含1_2_4_三唑杂环的新型Strobilurins衍生物的合成及杀菌活性

2008年第28卷有机化学V ol. 28, 2008第5期, 875～880 Chinese Journal of Organic Chemistry No. 5, 875～880
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Received September 12, 2007; revised October 15, 2007; accepted December 2, 2007.
国家自然科学基金(Nos. 20432010, 20476036, 20172017)、教育部跨世纪优秀人才资助计划、教育部重点科技项目及湖北省优秀创新群体(No.
876有机化学V ol. 28, 2008
a, R＝C6H5; b, 4-BrC6H4; c, 3,4-(CH3O)2C6H3; d, 4-CH3OC6H4; e, 3,4-Cl2C6H3; f, 4-CH3C6H4; g, 4-ClC6H4; h, 3-CH3C6H4; i, 2-BrC6H4; j, 4-CH3CH2C6H4; k, 3,4-(CH3)2C6H3; l, 4-t-BuC6H4; m, 3-BrC6H4; n, 4-(CH3)2NC6H4
Scheme 1
1 实验部分
1.1 仪器和试剂
Electrothermal数字熔点测定仪(温度计未经校正); MERCURY-PLUS400型核磁共振仪, 以氘代氯仿为溶剂, TMS为内标; MS用HP-5988A型质谱仪或Finnigan Trace MS质谱仪测定; 元素分析用Vario ElIII Chnso元素分析仪测定; 薄层层析硅胶GF25460型(青岛海洋化工厂).
所有进口或国产试剂均为AR, 使用前经常规处理. 中间体5-甲基-4-氨基-3-巯基-1,2,4-三唑(2)按文献[14]制备; (E)-β-甲氧基-2-(2-溴甲基苯基)丙烯酸甲酯(4)参照文献[15]制备.
1.2 3-巯基-5-甲基-4-芳基亚胺基-4H-1,2,4-三唑(3)的合成
将1.3 g (10 mmol) 5-甲基-4-氨基-3-巯基-1,2,4-三唑和10 mmol取代苯甲醛溶于30 mL无水乙醇, 并加入3滴冰醋酸, 加热, 回流2～3 h, 冷却至室温, 抽滤, 固体用乙醇重结晶, 得到无色晶体3a～3n.
3a: 无色晶体, 收率78%, m.p. 207～208 ℃(文献值[16] 205～206 ℃); 1H NMR (400 MHz, CDCl3) δ: 2.48 (s, 3H, Het-CH3), 7.44～7.56 (m, 3H, ArH), 7.89 (d, J＝7.6 Hz, 2H, ArH), 10.40 (s, 1H, ArCH＝), 10.93 (s, 1H, SH).
3b: 淡黄色晶体, 收率77%, m.p. 209～210 ℃(文献值[16] 206～208 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.43 (s, 3H, Het-CH3), 7.62 (t, J＝9.6 Hz, 2H, ArH), 7.76 (d, J＝8.4 Hz, 2H, ArH), 10.52 (s, 1H, ArCH＝), 13.49 (s, 1H, SH).
3c: 无色晶体, 收率71%, m.p. 219～221 ;
℃1H NMR (400 MHz, DMSO-d6) δ: 2.43 (s, 3H, Het-CH3), 3.96 (s, 6H, 2×OCH3), 6.96 (d, J＝8.4 Hz, 1H, ArH), 7.37 (d, J＝8.4 Hz, 1H, ArH), 7.49 (s, 1H, ArH), 9.86 (s, 1H, ArCH＝), 13.38 (s, 1H, SH). Anal. calcd for C12H14N4O2S: C 51.78, H 5.07, N 20.13, S 11.52; found C 51.77, H 5.34, N 19.87, S 11.80.
3d: 无色晶体, 收率75%, m.p. 207～208 ℃(文献值[16] 207～208 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.34 (s, 3H, Het-CH3), 3.86 (s, 3H, OCH3), 7.11 (d, J＝8.8 Hz, 2H, ArH), 7.87 (d, J＝8.8 Hz, 2H, ArH), 9.72 (s, 1H, ArCH＝), 13.69 (s, 1H, SH).
3e: 淡黄色晶体, 收率63%, m.p. 199～201 ;
℃1H NMR (400 MHz, DMSO-d6) δ: 2.38 (s, 3H, Het-CH3), 7.83 (d, J＝8.4 Hz, 1H, ArH), 7.91 (d, J＝8.0 Hz, 1H, ArH), 8.17 (s, 1H, ArH), 10.16 (s, 1H, ArCH＝), 13.81 (s, 1H, SH). Anal. calcd for C10H8Cl2N4S: C 41.82, H 2.81, N 19.51, S 11.17; found C 42.07, H 2.83, N 19.77, S 11.41.
3f: 无色晶体, 收率79%, m.p. 214～216 ℃(文献值[17] 223～225 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.37 (s, 3H, Het-CH3), 2.40 (s, 3H, CH3), 7.37 (d, J＝7.6 Hz, 2H, ArH), 7.80 (d, J＝8.0 Hz, 2H, ArH), 9.86 (s, 1H, ArCH＝), 13.72 (s, 1H, SH).
3g: 无色晶体, 收率74%, m.p. 227～229 ℃(文献值[16] 214～215 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.36 (s, 3H, Het-CH3), 7.64 (d, J＝8.8 Hz, 2H, ArH), 7.94 (d, J＝8.4 Hz, 2H, ArH), 10.05 (s, 1H, ArCH＝), 13.77 (s, 1H, SH).
3h: 无色晶体, 收率76%, m.p. 174～175 ℃(文献值[17] 161～163 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.35 (s, 3H, Het-CH3), 2.39 (s, 3H, CH3), 7.43 (d, J＝7.6 Hz, 2H, ArH), 7.64～7.72 (m, 2H, ArH), 9.90 (s, 1H, ArCH＝), 13.74 (s, 1H, SH).
3i: 淡黄色晶体, 收率72%, m.p. 252～253 ℃(文献值[17] 253～255 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.39 (s, 3H, Het-CH3), 7.50～7.59 (m, 2H, ArH), 7.79 (d, J＝7.2 Hz, 1H, ArH), 8.17 (d, J＝7.6 Hz, 1H, ArH), 10.82 (s, 1H, ArCH＝), 13.78 (s, 1H, SH).
3j: 无色晶体, 收率67%, m.p. 161～162 ℃(文献值[17] 157～159 ℃); 1H NMR (400 MHz, DMSO-d6) δ:
1.21 (t, J＝7.6 Hz, 3H, CH2CH3),
2.34 (s, 3H, Het-CH3),
2.69 (dd, J＝7.4, 14.8 Hz, 2H, CH2CH3), 7.40 (d, J＝8.0 Hz, 2H, ArH), 7.83 (d, J＝8.0 Hz, 2H, ArH), 9.87 (s, 1H, ArCH＝), 1
3.73 (s, 1H, SH).
No. 5 赵培亮等：含1,2,4-三唑杂环的新型Strobilurins衍生物的合成及杀菌活性877
3k: 无色晶体, 收率70%, m.p. 207～209 ℃(文献值[17] 201～203 ℃);1H NMR (400 MHz, DMSO-d6) δ: 2.24 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.34 (s, 3H, Het-CH3), 7.33 (d, J＝7.6 Hz, 1H, ArH), 7.62 (d, J＝8.0 Hz, 1H, ArH), 7.68 (s, 1H, ArH), 9.81 (s, 1H, ArCH＝), 13.71 (s, 1H, SH).
3l: 无色晶体, 收率66%, m.p. 227～229 ;
℃1H NMR (400 MHz, DMSO-d6) δ: 1.33 (s, 9H, 3×CH3), 2.34 (s, 3H, Het-CH3), 7.59 (d, J＝8.4 Hz, 2H, ArH), 7.84 (d, J＝8.4 Hz, 2H, ArH), 9.85 (s, 1H, ArCH＝), 13.73 (s, 1H, SH). Anal. calcd for C14H18N4S: C 61.28, H 6.61, N 20.42, S 11.69; found C 61.33, H 6.39, N 20.41, S 11.92.
3m: 淡黄色晶体, 收率73%, m.p. 230～232 ℃(文献值[17] 236～238 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.37 (s, 3H, Het-CH3), 7.53 (t, J＝7.6 Hz, 1H, ArH), 7.81 (d, J＝8.4 Hz, 1H, ArH), 7.91 (d, J＝8.0 Hz, 1H, ArH), 8.11 (s, 1H, ArH), 10.06 (s, 1H, ArCH＝), 13.79 (s, 1H, SH).
3n: 淡黄色晶体, 收率77%, m.p. 224～226 ℃(文献值[16] 214～215 ℃); 1H NMR (400 MHz, DMSO-d6) δ: 2.31 (s, 3H, Het-CH3), 3.02 (s, 6H, 2×CH3), 6.80 (d, J＝8.4 Hz, 2H, ArH), 7.69 (d, J＝8.8 Hz, 2H, ArH), 9.38 (s, 1H, ArH), 13.59 (s, 1H, SH).
1.3 1,2,4-三唑杂环修饰的Strobilurins衍生物5a～5n 的合成
向25 mL的圆底烧瓶中加入0.20 g (5 mmol) 氢氧化钠、5 mL水和5 mmol化合物3, 搅拌使其充分溶解得澄清液, 然后, 向其中滴加入 6 mmol (E)-β-甲氧基-2-(2-溴甲基苯基)丙烯酸甲酯的甲醇或DMF液(3 mL), 室温下搅拌反应15 h, 抽滤, 乙醚洗涤后, 干燥, 丙酮重结晶或者柱层析, 得到无色或淡黄色晶体5a～5n.
5a: 无色晶体, 收率83%, m.p. 79～81 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.51 (s, 3H, Het-CH3), 3.60 (s, 3H, COOCH3), 3.75 (s, 3H, ＝CHOCH3), 4.42 (s, 2H, CH2), 7.13 (dd, J＝1.8, 7.0 Hz, 1H, ArH), 7.24～7.29 (m, 2H, ArH), 7.41～7.55 (m, 5H, ＝CHOCH3, ArH), 7.77 (t, J＝4.4 Hz, 2H, ArH), 8.33 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 423 ([M＋1]＋, 6), 422 (M＋, 13), 345 (31), 286 (18), 205 (38), 204 (29), 173 (12), 144 (100), 131 (22), 130 (14), 114 (49), 102 (35), 101 (19). Anal. calcd for C22H22N4O3S: C 62.54, H 5.25, N 13.26, S 7.59; found C 62.30, H 5.51, N 12.96, S 7.50.
5b: 无色晶体, 收率88%, m.p. 97～99 ;
℃1H NMR (400 MHz, CDCl) δ: 2.51 (s, 3H, Het-CH), 3.61 (s, 3H, COOCH3), 3.77 (s, 3H, ＝CHOCH3), 4.42 (s, 2H, CH2),
7.13 (d, J＝1.6 Hz, 1H, ArH), 7.23～7.28 (m, 2H, ArH),
7.39 (t, J＝2.4 Hz, 1H, ArH), 7.52 (s, 1H, ＝CHOCH3),
7.61～7.63 (m, 4H, ArH), 8.30 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 502 ([M＋1]＋, 2), 501 (M＋, 3), 205 (12), 146 (17), 144 (100), 131 (14), 130 (10), 114 (40), 103 (14), 101 (28). Anal. calcd for C22H21BrN4O3S: C 52.70, H 4.22, N
11.17, S 6.40; found C 52.42, H 4.45, N 10.97, S 6.11.
5c: 无色晶体, 收率81%, m.p. 178～179 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.50 (s, 3H, Het-CH3), 3.60 (s,
3H, COOCH3), 3.75 (s, 3H, ＝CHOCH3), 3.96 (s, 3H, ArOCH3), 3.98 (s, 3H, ArOCH3), 4.40 (s, 2H, CH2), 6.92 (d, J＝8.4 Hz, 1H, ArH), 7.13 (d, J＝7.2 Hz, 1H, ArH),
7.20～7.29 (m, 3H, ArH), 7.42 (d, J＝6.0 Hz, 2H, ArH),
7.53 (s, 1H, ＝CHOCH3), 8.32 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 483 ([M＋1]＋, 5), 482 (M＋, 7), 163 (21), 162 (24), 146 (27), 144 (100), 136 (13), 130 (28), 129 (12), 114 (41), 102 (24), 101 (19). Anal. calcd for C23H23N4O4S: C
61.18, H 5.13, N 12.41, S 7.10; found C 61.14, H 4.96, N
12.49, S 7.28.
5d: 无色晶体, 收率85%, m.p. 116～118 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.50 (s, 3H, Het-CH3), 3.60 (s,
3H, COOCH3), 3.75 (s, 3H, ＝CHOCH3), 3.88 (s, 3H,
Ar-OCH3), 4.40 (s, 2H, CH2), 6.96 (d, J＝8.4 Hz, 2H),
7.13 (t, J＝3.6 Hz, 1H, ArH), 7.24～7.28 (m, 2H, ArH),
7.41 (d, J＝1.6 Hz, 1H, ArH), 7.53 (s, 1H, ＝CHOCH3),
7.72 (d, J＝8.8 Hz, 2H, ArH), 8.22 (s, 1H, ArCH＝); MS
(70 eV) m/z (%): 452 (M＋, 7), 146 (24), 144 (100), 134 (21), 132 (65), 116 (11), 114 (37), 102 (25), 101 (14). Anal. calcd for C23H24N4O4S: C 61.05, H 5.35, N 12.38, S
7.09; found C 60.99, H 5.34, N 12.36, S 7.37.
5e: 无色晶体, 收率83%, m.p. 118～119 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.54 (s, 3H, Het-CH3), 3.63 (s,
3H, COOCH3), 3.79 (s, 3H, ＝CHOCH3), 4.42 (s, 2H,
CH2), 7.14 (d, J＝1.6 Hz, 1H), 7.24～7.30 (m, 3H, ArH),
7.40 (d, J＝1.6 Hz, 1H, ArH), 7.53～7.57 (m, 2H, ＝CHOCH3, ArH), 7.83 (d, J＝2.0 Hz, 1H, ArH), 8.31 (s,
1H, ArCH＝); MS (70 eV) m/z (%): 492 ([M＋1]＋, 3), 491
(M＋, 4), 171 (13), 147 (15), 146 (25), 144 (100), 130 (23),
129 (14), 114 (46), 102 (30), 101 (14). Anal. calcd for
C22H20Cl2N4O3S: C 53.77, H 4.10, N 11.40, S 6.53; found
C 53.49, H 4.31, N 11.62, S 6.61.
5f: 无色晶体, 收率89%, m.p. 68～70 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.43 (s, 3H, ArCH3), 2.50 (s, 3H,
Het-CH3), 3.60 (s, 3H, COOCH3), 3.75 (s, 3H,＝CHO-
878有机化学V ol. 28, 2008
CH3), 4.41 (s, 2H, CH2), 7.12 (dd, J＝1.6, 7.2 Hz, 2H, ArH), 7.23～7.30 (m, 3H, ArH), 7.41 (d, J＝7.6 Hz, 1H, ArH), 7.53 (s, 1H, ＝CHOCH3), 7.66 (d, J＝8.4 Hz, 2H, ArH), 8.27 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 437 ([M＋1]＋, 10), 436 (M＋, 11), 359 (13), 146 (24), 144 (85), 130 (29), 129 (14), 116 (33), 114 (60), 102 (41), 58 (100). Anal. calcd for C23H24N4O3S: C 63.28, H 5.54, N 12.83, S 7.35; found C 62.99, H 5.52, N 13.02, S 7.60.
5g: 无色晶体, 收率84%, m.p. 105～107 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.51 (s, 3H, Het-CH3), 3.61 (s,
3H, COOCH3), 3.77 (s, 3H, ＝CHOCH3), 4.42 (s, 2H, CH2), 7.13 (d, J＝1.6 Hz, 1H, ArH), 7.23～7.29 (m, 2H, ArH), 7.39～7.46 (m, 3H, ArH), 7.53 (s, 1H, ＝CHO- CH3), 7.70 (d, J＝8.8 Hz, 2H, ArH), 8.31 (s, 1H, Ar- CH＝); MS (70 eV) m/z (%): 457 ([M＋1]＋, 4), 456 (M＋, 3), 167 (29), 165 (70), 160 (23), 146 (19), 144 (100), 130 (37), 116 (19), 114 (53), 102 (54), 101 (33). Anal. calcd for
C22H21ClN4O3S: C 57.83, H 4.63, N 12.26, S 7.02; found C 58.05, H 4.46, N 12.09, S 7.23.
5h: 无色晶体, 收率79%, m.p. 75～77 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.41 (s, 3H, ArCH3), 2.51 (s, 3H, Het-CH3), 3.61 (s, 3H, COOCH3), 3.76 (s, 3H, ＝CHO- CH3), 4.42 (s, 2H, CH2), 7.12 (dd, J＝1.6, 6.8 Hz, 1H, ArH), 7.24～7.44 (m, 5H, ArH), 7.52～7.58 (m, 3H, ＝CHOCH3, ArH), 8.30 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 437 ([M＋1]＋, 1), 436 (M＋, 6), 359 (10), 205 (12), 146 (25), 144 (100), 130 (20), 116 (20), 114 (43), 102 (27), 101 (11). Anal. calcd for C23H24N4O3S: C 63.28, H 5.54, N 12.83, S 7.35; found C 63.17, H 5.61, N 12.69, S 7.33.
5i: 无色晶体, 收率79%, m.p. 158～160 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.56 (s, 3H, Het-CH3), 3.63 (s,
3H, COOCH3), 3.80 (s, 3H, ＝CHOCH3), 4.49 (s, 2H, CH2), 7.12 (t, J＝4.6 Hz, 1H, ArH), 7.23～7.27 (m, 2H, ArH), 7.38～7.42 (m, 2H, ArH), 7.49～7.55 (m, 2H, ＝CHOCH, ArH), 7.64 (t, J＝3.8 Hz, 1H, ArH), 8.09 (dd,
J＝2.4, 7.2 Hz, 1H, ArH), 8.30 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 502 ([M＋1]＋, 4), 501 (M＋, 3), 260 (42), 204(36), 146 (25), 144 (100), 130 (27), 127 (33), 114 (69), 102 (27), 58 (21). Anal. calcd for C22H21BrN4O3S: C 52.70, H 4.22, N 11.17, S 6.40; found C 52.93, H 4.20, N 11.31, S 6.67.
5j: 无色晶体, 收率87%, m.p. 118～120 ;
℃1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J＝7.6 Hz, 3H, CH2CH3), 2.52 (s, 3H, Het-CH3), 2.73 (dd, J＝7.4, 14.8 Hz, 2H, CH2CH3), 3.61 (s, 3H, COOCH3), 3.76 (s, 3H, ＝CHOCH3), 4.43 (s, 2H, CH2), 7.12 (d, J＝6.8 Hz, 1H, ArH), 7.25～7.31 (m, 4H, ArH), 7.42 (d, J＝7.2 Hz, 1H, ArH), 7.54 (s, 1H, ＝CHOCH3), 7.69 (d, J＝6.8 Hz, 2H, ArH), 8.30 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 451 ([M＋1]＋, 3), 450 (M＋, 4), 205 (12), 146 (28), 144 (100), 130 (25), 116 (22), 114 (40), 102 (19), 101 (10). Anal. calcd for C24H26N4O3S: C 63.98, H 5.82, N 12.44, S 7.12; found C 63.94, H 5.86, N 12.65, S 7.39.
5k: 无色晶体, 收率81%, m.p. 83～85 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.31 (s, 3H, ArCH3), 2.33 (s, 3H, ArCH3), 2.50 (s, 3H, Het-CH3), 3.61 (s, 3H, COOCH3),
3.75 (s, 3H, ＝CHOCH3),
4.41 (s, 2H, CH2), 7.12 (d, J＝
1.6 Hz, 1H, ArH), 7.21～7.28 (m, 3H, ArH), 7.42～7.52 (m, 3H, ArH), 7.54 (s, 1H, ＝CHOCH3), 8.26 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 451 ([M＋1]＋, 5), 450 (M＋, 9), 373 (15), 146 (29), 144 (100), 131 (19), 130 (41),
116 (21), 115 (29), 114 (55), 102 (31), 101 (13). Anal. calcd for C24H26N4O3S: C 63.98, H 5.82, N 12.44, S 7.12; found C 63.75, H 5.93, N 12.23, S 7.16.
5l: 无色晶体, 收率76%, m.p. 148～150 ;
℃1H NMR (400 MHz, CDCl3) δ: 1.35 (s, 9H, 3×CH3), 2.50 (s,
3H, Het-CH3), 3.61 (s, 3H, COOCH3), 3.75 (s, 3H, ＝CHOCH3), 4.41 (s, 2H, CH2), 7.12 (dd, J＝1.2, 7.2 Hz,
2H, ArH), 7.23～7.31 (m, 2H, ArH), 7.42 (t, J＝2.0 Hz,
1H, ArH), 7.50 (d, J＝8.8 Hz, 1H, ArH), 7.53 (s, 1H, ＝CHOCH3), 7.70 (d, J＝8.4 Hz, 2H, ArH), 8.27 (s, 1H, ArCH＝); MS (70 eV) m/z (%): 480 ([M＋2]＋, 4), 478 (M＋, 16), 401 (22), 159 (21), 146 (39), 144 (100), 143 (59), 130 (31), 115 (38), 114 (62), 102 (28), 101 (14). Anal. calcd for C26H30N4O3S: C 65.25, H 6.32, N 11.71, S
6.70; found C 65.37, H 6.01, N 11.53, S 6.46.
5m: 无色晶体, 收率85%, m.p. 122～124 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.52 (s, 3H, Het-CH3), 3.62 (s,
3H, COOCH3), 3.77 (s, 3H, ＝CHOCH3), 4.40 (s, 2H,
CH2), 7.15 (d, J＝1.6 Hz, 1H, ArH), 7.25～7.36 (m, 3H, ArH), 7.40 (dd, J＝1.6, 7.6 Hz, 1H, ArH), 7.54 (s, 1H,
＝CHOCH3), 7.66 (dd, J＝1.6, 8.8 Hz, 1H, ArH), 7.91 (d,
J＝1.6 Hz, 2H, ArH), 8.27 (s, 1H, ArCH＝); MS (70 eV)
m/z (%): 502 ([M＋1]＋, 21), 501 (M＋, 12), 425 (29), 423 (26), 157 (26), 155 (25), 146 (38), 144 (100), 131 (39), 115 (73), 103 (64), 102 (48). Anal. calcd for C22H21BrN4O3S: C 52.70, H 4.22, N 11.17, S 6.40; found C 52.76, H 4.31, N 11.17, S 6.56.
5n: 淡黄色晶体, 收率75%, m.p. 145～147 ;
℃1H NMR (400 MHz, CDCl3) δ: 2.45 (s, 3H, Het-CH3), 3.08 (s,
No. 5
赵培亮等：含1,2,4-三唑杂环的新型Strobilurins 衍生物的合成及杀菌活性
879
6H, 2×CH 3), 3.61 (s, 3H, COOCH 3), 3.75 (s, 3H, ＝CHOCH 3), 4.40 (s, 2H, CH 2), 6.68 (d, J ＝8.8 Hz, 2H, ArH), 7.11 (dd, J ＝1.6, 7.2 Hz, 1H, ArH), 7.24～7.28 (m, 2H, ArH), 7.43 (dd, J ＝1.6, 7.6 Hz, 1H, ArH), 7.53 (s, 1H,＝CHOCH 3), 7.63 (d, J ＝8.8 Hz, 2H, ArH), 8.08 (s, 1H, ArCH ＝); MS (70 eV) m /z (%): 465 (M ＋, 7), 147 (27), 146 (92), 144 (100), 131 (12), 130 (15), 117 (11), 114 (19), 102 (11). Anal. calcd for C 24H 27N 5O 3S: C 61.92, H 5.85, N 15.04, S 6.89; found C 61.93, H 5.79, N 15.29, S 7.02. 1.4 化合物5i 的晶体结构测定
化合物5i 从丙酮中培养得到无色透明单晶, 选取化合物5i 尺寸为0.30 mm ×0.20 mm ×0.10 mm 的无色晶体放置在X 射线单晶衍射仪上, 测定温度为20 ℃, 采用石墨单色化的Mo K α (λ＝0.071073 nm)射线, 以ω/2θ 扫描方式在2.14°＜θ＜28.23°范围内共收集到5293个独立衍射点, 其中I ＞2σ(I )的可观测衍射点3215个. 收集的衍射数据使用SAINT 软件进行还原, 经验吸收校正在SADAB 程序上进行(T min ＝0.5920; T max ＝0.8287). 晶体结构采用直接法使用SHELXL-97程序解出, 对F 2进行全矩阵最小二乘法修正. 所有的非氢原子经各向异性修正. 氢原子被几何固定, 并置于所联结的相应原子上. 最终的偏离因子为R ＝0.0824, wR ＝0.1233, 差值电子云密度的最高和最低峰为738和－433 e•nm －3
.
2 结果与讨论
2.1 合成
亚胺席夫碱的合成通常用相应的醛与氨基化合物在醇中回流反应或通过分水的方法而得. 由于化合物2在乙醇中溶解性较差, 与醛难以反应. 加入少量的冰乙酸能明显改善化合物2的溶解性, 同时也提供适宜的酸度, 使亚胺中间体3得以顺利生成. 从亚胺碳氢化学位移单峰可表明, 席夫碱亚胺双键只存在一种几何异构, 从稳定的趋向判断取代基应处于反式E-式构型, 说明2与取代苯甲醛的缩合进程受热力学控制. 选用NaOH 水溶液做碱, 使3-巯基-5-甲基-4-芳基亚胺基-4H-1,2,4-三唑(3)生成巯基负离子, 能很好地与卤化苄发生亲核取代反应生成目标化合物. 而且随着反应进行, 不溶于水的目标化合物会不断以沉淀形式析出, 简化了实验操作, 同时也大大减少了有机溶剂的使用量. 2.2 化合物5i 的晶体结构分析
化合物5i 晶体属于单斜晶系,空间群为P 2(1)/c , 晶胞参数a ＝1.4765(2) nm, b ＝0.80087(13) nm, c ＝1.9700(3) nm, α＝90(2)°, β＝105.164(3)°, γ＝90°. V ＝
2.2483(6) nm 3, Z ＝4, D c ＝1.481 g/cm 3, µ＝1.952 mm －
1,
F (000)＝1024, R ＝0.0824, wR ＝0.1233. 图1是化合物5i 的分子结构图. 晶体结构分析表明：亚胺双键呈E -式构型, N(2)—N(1)—C(7)—C(1)的扭转角为176.51(2)°; 而丙烯酸甲酯中双键也呈E -式构型, C(19)—C(18)— C(21)—O(3)的扭转角为
179.75(2)°.
图1 化合物5i 的分子结构
Figure 1 Molecular structure of compound 5i
晶体结构中存在3个分子间氢键: C(4)—H(4) 0.093 nm, H(4)—N(4) 0.261 nm, C(4)—N(4) 0.3369(4) nm, N —H —O 键角为139.0°; C(7)—H(7) 0.093 nm, H(7)—N(3) 0.261 nm, C(7)—N(3) 0.3383(4) nm, N —H —O 键角为141.0°; C(14)—H(14) 0.093 nm, H(14)—0(2) 0.252 nm, C(14)—O (2) 0.3407(4) nm, N —H —O 键角为158.7°. 分子间通过氢键相互作用形成一维有序的链状结构, 在此基础上通过C —H …π和π…π共轭相互作用, 进行二维和三维的空间排列. C(20)与苯环[C(12)～C(17)]中心距离为0.3486(6) nm. 苯环[C(1)—C(6)]与相邻晶体分子中的苯环[C(1)—C(6)]中心距离为0.36042(18) nm 2.3 生物活性
由国家南方农药创制中心浙江基地采用活体盆栽法对目标化合物进行了室内生物活性测定. 抑菌活性测试靶标为温室培养的黄瓜霜霉病(Pseudoperonospora cubensis )、黄瓜白粉病(Sphaerotheca fuliginea )、黄瓜灰霉病(Botrytis cinerea )和水稻纹枯病(Rhizoctonia solani ), 普筛浓度为200 mg/L. 测试结果见表1.
杀菌活性测试表明, 所有目标化合物对黄瓜灰霉病菌均没有表现出抑制活性, 而大部分化合物对黄瓜霜霉病菌、黄瓜白粉病菌、水稻纹枯病菌具有一定的抑菌活性, 其中化合物5e 对黄瓜霜霉病菌, 5n 对黄瓜白粉病菌的抑制活性均超过50%.
880有机化学V ol. 28, 2008
表1化合物5a～5n的杀菌活性(抑制率/%)
Table 1 Fungicidal activities of compounds (inhibitory ratio/%)
5a～5n
Compd. 黄瓜霜霉病黄瓜白粉病黄瓜灰霉病水稻纹枯病
5a 33.33 15.47 0 11.26
5b 0 0 0 15.74 5c 42.67 12.62 0 0
5d 0 0 0 22.58 5e 61.11 10.53 0 0
5f 0 15.47 0 6.79 5g 16.94 0 0 0
5h 13.35 0 0 10.25 5i 0 22.22 0 30.64 5j 0 6.79 0 43.55 5k 12.63 44.38 0 0
5l 16.48 22.22 0 6.45
5m 0 6.79 0 0 5n 26.58 66.67 0 0
醚菌酯 100 100 ——
致谢本实验中化合物生物活性的测试由国家南方农
药创制中心浙江基地陈杰博士提供帮助, 在此表示衷心
感谢!
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