Design, Synthesis and Biological Activity of Novel Sulfonylurea Derivatives Containing Dimethoxymethyl-substituted Pyrimidine Moiety†

doi:10.7503/cjcu20150100

Abstract

Abstract:

Sulfonylureas(SUs) as one of the most active herbicides targeted on acetolactate synthase(ALS). ALS was found not only in plants, but also in fungi and bacteria. In order to study the multi-biological activity of sulfonylurea(SU), a series of novel SU derivatives containing dimethoxymethyl pyrimidine moiety was designed, synthesized according to bioisosteric principles. The bioassay results indicated that the title compounds exhibited favorable herbicidal activity. Compounds 6a and 6g showed 100% pre-emergence inhibition activity against Brassica napus at the dosage of 75 g/ha, which were near to that of Monosulfuron and Chlorsulfuron(100%). In addtion, some of the title compounds also exhibited moderate antifungal activity. Compounds 6i and 6o showed over 80% antifungal activity against three fungi in vitro at the concentration of 50 mg/L, and closed to that of Chlorothalonil and Carbendazim. It provided useful information for designing new SU with highly herbicidal activity and fungicidal activity.

Key words: Sulfonylurea, Dimethoxymethyl, Acetolactate synthase, Herbicidal activity, Antifungal activity

CLC Number:

O625.7

TrendMD:

CHEN Wei, WEI Wei, LIU Ming, HUA Xuewen, LI Yuxin, LI Yonghong, ZHANG Xiao, LI Zhengming. Design, Synthesis and Biological Activity of Novel Sulfonylurea Derivatives Containing Dimethoxymethyl-substituted Pyrimidine Moiety^†[J]. Chem. J. Chinese Universities, 2015, 36(7): 1291.

Figures/Tables 7

References 28

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Compd.	m. p./℃	Compd.	m. p./℃	Compd.	m. p./℃
5a	146—147(151—153^[19])	5e	129—130(132—134^[22])	5l	140—141(140—141^[2])
5b	114—115(115—117^[20])	5f	128—129(128—129^[23])	5m	137—139(143—144^[2])
5c	175—177(175—177^[21])	5g	73—74(70—72.5^[24])	5n	129—130(130^[2])
5d	151—152(153—155^[22])	5i	132—133(131—133^[25])	5o	103—104(102—104^[26])

Compd.	m. p./℃	Compd.	m. p./℃	Compd.	m. p./℃
5a	146—147(151—153^[19])	5e	129—130(132—134^[22])	5l	140—141(140—141^[2])
5b	114—115(115—117^[20])	5f	128—129(128—129^[23])	5m	137—139(143—144^[2])
5c	175—177(175—177^[21])	5g	73—74(70—72.5^[24])	5n	129—130(130^[2])
5d	151—152(153—155^[22])	5i	132—133(131—133^[25])	5o	103—104(102—104^[26])

Compd.	Appearance	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺	Compd.	Appearance	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺
6a	White soild	76.3	165—167	387.0532(387.0530)	6i	White soild	84.1	124—125	421.0789(421.0793)
6b	White soild	73.3	171—173	387.0526(387.0530)	6j	White soild	74.7	167—169	437.0739(437.0743)
6c	White soild	65.3	186—188	432.0380(432.0381)	6k	White soild	59.4	170—171	431.0790(431.0792)
6d	White soild	75.3	169—171	398.0770(3980770)	6l	White soild	76.8	167—168	452.0849(452.0852)
6e	White soild	65.7	193—195	398.0767(398.0770)	6m	White soild	69.1	167—168	485.0910(485.0913)
6f	White soild	74.7	207—209	403.0632(403.0633)	6n	White soild	50.0	161—162	449.0643(449.0646)
6g	White soild	70.3	169—171	412.0927(412.0927)	6o	White soild	65.7	150—151	429.1196(429.1192)
6h	White soild	65.4	191—193	536.9930(536.9941)

Compd.	Appearance	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺	Compd.	Appearance	Yield(%)	m.p./℃	HRMS(calcd.), m/z [M+H]⁺
6a	White soild	76.3	165—167	387.0532(387.0530)	6i	White soild	84.1	124—125	421.0789(421.0793)
6b	White soild	73.3	171—173	387.0526(387.0530)	6j	White soild	74.7	167—169	437.0739(437.0743)
6c	White soild	65.3	186—188	432.0380(432.0381)	6k	White soild	59.4	170—171	431.0790(431.0792)
6d	White soild	75.3	169—171	398.0770(3980770)	6l	White soild	76.8	167—168	452.0849(452.0852)
6e	White soild	65.7	193—195	398.0767(398.0770)	6m	White soild	69.1	167—168	485.0910(485.0913)
6f	White soild	74.7	207—209	403.0632(403.0633)	6n	White soild	50.0	161—162	449.0643(449.0646)
6g	White soild	70.3	169—171	412.0927(412.0927)	6o	White soild	65.7	150—151	429.1196(429.1192)
6h	White soild	65.4	191—193	536.9930(536.9941)

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(101 MHz), δ
6a^a	13.11(br, 1H, SO₂NH), 9.70(s, 1H, CONH—Pyrim), 8.82(d, J=4.9 Hz, 1H, Pyrim—H), 8.29(d, J=7.2 Hz, 1H, Ph—H), 7.80—7.62(m, 3H, Ph—H), 7.38(d, J=4.9 Hz, 1H, Pyrim—H), 5.38(s, 1H, CH), 3.49(s, 6H, 2×OCH₃)	166.58, 159.61, 157.09, 148.53, 136.91, 134.94, 132.72, 131.66, 131.46, 127.33, 113.08, 101.98, 53.42
6b^a	12.84(br, 1H, SO₂NH), 9.68(s, 1H, CONH—Pyrim), 8.79(d, J=4.6 Hz, 1H, Pyrim—H), 8.14(d, J=8.0 Hz, 2H, Ph—H), 7.71(d, J=7.9 Hz, 2H, Ph—H), 7.35(d, J=4.6 Hz, 1H, Pyrim—H), 5.36(s, 1H, CH), 3.48(s, 6H, 2×OCH₃)	166.64, 159.39, 157.08, 148.88, 139.36, 138.60, 130.12, 129.08, 113.00, 101.92, 53.38
6c^b	13.47(br, 1H, SO₂NH), 11.09(s, 1H, CONH—Pyrim), 8.52(d, J=6.6 Hz, 1H, Pyrim—H), 8.09—7.94(m, 3H, Ph—H), 7.17(d, J=6.6 Hz, 1H, Pyrim—H), 5.35(s, 1H, CH), 3.36(s, 6H, 2×OCH₃)	163.76, 159.11, 156.88, 146.38, 137.82, 134.07, 129.36, 128.66, 127.23, 124.13, 107.02, 101.61, 54.07
6d^a	13.16(br, 1H, SO₂NH), 9.76(br, 1H, CONH—Pyrim), 8.79(d, J=5.1 Hz, 1H, Pyrim—H), 8.40(d, J=7.4 Hz, 1H, Ph—H), 8.03—7.93(m, 3H, Ph—H), 7.35(d, J=5.1 Hz, 1H, Pyrim—H), 5.33(s, 1H, CH), 3.45(s, 6H, 2×OCH₃)	166.91, 159.34, 156.95, 148.73, 148.40, 135.32, 133.26, 132.26, 131.44, 124.76, 113.06, 102.24, 53.56
6e^b	12.95(br, 1H, SO₂NH), 10.89(s, 1H, CONH—Pyrim), 8.74(d, J=4.9 Hz, 1H, Pyrim—H), 8.44(d, J=8.4 Hz, 2H, Ph—H), 8.26(d, J=8.4 Hz, 2H, Ph—H),7.25(d, J=4.9 Hz, 1H, Pyrim—H), 5.32(s, 1H, CH), 3.36(s, 6H, 2×OCH₃)	165.92, 158.71, 156.75, 150.14, 129.35, 127.22, 124.39, 112.91, 106.54, 101.37, 53.61
6f^a	13.18(br, 1H, SO₂NH), 9.80(s, 1H, CONH—Pyrim), 8.79(d, J=4.9 Hz, 1H, Pyrim—H), 7.80(t, J=7.8 Hz, 1H, Ph—H), 7.71—7.61(m, 2H, Ph—H), 7.35(d, J=5.1 Hz, 1H, Pyrim—H), 5.35(s, 1H, CH), 3.45(s, 6H, 2×OCH₃), 2.91(s, 3H, CH₃)	167.59, 160.47, 157.84, 152.35, 150.00, 143.27, 136.70, 135.17, 130.18, 123.39, 114.07, 102.83, 54.34, 21.98
6g^a	12.73(br, 1H, SO₂NH), 9.83(br, 1H, CONH—Pyrim), 8.81(d, J=4.2 Hz, 1H, Pyrim—H), 8.30(d, J=5.7 Hz, 1H, Ph—H), 7.86—7.70(m, 3H, Ph—H), 7.34(d, J=4.3 Hz, 1H, Pyrim—H), 5.37(s, 1H, CH), 3.94(s, 3H, COOCH₃), 3.45(s, 6H, 2×OCH₃)	167.16, 166.94, 159.21, 157.04, 148.94, 136.99, 133.71, 132.59, 131.94, 130.64, 129.40, 112.96, 102.25, 53.54, 52.60
6h^a	12.84(br, 1H, SO₂NH), 9.72(br, 1H, CONH—Pyrim), 8.83(d, J=4.4 Hz, 1H, Pyrim—H), 8.66(s, 1H, Ph—H), 8.25(d, J=7.4 Hz, 1H, Ph—H), 7.59(d, J=7.7 Hz, 1H, Ph—H), 7.37(d, J=4.4 Hz, 1H, Pyrim—H), 5.39(s, 1H, CH), 3.96(s, 3H, COOCH₃), 3.49(s, 6H, 2×OCH₃)	167.00, 166.55, 159.14, 156.99, 148.78, 142.65, 140.27, 138.28, 131.88, 131.07, 113.00, 102.32, 95.58, 53.55, 52.71
6i^a	13.08(s, 1H, SO₂NH), 9.78(s, 1H, CONH—Pyrim), 8.79(d, J=4.9 Hz, 1H, Pyrim—H), 8.53(d, J=4.9 Hz, 1H, Ph—H), 8.03—7.98(m, 3H, Ph—H), 7.35(d, J=4.8 Hz, 1H, Pyrim—H), 5.32(s, 1H, CH), 3.45(s, 6H, 2×OCH₃)	167.33, 159.94, 157.63, 149.20, 138.24, 134.73, 134.65, 133.24, 128.85(q, ³J_FC=6.3 Hz), 127.79(q, ²J_FC=33.2 Hz), 123.74(q, ¹J_FC=273.5 Hz), 113.63, 102.58, 53.97
6j^a	13.04(br, 1H, SO₂NH), 9.75(s, 1H, CONH—Pyrim), 8.78(d, J=4.0 Hz, 1H, Pyrim—H), 8.14(d, J=7.4 Hz, 1H, Ph—H), 7.88(t, J=7.6 Hz, 1H, Ph—H), 7.67—7.62(m, 2H, Ph—H), 7.27(d, J=4.0 Hz, 1H, Pyrim—H), 5.29(s, 1H, CH), 3.44(s, 6H, 2×OCH₃)	167.83, 160.11, 157.98, 149.56, 146.72, 136.83, 133.60, 132.46, 127.99, 121.47, 121.27(d,J=259.3 Hz), 113.96, 102.96, 54.29
6k^b	12.54(br, 1H, SO₂NH), 10.76(s, 1H, CONH—Pyrim), 8.76(d, J=6.6 Hz, 1H, Pyrim—H), 8.27—7.68(m, 4H, Ph—H), 7.27(d, J=6.6 Hz, 1H, Pyrim—H), 5.29(s, 1H, CH), 4.39(t, J=7.1 Hz, 2H, OCH₂CH₂Cl), 3.80(t, J=7.1 Hz, 2H, OCH₂CH₂Cl), 3.38(s, 6H, 2×OCH₃)	159.12, 158.65, 157.02, 148.74, 135.74, 131.16, 120.64, 113.95, 112.70, 106.56, 102.76, 101.66, 69.13, 53.76, 53.32
6l^a	12.76(s, 1H, SO₂NH), 9.64(s, 1H, CONH—Pyrim), 8.78(d, J=5.1 Hz, 1H, Pyrim—H), 8.31(d, J=4.2 Hz, 1H, Py—H), 7.92(d, J=8.5 Hz, 1H, Py—H), 7.73(dd, J=8.4, 4.4 Hz, 1H, Py—H), 7.34(d, J=5.1 Hz, 1H, Pyrim—H), 5.30(s, 1H, CH), 4.93(q, ³J_FH=8.4 Hz, 2H, OCH₂CF₃), 3.43(s, 6H, 2×OCH₃)	167.62, 159.96, 158.00, 152.37, 150.04, 145.93, 142.72, 129.84, 124.73, 124.24(q, ¹J_FC=277.5 Hz), 113.62, 102.88, 66.83(q, ²J_FC=36.0 Hz), 54.16
6m^b	13.60(br, 1H, SO₂NH), 11.02(s, 1H, CONH—Pyrim), 9.18(d, J=6.7 Hz, 1H, Py—H), 8.76(d, J=4.9 Hz, 1H, Pyrim—H), 8.00(d, J=8.7 Hz, 1H, Py—H), 7.79(t, J=7.7 Hz, 1H, Py—H), 7.48(t, J=6.7 Hz, 1H, Py—H), 7.27(d, J=4.9 Hz, 1H, Pyrim—H), 5.29(s, 1H, CH), 3.61(d, J=7.3 Hz, 2H, SO₂CH₂CH₃), 3.36(s, 6H, 2×OCH₃), 1.16(t, J=7.1 Hz, 3H, SO₂CH₂CH₃)	167.50, 159.49, 156.79, 145.92, 144.79, 130.98, 128.75, 126.25, 118.96, 117.25, 113.40, 108.20, 102.09, 54.33, 49.06, 7.15
6n^a	13.24(s, 1H, SO₂NH), 10.01(s, 1H, CONH—Pyrim), 8.86(d, J=5.1 Hz, 1H, Pyrim—H), 7.39(d, J=5.1 Hz, 1H, Pyrim—H), 5.39(s, 1H, CH), 4.31(s, 3H, Pyrazole—CH₃), 3.86(s, 3H, COOCH₃), 3.47(s, 6H, 2×OCH₃)	167.03, 160.16, 159.23, 156.75, 149.80, 139.69, 138.28, 113.37, 113.19, 102.10, 53.52, 51.94, 41.11
6o^a	13.11(s, 1H, SO₂NH), 9.92(s, 1H, CONH—Pyrim), 8.81(d, J=4.8 Hz, 1H, Pyrim—H), 7.93(s, 1H, Pyrazole—H), 7.37(d, J=4.8 Hz, 1H, Pyrim—H), 5.38(s, 1H, CH), 4.32(s, 3H, Pyrazole—CH₃), 4.25(q, J=7.0 Hz, 2H, CO₂CH₂CH₃), 3.47(s, 6H, 2×OCH₃), 1.26(t, J=7.0 Hz, 3H, CO₂CH₂CH₃)	167.83, 161.27, 159.99, 157.55, 150.52, 140.71, 139.45, 116.73, 113.89, 103.15, 61.44, 54.43, 41.58, 29.84