新型含取代哌嗪的5-(吡啶-3-基)-1,2,4-三唑Mannich碱和双Mannich碱的合成及生物活性

doi:10.7503/cjcu20160042

摘要/Abstract

摘要：

根据药物分子设计的活性基团组合原理, 通过在1,2,4-三唑环的5位引入吡啶基, 同时在4位芳基亚甲氨基的苯环上引入氟或三氟甲基, 设计合成了一系列含氟、吡啶和哌嗪基团的1,2,4-三唑Mannich碱和双Mannich碱类化合物. 通过核磁共振氢谱(¹H NMR)、碳谱(¹³C NMR)和元素分析确证了目标化合物的结构. 生物活性测试结果表明, 部分化合物对油菜具有一定的除草活性; 化合物2a, 2d和2f(50 mg/L)对苹果轮纹病菌表现出较好的抑制活性, 与对照药三唑酮活性相当; 化合物2a, 2b, 2d和2i(180 mg/L)对酮醇酸还原异构酶(KARI酶)表现出了显著的离体抑制活性(抑制率51.7%~88.7%).

关键词: 吡啶, 1,2,4-三唑Mannich碱, 哌嗪, 生物活性

Abstract:

According to the drug design principle of active groups combination, a series of 5-(pyridine-3-yl)-1,2,4-triazole Mannich bases and bis-Mannich bases containing piperazine and fluorine moieties was designed and synthesized through the Mannich reaction of 1,2,4-triazole thiol intermediate. All the structures of new title compounds were characterized by ¹H NMR, ¹³C NMR and elemental analysis. The bioassay results showed that several compounds exhibited herbicidal activities against Brassica campestris in certain extent; compounds 2a, 2d and 2f possessed significant antifungal activities against P. piricola and were comparable with the control fungicide, triadimefon, at the concentration of 50 mg/L. Also, compounds 2a, 2b, 2d and 2i showed favorable in vitro ketol-acid reductoisomerase(KARI) inhibitory activities with inhibition rate of 51.7%—88.7% at 180 mg/L.

Key words: Pyridine, 1,2,4-Triazole Mannich base, Piperazine, Biological activity

中图分类号:

O626.32

TrendMD:

张燕, 王宝雷, 詹益周, 张丽媛, 李永红, 李正名. 新型含取代哌嗪的5-(吡啶-3-基)-1,2,4-三唑Mannich碱和双Mannich碱的合成及生物活性. 高等学校化学学报, 2016, 37(6): 1100.

ZHANG Yan, WANG Baolei, ZHAN Yizhou, ZHANG Liyuan, LI Yonghong, LI Zhengming. Synthesis and Biological Activities of Novel 5-(Pyridine-3-yl)-1,2,4-triazole Mannich Bases and Bis-Mannich Bases Containing Piperazine Moiety^†. Chem. J. Chinese Universities, 2016, 37(6): 1100.

图/表 6

参考文献 36

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Compd.	Apperance	m.p./℃	Yield(%)	Elemental analysis(%, calcd.)
Compd.	Apperance	m.p./℃	Yield(%)	C	H	N
1a	White solid	246—247	90	55.97(56.18)	3.52(3.37)	23.15(23.40)
1b	White solid	261—262	94	51.60(51.57)	2.75(2.89)	19.98(20.05)
2a	White solid	118—119	83	59.85(59.82)	4.89(4.83)	18.60(18.78)
2b	White solid	137—138	86	56.47(56.12)	4.26(4.35)	17.62(17.78)
2c	White solid	134—135	91	63.67(63.41)	4.78(5.11)	20.91(20.70)
2d	White solid	190—191	81	59.26(59.62)	5.20(5.20)	24.62(25.03)
2e	White solid	147—148	74	60.73(60.74)	4.89(4.89)	23.39(23.61)
2f	White solid	125—127	99	56.84(56.69)	4.61(4.41)	17.23(17.14)
2g	White solid	136—138	89	53.38(53.47)	3.92(3.99)	16.23(16.17)
2h	White solid	130—131	83	59.51(59.64)	4.80(4.62)	18.49(18.73)
2i	White solid	128—130	99	55.51(55.65)	4.80(4.48)	23.73(23.36)
2j	White solid	125—126	66	56.18(56.41)	4.70(4.73)	22.56(22.77)
2k	White solid	151—152	90	56.95(57.24)	4.45(4.42)	21.22(21.36)
3a	White solid	235—236	58	57.60(57.61)	4.21(4.27)	24.05(23.71)
3b	White solid	224—226	99	53.33(53.46)	3.81(3.74)	20.90(20.78)

Compd.	Apperance	m.p./℃	Yield(%)	Elemental analysis(%, calcd.)
Compd.	Apperance	m.p./℃	Yield(%)	C	H	N
1a	White solid	246—247	90	55.97(56.18)	3.52(3.37)	23.15(23.40)
1b	White solid	261—262	94	51.60(51.57)	2.75(2.89)	19.98(20.05)
2a	White solid	118—119	83	59.85(59.82)	4.89(4.83)	18.60(18.78)
2b	White solid	137—138	86	56.47(56.12)	4.26(4.35)	17.62(17.78)
2c	White solid	134—135	91	63.67(63.41)	4.78(5.11)	20.91(20.70)
2d	White solid	190—191	81	59.26(59.62)	5.20(5.20)	24.62(25.03)
2e	White solid	147—148	74	60.73(60.74)	4.89(4.89)	23.39(23.61)
2f	White solid	125—127	99	56.84(56.69)	4.61(4.41)	17.23(17.14)
2g	White solid	136—138	89	53.38(53.47)	3.92(3.99)	16.23(16.17)
2h	White solid	130—131	83	59.51(59.64)	4.80(4.62)	18.49(18.73)
2i	White solid	128—130	99	55.51(55.65)	4.80(4.48)	23.73(23.36)
2j	White solid	125—126	66	56.18(56.41)	4.70(4.73)	22.56(22.77)
2k	White solid	151—152	90	56.95(57.24)	4.45(4.42)	21.22(21.36)
3a	White solid	235—236	58	57.60(57.61)	4.21(4.27)	24.05(23.71)
3b	White solid	224—226	99	53.33(53.46)	3.81(3.74)	20.90(20.78)

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(101 MHz), δ
1a^a	14.42(s, 1H, SH), 9.81(s, 1H, N=CH), 9.04(s, 1H, Pyridine-H), 8.74(d, J=4.5 Hz, 1H, Pyridine-H ), 8.28(d, J=7.8 Hz, 1H, Pyridine-H), 8.01—7.95(m, 2H, Ph—H), 7.63—7.58(m, 1H, Pyridine-H), 7.42(t, J=8.5 Hz, 2H, Ph—H)	165.7, 163.6(C=S), 162.5, 151.3(CH=N), 148.7, 146.8(Triazole-C), 135.9, 131.40(d, J=9.0 Hz, F—Ph—C), 128.6, 123.8 , 122.0, 116.5
1b^a	14.47(s, 1H, SH), 10.09(s, 1H, N=CH), 9.05(s, 1H, Pyridine-H), 8.75(d, J=4.5 Hz, 1H, Pyridine-H), 8.27(d, J=7.9 Hz, 1H, Pyridine-H), 8.12(d, J=8.0 Hz, 2H, Ph—H), 7.94(d, J=8.0 Hz, 2H, Ph—H), 7.60(dd, J=7.9, 4.5 Hz, 1H, Pyridine-H)	163.9(C=S), 162.6(s), 151.0(CH=N), 148.5, 147.0(Triazole-C), 136.7, 135.9, 132.3(d, J=33.3 Hz, CF₃—Ph—C), 129.5, 126.3, 124.1, 123.9(q, J=273.7 Hz, CF₃), 122.2
2a^b	10.23(s, 1H, N=CH), 9.21(s, 1H, Pyridine-H), 8.74(s, 1H, Pyridine-H), 8.26(s, 1H, Pyridine-H), 7.89—7.85(m, 2H, Ph—H), 7.46—7.42(s, 1H, Pyridine-H), 7.27—7.16(m, 6H, Ph—H), 5.26(s, 2H, CH₂), 3.45(s, 2H, CH₂), 2.98—2.91(m, 4H, Piperazine-CH₂), 2.65—2.25(m, 4H, Piperazine-CH₂)	165.5, 164.0(C=S), 162.3, 151.4(CH=N), 149.5, 146.0(Triazole-C), 136.6, 135.9, 132.8, 131.2(d, J=9.0 Hz, F—Ph—C), 130.4, 128.5, 128.4, 123.3, 122.0, 116.1, 69.6, 62.3, 53.0, 50.5
2b^b	10.25(s, 1H, N=CH), 9.22(s, 1H, Pyridine-H), 8.74(d, J=4.7 Hz, 1H, Pyridine-H), 8.27(d, J=8.0 Hz, 1H, Pyridine-H), 7.90—7.86(m, 2H, Ph—H), 7.44(dd, J=8.0, 4.7 Hz, 1H, Pyridine-H), 7.38—7.32(m, 2H, Ph—H), 7.20—7.16(m, 3H, Ph—H), 5.28(s, 2H, CH₂), 3.56(s, 2H, CH₂), 2.98—2.90(m, 4H, Piperazine-CH₂), 2.61—2.48(m, 4H, Piperazine-CH₂)	165.5, 164.1(C=S), 162.3, 151.4(CH=N), 149.5, 146.0(Triazole-C), 135.9, 134.8, 134.5, 133.1, 131.4, 131.2(d, J=9.0 Hz, F—Ph—C), 129.2, 128.5, 126.9, 123.3, 122.1, 116.5, 69.7, 58.7, 53.1, 50.6
2c^b	10.24(s, 1H, N=CH), 9.21(s, 1H, Pyridine-H), 8.74(d, J=3.8 Hz, 1H, Pyridine-H), 8.27(d, J=8.0 Hz, 1H, Pyridine-H), 7.91—7.85(m, 2H, Ph—H), 7.44(dd, J=8.0, 3.8 Hz, 1H, Pyridine-H), 7.28—7.23(m, 2H, Ph—H), 7.18(t, J=8.5 Hz, 2H, Ph—H), 6.91(d, J=8.1 Hz, 2H, Ph—H), 6.86(t, J=7.2 Hz, 1H, Ph—H), 5.34(s, 2H, CH₂), 3.24—3.20(m, 4H, Piperazine-CH₂), 3.10—3.04(m, 4H, Piperazine-CH₂)	165.6, 165.1(C=S), 162.4, 151.5(CH=N), 151.3, 149.5, 146.1(Triazole-C), 136.0, 131.2(d, J=9.0 Hz, F—Ph—C), 129.2, 128.5, 123.4, 122.0, 120.0, 116.5, 116.4, 69.6, 50.6, 49.6
2d^b	10.24(s, 1H, N=CH), 9.20(s, 1H, Pyridine-H), 8.73(d, J=4.5 Hz, 1H, Pyridine-H), 8.25(d, J=7.9 Hz, 1H, Pyridine-H), 7.91—7.84(m, 2H, Ph—H), 7.43(dd, J=7.9, 4.5 Hz, 1H, Pyridine-H), 7.18(t, J=8.4 Hz, 2H, Ph—H), 6.23(s, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.95—3.87(m, 4H, Piperazine-CH₂), 2.97—2.90(m, 4H, Piperazine-CH₂), 2.25(s, 6H, CH₃)	167.1(C=S), 165.5, 164.1, 162.3, 161.6, 151.4(CH=N), 149.5, 146.0(Triazole-C), 135.9, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.3, 122.0, 116.5, 108.9, 69.9, 50.7, 43.6, 24.1
2e^b	10.23(s, 1H, N=CH), 9.20(s, 1H, Pyridine-H), 8.73(s, 1H, Pyridine-H), 8.26(d, J=6.3 Hz, 1H, Pyridine-H), 8.16(s, 1H, Pyridine-H), 7.87(d, J=7.1 Hz, 2H, Ph—H), 7.50—7.37(m, 2H, Pyridine-H), 7.19(d, J=7.1 Hz, 2H, Ph—H), 6.68—6.50(m, 2H, Pyridine-H), 5.34(s, 2H, CH₂), 3.68—3.52(s, 4H, Piperazine-CH₂), 3.10—2.93(s, 4H, Piperazine-CH₂)	165.5, 164.0(C=S), 162.4, 159.3, 151.5(CH=N), 149.5, 148.0, 146.1(Triazole-C), 137.5, 136.0, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.4, 122.0, 116.5, 113.3, 107.1, 69.7, 50.4, 45.2
2f^b	10.58(s, 1H, N=CH), 9.19(d, J=1.6 Hz, 1H, Pyridine-H), 8.75(d, J=4.8 Hz, 1H, Pyridine-H), 8.24(dd, J=8.0, 1.6 Hz, 1H, Pyridine-H), 7.97(d, J=8.1 Hz, 2H, Ph—H), 7.75(d, J=8.1 Hz, 2H, Ph—H), 7.45(dd, J=8.0, 4.8 Hz, 1H, Pyridine-H), 7.26—7.18(m, 4H, Ph—H), 5.28(s, 2H, CH₂), 3.45(s, 2H, CH₂), 2.96—2.88(m, 4H, Piperazine-CH₂), 2.53—2.43(m, 4H, Piperazine-CH₂)	164.0(C=S), 160.5, 151.6(CH=N), 149.6, 146.2(Triazole-C), 136.6, 136.1, 135.7, 133.9(d, J=33.0 Hz, CF₃—Ph—C), 132.8, 130.4, 129.1, 128.4, 126.1, 123.6(q, J=272.7 Hz, CF₃), 123.4, 121.9, 69.6, 62.3, 53.0, 50.5
2g^b	10.58(s, 1H, N=CH), 9.19(d, J=1.6 Hz, 1H, Pyridine-H), 8.76(d, J=5.0 Hz, 1H, Pyridine-H), 8.26(dd, J=8.0 Hz, 1.6 Hz, 1H, Pyridine-H), 7.97(d, J=8.1 Hz, 2H, Ph—H), 7.75(d, J=8.1 Hz, 2H, Ph—H), 7.46(dd, J=8.0, 5.0 Hz, 1H, Pyridine-H), 7.35(m, 2H, Ph—H), 7.17(dd, J=8.2, 1.8 Hz, 1H, Ph—H), 5.26(s, 2H, CH₂), 3.56(s, 2H, CH₂), 2.97—2.92(m, 4H, Piperazine-CH₂), 2.85—2.30(m, 4H, Piperazine-CH₂)	164.0(C=S), 160.5, 151.6(CH=N), 149.6, 146.2(Triazole-C), 136.1, 135.7, 135.1, 134.9, 134.5, 134.0(d, J=32.3 Hz, CF₃—Ph—C), 133.1, 131.4, 129.1, 126.9, 126.1, 123.6(q, J=275.7 Hz, CF₃), 123.4, 121.9, 69.6, 58.7, 53.1, 50.6
2h^b	10.59(s, 1H, N=CH), 9.20(d, J=1.4 Hz, 1H, Pyridine-H), 8.76(d, J=4.4 Hz, 1H, Pyridine-H), 8.25(d, J=8.3, 1.4 Hz, 1H, Pyridine-H), 7.97(d, J=8.0 Hz, 2H, Ph—H), 7.75(d, J=8.0 Hz, 2H, Ph—H), 7.46(dd, J=8.3, 4.4 Hz, 1H, Pyridine-H) , 7.25(d, J=9.5 Hz, 2H, Ph—H), 6.92(d, J=7.9 Hz, 2H, Ph—H), 6.86(t, J=7.1 Hz, 1H, Ph—H), 5.34(s, 2H, CH₂), 3.26—3.18(m, 4H, Piperazine-CH₂), 3.11—2.98(m, 4H, Piperazine-CH₂)	164.1(C=S), 160.6, 151.6(CH=N), 151.3, 149.6, 146.3(Triazole-C), 136.1, 135.7, 134.0(d, J=32.3 Hz, CF₃—Ph—C), 129.2, 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 120.1, 116.5, 69.6, 50.6, 49.5
2i^b	10.57(s, 1H, N=CH), 9.19(s, 1H, Pyridine-H), 8.75(d, J=4.0 Hz, 1H, Pyridine-H), 8.24(d, J=7.8 Hz, 1H, Pyridine-H), 8.13(d, J=4.8 Hz, 1H, Pyrimidin-H), 7.96(d, J=7.8 Hz, 2H, Ph—H), 7.74(d, J=7.9 Hz, 2H, Ph—H), 7.47—7.42(m, 1H, Pyridine-H), 6.34(d, J=4.8 Hz, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.92—3.86(m, 4H, Piperazine-CH₂), 2.99—2.93(m, 4H, Piperazine-CH₂), 2.30(s, 3H, CH₃)	167.7(C=S), 164.0, 161.5, 160.6, 157.2, 151.5(CH=N), 149.6, 146.2(Triazole-C), 136.2, 135.9, 133.9(d, J=33.3 Hz, CF₃—Ph—C) 129.1, 126.1, 123.6(q, J=274.7 Hz, CF₃), 123.4, 121.9, 109.5, 69.8, 50.6, 43.6, 24.3
2j^b	10.57(s, 1H, N=CH), 9.18(d, J=1.5 Hz, 1H, Pyridine-H), 8.74(dd, J=4.9, 1.5 Hz, 1H, Pyridine-H), 8.23(d, J=8.0 Hz, 1H, Pyridine-H), 7.96(d, J=8.1 Hz, 2H, Ph—H), 7.74(d, J=8.1 Hz, 2H, Ph—H), 7.44(dd, J=8.0, 4.9 Hz, 1H, Pyridine-H), 6.23(s, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.92—3.88(m, 4H, Piperazine-CH₂), 2.97—2.93(m, 4H, Piperazine-CH₂), 2.26(s, 6H, CH₃)	167.1(C=S), 164.0, 161.6, 160.6, 151.5(CH=N), 149.6, 146.2(Triazole-C), 136.1, 135.7, 133.9(q, J=32.3 Hz, CF₃—Ph—C), 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 109.0, 69.9, 50.7, 43.5, 24.1
2k^b	10.58(s, 1H, N=CH), 9.19(s, 1H, Pyridine-H), 8.75(d, J=4.4 Hz, 1H, Pyridine-H), 8.24(d, J=7.5 Hz, 1H, Pyridine-H), 8.16(d, J=3.4 Hz, 1H, Pyridine-H), 7.97(d, J=7.8 Hz, 2H, Ph—H), 7.74(d, J=7.8 Hz, 2H, Ph—H), 7.45(dd, J=10.5, 5.9 Hz, 2H, Pyridine-H), 6.61(dd, J=13.4, 7.4 Hz, 2H, Pyridine-H), 5.34(s, 2H, CH₂), 3.62—3.53(m, 4H, Piperazine-CH₂), 3.05—2.96(m, 4H, Piperazine-CH₂)	164.1(C=S), 160.6, 159.3, 151.6(CH=N), 149.6, 148.0, 146.3(Triazole-C), 133.9(d, J=33.3 Hz, CF₃—Ph—C), 137.5, 136.1, 135.7, 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 113.4, 107.1, 69.7, 50.4, 45.23
3a^b	10.23(s, 2H, N=CH), 9.20(s, 2H, Pyridine-H), 8.74(d, J=3.6 Hz, 2H, Pyridine-H), 8.25(d, J=7.2 Hz, 2H, Pyridine-H), 7.87(t, J=8.2 Hz, 4H, Ph—H), 7.46—7.41(m, 2H, Pyridine-H), 7.18(t, J=8.2 Hz, 4H, Ph—H), 5.24(s, 4H, CH₂), 2.96(s, 8H, Piperazine-CH₂)	165.5, 164.0(C=S), 160.6, 151.4(CH=N), 149.5, 146.0(Triazole-C), 136.1, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.3, 122.0, 116.5, 69.9, 50.6
3b^b	10.57(s, 2H, N=CH), 9.18(s, 2H, Pyridine-H), 8.75(s, 2H, Pyridine-H), 8.24(s, 2H, Pyridine-H), 7.96(d, J=7.2 Hz, 4H, Ph—H), 7.74(d, J=7.2 Hz, 4H, Ph—H), 7.45(s, 2H, Pyridine-H), 5.24(s, 4H, CH₂), 2.96(s, 8H, Piperazine-CH₂)	163.9(C=S), 160.5, 151.6(CH=N), 149.6, 146.3(Triazole-C), 136.1, 135.6, 133.9(d, J=33.3 Hz, CF₃—Ph—C), 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.8, 69.6, 50.5

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(101 MHz), δ
1a^a	14.42(s, 1H, SH), 9.81(s, 1H, N=CH), 9.04(s, 1H, Pyridine-H), 8.74(d, J=4.5 Hz, 1H, Pyridine-H ), 8.28(d, J=7.8 Hz, 1H, Pyridine-H), 8.01—7.95(m, 2H, Ph—H), 7.63—7.58(m, 1H, Pyridine-H), 7.42(t, J=8.5 Hz, 2H, Ph—H)	165.7, 163.6(C=S), 162.5, 151.3(CH=N), 148.7, 146.8(Triazole-C), 135.9, 131.40(d, J=9.0 Hz, F—Ph—C), 128.6, 123.8 , 122.0, 116.5
1b^a	14.47(s, 1H, SH), 10.09(s, 1H, N=CH), 9.05(s, 1H, Pyridine-H), 8.75(d, J=4.5 Hz, 1H, Pyridine-H), 8.27(d, J=7.9 Hz, 1H, Pyridine-H), 8.12(d, J=8.0 Hz, 2H, Ph—H), 7.94(d, J=8.0 Hz, 2H, Ph—H), 7.60(dd, J=7.9, 4.5 Hz, 1H, Pyridine-H)	163.9(C=S), 162.6(s), 151.0(CH=N), 148.5, 147.0(Triazole-C), 136.7, 135.9, 132.3(d, J=33.3 Hz, CF₃—Ph—C), 129.5, 126.3, 124.1, 123.9(q, J=273.7 Hz, CF₃), 122.2
2a^b	10.23(s, 1H, N=CH), 9.21(s, 1H, Pyridine-H), 8.74(s, 1H, Pyridine-H), 8.26(s, 1H, Pyridine-H), 7.89—7.85(m, 2H, Ph—H), 7.46—7.42(s, 1H, Pyridine-H), 7.27—7.16(m, 6H, Ph—H), 5.26(s, 2H, CH₂), 3.45(s, 2H, CH₂), 2.98—2.91(m, 4H, Piperazine-CH₂), 2.65—2.25(m, 4H, Piperazine-CH₂)	165.5, 164.0(C=S), 162.3, 151.4(CH=N), 149.5, 146.0(Triazole-C), 136.6, 135.9, 132.8, 131.2(d, J=9.0 Hz, F—Ph—C), 130.4, 128.5, 128.4, 123.3, 122.0, 116.1, 69.6, 62.3, 53.0, 50.5
2b^b	10.25(s, 1H, N=CH), 9.22(s, 1H, Pyridine-H), 8.74(d, J=4.7 Hz, 1H, Pyridine-H), 8.27(d, J=8.0 Hz, 1H, Pyridine-H), 7.90—7.86(m, 2H, Ph—H), 7.44(dd, J=8.0, 4.7 Hz, 1H, Pyridine-H), 7.38—7.32(m, 2H, Ph—H), 7.20—7.16(m, 3H, Ph—H), 5.28(s, 2H, CH₂), 3.56(s, 2H, CH₂), 2.98—2.90(m, 4H, Piperazine-CH₂), 2.61—2.48(m, 4H, Piperazine-CH₂)	165.5, 164.1(C=S), 162.3, 151.4(CH=N), 149.5, 146.0(Triazole-C), 135.9, 134.8, 134.5, 133.1, 131.4, 131.2(d, J=9.0 Hz, F—Ph—C), 129.2, 128.5, 126.9, 123.3, 122.1, 116.5, 69.7, 58.7, 53.1, 50.6
2c^b	10.24(s, 1H, N=CH), 9.21(s, 1H, Pyridine-H), 8.74(d, J=3.8 Hz, 1H, Pyridine-H), 8.27(d, J=8.0 Hz, 1H, Pyridine-H), 7.91—7.85(m, 2H, Ph—H), 7.44(dd, J=8.0, 3.8 Hz, 1H, Pyridine-H), 7.28—7.23(m, 2H, Ph—H), 7.18(t, J=8.5 Hz, 2H, Ph—H), 6.91(d, J=8.1 Hz, 2H, Ph—H), 6.86(t, J=7.2 Hz, 1H, Ph—H), 5.34(s, 2H, CH₂), 3.24—3.20(m, 4H, Piperazine-CH₂), 3.10—3.04(m, 4H, Piperazine-CH₂)	165.6, 165.1(C=S), 162.4, 151.5(CH=N), 151.3, 149.5, 146.1(Triazole-C), 136.0, 131.2(d, J=9.0 Hz, F—Ph—C), 129.2, 128.5, 123.4, 122.0, 120.0, 116.5, 116.4, 69.6, 50.6, 49.6
2d^b	10.24(s, 1H, N=CH), 9.20(s, 1H, Pyridine-H), 8.73(d, J=4.5 Hz, 1H, Pyridine-H), 8.25(d, J=7.9 Hz, 1H, Pyridine-H), 7.91—7.84(m, 2H, Ph—H), 7.43(dd, J=7.9, 4.5 Hz, 1H, Pyridine-H), 7.18(t, J=8.4 Hz, 2H, Ph—H), 6.23(s, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.95—3.87(m, 4H, Piperazine-CH₂), 2.97—2.90(m, 4H, Piperazine-CH₂), 2.25(s, 6H, CH₃)	167.1(C=S), 165.5, 164.1, 162.3, 161.6, 151.4(CH=N), 149.5, 146.0(Triazole-C), 135.9, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.3, 122.0, 116.5, 108.9, 69.9, 50.7, 43.6, 24.1
2e^b	10.23(s, 1H, N=CH), 9.20(s, 1H, Pyridine-H), 8.73(s, 1H, Pyridine-H), 8.26(d, J=6.3 Hz, 1H, Pyridine-H), 8.16(s, 1H, Pyridine-H), 7.87(d, J=7.1 Hz, 2H, Ph—H), 7.50—7.37(m, 2H, Pyridine-H), 7.19(d, J=7.1 Hz, 2H, Ph—H), 6.68—6.50(m, 2H, Pyridine-H), 5.34(s, 2H, CH₂), 3.68—3.52(s, 4H, Piperazine-CH₂), 3.10—2.93(s, 4H, Piperazine-CH₂)	165.5, 164.0(C=S), 162.4, 159.3, 151.5(CH=N), 149.5, 148.0, 146.1(Triazole-C), 137.5, 136.0, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.4, 122.0, 116.5, 113.3, 107.1, 69.7, 50.4, 45.2
2f^b	10.58(s, 1H, N=CH), 9.19(d, J=1.6 Hz, 1H, Pyridine-H), 8.75(d, J=4.8 Hz, 1H, Pyridine-H), 8.24(dd, J=8.0, 1.6 Hz, 1H, Pyridine-H), 7.97(d, J=8.1 Hz, 2H, Ph—H), 7.75(d, J=8.1 Hz, 2H, Ph—H), 7.45(dd, J=8.0, 4.8 Hz, 1H, Pyridine-H), 7.26—7.18(m, 4H, Ph—H), 5.28(s, 2H, CH₂), 3.45(s, 2H, CH₂), 2.96—2.88(m, 4H, Piperazine-CH₂), 2.53—2.43(m, 4H, Piperazine-CH₂)	164.0(C=S), 160.5, 151.6(CH=N), 149.6, 146.2(Triazole-C), 136.6, 136.1, 135.7, 133.9(d, J=33.0 Hz, CF₃—Ph—C), 132.8, 130.4, 129.1, 128.4, 126.1, 123.6(q, J=272.7 Hz, CF₃), 123.4, 121.9, 69.6, 62.3, 53.0, 50.5
2g^b	10.58(s, 1H, N=CH), 9.19(d, J=1.6 Hz, 1H, Pyridine-H), 8.76(d, J=5.0 Hz, 1H, Pyridine-H), 8.26(dd, J=8.0 Hz, 1.6 Hz, 1H, Pyridine-H), 7.97(d, J=8.1 Hz, 2H, Ph—H), 7.75(d, J=8.1 Hz, 2H, Ph—H), 7.46(dd, J=8.0, 5.0 Hz, 1H, Pyridine-H), 7.35(m, 2H, Ph—H), 7.17(dd, J=8.2, 1.8 Hz, 1H, Ph—H), 5.26(s, 2H, CH₂), 3.56(s, 2H, CH₂), 2.97—2.92(m, 4H, Piperazine-CH₂), 2.85—2.30(m, 4H, Piperazine-CH₂)	164.0(C=S), 160.5, 151.6(CH=N), 149.6, 146.2(Triazole-C), 136.1, 135.7, 135.1, 134.9, 134.5, 134.0(d, J=32.3 Hz, CF₃—Ph—C), 133.1, 131.4, 129.1, 126.9, 126.1, 123.6(q, J=275.7 Hz, CF₃), 123.4, 121.9, 69.6, 58.7, 53.1, 50.6
2h^b	10.59(s, 1H, N=CH), 9.20(d, J=1.4 Hz, 1H, Pyridine-H), 8.76(d, J=4.4 Hz, 1H, Pyridine-H), 8.25(d, J=8.3, 1.4 Hz, 1H, Pyridine-H), 7.97(d, J=8.0 Hz, 2H, Ph—H), 7.75(d, J=8.0 Hz, 2H, Ph—H), 7.46(dd, J=8.3, 4.4 Hz, 1H, Pyridine-H) , 7.25(d, J=9.5 Hz, 2H, Ph—H), 6.92(d, J=7.9 Hz, 2H, Ph—H), 6.86(t, J=7.1 Hz, 1H, Ph—H), 5.34(s, 2H, CH₂), 3.26—3.18(m, 4H, Piperazine-CH₂), 3.11—2.98(m, 4H, Piperazine-CH₂)	164.1(C=S), 160.6, 151.6(CH=N), 151.3, 149.6, 146.3(Triazole-C), 136.1, 135.7, 134.0(d, J=32.3 Hz, CF₃—Ph—C), 129.2, 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 120.1, 116.5, 69.6, 50.6, 49.5
2i^b	10.57(s, 1H, N=CH), 9.19(s, 1H, Pyridine-H), 8.75(d, J=4.0 Hz, 1H, Pyridine-H), 8.24(d, J=7.8 Hz, 1H, Pyridine-H), 8.13(d, J=4.8 Hz, 1H, Pyrimidin-H), 7.96(d, J=7.8 Hz, 2H, Ph—H), 7.74(d, J=7.9 Hz, 2H, Ph—H), 7.47—7.42(m, 1H, Pyridine-H), 6.34(d, J=4.8 Hz, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.92—3.86(m, 4H, Piperazine-CH₂), 2.99—2.93(m, 4H, Piperazine-CH₂), 2.30(s, 3H, CH₃)	167.7(C=S), 164.0, 161.5, 160.6, 157.2, 151.5(CH=N), 149.6, 146.2(Triazole-C), 136.2, 135.9, 133.9(d, J=33.3 Hz, CF₃—Ph—C) 129.1, 126.1, 123.6(q, J=274.7 Hz, CF₃), 123.4, 121.9, 109.5, 69.8, 50.6, 43.6, 24.3
2j^b	10.57(s, 1H, N=CH), 9.18(d, J=1.5 Hz, 1H, Pyridine-H), 8.74(dd, J=4.9, 1.5 Hz, 1H, Pyridine-H), 8.23(d, J=8.0 Hz, 1H, Pyridine-H), 7.96(d, J=8.1 Hz, 2H, Ph—H), 7.74(d, J=8.1 Hz, 2H, Ph—H), 7.44(dd, J=8.0, 4.9 Hz, 1H, Pyridine-H), 6.23(s, 1H, Pyrimidin-H), 5.34(s, 2H, CH₂), 3.92—3.88(m, 4H, Piperazine-CH₂), 2.97—2.93(m, 4H, Piperazine-CH₂), 2.26(s, 6H, CH₃)	167.1(C=S), 164.0, 161.6, 160.6, 151.5(CH=N), 149.6, 146.2(Triazole-C), 136.1, 135.7, 133.9(q, J=32.3 Hz, CF₃—Ph—C), 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 109.0, 69.9, 50.7, 43.5, 24.1
2k^b	10.58(s, 1H, N=CH), 9.19(s, 1H, Pyridine-H), 8.75(d, J=4.4 Hz, 1H, Pyridine-H), 8.24(d, J=7.5 Hz, 1H, Pyridine-H), 8.16(d, J=3.4 Hz, 1H, Pyridine-H), 7.97(d, J=7.8 Hz, 2H, Ph—H), 7.74(d, J=7.8 Hz, 2H, Ph—H), 7.45(dd, J=10.5, 5.9 Hz, 2H, Pyridine-H), 6.61(dd, J=13.4, 7.4 Hz, 2H, Pyridine-H), 5.34(s, 2H, CH₂), 3.62—3.53(m, 4H, Piperazine-CH₂), 3.05—2.96(m, 4H, Piperazine-CH₂)	164.1(C=S), 160.6, 159.3, 151.6(CH=N), 149.6, 148.0, 146.3(Triazole-C), 133.9(d, J=33.3 Hz, CF₃—Ph—C), 137.5, 136.1, 135.7, 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.9, 113.4, 107.1, 69.7, 50.4, 45.23
3a^b	10.23(s, 2H, N=CH), 9.20(s, 2H, Pyridine-H), 8.74(d, J=3.6 Hz, 2H, Pyridine-H), 8.25(d, J=7.2 Hz, 2H, Pyridine-H), 7.87(t, J=8.2 Hz, 4H, Ph—H), 7.46—7.41(m, 2H, Pyridine-H), 7.18(t, J=8.2 Hz, 4H, Ph—H), 5.24(s, 4H, CH₂), 2.96(s, 8H, Piperazine-CH₂)	165.5, 164.0(C=S), 160.6, 151.4(CH=N), 149.5, 146.0(Triazole-C), 136.1, 131.2(d, J=9.0 Hz, F—Ph—C), 128.5, 123.3, 122.0, 116.5, 69.9, 50.6
3b^b	10.57(s, 2H, N=CH), 9.18(s, 2H, Pyridine-H), 8.75(s, 2H, Pyridine-H), 8.24(s, 2H, Pyridine-H), 7.96(d, J=7.2 Hz, 4H, Ph—H), 7.74(d, J=7.2 Hz, 4H, Ph—H), 7.45(s, 2H, Pyridine-H), 5.24(s, 4H, CH₂), 2.96(s, 8H, Piperazine-CH₂)	163.9(C=S), 160.5, 151.6(CH=N), 149.6, 146.3(Triazole-C), 136.1, 135.6, 133.9(d, J=33.3 Hz, CF₃—Ph—C), 129.1, 126.1, 123.6(q, J=273.7 Hz, CF₃), 123.4, 121.8, 69.6, 50.5

Compd.	Herbicidal activity(%)		Compd.	Herbicidal activity(%)		Compd.	Herbicidal activity(%)
Compd.	Brassica campestris		Echinochloa crusgalli		Brassica campestris	Echinochloa crusgalli	Brassica campestris	Echinochloa crusgalli
2a	16.7	5.0	2f	0	20.0	2k	0	9.0
2b	42.2	5.0	2g	28.1	13.0	3a	10.3	0
2c	0	0	2h	0	5.0	3b	0	0
2d	3.4	0	2i	0	10.0	Chlorsulfuron	80.4	22.9
2e	0	10.0	2j	29.3	13.0	CPD	76.8	7.0