Synthesis and Biological Activity of 2-Methyl-6-nitrobenzenesulfonylurea Derivatives†

doi:10.7503/cjcu20141121

Abstract

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

CLC Number:

O625.7

TrendMD:

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^†[J]. Chem. J. Chinese Universities, 2015, 36(5): 907.

Figures/Tables 7

References 21

[1]	Levitt, G. , Synthesis and Chemistry of Agrochemicals Ⅱ, , American Chemistry, Society , Washington DC, 1991, 16-31
[2]	Hay J., V. , Pesti. Sci., 1990, 29( 3), 247- 261
[3]	潘里, 刘卓, 陈有为, 李永红, 李正名. 高等学校化学学报, 2013, 34( 6), 1416- 1422
	Pan, L. , Liu, Z. , Chen Y., W. , Li Y., H. , Li Z., M. , Chem. J. Chinese Universities, 2013, 34( 6), 1416- 1422
[4]	Langenfeld H. J., W. , Odenthal K. K., Process for Preparation of Alkoxytriazolinoes, US 5599945, 1997- 03-14
[5]	李正名, 贾国锋, 王玲秀, 杨志强, 赖城明. 防治玉米田杂草组合物, CN 1080116A, 1994- 1-5)
	Li Z., M. , Jia G. F., Wang L. X., Yang Z. Q., Lai C. M., Composite for Preventing and Killing Weeds in the Corn Field, CN 1080116A, 1994- 1-5(
[6]	李正名, 贾国锋, 王玲秀, 范传文, 杨炤. 新型磺酰脲类化合物除草剂, CN 1106393A, 1995- 08-09)
	Li Z., M. , Jia G. F., Wang L. X., Fan C. W., Yang Z., New Sulfonylureas Herbicide, CN 1106393A, 1995- 08-09(
[7]	Li, Z.M. , Ma, Y. , Guddat, L. , Cheng P., Q. , Wang J., G. , Pang S., S. , Dong Y., H. , Lai C., M. , Wang L., X. , Jia G., F. , Li Y., H. , Wang S., H. , Liu, J. , Zhao W., G. , Wang B., L. , Pest Manag. Sci., 2014, 68( 4), 618- 628
[8]
[9]	李秉华, 王贵启, 李香菊. 云南农业大学学报, 2005, 20( 6), 835- 839
	Li B., H. , Wang G., Q. , Li X., J. , J. Yunnan Agri. Univ., 2005, 20( 6), 835- 839
[10]	祝春强, 陈会柱, 刘明熙, 万贤宗. 钱国华. 农药科学与管理, 2005, 26( 5), 25- 27
	Zhu C., Q. , Chen H., Z. , Liu M., X. , Wan X., Z. , Qian G., H. , Pesti. Sci. Admin., 2005, 26( 5), 25- 27
[11]	刘金胜, 寇俊杰, 刘桂龙. 农药, 2007, 46( 3), 145- 147
	Liu J., S. , Kou J., J. , Liu G., L. , Agrochemicals, 2007, 46( 3), 145- 147
[12]	朱荷锄. 中国植保导刊, 2012, 32( 8), 49- 50
	Zhu H., C. , China Plant Protection, 2012, 32( 8), 49- 50
[13]	苏少泉. 农药, 1998, 37( 12), 4- 7
	Su S., Q. , Pesticides, 1998, 37( 12), 4- 7
[14]	刘刚, 阳光. 农药市场信息, 2014, 1, 13)
	Liu, G. , Yang, G. , Pesticides Market News, 2014, 1, 13(
[15]	Chaleff R., S. , Mauvais C., J. , Science, 1984, 224( 4656), 1443- 1445
[16]	Liu, Z. , Pan, L. , Li Y., H. , Wang S., H. , Li Z., M. , Chem. Res. Chinese Universities, 2013, 29( 3), 466- 472
[17]	Hoffman R., V. , Org. Synth., 1981, 60, 121- 126
[18]	刘卓, 潘里, 于淑晶, 李正名. 高等学校化学学报, 2013, 34( 8), 1868- 1872
	Liu, Z. , Pan, L. , Yu S., J. , Li Z., M. , Chem. J. Chinese Universities, 2013, 34( 8), 1868- 1872
[19]	王红学, 李芳, 许丽萍, 李永红, 王素华, 李正名. 高等学校化学学报, 2010, 31( 1), 64- 67
	Wang H., X. , Li, F. , Xu L., P. , Li Y., H. , Wang S., H. , Li Z., M. , Chem. J. Chinese Universities, 2010, 31( 1), 64- 67
[20]	Peng, H. , Deng X., Y. , Gao, L. , Tan X., S. , He H., W. , Chem. Res. Chinese Universities, 2014, 30( 1), 82- 86
[21]	范世丽, 张博, 高丽叶, 王兰芝, 边艳青, 李媛. 高等学校化学学报, 2014, 35( 12), 2574- 2583
	Fan S., L. , Zhang, B. , Gao L., Y. , Wang L., Z. , Bian Y., Q. , Li, Y. , Chem. J. Chinese Universities, 2014, 35( 12), 2574- 2583

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