s, 3H, SCH₃)
4f^a	12.31(br, 1H, SO₂NH), 10.91(s, 1H, CONH-Pyrim), 9.04(d, J=4.5 Hz, 1H, Pyrim-H), 7.81—7.62(m, 4H, Ph-H), 2.75(s, 3H, Ph-CH₃)
4g^b	13.72(br, 1H, SO₂NH), 9.40(s, 1H, CONH-Pyrim), 7.77(d, J=7.7 Hz, 1H, Ph-H), 7.71—7.65(m, 2H, Ph-H), 7.01(s, 1H, Pyrim-H), 2.92(s, 3H, Ph-CH₃), 2.47(s, 6H, 2Pyrim-CH₃)
4h^b	13.75(br, 1H, SO₂NH), 9.50(br, 1H, CONH-Pyrim), 7.79(t, J=7.8 Hz, 1H, Ph-H), 7.71—7.66(m, 2H, Ph-H), 6.51(s, 1H, Pyrim-H), 3.95(s, 3H, Pyrim-OCH₃), 2.92(s, 3H, Ph-CH₃), 2.47(s, 3H, Pyrim-CH₃)
4i^a	13.62(s, 1H, SO₂NH), 10.87(s, 1H, CONH-Pyrim), 7.74—7.68(m, 3H, Ph-H), 7.11(s, 1H, Pyrim-H), 2.76(s, 3H, SCH₃), 2.55(s, 3H, Ph-CH₃), 2.38(s, 3H, Pyrim-CH₃)
4j^b	13.02(br, 1H, SO₂NH), 9.77(br, 1H, CONH-Pyrim), 7.81(t, J=7.8 Hz, 1H, Ph-H), 7.73—7.68(m, 2H, Ph-H), 7.26(s, 1H, Pyrim-H), 2.93(s, 3H, Ph-CH₃), 2.59(s, 3H, Pyrim-CH₃)
4k^b	12.48(br, 1H, SO₂NH), 9.81(br, 1H, CONH-Pyrim), 7.83(t, J=7.8 Hz, 1H, Ph-H), 7.75—7.70(m, 2H, Ph-H), 6.74(s, 1H, Pyrim-H), 4.08(s, 3H, Pyrim-OCH₃), 2.94(s, 3H, Ph-CH₃)
4l^c	12.88(s, 1H, CONH-Pyrim), 7.59—7.52(m, 2H, Ph-H), 7.44(d, J=7.5 Hz, 1H, Ph-H), 7.30(br, 1H, SO₂NH), 5.81(s, 1H, Pyrim-H), 3.97(s, 6H, 2Pyrim-OCH₃), 2.98(s, 3H, Ph-CH₃)
4m^c	12.91(s, 1H, SO₂NH), 7.58(t, J=7.7 Hz, 1H, Ph-H), 7.52(d, J=7.4 Hz, 1H, Ph-H), 7.43(d, J=7.5 Hz, 1H, Ph-H), 7.37(s, 1H, CONH-Pyrim), 6.32(s, 1H, Pyrim-H), 3.96(s, 3H, Pyrim-OCH₃), 2.96(s, 3H, Pyrim-SCH₃), 2.55(s, 3H, Ph-CH₃)
4n^b	12.40(br, 1H, SO₂NH), 9.44(s, 1H, CONH-Pyrim), 8.61(s, 1H, Pyrim-H), 7.80(t, J=7.8 Hz, 1H, Ph-H), 7.72—7.66(m, 2H, Ph-H), 6.68(s, 1H, Pyrim-H), 3.97(s, 3H, Pyrim-OCH₃), 2.89(s, 3H, Ph-CH₃)
4o^b	13.07(br, 1H, SO₂NH), 9.92(s, 1H, CONH-Pyrim), 7.82—7.72(m, 3H, Ph-H), 4.03(s, 3H, Triazine-OCH₃), 2.92(s, 3H, Ph-CH₃), 2.55(s, 3H, Triazine-CH₃)
4p^a	13.63(br, 1H, SO₂NH), 10.81(s, 1H, CONH-Pyrim), 8.36(br, 1H, NHCH₃), 7.71—7.63(m, 3H, Ph-H), 4.30(q, J=7.1 Hz, 2H, OCH₂CH₃), 2.83(s, 3H, NHCH₃), 2.75(s, 3H, Ph-CH₃), 1.30(t, J=7.1 Hz, 3H, OCH₂CH₃)

Compd.	¹H NMR(400 MHz), δ
4a^a	12.42(br, 1H, SO₂NH),10.97(s, 1H, CONH-Pyrim), 8.69(d, J=5.4 Hz, 1H, Pyrim-H), 7.82—7.75(m, 2H, Ph-H), 7.71(dd, J=6.6, 2.1 Hz, 1H, Ph-H), 7.41(d, J=5.4 Hz, 1H, Pyrim-H), 2.76(s, 3H, Ph-CH₃)
4b^b	13.40(s, 1H, SO₂NH), 9.58(s, 1H, CONH-Pyrim), 8.57(d, J=5.1 Hz, 1H, Pyrim-H), 7.78(d, J=7.8 Hz, 1H, Ph-H), 7.73—7.62(m, 2H, Ph-H), 7.15(d, J=5.1 Hz, 1H, Pyrim-H), 2.91(s, 3H, Ph-CH₃), 2.54(s, 3H, Pyrim-CH₃)
4c^b	13.40(br, 1H, SO₂NH), 9.60(br, 1H, CONH-Pyrim), 8.43(d, J=6.0 Hz, 1H, Pyrim-H), 7.77(d, J=7.9 Hz, 1H, Ph-H), 7.70—7.64(m, 2H, Ph-H), 6.64(d, J=6.0 Hz, 1H, Pyrim-H), 3.99(s, 3H, Pyrim-OCH₃), 2.89(s, 3H, Ph-CH₃)
4d^b	13.44(br, 1H, SO₂NH), 9.57(br, 1H, CONH-Pyrim), 8.42(d, J=6.0 Hz, 1H, Pyrim-H), 7.77(t, J=7.8 Hz, 1H, Ph-H), 7.63—7.69(m, 2H, Ph-H), 6.61(d, J=6.0 Hz, 1H, Pyrim-H), 4.43(q, J=7.0 Hz, 2H, OCH₂CH₃), 2.89(s, 3H, Ph-CH₃), 1.38(t, J=7.0 Hz, 3H, OCH₂CH₃)
4e^b	13.15(br, 1H, SO₂NH), 9.67(br, 1H, CONH-Pyrim), 8.35(d, J=5.6 Hz, 1H, Pyrim-H), 7.78(d, J=7.8 Hz, 1H, Ph-H), 7.72—7.66(m, 2H, Ph-H), 7.15(d, J=5.6 Hz, 1H, Pyrim-H), 2.90(s, 3H, Ph-CH₃), 2.60(s, 3H, SCH₃)
4f^a	12.31(br, 1H, SO₂NH), 10.91(s, 1H, CONH-Pyrim), 9.04(d, J=4.5 Hz, 1H, Pyrim-H), 7.81—7.62(m, 4H, Ph-H), 2.75(s, 3H, Ph-CH₃)
4g^b	13.72(br, 1H, SO₂NH), 9.40(s, 1H, CONH-Pyrim), 7.77(d, J=7.7 Hz, 1H, Ph-H), 7.71—7.65(m, 2H, Ph-H), 7.01(s, 1H, Pyrim-H), 2.92(s, 3H, Ph-CH₃), 2.47(s, 6H, 2Pyrim-CH₃)
4h^b	13.75(br, 1H, SO₂NH), 9.50(br, 1H, CONH-Pyrim), 7.79(t, J=7.8 Hz, 1H, Ph-H), 7.71—7.66(m, 2H, Ph-H), 6.51(s, 1H, Pyrim-H), 3.95(s, 3H, Pyrim-OCH₃), 2.92(s, 3H, Ph-CH₃), 2.47(s, 3H, Pyrim-CH₃)
4i^a	13.62(s, 1H, SO₂NH), 10.87(s, 1H, CONH-Pyrim), 7.74—7.68(m, 3H, Ph-H), 7.11(s, 1H, Pyrim-H), 2.76(s, 3H, SCH₃), 2.55(s, 3H, Ph-CH₃), 2.38(s, 3H, Pyrim-CH₃)
4j^b	13.02(br, 1H, SO₂NH), 9.77(br, 1H, CONH-Pyrim), 7.81(t, J=7.8 Hz, 1H, Ph-H), 7.73—7.68(m, 2H, Ph-H), 7.26(s, 1H, Pyrim-H), 2.93(s, 3H, Ph-CH₃), 2.59(s, 3H, Pyrim-CH₃)
4k^b	12.48(br, 1H, SO₂NH), 9.81(br, 1H, CONH-Pyrim), 7.83(t, J=7.8 Hz, 1H, Ph-H), 7.75—7.70(m, 2H, Ph-H), 6.74(s, 1H, Pyrim-H), 4.08(s, 3H, Pyrim-OCH₃), 2.94(s, 3H, Ph-CH₃)
4l^c	12.88(s, 1H, CONH-Pyrim), 7.59—7.52(m, 2H, Ph-H), 7.44(d, J=7.5 Hz, 1H, Ph-H), 7.30(br, 1H, SO₂NH), 5.81(s, 1H, Pyrim-H), 3.97(s, 6H, 2Pyrim-OCH₃), 2.98(s, 3H, Ph-CH₃)
4m^c	12.91(s, 1H, SO₂NH), 7.58(t, J=7.7 Hz, 1H, Ph-H), 7.52(d, J=7.4 Hz, 1H, Ph-H), 7.43(d, J=7.5 Hz, 1H, Ph-H), 7.37(s, 1H, CONH-Pyrim), 6.32(s, 1H, Pyrim-H), 3.96(s, 3H, Pyrim-OCH₃), 2.96(s, 3H, Pyrim-SCH₃), 2.55(s, 3H, Ph-CH₃)
4n^b	12.40(br, 1H, SO₂NH), 9.44(s, 1H, CONH-Pyrim), 8.61(s, 1H, Pyrim-H), 7.80(t, J=7.8 Hz, 1H, Ph-H), 7.72—7.66(m, 2H, Ph-H), 6.68(s, 1H, Pyrim-H), 3.97(s, 3H, Pyrim-OCH₃), 2.89(s, 3H, Ph-CH₃)
4o^b	13.07(br, 1H, SO₂NH), 9.92(s, 1H, CONH-Pyrim), 7.82—7.72(m, 3H, Ph-H), 4.03(s, 3H, Triazine-OCH₃), 2.92(s, 3H, Ph-CH₃), 2.55(s, 3H, Triazine-CH₃)
4p^a	13.63(br, 1H, SO₂NH), 10.81(s, 1H, CONH-Pyrim), 8.36(br, 1H, NHCH₃), 7.71—7.63(m, 3H, Ph-H), 4.30(q, J=7.1 Hz, 2H, OCH₂CH₃), 2.83(s, 3H, NHCH₃), 2.75(s, 3H, Ph-CH₃), 1.30(t, J=7.1 Hz, 3H, OCH₂CH₃)

Compd.	Brassica napus		Amaranthus retroflexus		Echinochloa crusgalli		Digitariasanguinalis
Compd.	Soil treatment	Foliage spray	Soil treatment	Foliage spray	Soil treatment	Foliage spray	Soil treatment	Foliage spray
4a	98.0	100	100	100	39.1	29.8	26.5	43.0
4b	100	100	100	100	100	85.7	100	100
4c	100	100	100	100	94.1	32.2	40.7	10.4
4d	100	100	81.0	77.4	50.8	30.7	15.8	11.3
4e	100	100	100	73.2	30.0	0	9.1	0
4f	100	100	100	100	40.9	29.8	17.0	21.8
4g	100	100	100	100	100	80.7	49.1	90.4
4h	100	100	100	100	100	48.0	100	88.4
4i	100	100	93.8	100	80.8	32.2	47.9	37.9
4j	100	96.1	100	100	47.0	45.6	15.3	46.3
4k	100	100	100	92.6	99.5	82.1	12.3	17.5
4l	100	100	100	100	99.1	42.0	29.8	35.8
4m	100	100	85.0	80.1	82.7	46.1	24.5	23.5
4n	100	100	28.6	89.6	45.7	21.2	14.2	18.2
4o	100	100	94.6	100	38.7	26.1	71.2	25.4
4p	100	100	100	100	100	42.0	37.2	80.9
Monosulfuron	100	100	100	100	100	74.1	100	86.1
Chlorsulfuron	100	100	100	100	96.3	73.1	100	22.7