微波促进下2_芳氧甲基苯并咪唑_1_乙酸衍生物的合成及生物活性研究_图文

1、2007年第27卷有机化学V ol. 27, 2007第9期, 11161120 Chinese Journal of Organic Chemistry No. 9, 11161120 * E-mail: zhangnwnuReceived December 11, 2006; revised and accepted March 30, 2007.国家自然科学基金(No. 20671077、教育部科学技术研究重点(No. 205161、甘肃省自然科学基金(No. 3ZS061-A25-027、甘肃省中青年科技研究基金(No. 3YS051-A25-010、甘肃省教育厅研究生导师科研(No.

2、 0601-24资助项目.No. 9魏太保等:微波促进下2-芳氧甲基苯并咪唑-1-乙酸衍生物的合成及生物活性研究1117 R = 3a : H, 3b : o -CH 3, 3c : m -CH 3, 3d : p -CH 3, 3e : p -Cl, 3f : o -Cl, 3g : p -OCH 3, 3h : o -NO 2, 3i : m -NO 2, 3j : p -NO 2Scheme 11 实验部分1.1 仪器和试剂X-4型显微熔点仪(温度计未校正; WP 750B 型家用微波炉; Digilab FTS-3000 型红外光谱仪(KBr 压片; Varian Mercury pl

3、us-400 MHz 型核磁共振仪; PE-2400 C H N 元素分析仪. 所用试剂均为市售分析纯. 1.2 化合物的合成 1.2.1 原料的合成化合物1a 1j 的合成依照文献8中报道的方法. 化合物2a 2j 的合成依照文献9中报道的方法. 1.2.2 目标化合物3a 3j 的合成以3a 为例, 将2-苯氧甲基苯并咪唑(5 mmol, 1.12 g, 氯乙酸甲酯(5 mmol, 0.54 g和无水K 2CO 3 (5 mmol, 0.70 g在100 mL 圆底烧瓶中混和均匀, 再加入PEG-400 (1 mL和二甲基甲酰胺(23 mL搅拌均匀后, 置于装有回流冷凝管的家用微波炉中,

4、300 W 下间歇辐射约5 min. 然后加入2 mol/L NaOH 调至550 W 下间歇辐射57 min; 冷却至室温后, 加稀盐酸酸化至 pH =45时析出大量沉淀. 抽滤、EtOH/H 2O 重结晶得纯品.化合物3a 3j 的熔点、红外光谱、元素分析及核磁共振氢谱、碳谱的数据如下:3a : 浅黄色晶体, 产率88.65%, m.p. 212214 ;1H NMR (DMSO-d 6, 400 MHz : 13.24 (s, 1H, COOH,7.706.95 (m, 9H, ArH, 5.41 (s, 2H, CH 2O, 5.20 (s, 2H, NCH 2;13C NMR (DM

5、SO-d 6, 100 MHz : 169.50,157.79, 149.84, 141.86, 136.07, 129.57, 123.03, 122.07, 121.39, 119.34, 114.86, 110.64, 62.77, 45.09; IR (KBr : 1703.02 (C =O; 1593.85, 1533.41, 1482.23 (C =N, C =C; 1150.49, 1081.70, 1033.84 (Ar O C cm -1. Anal. calcd for C 16H 14N 2O 3: C 68.08, H 5.00, N 9.92; found 68.24

6、, H 4.86, N 10.01.3b : 白色晶体, 产率82.75%, m.p. 222224 ; 1HNMR (DMSO-d 6, 400 MHz : 13.24 (s, 1H, COOH, 7.716.85 (m, 8H, ArH, 5.40 (s, 2H, CH 2O, 5.20 (s, 2H, NCH 2, 2.15 (s, 3H, CH 3; 13C NMR (DMSO-d 6, 100 MHz : 169.38, 155.89, 149.86, 141.86, 136.05, 130.60, 126.93, 126.00, 122.97, 122.02, 120.91, 11

7、9.33, 111.58, 110.69, 62.68, 44.98; IR (KBr : 1718.57 (C =O; 1597.29, 1491.73, 1452.48 (C =N, C =C; 1187.99, 1121.85, 1036.03 (Ar O C cm -1. Anal. calcd for C 17H 16N 2O 3: C 68.91, H 5.44, N 9.45; found C 69.17, H 5.30, N 9.58.3c : 白色针状色晶体, 产率87.84%, m.p. 209211 ; 1H NMR (DMSO-d 6, 400 MHz : 13.17

8、(s, 1H, COOH, 7.686.78 (m, 8H, ArH, 5.35 (s, 2H, CH 2O, 5.16 (s, 2H, NCH 2, 2.28 (s, 3H, CH 3;13C NMR(DMSO-d 6, 100 MHz : 169.38, 157.74, 149.78, 141.62, 139.00, 136.00, 129.22, 122.88, 122.06, 121.93, 119.25, 115.46, 111.69, 110.54, 62.68, 44.95; IR (KBr : 1728.22 (C =O; 1610.30, 1517.97, 1483.72 (

9、C =N, C =C; 1217.31, 1162.34, 1050.90 (Ar O C cm -1. Anal. calcdfor C 17H 16N 2O 3: C 68.91, H 5.44, N 9.45; found C 68.75,H 5.41, N 9.50. 3d : 白色针状色晶体, 产率94.59%, m.p. 215 217 ; 1H NMR (DMSO-d 6, 400 MHz : 13.11 (s, 1H, COOH, 7.576.95 (m, 8H, ArH, 5.35 (s, 2H, CH 2O, 5.17 (s, 2H, NCH 2, 2.22 (s, 3H,

10、 CH 3; 13C NMR (DMSO- d 6, 100 MHz : 169.41, 155.65, 149.89, 141.64, 136.03, 130.10, 129.82, 122.90, 121.96, 119.27, 114.70, 110.57, 62.88, 45.00; IR (KBr : 1703.14 (C =O; 1624.08, 1512.37, 1458.52 (C =N, C =C; 1177.38, 1112.91, 1040.93 (Ar O C cm -1. Anal. calcd for C 17H 16N 2O 3: C 68.91, H 5.44,

11、 N 9.45; found C 68.68, H 5.28, N 9.37.3e : 白色粉末, 产率88.61%, m.p. 229231 ; 1H NMR (DMSO-d 6, 400 MHz : 13.23 (s, 1H, COOH, 7.697.06 (m, 8H, ArH, 5.42 (s, 2H, CH 2O, 5.19 (s, 2H,1118有机化学V ol. 27, 2007NCH2, 2.50 (s, 3H, CH3; 13C NMR (DMSO-d6, 100 MHz : 169.42, 156.58, 149.45, 141.62, 136.00, 129.24, 12

12、5.10, 123.00, 122.03, 119.32, 116.64, 110.60, 63.03, 45.00; IR (KBr : 1714.90 (C=O; 1597.06, 1488.93, 1453.72 (C=N, C=C; 1180.51, 1093.64, 1019.56 (ArOC; 683.64 (ArCl cm-1. Anal. calcd for C16H13- N2O3Cl: C 60.67, H 4.14, N 8.84; found C 60.43, H 4.36, N 8.55.3f: 白色粉末, 产率82.28%, m.p. 207209 ; 1H NMR

13、 (DMSO-d6, 400 MHz : 13.74 (s, 1H, COOH, 7.706.96 (m, 8H, ArH, 5.49 (s, 2H, CH2O, 5.24 (s, 2H, NCH2; 13C NMR (DMSO-d6, 100 MHz : 169.21, 153.05, 149.17, 141.62, 135.98, 130.04, 128.23, 123.08, 122.29, 122.10, 121.61, 119.37, 114.47, 110.69, 63.49, 44.92; IR (KBr : 1722.43 (C=O; 1591.37, 1519.90, 148

14、3.60 (C=N , C=C; 1163.84, 1135.03, 1061.24 (ArOC cm-1. Anal. calcd for C16H13N2O3Cl: C 60.67, H 4.14, N 8.84; found C 60.39, H 4.27, N 8.57.3g: 白色粉末, 产率94.94%, m.p. 209211 ; 1H NMR (DMSO-d6, 400 MHz : 13.16 (s, 1H, COOH, 7.686.85 (m, 8H, ArH, 5.19 (s, 2H, CH2O, 5.12 (s, 2H, NCH2, 3.68 (s, 3H, OCH3;

15、13C NMR (DMSO-d6, 100 MHz : 169.50, 154.06, 151.78, 150.06, 141.64, 136.09, 123.08, 122.13, 119.34, 115.98, 114.69, 110.66, 63.47, 55.48; IR (KBr : 1721.14 (C=O; 1627.92, 1508.42, 1470.10 (C=N, C=C; 1230.89, 1110.71, 1037.24 (ArOC; 686.27 (ArCl cm-1. Anal. calcd for C17H16- N2O4: C 65.38, H 5.16, N

16、8.97; found C 65.59, H 5.42, N 8.84.3h: 棕色晶体, 产率, 85.37%, m.p. 235237 ; 1H NMR (DMSO-d6, 400 MHz : 13.21 (s, 1H, COOH, 7.927.13 (m, 8H, ArH, 5.62 (s, 2H, CH2O, 5.23 (s, 2H, NCH2; 13C NMR (DMSO-d6, 100 MHz : 169.20, 150.49, 148.69, 141.64, 139.41, 135.91, 134.47, 125.21, 123.17, 122.16, 121.30, 119.4

17、4, 115.59, 110.72, 63.73, 44.80; IR (KBr : 1724.25 (C=O; 1609.29, 1525.92, 1479.75 (C=N, C=C; 1168.86, 1088.15, 1014.55 (ArOC cm-1. Anal. calcd for C16H13N3O5: C 58.72, H 4.00, N 12.84; found C 58.57, H 4.23, N 12.55.3i: 浅灰色粉末, 产率79.27%, m.p. 239241 ; 1H NMR (DMSO-d6, 400 MHz : 13.28 (s, 1H, COOH, 7

18、.967.20 (m, 8H, ArH, 5.59 (s, 2H, CH2O, 5.23 (s, 2H, NCH2; 13C NMR (DMSO-d6, 100 MHz : 169.52, 158.23, 149.04, 148.63, 141.65, 136.00, 130.68, 123.09, 122.07, 122.02, 119.39, 116.19, 110.63, 109.57, 63.25, 45.01; IR (KBr : 1719.86 (C=O; 1622.21, 1527.26, 1474.18 (C=N, C=C; 1236.37, 1103.04, 1016.97

19、(ArOC cm-1. Anal. calcd for C16H13N3O5: C 58.72, H 4.00, N 12.84; found C 58.61, H 4.18, N 12.63.3j: 白色粉末, 产率91.46%, m.p. 263265 ; 1H NMR (DMSO-d6, 400 MHz : 13.28 (s, 1H, COOH, 8.307.21 (m, 8H, ArH, 5.61 (s, 2H, CH2O, 5.23 (s, 2H, NCH2; 13C NMR (DMSO-d6, 100 MHz : 169.47, 162.93, 148.86, 141.63, 14

20、1.38, 135.99, 125.80, 123.14, 122.13, 119.40, 115.44, 110.66, 63.33, 45.00; IR (KBr : 1715.17 (C=O; 1593.17, 1510.26, 1471.15 (C=N, C= C; 1180.51, 1112.46, 1016.50 (ArOC cm-1. Anal. calcd for C16H13N3O5: C 58.72, H 4.00, N 12.84; found C 58.83, H 3.88, N 12.59.2 结果和讨论2.1 波谱分析从化合物3a3j的红外光谱可以发现在1703 1

21、729 cm-1之间出现C=O的强吸收特征峰, 在氢谱中, COOH中活泼氢吸收峰明显, 化学位移均在低场, 基本上在13.1113.74之间, 这是由于形成了分子内氢键所致, 两个亚甲基CH2O和NCH2的化学位移也出现在较低场. 从碳谱可以看出各种碳的出峰位置比较明显, 由于苯环上存在对称碳, 所以碳的出峰数比分子式中碳原子数目要少.2.2 反应条件与产率的关系为了优化反应条件, 我们考察了微波功率对反应产率的影响, 以化合物3a为例, 讨论结果见表1.表1 微波辐射功率对产率的影响Table 1 Power effect of microwave irradiation on the y

22、ieldsP1a/W200250300350 300 300 300300P2b/W550550550550 450 500 550600 Yield/%60.9864.0288.6579.22 73.17 70.1288.6570.12 a N-烷化反应阶段的功率; b水解反应阶段的功率.表1结果表明, 化合物3a不论在N-烷化反应还是水解反应阶段, 在微波功率较低时产率随功率的增大而提高; 但当功率增大到一定程度后, 随着功率的增大又开始下降, 最佳功率为300和500 W.为了得到最佳反应条件, 我们还考察了溶剂对该反应产率的影响. 同样以化合物3a为例, 实验结果见表2.从表2我们看出

23、该反应在DMF和DMSO中产率最高, 而在H2O, EtOH和CH3CN等溶剂中产率较低. 这主要是因为DMF和DMSO为强极性非质子溶剂, 不仅有No. 9 魏太保等:微波促进下2-芳氧甲基苯并咪唑-1-乙酸衍生物的合成及生物活性研究1119利于微波吸收, 而且有利于亲核反应的进行. 在本反应中我们选用DMF作溶剂以较高的产率得到了目标化合物.2.3 生物活性将该系列化合物分别配成100, 10, 1, 0.1, 0.01和0.001 mg/L浓度的溶液. 采用平皿培养法研究对小麦宁春5号幼苗根系和芽的生长调节作用, 用蒸馏水作空白实验, 相同浓度的吲哚乙酸溶液作为标准对照. 室温生长5 d

24、测量小麦根系和芽的长度, 用下面公式计算该系列化合物在各个浓度下对小麦幼苗根系和芽的生长调节活性: A=(N-N0/N0×100%, 其中: A为样品生物活性, N为溶液中小麦根和芽的生长长度, N0为蒸馏水中小麦根和芽的生长长度. 计算结果列于表3.表3实验结果表明该系列化合物对单子叶植物小麦幼苗根系和芽在低浓度多数都具有较小的抑制作用, 在高浓度具有较强的抑制作用, 但化合物3c, 3f和3j在0.01 mg/L时对芽具有较好的促进活性, 3h, 3i和3j在0.1 mg/L时对根具有较好的促进活性, 且优于吲哚乙酸.表2 溶剂对产率的影响Table 2 Effect of so

25、lvent on the yieldsSolvent DMF DMSO CH3COOEt CH3COCH3 CH3CN EtOH H2OYield/% 88.65 90.23 48.78 48.7842.6836.5923.53表3植物生长调节活性数据Table 3 The data of plant growth regulating activityc/(mgL-1 Idaa c3a 3b 3c 3d 3e 3f 3g 3h 3i 3j0.001 -12.4 -3.1 0.2 -3.3-3.6-7.0 5.3 -17.7 -2.3 -17.2-2.40.01 -2.0 -1.2 -5.4

26、2.3 -1.5-1.28.2 -5.1 -6.6 -11.9 1.00.1 -1.8 -9.2 -0.1 -1.2 1.6 -2.6-9.0-12.4 -1.6 -2.9 1.51 -38.3 -8.4 -0.8 -9.1-3.1-6.9-2.80.5 -0.8 -25.1 5.410 -55.9 -39.3 4.3 9.5 -0.6-7.0 2.4 -42.1 -40.9 -50.1-50.6bs a100 -100 -100 -21.1 -53.8-19.6-53.6-44.7-87.4 -100 -100-1000.001 -30.0 14.4 -26.5 0.2 -5.1-6.4-1

27、.6-7.8 -4.3 -1 -5.4 17.2 3.0 3.2 -7.50.2 1.6 4.6 3.7 - 8.25.3-11.6 -11.9-0.4-3.7-15.2-16.8 21.4 9.7 16.11 -67.0 10.7 -8.2 -14.4-0.4-3.3 2.5 15.8 2.4 -40.79.410 -88.0 -32.6 -6.3 -7.7-10.3-10.4-10.6-23.0 -44.3 -49.2-60.2br b100 -100 -100 -33.6 -68.6-47.1-64.9-44.6-87.4 -100 -100-100a

28、化合物3a3j对小麦芽的生物活性; b化合物3a3j对小麦根的生物活性; c Idaa代表吲哚乙酸.References1 Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.2003, 103, 893.2 Miao, Z.-W.; Zhou, W.-H.; Liu, X.-L.; Miao, F.-M. Chin. J.Org. Chem. 1999, 19, 537 (in Chinese.(苗志伟, 周卫红, 刘小兰, 缪方明, 有机化学, 1999, 19, 537.3 Bei, F.-L.; Chen, H.-Q.; Yang

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