[0022] 下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
[0023] 本发明的含吡啶的三唑类化合物(I)可以如下方法合成:
[0024] 将二硫化碳(30mmol),3-氯-2-肼基吡啶(143 mg, 1mmol)回流反应30小时辐射工作。结束后将混合物旋干,然后水洗得粗产品,粗产品在乙醇中重结晶得到式(II)。将DMF (5 mL)、式(II) (1mmol)、RCH2Cl (1.1 mmol) 和碳酸钾 (0.05 g, 1.2mmol) 在室温条件下反应24小时。反应结束后,将混合物倒入碎冰中形成沉淀后过滤,重结晶收集,粗产物通过柱层析进行纯化。制得式(I)。
[0025] 实施例1
[0026] 3-(苯甲硫基)-8-氯-[1,2,4]三唑[4,3-a]吡啶 产率87%, m.p.140-141℃;1H NMR (CDCl3, 400 MHz), δ: 4.29 (s, 2H, SCH2), 6.62(t, J=7.0Hz, 1H, Py-H), 7.09-7.11(m, 2H, Ar-H), 7.15-7.16(m, 3H, Py-H and Ar-H), 7.27(s, 1H, Ar-H), 7.62(d, J=6.8Hz, 1H, Py-H). Elemental analysis for C13H10ClN3S: found C 56.74, H
3.76, N 15.43; calcd. C, 56.62; H, 3.66; N, 15.24.
[0027] 实施例2
[0028] 8-氯-3-((3,4-二氯苄基)硫基)-[1,2,4]三唑[4,3-a]吡啶 产率 81%, m.p.152- 1
153℃; H NMR (CDCl3, 400 MHz), δ: 4.30 (s, 2H, SCH2), 6.75(t, J=7.0Hz, 1H, Py-H), 7.02(d, J=6.2Hz, 1H, Py-H), 7.33(d, J=6.5Hz, 1H, Py-H),. Elemental analysis for C13H8Cl3N3S: found C 45.44, H 2.53, N 11.98; calcd. C, 45.30; H,
2.34; N, 12.19.
[0029] 实施例3
[0030] (Z)-甲基 2-(2-(((8-氯-[1,2,4]三唑[4,3-a]吡啶-3-基)硫基)甲基)苯基)-2-(甲氧亚胺基)乙酸酯 产率 77%, m.p.155-156℃; 1H NMR (CDCl3, 400 MHz), δ: 3.77(s, 3H, OCH3), 3.89(s, 3H, OCH3), 4.10 (s, 2H, SCH2), 6.53(t, J=7.0Hz, 1H, Py-H), 6.66(d, J=7.0Hz, 1H, Ar-H), 6.90(d, J=7.5Hz, 1H, Ar-H), 7.13(d, J=7.5Hz, 1H, Ar-H), 7.19(t, J=7.5Hz, 1H, Ar-H), 7.25(d, J=7.0Hz, 1H, Py-H), 7.71(d, J=
6.9Hz, 1H, Py-H),. Elemental analysis for C17H15ClN4O3S: found C 52.33, H 3.97, N 14.45; calcd. C, 52.24; H, 3.87; N, 14.33
[0031] 实施例4
[0032] 2-((8-氯-[1,2,4]三唑[4,3-a]吡啶-3-基)硫基)乙腈 产率68%, m.p.200-201℃; 1H NMR (CDCl3, 400 MHz), δ: 3.90 (s, 2H, SCH2), 7.00(t, J=7.0Hz, 1H, Py-H), 7.48(d, J=7.2Hz, 1H, Py-H), 7.24-7.28(m, 2H, Ar-H), 7.31(d, J=6.5Hz, 1H, Py-H), 7.31(d, J=6.8Hz, 1H, Py-H),. Elemental analysis for C8H5ClN4S: found C 42.97, H 2.31, N 24.99; calcd. C, 42.77; H, 2.24; N, 24.94.
[0033] 实施例5
[0034] 4-(((8-氯-[1,2,4]三唑[4,3-a]吡啶-3-基)硫基)甲基)苄腈 产率 76%, m.p.194-195℃; 1H NMR (CDCl3, 400 MHz), δ: 4.50 (s, 2H, SCH2), 6.89(t, J=7.0Hz, 1H, Py-H), 7.40(d, J=8.1Hz, 1H, Ar-H), 7.45(d, J=6.5Hz, 1H, Py-H),
7.54(d, J=8.1Hz, 1H, Ar-H), 7.82(d, J=6.8Hz, 1H, Py-H). Elemental analysis for C14H9ClN4S: found C 55.89, H 2.97, N 18.87; calcd. C, 55.91; H, 3.02; N,
18.63.
[0035] 实施例6
[0036] 8-氯-3-(((6-氯吡啶-3-基)甲基)硫基)-[1,2,4]三唑 [4,3-a]吡啶 产率82%, m.p.150-151℃; 1H NMR (CDCl3, 400 MHz), δ: 4.40 (s, 2H, SCH2), 6.81(t, J=7.0Hz, 1H, Py-H), 7.18(d, J=8.2Hz, 1H, Py-H), 7.34(d, J=7.2Hz, 1H, Py-H),
7.58(dd, J=2.5, 2.5Hz, 1H, Py-H), 7.78(d, J=6.9Hz, 1H, Py-H), 8.31(d, J=
2.3Hz, 1H, Py-H). Elemental analysis for C12H8Cl2N4S: found C 46.42, H 2.75, N
17.96; calcd. C, 46.32; H, 2.59; N, 18.00.
[0037] 实施例7
[0038] 8-氯-3-((3-氟苯基)硫基)-[1,2,4]三唑[4,3-a]吡啶 产率 81%, m.p.99-100℃; 1H NMR (CDCl3, 400 MHz), δ: 4.30 (s, 2H, SCH2), 6.69(t, J=7.0Hz, 1H, Py-H), 6.85-6.91(m, 2H, Ar-H), 6.93(d, J=1.6Hz, 1H, Ar-H), 7.09-7.13(m, 1H, Ar-H), 7.27(d, J=7.2Hz, 1H, Py-H), 7.71(d, J=7.5Hz, 1H, Py-H). Elemental analysis for C13H9ClFN3S: found C 53.22, H 2.97, N 14.51; calcd. C, 53.15; H, 3.09; N, 14.30.
[0039] 实施例8
[0040] 8-氯-3-((2-氯苯基)硫基)-[1,2,4]三唑[4,3-a]吡啶 产率79%, m.p.152-153℃; 1H NMR (CDCl3, 400 MHz), δ: 4.42 (s, 2H, SCH2), 6.67(t, J=7.0Hz, 1H, Py-H), 6.97(d, J=4.0Hz, 2H, Ar-H), 7.13-7.17(m, 1H, Ar-H), 7.27-7.29(m, 1H, Ar-H), 7.34(d, J=7.9Hz, 1H, Py-H), 7.72(d, J=6.9Hz, 1H, Py-H). Elemental analysis for C13H9Cl2N3S: found C 50.46, H 2.90, N 13.64; calcd. C, 50.33; H, 2.92; N, 13.55.
[0041] 实施例9
[0042] 3-((4-溴苯基)硫基)-8-氯-[1,2,4]三唑[4,3-a]吡啶 产率89%, m.p.168-169℃; 1H NMR (CDCl3, 400 MHz), δ: 4.42 (s, 2H, SCH2), 6.72(t, J=6.9Hz, 1H, Py-H), 7.04(d, J=7.8Hz, 2H, Ar-H), 7.28-7.33(m, 3H, Ar-H and Py-H), 7.69(d, J=6.9Hz, 1H, Py-H). Elemental analysis for C13H9BrClN3S: found C 44.33, H2.61, N
11.68; calcd. C, 44.03; H, 2.56; N, 11.85.
[0043] 实施例10
[0044] 3-(((8-氯-[1,2,4]三唑[4,3-a]吡啶-3-基)硫基)甲基)苄腈 产率 83%, m.p.186-187℃; 1H NMR (CDCl3, 400 MHz), δ: 4.44 (s, 2H, SCH2), 6.82(t, J=6.9Hz, 1H, Py-H), 7.31-7.37(m, 2H, Ar-H), 7.47(d, J=7.8Hz, 1H, Ar-H), 7.51(d, J=7.8Hz, 1H, Py-H), 7.61(s, 1H, Ar-H), 7.80(d, J=6.7Hz, 1H, Py-H). Elemental analysis for C14H9ClN4S: found C 55.89, H 2.88, N 18.86; calcd. C, 55.91; H,
3.02; N, 18.63.
[0045] 实施例11
[0046] 8-氯-3-((4-氯苯基)硫基) -[1,2,4]三唑[4,3-a]吡啶 产率 81%, m.p.162-163℃; 1H NMR (CDCl3, 400 MHz),δ: 4.28 (s, 2H, SCH2), 6.69(t, J=7.0Hz, 1H, Py-H), 7.06(d, J=8.4Hz, 2H, Ar-H), 7.14(d, J=8.4Hz, 2H, Ar-H), 7.29(d, J=7.7Hz, 1H, Py-H), 7.67(d, J=7.4Hz, 1H, Py-H). Elemental analysis for C13H9Cl2N3S: found C
50.13, H 3.05, N 13.71; calcd. C, 50.33; H, 2.92; Cl, 22.86; N, 13.55.[0047] 实施例12
[0048] 杀菌活性测试
[0049] 试验对象:番茄细菌性斑点病、黄瓜枯萎病、番茄灰霉病。
[0050] 试验方法:采用盆栽试验法。分别将黄瓜种子和番茄种子经过50℃浸泡后,催芽后播种于育苗钵中,待生长至2片真叶供试验。
[0051] 药剂准备:供试药:取药配成100ppm,取89种化合物各5mg,加丙酮溶解后再加10%土温80,最后加水充分溶解。因100ppm为100mg/L所以加水量 =5mg*1000/100mg=50ml,因有机溶剂最终含量≤1% 所以加丙酮的量=50ml*1%=0.5ml(溶解),因吐温最终含量为0.1% 所以50 ml水里应有吐温 0.05 ml,即:应加10%吐温0.05 ml.
[0052] 对照药剂:3%中生菌素WP→800倍液 0.01g药+8ml水
[0053] 75%甲基托布津WP→1000倍液 0.01g药+15ml水
[0054] 50%嘧菌环胺水分散粒剂→1000倍液 0.01g药+15ml水
[0055] 施药方法:番茄细菌性斑点病和番茄灰霉病实验中,番茄苗长出两片复叶时,用喷壶将供试药剂与对照药剂均匀喷施在供试植株上。
[0056] 黄瓜枯萎病实验中,将黄瓜种子浸泡于各要处理2h后进行接种处理。
[0057] 接种方法:
[0058] 番茄细菌性斑点病采用菌悬液喷雾法接种:将培养好的番茄细菌性斑点病菌兑蒸馏水稀释成3×107cfu/ml菌悬液,用喷壶喷雾接种。接种后保湿培养。
[0059] 番茄灰霉病采用打菌丝接种法接种:通过纱布过滤把液体培养基和菌块分开,用粉碎仪把带有少量液体的培养基的菌块打碎,再用过滤好的液体培养基与打碎的菌块混合配成一定浓度的溶液,并用分光光度计测定溶液透光率(λ=630nm,OD=9.8)。
[0060] 黄瓜枯萎病采用培根浸种法接种:将在PD培养基中培养好的黄瓜枯萎病菌用纱布过滤菌丝,调节孢子浓度到1×106cfu/ml浸泡种子。
[0061] 待清水充分发病后进行病情调查,并计算病情指数和防治效果。
[0062] 式中:EF: 相对防治效果;CK: 对照区终期平均病情指数;PT: 处理区终期平均病情指数。
[0063] 杀菌活性测试试验结果如表1所示。
[0064] 表1 100ppm下各化合物的杀菌活性(%防效)
[0065] 。