噁唑是含有氮、氧原子的五元芳香性杂环.含噁唑环化合物在农药和医药领域具有杀虫[1]、除草[2]、杀菌[3]、抗癌[4]等活性.如Wang等[5]研制的化合物A(图 1)在测试剂量为50 mg/L时对粘虫的杀灭活性为70%, Shen课题组[6]研究发现化合物B(图 1)在测试剂量为500 μg/mL时对粘虫、蚜虫和螨虫均有100%的杀灭效果; Fu等[7]报道的化合物C(图 1)在测试剂量为20 mg/kg时对玉米植株鲜重的恢复效果为95.45%.吡唑酰胺作为含氮杂环体系中的重要一员, 在农业生产与医疗保健方面扮演着重要的角色, 在杀虫、杀菌、除草及抗癌等领域[8~14]有着广泛的应用, 如日本三菱化学公司相继研制出的吡螨胺(Tebufenpyrad)与唑虫酰胺(Tolfenpyrad)(图 1), 它们常常被用于防治附线螨、小菜蛾等害虫[15, 16].近年来, 一些科研工作者在此基础上衍生制备出了许多具有新颖结构的吡唑酰胺衍生物.如美国杜邦公司成功开发的氯虫苯甲酰胺(Chlorantraniliprole, 图 1)有杀虫谱广、毒性低等特点, 对粘虫和小菜蛾等害虫都表现出良好的杀虫作用[17]; Kang等[18]基于氯虫苯甲酰胺的结构制备出的化合物D(图 1)对小菜蛾呈现优异的杀灭活性, 其LC50值为2.04 μg/mL; Zhu等[19]报道的化合物E(图 1)对粘虫显示出良好的杀虫效果; Wang课题组[20]研发的化合物F(图 1)表现出较好的杀虫和杀菌活性, 化合物F在200 μg/mL测试剂量下对粘虫的杀灭活性为100%, 在50 μg/mL测试剂量下对苹果轮纹病菌的抑制效果达89.7%.因此, 本课题组基于商品化的杀虫剂氯虫苯甲酰胺的结构, 将取代噁唑环通过亚甲基桥引入吡唑酰胺分子结构中, 设计合成了一系列新颖的吡唑酰胺化合物(图 2), 同时测试了目标产物的杀虫活性, 生物活性测试结果显示, 部分目标化合物呈现出较好的杀虫作用.目标化合物的合成路线见Scheme 1.
11a: R = 3-F, 11b: R = 2-Cl, 11c: R = 3-Cl, 11d: R = 4-Cl, 11e: R = 3-Br, 11f: R = 4-Br; 11g: R = 2-CF3, 11h: R = 4-CF3, 11i: R = 4-CN, 11j: R1 = 4-CH3, 11k: R = 3-CH3-4-NO2, 11l: R = 3-NO2-4-CH3, 11m: R = 2-F-6-Cl, 11n: R = 2, 4-Cl2; 11o: R = 3, 5-Cl2; 11p: R = 2, 6-F2
在目标化合物11的制备时, 选取取代基为4-Cl的化合物11d为例, 以中间体5d和10为原料, 探索了不同的溶剂和缚酸剂对化合物11d收率的影响(表 1).在试验过程中发现, 当选取二氯甲烷作为反应溶剂, 三乙胺作为缚酸剂, 室温搅拌12 h, 反应转化率相对较佳, 化合物11d收率为70%, 同时后续处理也较为简便.因此, 选用该方法顺利合成了其它目标化合物.
以化合物11a为例, 对其1H NMR和13C NMR数据进行剖析.从化合物11a的1H NMR数据可发现, 噁唑
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| Entry | Base | Solvent | Reaction condition | Yield/% |
| 1 | Pyridine | CH3COCH3 | r.t. for 12 h | 20 |
| 2 | Pyridine | CH2Cl2 | r.t. for 12 h | 61 |
| 3 | Pyridine | THF | r.t. for 12 h | 33 |
| 4 | Pyridine | CH3CN | r.t. for 12 h | 52 |
| 5 | Pyridine | CH2Cl2 | Reflux for 12 h | 56 |
| 6 | Pyridine | CH3CN | Reflux for 12 h | 45 |
| 7 | Et3N | CH2Cl2 | r.t. for 12 h | 70 |
| 8 | Et3N | THF | r.t. for 12 h | 43 |
| 9 | Et3N | CH3CN | r.t. for 12 h | 59 |
| 10 | Et3N | CH2Cl2 | Reflux for 12 h | 63 |
| 11 | Et3N | CH3CN | Reflux for 12 h | 50 |
| 12 | K2CO3 | CH2Cl2 | r.t. for 12 h | 12 |
| 13 | KOH | CH2Cl2 | r.t. for 12 h | 0 |
环上的氢在δ 7.62以单峰形式出现, 3-F取代苯环上两个氢在δ 7.80和7.70分别以双重峰形式出现, 3-F取代苯环上其它两个氢在δ 7.48~7.44和7.21~7.16分别以多重峰形式出现, CONH上氢的化学位移在δ 7.05, 取代吡唑环上4-位氢在δ 6.81以单峰形式出现, 与NH相连的CH2两个氢在δ 4.45以双重峰形式出现; 从化合物11a的13C NMR数据数据可知, 酰胺键上羰基碳原子的δ值为164.1, 吡唑环上的4-位碳原子的δ值为110.1, 与噁唑环相连的亚甲基碳原子的δ值为35.3.
采用浸叶法[21]测试了化合物11a~11p对粘虫(Mythimna separata)的杀虫活性, 同时利用喷雾法[22]测试了化合物11a~11p对朱砂叶螨(Tetranychus cinnabar- rinus)与苜蓿蚜(Aphis craccivora)的杀虫活性, 其相关数据如表 2所示.
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| Compd. | Mythimna separata | Aphis craccivora | Tetranychus cinnabarinus | |||||||
| 500 μg/mL | 100 μg/mL | 20 μg/mL | 500 μg/mL | 100 μg/mL | 20 μg/mL | 500 μg/mL | 100 μg/mL | |||
| 11a | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11b | 100 | 0 | - | 100 | 90 | 30 | 0 | - | ||
| 11c | 100 | 0 | - | 0 | - | 0 | - | |||
| 11d | 100 | 100 | 30 | 0 | - | - | 0 | - | ||
| 11e | 90 | 0 | - | 0 | - | - | 0 | - | ||
| 11f | 100 | 100 | 40 | 0 | - | - | 0 | - | ||
| 11g | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11h | 100 | 100 | 50 | 100 | 100 | 30 | 100 | 0 | ||
| 11i | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11j | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11k | 100 | 100 | 40 | 100 | 100 | 20 | 80 | 0 | ||
| 11l | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11m | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11n | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11o | 100 | 90 | 0 | 0 | - | - | 0 | - | ||
| 11p | 100 | 0 | - | 0 | - | - | 0 | - | ||
| Tolfenpyrad | 100 | 50 | 40 | - | - | - | - | - | ||
| Imidacloprid | - | - | - | 100 | 100 | 100 | - | - | ||
| Fenpyroximate | - | - | - | - | - | - | 100 | 100 | ||
| a - refers to “not tested”. | ||||||||||
化合物11a~11p在500 μg/mL时对粘虫都显示出优异的杀虫作用, 化合物11a~11p对粘虫的杀死率为90%~100%, 与对照药唑虫酰胺的杀虫效果相接近.部分化合物在100 μg/mL时对粘虫的杀死率均在90%以上, 通过构效关系分析不难发现, 当在苯环上引入氯、溴原子或三氟甲基基团时, 其对位取代物对粘虫的杀虫活性要优于邻位或间位的杀虫效果, 如取代基R为4-Cl的化合物11d对粘虫的杀死率为100%, 明显高于取代基R为2-Cl的化合物11b和3-Cl的化合物11c的药效, 当苯环对位含有吸电子基团如氯、溴原子、三氟甲基或硝基基团时, 化合物11d、11f、11h和11k对粘虫的杀虫活性比苯环对位含有给电子基团甲基的化合物11j和11l要好.在浓度降至20 μg/mL时, 化合物11d、11f、11h和11k对粘虫仍有30%~50%的杀虫活性, 接近于对照药剂唑虫酰胺的杀虫效果.同时, 化合物11b、11h和11k在500和100 μg/mL浓度下对苜蓿蚜的杀死率均超过90%, 与对照药剂吡虫啉的杀虫活性相当, 当浓度降为20 μg/mL时, 化合物11b、11h和11k对苜蓿蚜还显示出20%~30%的杀虫作用, 明显优于其它目标化合物.此外, 化合物11h和11k在500 μg/mL时对朱砂叶螨具有100%和80%的杀虫效果.从构效关系分析也能看出, 目标化合物11h (R=4-CF3)和11k (R=3-CH3-4- NO2)有广谱的杀虫活性, 对所测定的害虫均显示出较好的杀虫效果, 可作为杀虫先导做进一步的结构优化与杀虫活性研究.
本研究合成出了16个含噁唑单元的新型吡唑酰胺类化合物.试验结果表明, 所有化合物在浓度为500 μg/mL时对粘虫的杀死率在90%~100%, 在100 μg/mL浓度下化合物11d、11f、11h、11k和11o对粘虫的杀虫活性大于90%;化合物11b、11h和11k在100 μg/mL时对苜蓿蚜具有90%以上的杀虫效果, 在20 μg/mL时活性不明显; 化合物11h和11k在500 μg/mL时朱砂叶螨的杀虫活性分别为100%和80%.本文为今后继续从事吡唑酰胺类杀虫剂的创制提供了重要的试验数据.
1H NMR和13C NMR的数据经BRUKER 400 MHz核磁共振仪(TMS为内标)测定; 熔点由X-4显微熔点测定仪(温度计未经校正)测试; 元素分析利用Yanaco- CHN CORDER MT-3自动元素分析仪测定.所用试剂都是分析纯.
化合物1~2的合成参照文献[23], 化合物6~10的合成参照文献[24]和[25].
将中间体2 (0.05 mol)及1, 3-二氯丙酮(0.09 mol)加入一反应瓶中, 加完后, 升温至130 ℃, 反应6~9 h.反应完成后, 将反应液冷却至室温, 向其加入100 mL水, 用氯仿萃取数次, 有机层经干燥、过滤、浓缩得到中间体3, 直接用于下一步的反应.
为验证化合物3的结构, 以取代基R为2, 4-Cl2的化合物作为代表, 通过柱层析分离[V(乙酸乙酯):V(石油醚)=1:6]得白色固体, 产率65%. m.p. 61~63 ℃; 1H NMR (CDCl3, 400 MHz) δ: 7.94 (d, J=8.80 Hz, 1H), 7.78 (s, 1H), 7.51 (d, J=2.02 Hz, 1H), 7.35~7.32 (m, 1H), 4.59 (s, 2H); 13C NMR (CDCl3, 101 MHz) δ: 159.4, 139.0, 136.9, 136.8, 133.4, 131.9, 131.0, 127.3, 124.6, 36.9. Anal. calcd for C10H6Cl3NO: C 45.75, H 2.30, N 5.34; found C 45.59, H 2.43, N 5.49.
将中间体3 (20 mmol)、邻苯二甲酰亚胺钾盐(36 mmol)及60 mL N, N-二甲基甲酰胺(DMF)加入反应瓶中, 加完后室温反应12~18 h.反应结束后, 将反应液倒入盛有150 mL水的烧杯中, 静置析出固体, 经抽滤、烘干得中间体4, 不经纯化直接用于后面的反应.
将中间体4 (10 mmol)、80%水合肼(30 mmol)及30 mL无水乙醇加入反应瓶中, 加完后, 加热回流反应6~8 h, 薄层色谱(TLC)跟踪反应的进度.反应完成后, 将反应液冷却至室温, 过滤除去不溶物, 母液旋蒸除去溶剂得到中间体5, 不经提纯化直接投入下一步反应.
将中间体5 (2 mmol)、三乙胺(4 mmol)及20 mL二氯甲烷加入反应瓶中, 冰浴搅拌下向其滴加4 mmol中间体10的二氯甲烷(3 mL)溶液.滴加完毕后室温反应10~18 h.反应结束后过滤, 母液旋蒸除去溶剂, 得到的粗品经柱层析分离[V(乙酸乙酯):V(石油醚)=1:6]得到目标产物11a~11p.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3-氟苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11a):白色固体, 产率63%. m.p. 183~185 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.47 (d, J=3.62 Hz, 1H), 7.90~7.88 (m, 1H), 7.80 (d, J=8.02 Hz, 1H), 7.70 (d, J=9.22 Hz, 1H), 7.62 (s, 1H), 7.48~7.44 (m, 1H), 7.41~7.38 (m, 1H), 7.21~7.16 (m, 1H), 7.05 (s, 1H), 6.81 (s, 1H), 4.45 (d, J=5.22 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 164.1, 161.7, 161.0, 157.5, 148.9, 146.8, 139.2, 137.7, 136.1, 130.7, 129.2, 128.8, 128.0, 125.8, 122.2, 117.8, 113.4, 110.1, 35.3. Anal. calcd for C19H12BrClFN5O2: C 47.87, H 2.54, N 14.69; found C 47.71, H 2.39, N 14.82.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(2-氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11b):黄色固体, 产率62%. m.p. 121~123 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.48~8.46 (m, 1H), 8.00~7.96 (m, 1H), 7.89~7.87 (m, 1H), 7.65 (s, 1H), 7.49~7.19 (m, 5H), 6.80 (s, 1H), 4.46 (d, J=5.62 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 161.2, 158.7, 158.4, 157.5, 148.9, 146.8, 139.2, 137.6, 132.5, 129.5, 129.2, 127.9, 125.8, 124.5, 117.0, 115.3, 110.1, 35.3. Anal. calcd for C19H12BrCl2N5O2: C 46.28, H 2.45, N 14.20; found C 46.40, H 2.30, N 14.09.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3-氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11c):白色固体, 产率65%. m.p. 177~179 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.48~8.46 (m, 1H), 8.02 (s, 1H), 7.93~7.88 (m, 2H), 7.63 (s, 1H), 7.48~7.39 (m, 3H), 6.94 (s, 1H), 6.83 (s, 1H), 4.46 (d, J=5.20 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 160.9, 157.4, 148.9, 146.8, 139.2, 137.5, 136.1, 135.1, 131.0, 130.3, 129.2, 128.2, 128.0, 126.6, 125.8, 124.6, 110.2, 35.2. Anal. calcd for C19H12BrCl2N5O2: C 46.28, H 2.45, N 14.20; found C 46.12, H 2.59, N 14.31.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(4-氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11d):白色固体, 产率70%. m.p. 169~171 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.46 (d, J=3.62 Hz, 1H), 7.95 (d, J=8.81 Hz, 2H), 7.90~7.87 (m, 1H), 7.61 (s, 1H), 7.46 (d, J=8.42 Hz, 2H), 7.41~7.38 (m, 1H), 7.06 (s, 1H), 6.82 (s, 1H), 4.45 (d, J=5.62 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 161.3, 157.4, 148.9, 146.8, 139.2, 139.1, 137.5, 137.2, 135.9, 129.3, 129.2, 128.0, 127.8, 125.8, 125.2, 110.1, 35.2. Anal. calcd for C19H12BrCl2N5O2: C 46.28, H 2.45, N 14.20; found C 46.43, H 2.38, N 14.36.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3-溴苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11e):黄色固体, 产率64%. m.p. 166~168 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.47~8.45 (m, 1H), 8.16 (s, 1H), 7.94~7.88 (m, 2H), 7.62~7.59 (m, 2H), 7.41~7.35 (m, 2H), 7.05 (s, 1H), 6.81 (s, 1H), 4.44 (d, J=5.21 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 160.5, 157.5, 148.9, 146.8, 139.3, 139.1, 137.6, 136.2, 133.9, 130.5, 129.4, 128.5, 128.0, 125.9, 125.0, 123.0, 110.2, 35.2. Anal. calcd for C19H12Br2ClN5O2: C 42.45, H 2.25, N 13.03; found C 42.59, H 2.32, N 13.16.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(4-溴苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11f):白色固体, 产率73%. m.p. 195~197 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.47~8.45 (m, 1H), 7.89~7.87 (m, 3H), 7.63~7.61 (m, 3H), 7.41~7.39 (m, 1H), 7.02 (s, 1H), 6.82 (s, 1H), 4.45 (d, J=5.22 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 161.3, 157.4, 148.9, 146.8, 139.2, 139.0, 137.5, 135.9, 132.2, 129.2, 128.0, 127.9, 125.8, 125.6, 125.5, 110.1, 35.3. Anal. calcd for C19H12Br2ClN5O2: C 42.45, H 2.25, N 13.03; found C 42.28, H 2.12, N 12.88.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(2-三氟甲基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11g):黄色固体, 产率60%. m.p. 133~135 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.47~8.45 (m, 1H), 7.95 (d, J=7.61 Hz, 1H), 7.90~7.87 (m, 1H), 7.83 (d, J=7.62 Hz, 1H), 7.70 (s, 1H), 7.68~7.60 (m, 2H), 7.41~7.37 (m, 1H), 7.17 (s, 1H), 6.79 (s, 1H), 4.48 (d, J=5.62 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 160.1, 157.5, 148.9, 146.8, 139. 2, 137.6, 137.0, 132.0, 131.5, 130.7, 129.2, 128.7, 128.0, 127.0, 125.8, 125.6, 124.7, 122.0, 110.1, 35.2. Anal. calcd for C20H12Br- ClF3N5O2: C 45.61, H 2.30, N 13.30; found C 45.50, H 2.43, N 13.46.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(4-三氟甲基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11h):白色固体, 产率65%. m.p. 170~172 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.48~8.46 (m, 1H), 8.16 (d, J=8.02 Hz, 2H), 7.90~7.88 (m, 1H), 7.75 (d, J=8.41 Hz, 2H), 7.68 (s, 1H), 7.42~7.39 (m, 1H), 6.97 (s, 1H), 6.84 (s, 1H), 4.49 (d, J=5.61 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 160.8, 157.5, 148.9, 146.8, 139.2, 139.0, 137.7, 136.5, 129.7, 129.2, 128.0, 126.8, 126.0, 125.8, 110.1, 35.2. Anal. calcd for C20H12BrClF3N5O2: C 45.61, H 2.30, N 13.30; found C 45.78, H 2.39, N 13.15.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(4-氰基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11i):黄色固体, 产率68%. m.p. 176~178 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.47~8.45 (m, 1H), 8.11 (d, J=8.41 Hz, 2H), 7.91~7.88 (m, 1H), 7.77 (d, J=8.42 Hz, 2H), 7.69 (s, 1H), 7.42~7.39 (m, 1H), 7.03 (s, 1H), 6.80 (s, 1H), 4.47 (d, J=5.21 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 160.2, 157.5, 148.9, 146.8, 146.5, 139.3, 138.9, 138.4, 136.9, 132.8, 130.6, 129.2, 128.0, 126.9, 125.9, 118.2, 114.1, 110.0, 35.3. Anal. calcd for C20H12BrClN6O2: C 49.66, H 2.50, N 17.37; found C 49.50, H 2.62, N 17.23.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(4-甲基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11j):白色固体, 产率75%. m.p. 143~145 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.46~8.44 (m, 1H), 7.89~7.86 (m, 3H), 7.56 (s, 1H), 7.39~7.36 (m, 1H), 7.27 (d, J=6.02 Hz, 2H), 6.82 (s, 1H), 4.42 (d, J=5.22 Hz, 2H), 2.41 (s, 3H); 13C NMR (CDCl3, 101 MHz) δ: 162.4, 157.4, 148.9, 146.8, 141.3, 139.2, 137.2, 135.4, 129.6, 129.6, 129.2, 127.9, 126.4, 125.8, 124.1, 110.1, 35.3, 21.6. Anal. calcd for C20H15BrClN5O2: C 50.82, H 3.20, N 14.82; found C 50.71, H 3.06, N 14.99.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3-甲基-4-硝基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11k):白色固体, 产率66%. m.p. 180~182 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.40~8.38 (m, 1H), 8.00 (d, J=8.42 Hz, 1H), 7.93 (s, 1H), 7.89~7.81 (m, 2H), 7.62 (s, 1H), 7.35~7.32 (m, 1H), 7.02 (s, 1H), 6.74 (s, 1H), 4.40 (d, J=5.61 Hz, 2H), 2.61 (s, 3H); 13C NMR (CDCl3, 101 MHz) δ: 159.1, 156.5, 149.0, 147.9, 145.8, 138.2, 137.4, 136.0, 133.6, 131.1, 129.5, 128.2, 127.5, 127.0, 124.8, 124.5, 123.7, 109.0, 34.2, 19.5. Anal. calcd for C20H14BrClN6O4: C 46.40, H 2.73, N 16.23; found C 46.23, H 2.89, N 16.36.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3-硝基-4-甲基苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11l):黄色固体, 产率68%. m.p. 197~199 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.61 (s, 1H), 8.49~8.47 (m, 1H), 8.15~7.89 (m, 2H), 7.66 (s, 1H), 7.48 (d, J=8.02 Hz, 1H), 7.43~7.40 (m, 1H), 6.87 (s, 1H), 6.83 (s, 1H), 4.48 (d, J=5.22 Hz, 2H), 2.68 (s, 3H); 13C NMR (CDCl3, 101 MHz) δ: 160.0, 157.5, 149.6, 148.9, 146.8, 139.3, 139.0, 137.8, 136.3, 136.1, 133.6, 130.2, 129.2, 128.0, 126.0, 125.9, 122.6, 110.2, 35.3, 20.6. Anal. calcd for C20H14BrClN6O4: C 46.40, H 2.73, N 16.23; found C 46.28, H 2.59, N 16.33.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(2-氟-6-氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11m):白色固体, 产率60%. m.p. 162~164 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.49~8.47 (m, 1H), 7.90~7.87 (m, 1H), 7.76 (s, 1H), 7.46~7.38 (m, 2H), 7.34 (d, J=8.41 Hz, 1H), 7.20 (s, 1H), 7.17~7.12 (m, 1H), 6.76 (s, 1H), 4.50 (d, J=5.61 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 162.7, 160.2, 157.5, 154.8, 148.9, 146.8, 139.2, 137.1, 135.3, 132.6, 132.5, 129.1, 128.0, 126.1, 125.8, 114.9, 114.7, 110.1, 35.3. Anal. calcd for C19H11BrCl2FN5O2: C 44.65, H 2.17, N 13.70; found C 44.82, H 2.03, N 13.86.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(2, 4-二氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11n):黄色固体, 产率62%. m.p. 167~169 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.41~8.39 (m, 1H), 7.81 (d, J=8.42 Hz, 2H), 7.62 (s, 1H), 7.41 (d, J=2.02 Hz, 1H), 7.34~7.30 (m, 2H), 7.16 (s, 1H), 6.74 (s, 1H), 4.41 (d, J=5.62 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 158.2, 156.5, 147.89, 145.8, 138.2, 138.0, 136.5, 136.2, 135.5, 132.3, 130.7, 130.1, 128.2, 127.0, 126.5, 124.8, 123.2, 109.1, 34.1. Anal. calcd for C19H11BrCl3N5O2: C 43.26, H 2.10, N 13.27; found C 43.10, H 2.20, N 13.04.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(3, 5-二氯苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11o):黄色固体, 产率65%. m.p. 175~177 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.48~8.46 (m, 1H), 7.91~7.89 (m, 3H), 7.63 (s, 1H), 7.46~7.40 (m, 2H), 6.89 (s, 1H), 6.80 (s, 1H), 4.45 (d, J=5.21 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 159.6, 157.5, 148.9, 146.8, 139.3, 139.0, 138.0, 136.6, 135.8, 130.6, 129.4, 129.2, 128.5, 128.0, 126.0, 125.9, 124.8, 110.2, 35.3. Anal. calcd for C19H11BrCl3N5O2: C 43.26, H 2.10, N 13.27; found C 43.39, H 2.01, N 13.43.
3-溴-1-(3-氯吡啶-2-基)-N-{[2-(2, 6-二氟苯基)噁唑-4-基]甲基}-1H-吡唑-5-甲酰胺(11p):白色固体, 产率60%. m.p. 153~155 ℃; 1H NMR (CDCl3, 400 MHz) δ: 8.48~8.46 (m, 1H), 7.90~7.88 (m, 1H), 7.75 (s, 1H), 7.51~7.38 (m, 2H), 7.09~7.05 (m, 3H), 6.80 (s, 1H), 4.51 (d, J=5.61 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ: 162.0, 159.4, 157.5, 153.0, 148.9, 146.8, 139.2, 139.1, 137.4, 136.8, 132.5, 132.4, 129.1, 128.0, 125.8, 112.5, 112.2, 110.1, 35.2. Anal. calcd for C19H11BrClF2N5O2: C 46.13, H 2.24, N 14.16; found C 46.30, H 2.38, N 14.03.
辅助材料(Supporting Information) 目标化合物11a~11p的核磁共振氢谱和碳谱图谱.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
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图 1 化合物A~F、吡螨胺、唑虫酰胺和氯虫苯甲酰胺的化学结构
Figure 1 Chemical structures of compounds A~F, tebufenpyrad, tolfenpyrad and chlorantraniliprole
图式 1 目标化合物11的合成路线
Scheme 1 Synthetic route of the target compounds 11
11a: R = 3-F, 11b: R = 2-Cl, 11c: R = 3-Cl, 11d: R = 4-Cl, 11e: R = 3-Br, 11f: R = 4-Br; 11g: R = 2-CF3, 11h: R = 4-CF3, 11i: R = 4-CN, 11j: R1 = 4-CH3, 11k: R = 3-CH3-4-NO2, 11l: R = 3-NO2-4-CH3, 11m: R = 2-F-6-Cl, 11n: R = 2, 4-Cl2; 11o: R = 3, 5-Cl2; 11p: R = 2, 6-F2
表 1 反应条件对化合物11d收率的影响
Table 1. Effects of reaction conditions on the synthesis of compound 11d
| Entry | Base | Solvent | Reaction condition | Yield/% |
| 1 | Pyridine | CH3COCH3 | r.t. for 12 h | 20 |
| 2 | Pyridine | CH2Cl2 | r.t. for 12 h | 61 |
| 3 | Pyridine | THF | r.t. for 12 h | 33 |
| 4 | Pyridine | CH3CN | r.t. for 12 h | 52 |
| 5 | Pyridine | CH2Cl2 | Reflux for 12 h | 56 |
| 6 | Pyridine | CH3CN | Reflux for 12 h | 45 |
| 7 | Et3N | CH2Cl2 | r.t. for 12 h | 70 |
| 8 | Et3N | THF | r.t. for 12 h | 43 |
| 9 | Et3N | CH3CN | r.t. for 12 h | 59 |
| 10 | Et3N | CH2Cl2 | Reflux for 12 h | 63 |
| 11 | Et3N | CH3CN | Reflux for 12 h | 50 |
| 12 | K2CO3 | CH2Cl2 | r.t. for 12 h | 12 |
| 13 | KOH | CH2Cl2 | r.t. for 12 h | 0 |
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表 2 目标化合物11a~11p的杀虫活性(死亡率/%)a
Table 2. Insecticidal activities (mortality/%) of title compounds 11a~11p
| Compd. | Mythimna separata | Aphis craccivora | Tetranychus cinnabarinus | |||||||
| 500 μg/mL | 100 μg/mL | 20 μg/mL | 500 μg/mL | 100 μg/mL | 20 μg/mL | 500 μg/mL | 100 μg/mL | |||
| 11a | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11b | 100 | 0 | - | 100 | 90 | 30 | 0 | - | ||
| 11c | 100 | 0 | - | 0 | - | 0 | - | |||
| 11d | 100 | 100 | 30 | 0 | - | - | 0 | - | ||
| 11e | 90 | 0 | - | 0 | - | - | 0 | - | ||
| 11f | 100 | 100 | 40 | 0 | - | - | 0 | - | ||
| 11g | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11h | 100 | 100 | 50 | 100 | 100 | 30 | 100 | 0 | ||
| 11i | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11j | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11k | 100 | 100 | 40 | 100 | 100 | 20 | 80 | 0 | ||
| 11l | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11m | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11n | 100 | 0 | - | 0 | - | - | 0 | - | ||
| 11o | 100 | 90 | 0 | 0 | - | - | 0 | - | ||
| 11p | 100 | 0 | - | 0 | - | - | 0 | - | ||
| Tolfenpyrad | 100 | 50 | 40 | - | - | - | - | - | ||
| Imidacloprid | - | - | - | 100 | 100 | 100 | - | - | ||
| Fenpyroximate | - | - | - | - | - | - | 100 | 100 | ||
| a - refers to “not tested”. | ||||||||||
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