3-芳基异噁唑啉-吡唑-5-甲酰胺类化合物的合成及杀虫活性研究

引用本文: 钟良坤, 江涛, 张帆, 付庆, 刘幸海, 许天明, 丁成荣, 陈杰, 袁静, 谭成侠. 3-芳基异噁唑啉-吡唑-5-甲酰胺类化合物的合成及杀虫活性研究[J]. 有机化学, 2019, 39(9): 2655-2662. doi: 10.6023/cjoc201903056 shu

Citation: Zhong Liangkun, Jiang Tao, Zhang Fan, Fu Qing, Liu Xinghai, Xu Tianming, Ding Chengrong, Chen Jie, Yuan Jing, Tan Chengxia. Synthesis and Insecticidal Activity of 3-Arylisoxazoline-pyrazole-5-carboxamide Derivatives[J]. Chinese Journal of Organic Chemistry, 2019, 39(9): 2655-2662. doi: 10.6023/cjoc201903056 shu

3-芳基异噁唑啉-吡唑-5-甲酰胺类化合物的合成及杀虫活性研究

钟良坤 ^a,b, ,
江涛 ^a, ,
张帆 ^b, ,
付庆 ^a, ,
刘幸海 ^a, ,
许天明 ^b, ,
丁成荣 ^a, ,
陈杰 ^c, ,
袁静 ^{c,
,} ,
谭成侠 ^{a,
,}

a.
浙江工业大学化学工程学院杭州 310014
b.
浙江省化工研究院有限公司杭州 310023
c.
浙江农林大学林业与生物技术学院杭州 311300

通讯作者: 袁静, 1015251265@qq.com; 谭成侠, tanchengxia@zjut.edu.cn

基金项目:

国家重点研发计划（No.2017YFD0200507）资助项目

摘要: 以5，5-二甲氧基-2，4-二氧代戊酸乙酯为原料，设计合成了一系列含芳基异噁唑啉结构的吡唑-5-甲酰胺类化合物，产物结构经¹H NMR，¹³C NMR和HRMS确认.初步杀虫活性测试表明，多数化合物在500 mg/L浓度下对粘虫（Mythimna separate）有着较高的活性（致死率≥ 80%），在100 mg/L的浓度下，有三种化合物对粘虫仍有中等程度的活性（致死率≥ 60%）.在500 mg/L时，有四种化合物对苜蓿蚜（Aphis craccivora）也有较好的活性（致死率≥ 80%）.因此，对该类化合物的结构优化可作为寻求新型杀虫剂而进行深入研究.

关键词:

English

Synthesis and Insecticidal Activity of 3-Arylisoxazoline-pyrazole-5-carboxamide Derivatives

a.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014
b.
Zhejiang Research Institute of Chemical Industry. Ltd., Hangzhou 310023
c.
School of Forestry and Biotechnology, Zhejiang A & F University, Hangzhou 311300

Corresponding author: Yuan, Jing, E-mail: 1015251265@qq.com; Tan, Chengxia, tanchengxia@zjut.edu.cn

Received Date: 26 March 2019
Revised Date: 19 April 2019
Available Online: 25 September 2019
Fund Project:

Project supported by the National Key Research and Development Plan (No. 2017YFD0200507)

Abstract: A series of 3-arylisoxazoline-pyrazole-5-carboxamide derivatives derived from ethyl 5, 5-dimethoxy-2, 4-dioxopentanoate were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR and HRMS. The preliminary bioassay indicated that most title compounds exhibited positive potency against Mythimna separate (Walker) at 500 mg/L. At the concentration of 100 mg/L, three compounds were still moderately active against Mythimna separate (Walker) (lethal rate≈60%). At 500 mg/L, four compounds were also active against Aphis craccivora. The results indicated that the potential of these 3-arylisoxazoline-pyrazole-5-carboxamide derivatives can be utilized in insecticide research with further optimization.

Key words:

吡唑及其衍生物是一类非常常见而且重要的化学结构, 广泛被应用于医药^{[1, 2]}、农药^{[3, 4]}、兽药^{[5, 6]}等具有生物活性分子的研究中.在农业领域, 多种含有吡唑基团的小分子构成了如杀菌剂^[7~9]、杀虫剂^[10~13]、除草剂^[14~16]、杀线虫剂^[17]等一系列农药产品.作为一种合成较为简单的五元杂环结构, 吡唑被认为是其它诸如芳环、六元杂环等结构的电子等排体^[18], 因此在活性小分子的结构优化研究策略方面, 多数会使用吡唑及其取代物作为研究的重点.常见于农药中的吡唑类衍生物主要包括吡唑4-位和5-位甲酰基衍生物.例如琥珀酸脱氢酶抑制剂(SDHI)类杀菌剂, 呋吡菌胺(Furametpyr)、氟唑菌酰胺(Fluxapyroxad)和氟唑菌苯胺(Penflufen)等多种有效成分都属于吡唑-4-甲酰胺类衍生物.而类似于吡螨胺(Tebufenpyrad)、氯虫苯甲酰胺(Chlorantraniliprole)、腈吡螨酯(Cyenopyrafen)等具有高效杀虫杀螨活性的药物也具有吡唑-5-甲酰基或类似衍生结构(图 1).因此, 在开发新型杀虫剂的研究中, 合理的选择吡唑-5-甲酰基衍生结构是提高结构优化效率的一个重要方法.

图 1

图 1. 吡唑类衍生物

Figure 1. Pyrazole derivatives

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芳基异噁唑啉结构也是一种多用于抗癌^[19]、抗病毒^[20]、消炎^[21]、抗菌^[22]等活性分子的研究与开发.在农业及畜牧业的防治与保护中, 如兽药阿福拉纳(Afoxolaner)^[23]以及新型杀虫剂Isocycloseram^[24]等具有良好杀虫和杀螨活性.同时, 在该类活性结构中, 中心芳环衍生的酰胺部分也是成药的一个关键.根据生物电子等排原理, 设计合成了16个新型的取代吡唑-5-甲酰胺衍生物, 并对目标化合物进行结构鉴定与杀虫活性研究(Scheme 1).

图式 1

图式 1. 目标化合物的设计策略

Scheme 1. Design strategy of the target compounds

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1. 结果与讨论

1.1 目标产物的合成

目标产物合成路径如Scheme 2所示.中间体2由原料5, 5-二甲氧基-2, 4-二氧代戊酸乙酯和水合肼经缩合形成吡唑环, 反应在冰乙酸中进行, 这是一个经典的吡唑合成反应, 收率约93%.缩醛中间体使用质量分数为50%乙酸水溶液水解, 温度在60 ℃左右可进行完毕, 并且有87%左右的较高收率.中间体4由3和硫酸二甲酯进行甲基化, 由于吡唑环的特殊性质, 反应中会产生少量(≤10%)的吡唑异构体, 可以通过柱层析硅胶进行很好分离.肟中间体5在羟胺水溶液中进行, 但是使用盐酸羟胺时, 本反应的完成度较低.中间体6通过“一锅法”制备, 包括肟与N-氯代丁二酰亚胺(NCS)在N, N-二甲基甲酰胺(DMF)中反应, 反应完毕后直接加入芳基乙烯进行1, 3-偶极环加成反应.中间体7由6经NaOH溶液水解, 反应收率近87%.目标产物的合成由酸制备成酰氯, 在室温下与取代芳胺反应即可获得.

图式 2

图式 2. 目标化合物ZJ1~ZJ16的合成路线

Scheme 2. Synthetic routes of the target compounds ZJ1~ZJ16

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1.2 核磁解析

以目标化合物ZJ1的核磁氢谱为例在δ 1.32处的单峰为苯环上的叔丁基; 在δ 3.46和3.81处的两个双二重峰属于异噁唑啉的亚甲基, 属前手性氢原子; 在δ 4.23处的单峰为吡唑环上的甲基; 在δ 5.71处的双二重峰属于异噁唑啉上的单个氢的峰; 在δ 7.11处的多重峰属于芳胺芳环上的氢; 在δ 7.21处的单峰属于吡唑环的氢; 在δ 7.30~7.35和7.38~7.44处的氢分别包括了4-叔丁基芳基和芳胺环上的氢; δ在8.30处的单峰为酰胺的氢; 在δ 8.41处的双重峰为芳胺环上的氢.

1.3 杀虫活性测试

测试了目标化合物对粘虫(Mythimna separate)、朱砂叶螨(Tetranychus cinnabarinus)以及苜蓿蚜(Aphis craccivora)的活性(表 1, 2).测试结果显示, 大部分目标化合物在500 mg/L的浓度下对粘虫有着很高的活性, 化合物ZJ5, ZJ6, ZJ9和ZJ13对苜蓿蚜也有不低于70%的致死率, 但是目标化合物对朱砂叶螨则没有显示出效力.对于较高活性的化合物进行复筛, 在100 mg/L的浓度下, ZJ5, ZJ8和ZJ9对粘虫仍有中等程度的活性, 而在20 mg/L的剂量下则没有效力.而复筛的化合物在100 mg/L时对苜蓿蚜的活性很低.通过构效关系分析, R¹为H时活性高于Me取代, R²中卤素单取代或双取代的芳胺的活性低于烷基或卤代烷基, 而取代基的位置则并没有显示明显的区别.因此, 基于生物电子等排原理设计的吡唑-5-甲酰胺衍生物保留了与先导化合物类似的芳基异噁唑啉结构, 体现出一定的杀虫活性可能与Afoxolaner的作用机制相似, 属于γ-aminobutyric acid (GABA)受体抑制剂且主要作用于氯离子通道^[25].但是, 与广谱类杀虫剂阿维菌素相比^[26], 目标化合物的杀虫活性较低, 说明该类化合物可能对于靶标的亲和力不够, 需要进行更深入的结构优化与研究.

表 1

表 1 500 mg/L下目标化合物的杀虫活性(死亡率/%)

Table 1. Insecticidal activities (mortality/%) of title compounds at 500 mg/L

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Compd.	Mythimna separate	Aphis craccivora	Tetranychus cinnabarinus
ZJ1	50	0	0
ZJ2	100	0	0
ZJ3	60	0	0
ZJ4	0	30	0
ZJ5	100	80	0
ZJ6	80	80	0
ZJ7	100	0	0
ZJ8	100	0	0
ZJ9	100	80	0
ZJ10	0	50	0
ZJ11	50	0	0
ZJ12	60	0	0
ZJ13	0	90	0
ZJ14	100	0	0
ZJ15	0	60	0
ZJ16	90	30	0
Avermectin	100	100	100
空白对照	0	0	0

表 2

表 2 目标化合物在100, 20 mg/L浓度下对粘虫和苜蓿蚜的杀虫活性(死亡率/%)

Table 2. Insecticidal activities (mortality/%) of title compounds against M. separate and A. craccivora at 100 and 20 mg/L

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Compd.	Mythimna separate		Aphis craccivora
Compd.	100 mg/L	20 mg/L	100 mg/L
ZJ2	30	0	0
ZJ5	60	0	30
ZJ6	55	0	30
ZJ7	30	0	0
ZJ8	65	0	0
ZJ9	60	0	25
ZJ13	0	0	20
ZJ14	50	0	0
ZJ15	0	0	15
ZJ16	35	0	0
Avermectin	100	95	100
空白对照	0	0	0

2. 结论

设计合成了16个含芳基异噁唑啉结构的吡唑-5-甲酰胺类化合物.杀虫活性测试结果显示, 多数化合物在500 mg/L浓度下对粘虫有着较高的活性, 死亡率接近100%;在100 mg/L时, 化合物ZJ5, ZJ8, ZJ9仍有中等程度的活性, 降低至20 mg/L时活性基本不明显.化合物ZJ5, ZJ6, ZJ9和ZJ13在500 mg/L时对苜蓿蚜也有一定的活性, 在100 mg/L时无明显作用.因而, 基于吡唑-5-酰胺结构为主体, 在芳基异噁唑啉等结构上的继续优化可作为新型杀虫剂开发中进一步研究的方向.

3. 实验部分

3.1 仪器与试剂

Bruker Avance Ⅲ HD 600M核磁共振波谱仪(TMS为内标, 瑞士Bruker公司); X-4型数字显示显微熔点测定仪(北京泰克公司); LCQ-Advantage离子阱质谱仪(ThermoFinnigan); 柱层析硅胶和G₂₅₄薄层色谱硅胶(青岛海洋化工厂).所有的试剂全部购自于商业试剂公司, 均为分析纯.实验用水为二次蒸馏水.

3.2 实验方法

3.2.1 3-(二甲氧基甲基)-1H-吡唑-5-羧酸乙酯(2)的合成

在冰浴条件下将质量分数为80%的水合肼(6.88 g, 0.11 mol)滴加到1 (21.8 g, 0.1 mol)的乙醇体系中, 室温下搅拌3 h, 放置过夜.将反应液浓缩除去乙醇, 在体系中加入50 mL水, 乙酸乙酯(20 mL×4)萃取, 有机相用少量的氯化钠水溶液洗一次, 硫酸钠干燥, 过滤浓缩, 洗涤[V(石油醚):V(乙酸乙酯)＝1:1]得19.9 g红色油状液体2^[27], 收率93.1%. ¹H NMR (600 MHz, CDCl₃) δ: 1.38 (t, J＝7.2 Hz, 3H, CH₃), 3.37 (s, 6H, CH₃), 4.39 (q, J＝7.2 Hz, 2H, CH₂), 5.61 (s, 1H, CH), 6.88 (s, 1H, ArH); ¹³C NMR (CDCl₃, 150 MHz) δ: 14.2, 52.7, 61.2, 97.8, 107.0.

3.2.2 3-醛基-1H-吡唑-5-羧酸乙酯(3)的合成

中间体2 (30.0 g, 140.1 mmol)和300 mL质量分数为50%乙酸水溶液加入到500 mL的圆底烧瓶中, 温度控制在60 ℃, 搅拌反应3 h, 薄层色谱(TLC)跟踪检测.反应完全后, 将反应液真空浓缩得20.5 g淡黄色粘稠固体3^[28], 产率87.4%. ¹H NMR (600 MHz, CDCl₃) δ: 1.42 (t, J＝7.2 Hz, 3H, CH₃), 4.44 (q, J＝7.2 Hz, 2H, CH₂), 7.35 (s, 1H, ArH), 10.03 (s, 1H, CHO); ¹³C NMR (CDCl₃, 150 MHz) δ: 14.2, 53.8, 62.1, 98.9, 109.3, 159.4, 184.8.

3.2.3 1-甲基-3-醛基-1H-吡唑-5-羧酸乙酯(4)的合成

3-甲酰基-1H-吡唑-5-羧酸乙酯(15.0 g, 89.2 mmol)和碳酸钾(14.7 g, 107 mmol)加入到500 mL的圆底烧瓶中, 加入200 mL丙酮溶剂, 将硫酸二甲酯(12.3 g, 98.1 mmol)逐滴加入到反应液中, 室温过夜搅拌, TLC跟踪检测.完全反应后, 过滤, 脱溶, 柱层析分离[V(石油醚):V(乙酸乙酯)＝5:1]得12.0 g白色固体4^[29], 产率74.2%. m.p. 54~55 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.39 (t, J＝7.2 Hz, 3H, CH₃), 4.28 (s, 3H, NCH₃), 4.39 (q, 2H, J＝7.2 Hz, CH₂), 7.34 (s, 1H, pyrazole-H), 9.96 (s, 1H, CH); ¹³C NMR (CDCl₃, 150 MHz) δ: 14.2, 40.6, 61.6, 110.9, 134.6, 149.3, 159.3, 185.8.

3.2.4 1-甲基-3-(5-(4-(叔丁基)苯基)-4, 5-二氢异噁唑- 3-基)-1H-吡唑-5-羧酸乙酯(5)的合成

将3-甲酰基-1-甲基-1H-吡唑-5-羧酸乙酯(5.1 g, 28.0 mmol)溶于30 mL四氢呋喃(THF)中, 室温下滴入质量分数为50%羟胺水溶液(3.96 g, 60.0 mmol), TLC跟踪检测.完全反应后, 脱溶除去THF.剩余物加入100 mL N, N-二甲基甲酰胺(DMF)和N-氯代丁二酰亚胺(NCS, 4.0 g, 30.0 mmol), 60 ℃下搅拌1 h, TLC跟踪检测.完全反应后, 将4-叔丁基苯乙烯(4.5 g, 28.0 mmol)加入到DMF溶液中, 逐滴加入三乙胺(3.0 g, 30.0 mmol), 室温下搅拌2.5 h, TLC检测反应完全.在反应液中加入100 mL水, 乙酸乙酯萃取(50 mL×3), 将有机相柱层析分离[V(石油醚):V(乙酸乙酯)＝5:1]得7.9 g粘稠状固体5, 产率80.1%. ¹H NMR (600 MHz, CDCl₃) δ: 1.31 (s, 9H, CH₃), 1.38 (t, J＝7.2 Hz, 3H, CH₃), 3.42 (dd, J＝8.3, 17.1 Hz, 1H, isoxazole-H), 3.78 (dd, J＝10.9, 17.1 Hz, 1H, isoxazole- H), 4.17 (s, 3H, Ar-CH₃), 4.39 (q, J＝6.6 Hz, 2H, CH₂), 5.69 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 7.28 (s, 1H, pyrazole-H), 7.32 (d, J＝8.4 Hz, 2H, ArH), 7.39 (d, J＝8.4 Hz, 2H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 14.2, 31.3, 34.6, 39.8, 42.6, 61.3, 82.3, 109.7, 125.6, 125.7, 134.0, 137.6, 141.3, 151.2, 151.4, 159.5; ESI-MS m/z: 356 [M+H]⁺; HRMS calcd for C₂₀H₂₆N₃O₃ [M+H]⁺ 356.1979, found 356.1978.

3.2.5 1-甲基-3-(5-(4-(叔丁基)苯基)-4, 5-二氢异噁唑- 3-基)-1H-吡唑-5-羧酸(6)的合成

将3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-1-甲基-1H-吡唑-5-羧酸乙酯(4.9 g, 13.8 mmol)溶于20 mL的THF中, 加入质量分数为10% NaOH水溶液(0.62 g, 15.5 mmol), 加热回流2 h, TLC跟踪检测.反应完全后, 真空浓缩, 加入100 mL水, 盐酸调pH至固体全部析出, 过滤, 真空浓缩得3.9 g白色固体6, 收率87.3%. m.p. 200~201 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.31 (s, 9H, CH₃), 3.42 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.78 (dd, J＝10.9, 17.1 Hz, 1H, isoxazole-H), 4.20 (s, 3H, CH₃), 5.70 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 7.31 (d, J＝8.4 Hz, 2H, ArH), 7.39~7.40 (br, 3H, ArH, pyrazole-H); ¹³C NMR (150 MHz, CDCl₃) δ: 31.32, 34.64, 40.07, 42.62, 82.47, 111.16, 125.68, 125.75, 133.07, 137.39, 141.46, 151.37, 151.46, 163.12; ESI-MS m/z: 328 [M+H]⁺; HRMS calcd for C₁₈H₂₂N₃O₃ [M+H]⁺ 328.1665, found 328.1661.

3.2.6 目标产物的合成

目标产物参考文献[30]的合成方法合成.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(2-氯苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ1):白色固体, 收率88.3%. m.p. 167~168 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.32 [s, 9H, (CH₃)₃], 3.46 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.81 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole- H), 4.23 (s, 3H, Ar-CH₃), 5.71 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 7.09~7.03 (m, 1H, ArH), 7.21 (s, 1H, ArH), 7.30~7.35 (m, 3H, pyrazole-H, ArH), 7.38~7.44 (m, 3H, ArH), 8.30 (brs, 1H, NH), 8.41 (d, J＝8.4 Hz, 1H, CH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.9, 42.5, 82.5, 105.2, 121.7, 123.5, 125.5, 125.7, 125.8, 127.9, 129.3, 133.9, 136.5, 137.4, 141.4, 151.4, 151.7, 157.2; ESI-MS m/z: 437 [M+H]⁺; HRMS calcd for C₂₄H₂₆- ClN₄O₂ [M+H]⁺ 437.1753, found 437.1744.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(4-甲氧基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ2):白色固体, 收率86.5%. m.p. 159~160 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.31 [s, 9H, (CH₃)₃], 3.45 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.73~3.83 (m, 4H, isoxazole-H_, O-CH₃), 4.19 (s, 3H, Ar-CH₃), 5.68 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 6.83~6.88 (m, 2H, ArH), 7.21 (s, 1H, pyrazole-H), 7.27~7.30 (m, 2H, ArH), 7.37 (d, J＝8.4 Hz, 2H, ArH), 7.45 (d, J＝8.4 Hz, 2H, ArH), 8.00~8.10 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.5, 39.7, 42.6, 55.5, 82.5, 105.2, 114.2, 114.8, 116.5, 122.5, 125.6, 125.7, 130.0, 136.9, 137.3, 141.0, 151.4, 152.0, 156.9, 157.5; ESI-MS m/z: 433 [M+H]⁺; HRMS calcd for C₂₅H₂₉N₄O₃ [M+H]⁺ 433.2243, found 433.2240.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-氯苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ3):白色固体, 收率91.7%. m.p. 166~167 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.32 [s, 9H, (CH₃)₃], 3.46 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole- H), 4.20 (s, 3H, Ar-CH₃), 5.69 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 7.08~7.17 (m, 1H, ArH), 7.18~7.32 (m, 4H, ArH), 7.32~7.40 (m, 3H, pyrazole-H, ArH), 7.72~7.75 (m, 1H, ArH), 8.10~8.35 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.9, 42.6, 82.7, 105.7, 118.5, 120.7, 125.0, 125.7, 125.8, 130.0, 134.5, 136.5, 137.1, 138.3, 141.0, 151.5, 152.1, 157.6; ESI-MS m/z: 437 [M+H]⁺; HRMS calcd for C₂₄H₂₆ClN₄O₂ [M+H]⁺ 437.1747, found 437.1744.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-氟苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ4):淡黄色固体, 收率89.2%. m.p. 168~169 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.29 [s, 9H, (CH₃)₃], 3.46 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole- H), 4.20 (s, 3H, Ar-CH₃), 5.68 (dd, J＝8.4, 10.9 Hz, 1H, isoxazole-H), 6.80~6.88 (m, 1H, ArH), 7.16~7.33 (m, 5H, pyrazole-H, ArH), 7.33~7.42 (m, 2H, ArH), 7.51~7.57 (m, 1H, ArH), 8.07~8.40 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.8, 42.6, 82.7, 105.6, 107.9 (d, J＝26 Hz), 111.7 (d, J＝21 Hz), 115.7 (d, J＝3 Hz), 125.7, 125.8, 130.1 (d, J＝9 Hz), 136.6 (d, J＝82 Hz), 138.6 (d, J＝10 Hz), 141.1, 151.5, 152.0, 157.6, 162.1, 163.7; ESI-MS m/z: 421 [M+H]⁺; HRMS calcd for C₂₄H₂₆FN₄O₂ [M+H]⁺ 421.2040, found 421.2043.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(2-甲基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ5):白色固体, 收率92.2%. m.p. 141~142 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.32 [s, 9H, (CH₃)₃], 2.29 (s, 3H, CH₃), 3.46 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.21 (s, 3H, Ar-CH₃), 5.63 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 7.14 (t, J＝7.8 Hz, 1H, ArH), 7.19~7.30 (m, 5H, pyrazole-H, ArH), 7.38 (d, J＝8.4 Hz, 2H, ArH), 7.70~7.82 (m, 2H, ArH, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 17.8, 31.3, 34.6, 39.8, 42.5, 82.5, 105.1, 114.9, 118.6, 123.7, 125.6, 125.7, 126.8, 130.7, 134.6, 136.7, 137.2, 141.2, 151.3, 151.9, 157.6; ESI-MS m/z: 417 [M+H]⁺; HRMS calcd for C₂₅H₂₉N₄O₂ [M+H]⁺ 417.2295, found 417.2291.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(4-甲基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ6):白色固体, 收率93.1%. m.p. 169~170 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.31 [s, 9H, (CH₃)₃], 2.33 (s, 3H, Ph-CH₃), 3.45 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.19 (s, 3H, Ar-CH₃), 5.68 (m, 1H, isoxazole-H), 7.13 (t, J＝7.2 Hz, 2H, ArH), 7.18~7.22 (m, 1H, ArH), 7.26~7.31 (m, 2H, pyrazole-H, ArH), 7.37 (d, J＝7.8 Hz, 2H, ArH), 7.44 (d, J＝7.8 Hz, 2H, Ar-H), 7.93~8.08 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 21.0, 31.3, 34.6, 39.7, 42.6, 82.5, 105.3, 115.3, 120.6, 123.0, 125.7, 125.8, 129.6, 134.5, 134.8, 137.0, 137.3, 141.1, 151.4, 152.0, 157.5; ESI-MS m/z: 417 [M+H]⁺; HRMS calcd for C₂₅H₂₉N₄O₂ [M+H]⁺ 417.2288, found 417.2291.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-三氟甲基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ7):淡黄色固体, 收率83.5%. m.p. 155~156 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.46 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.82 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.21 (s, 3H, Ar-CH₃), 5.63 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 7.22~7.28 (m, 2H, pyrazole-H, Ar-H), 7.32~7.37 (m, 3H, ArH), 7.38~7.43 (m, 2H, Ar-H), 7.66~7.71 (m, 1H, ArH), 7.79 (s, 1H, ArH), 8.28~8.39 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.9, 42.6, 82.7, 105.8, 117.3 (q, J＝4 Hz), 121.5 (d, J＝4 Hz), 122.9 (q, J＝272 Hz), 123.6, 125.7, 125.8, 129.5, 131.4 (q, J＝32 Hz), 136.4, 137.0, 137.7, 141.1, 151.5, 152.1, 157.7; ESI-MS m/z: 471 [M+H]⁺; HRMS calcd for C₂₅H₂₆F₃N₄O₂ [M+H]⁺ 471.2006, found 471.2008.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-甲基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ8):白色固体, 收率92.3%. m.p. 152~153 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.31 [s, 9H, (CH₃)₃], 2.33 (s, 3H, Ar-CH₃), 3.45 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.79 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.19 (s, 3H, Ar-CH₃), 5.68 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 6.79 (d, J＝7.2 Hz, 2H, ArH), 7.18~7.24 (m, 2H, pyrazole-H, ArH), 7.25~7.30 (m, 2H, ArH), 7.33 (d, J＝8.4 Hz, 2H, ArH), 7.37 (d, J＝7.8 Hz, 2H, ArH), 7.43 (s, 1H, ArH), 7.96~8.18 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 21.5, 31.2, 34.6, 39.8, 42.6, 82.5, 105.3, 116.0, 117.7, 119.5, 121.2, 125.7, 125.8, 128.9, 136.9, 137.3, 139.1, 141.1, 151.4, 152.0, 157.6; ESI-MS m/z: 417 [M+H]⁺; HRMS calcd for C₂₅H₂₉N₄O₂ [M+H]⁺ 417.2294, found 417.2291.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(4-苯氧基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ9):白色固体, 收率91.1%. m.p. 174~175 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.29 [s, 9H, (CH₃)₃], 3.45 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.19 (s, 3H, Ar-CH₃), 5.67 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 6.92~6.97 (m, 2H, ArH), 6.98 (d, J＝7.8 Hz, 2H, ArH), 7.10 (t, J＝7.2 Hz, 1H, ArH), 7.24~7.28 (m, 2H, ArH), 7.28~7.38 (m, 5H, pyrazole-H, ArH), 7.50 (d, J＝9.0 Hz, 2H, ArH), 8.19~8.33 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.8, 42.7, 82.6, 105.6, 118.6, 119.5, 122.5, 123.3, 125.7, 125.8, 129.8, 132.4, 136.9, 137.2, 141.0, 151.3, 152.1, 154.1, 157.4, 157.7; ESI-MS m/z: 495 [M+H]⁺; HRMS calcd for C₃₀H₃₁N₄O₃ [M+H]⁺ 495.2399, found 495.2396.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-甲基苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ10):淡黄色粘稠固体, 收率81.1%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 2.33 (s, 3H, Ph-CH₃), 3.32 (dd, J＝8.2, 17.1 Hz, 1H, isoxazole-H), 3.44 (s, 3H, NCH₃), 3.66 (dd, J＝10.8, 17.1 Hz, 1H, isoxazole-H), 4.09 (s, 3H, Ar-CH₃), 5.59 (m, 1H, isoxazole-H), 6.00 (brs, 1H, ArH), 6.88 (d, J＝7.8 Hz, 1H, ArH), 6.94 (s, 1H, ArH), 7.11 (d, J＝7.2 Hz, 1H, ArH), 7.21 (t, J＝7.8 Hz, 1H, ArH), 7.24~7.28 (m, 2H, pyrazole-H, ArH), 7.33~7.88 (m, 2H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 37.4, 38.3, 39.0, 42.6, 82.2, 105.5, 123.8, 125.6, 125.7, 127.1, 128.9, 129.5, 137.0, 137.5, 139.9, 140.5, 143.5, 151.2, 151.6, 161.6; ESI-MS m/z: 431 [M+H]⁺; HRMS calcd for C₂₆H₃₁N₄O₂ [M+H]⁺ 431.2457, found 431.2447.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(2, 4-二氟苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ11):淡黄色粘稠固体, 收率77.5%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.34 (dd, J＝8.0, 17.1 Hz, 1H, isoxazole-H), 3.40 (s, 3H, N-CH₃), 3.68 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 4.06 (s, 3H, Ar-CH₃), 5.60 (m, 1H, isoxazole-H), 6.10 (br, 1H, ArH), 6.79~6.86 (m, 1H, ArH), 6.92 (t, J＝7.8 Hz, 1H, ArH), 7.20~7.31 (m, 3H, pyrazole-H, ArH), 7.37 (d, J＝8.4 Hz, 2H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 37.4, 39.0, 42.6, 82.2, 105.5 (t, J＝25 Hz), 106.5, 112.6 (d, J＝22 Hz), 125.6, 125.7, 129.5 (d, J＝10 Hz), 136.4, 137.5, 140.7, 151.2, 151.6, 156.7 (d, J＝10 Hz), 161.1 (d, J＝11 Hz), 161.6, 162.8 (d, J＝11 Hz); ESI-MS m/z: 453 [M+H]⁺; HRMS calcd for C₂₅H₂₇F₂N₄O₂ [M+H]⁺453.2108, found 453.2102.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3, 5-二氯苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ12):淡黄色粘稠固体, 收率80.3%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.37 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.44 (s, 3H, N-CH₃), 3.70 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 4.10 (s, 3H, Ar-CH₃), 5.63 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 6.18 (brs, 1H, ArH), 7.05 (d, J＝1.5 Hz, 2H, ArH), 7.27~7.30 (m, 2H, pyrazole-H, ArH), 7.32 (t, J＝7.8 Hz, 1H, ArH), 7.36~7.39 (m, 2H, Ar-H); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 38.4, 39.5, 42.6, 82.3, 107.5, 125.3, 125.6, 125.8, 128.3, 135.8, 136.0, 137.4, 140.9, 145.3, 151.3, 151.6, 160.5; ESI-MS m/z: 485 [M+H]⁺; HRMS calcd for C₂₅H₂₇Cl₂N₄O₂ [M+H]⁺ 485.1509, found 485.1511.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(2-甲基-4-氯苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ13):淡黄色粘稠固体, 收率79.3%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 2.16 (d, J＝10.2 Hz, 3H, Ph-CH₃), 3.27~3.38 (m, 4H, isoxazole-H, N-CH₃), 3.66 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 4.11 (s, 3H, Ar-CH₃), 5.60 (m, 1H, isoxazole-H), 5.91 (d, J＝2.5 Hz, 1H, ArH), 7.04 (q, J＝8.4 Hz, 1H, ArH), 7.17~7.22 (m, 1H, ArH), 7.22~7.30 (m, 3H, pyrazole-H, ArH), 7.36 (d, J＝7.8 Hz, 2H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 17.4, 31.3, 34.6, 37.3, 39.7, 42.7, 82.1 107.0, 125.6, 125.7, 127.9, 129.0, 131.7, 134.3, 136.2, 136.7, 140.6, 140.9, 151.2, 151.6, 160.8; ESI-MS m/z: 465 [M+H]⁺; HRMS calcd for C₂₆H₃₀ClN₄O₂ [M+H]⁺ 465.2063, found 465.2057.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(4-甲氧羰基苯基)-1-甲基-1H-吡唑-5-甲酰胺(ZJ14):白色固体, 收率84.7%. m.p. 173~174 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.46 (dd, J＝9.0, 16.8 Hz, 1H, isoxazole-H), 3.80 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 3.90 (s, 3H, O-CH₃), 4.19 (s, 3H, Ar-CH₃), 5.66 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 7.25 (d, J＝8.4 Hz, 2H, ArH), 7.35 (q, J＝8.4 Hz, 2H, ArH), 7.38 (s, 1H, pyrazole-H), 7.65 (d, J＝9.0 Hz, 2H, ArH), 7.95 (d, J＝9.0 Hz, 2H, ArH), 8.58~8.66 (brs, 1H, NH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 39.9, 42.6, 52.1, 82.6, 106.0, 113.8, 119.7, 125.7, 125.9, 126.0, 130.7, 131.6, 136.7, 137.0, 140.9, 141.6, 151.6, 152.1, 157.8, 166.6; ESI-MS m/z: 461 [M+H]⁺; HRMS calcd for C₂₆H₂₉N₄O₄ [M+H]⁺ 461.2188, found 461.2189.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ15):淡黄色粘稠固体, 收率83.2%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.31 (dd, J＝8.4, 17.0 Hz, 1H, isoxazole-H), 3.47 (s, 3H, N-CH₃), 3.65 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 4.09 (s, 3H, Ar-CH₃), 5.58 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 5.96 (brs, 1H, ArH), 7.11 (q, J＝7.2 Hz, 2H, ArH), 7.23~7.26 (m, 2H, ArH), 7.29~7.33 (m, 1H, ArH), 7.33~7.37 (m, 4H, pyrazole-H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 38.2, 39.5, 42.6, 82.1, 107.6, 125.6, 125.7, 126.7, 128.1, 129.8, 136.9, 137.5, 140.5, 143.5, 151.2, 151.7, 160.8; ESI-MS m/z: 417 [M+H]⁺; HRMS calcd for C₂₅H₂₉N₄O₂ [M+H]⁺ 417.2295, found 417.2298.

3-(5-(4-叔丁基苯基)-4, 5-二氢异噁唑-3-基)-N-(3-苯氧基苯基)-1-甲基-1H-吡唑-5-甲酰甲胺(ZJ16):淡黄色粘稠固体, 收率81.9%. ¹H NMR (600 MHz, CDCl₃) δ: 1.30 [s, 9H, (CH₃)₃], 3.26 (dd, J＝8.4, 17.1 Hz, 1H, isoxazole-H), 3.44 (s, 3H, N-CH₃), 3.70 (dd, J＝10.8, 17.0 Hz, 1H, isoxazole-H), 4.01 (s, 3H, Ar-CH₃), 5.63 (dd, J＝8.6, 10.9 Hz, 1H, isoxazole-H), 6.09 (brs, 1H, ArH), 6.65 (s, 1H, ArH), 6.87 (d, J＝7.8 Hz, 2H, ArH), 6.90 (dd, J＝1.2, 7.8 Hz, 1H, ArH), 6.94~6.98 (m, 1H, ArH), 7.10 (t, J＝7.2 Hz, 1H, ArH), 7.23~7.40 (m, 7H, pyrazole-H, ArH); ¹³C NMR (150 MHz, CDCl₃) δ: 31.3, 34.6, 37.9, 39.2, 42.6, 82.2, 107.4, 117.4, 118.5, 119.0, 120.9, 123.8, 125.6, 125.7, 129.9, 130.9, 136.9, 137.5, 140.6, 144.8, 151.2, 151.6, 156.5, 158.1, 160.7; ESI-MS m/z: 509 [M+H]⁺; HRMS calcd for C₃₁H₃₃N₄O₃ [M+H]⁺ 509.2556, found 509.2553.

3.3 生物活性测试

浸叶法:供试靶标为粘虫(Mythimna separate), 将适量玉米叶在配好的药液中充分浸润后自然阴干, 放入垫有滤纸的培养皿中, 接粘虫3龄中期幼虫10头/皿，置于24~27 ℃观察室内培养, 3 d后调查结果.以毛笔触动虫体, 无反应视为死虫.试验浓度分别为500, 100和20 mg/L.

喷雾法:供试靶标为朱砂叶螨(Tetranychus cinnabarinus)和苜蓿蚜(Aphis craccivora), 分别将接有朱砂叶螨和苜蓿蚜的蚕豆叶片于Potter喷雾塔下喷雾处理, 处理后朱砂叶螨置于24~27 ℃观察室内培养, 苜蓿蚜置于20~22 ℃观察室内培养, 48 h后调查结果, 以毛笔触动虫体, 无反应视为死虫.试验浓度分别为500和100 mg/L.

辅助材料(Supporting Information) 中间体2~6及目标化合物ZJ1~ZJ16的¹H NMR和¹³C NMR谱图.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

1. [1]
  Pirol, S.-C.; Caliskan, B.; Durmaz, I.; Atalay, R.; Banoglu, E. Eur. J. Med. Chem. 2014, 87, 140. doi: 10.1016/j.ejmech.2014.09.056
2. [2]
  龚超超, 谈寒一, 张倩, 有机化学, 2018, 38, 3086. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346666.shtmlGong, C.-C.; Tan, H.-Y.; Zhang, Q. Chin. J. Org. Chem. 2018, 38, 3086 (in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346666.shtml
3. [3]
  何波, 王大伟, 杨文超, 陈琼, 杨光富, 有机化学, 2017, 37, 2895. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346167.shtmlHe, B.; Wang, D.-W.; Yang, W.-C.; Chen, Q.; Yang, G.-F. Chin. J. Org. Chem. 2017, 37, 2895 (in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346167.shtml
4. [4]
  Li, Y.-X.; Liu, S.-H.; Li, Y.-H.; Song, H.-B.; Wang, Q.-M. Bioorg. Med. Chem. Lett. 2009, 19, 2953. doi: 10.1016/j.bmcl.2009.04.048
5. [5]
  Bizikova, P.; Linder, K.; Olivry, T. Vet. Dermatol. 2014, 25, 103. doi: 10.1111/vde.12117
6. [6]
  Aloisi, A.; Franchet, A.; Ferrandon, D.; Bianco, A.; Moyon, C. Bioorg. Med. Chem. Lett. 2018, 28, 2631. doi: 10.1016/j.bmcl.2018.06.036
7. [7]
  Xiong, L.; Li, H.; Jiang, L.-N.; Ge, J.-M.; Yang, W.-C.; Zhu, X.-L.; Yang, G.-F. J. Agric. Food Chem. 2017, 65, 1021. doi: 10.1021/acs.jafc.6b05134
8. [8]
  孙娜波, 沈钟华, 翟志文, 韩亮, 翁建全, 谭成侠, 刘幸海, 有机化学, 2017, 37, 2705. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346147.shtmlSun, N.-B.; Shen, Z.-H.; Zhai, Z.-W.; Han, L.; Weng, J.-Q.; Tan, C.-X.; Liu, X.-H. Chin. J. Org. Chem. 2017, 37, 2705 (in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346147.shtml
9. [9]
  Li, X.-H.; Zhi, L.-P.; Song, B.-A.; Xu, H.-L. Chem. Res. Chin. Univ. 2008, 24, 454. doi: 10.1016/S1005-9040(08)60095-1
10. [10]
  石玉军, 周钱, 王杨, 钱宏炜, 叶林玉, 冯霞, 陈辉, 李雅婷, 戴红, 魏中昊, 吴锦明, 有机化学, 2018, 38, 2450. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346732.shtmlShi, Y.-J.; Zhou, Q.; Wang, Y.; Qian, H.-W.; Ye, L.-Y.; Feng, X.; Chen, H.; Li, Y.-T.; Dai, H.; Wei, Z.-H.; Wu, J.-M. Chin. J. Org. Chem. 2018, 38, 2450 (in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract346732.shtml
11. [11]
  张秀兰, 王宝雷, 毛明珍, 熊丽霞, 于淑晶, 李正名, 高等学校化学学报, 2013, 34, 96. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=gdxxhxxb201301015Zhang, X.-L.; Wang, B.-L.; Mao, M.-Z.; Xiong, L.-X.; Yu, S.-J.; Li, Z.-M. Chem. J. Chin. Univ. 2013, 34, 96 (in Chinese). http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=gdxxhxxb201301015
12. [12]
  Song, H.-J.; Liu, Y.-X.; Xiong, L.-X.; Li, Y.-Q.; Yang, N.; Wang, Q.-M. J. Agric. Food Chem., 2013, 61, 8730. doi: 10.1021/jf402719z
13. [13]
  Zhao, Y.; Li, Y.-Q.; Xiong, Li.-X.; Xu, L.-P.; Peng, L.-N.; Li, F.; Li, Z.-M. Chem. Res. Chin. Univ. 2013, 29, 51. doi: 10.1007/s40242-013-2167-y
14. [14]
  Grossmann, K.; Ehrhardt, T. Pest. Manage. Sci. 2007, 63, 429. doi: 10.1002/ps.1341
15. [15]
  Yang, S.-G.; Hao, G.-F.; Dayan, F.-E.; Tranel, P.; Yang, G.-F. Chin. J. Chem. 2013, 31, 1153. doi: 10.1002/cjoc.201300449
16. [16]
  Monicka, J.; James, C. J. Mol. Struct. 2014, 1075, 335. doi: 10.1016/j.molstruc.2014.07.002
17. [17]
  Chen, X.-L.; Xiao, Y.-X.; Wang, G.-L.; Li, Z.; Xu, X.-Y. Res. Chem. Intermed. 2016, 42, 5495. doi: 10.1007/s11164-015-2381-y
18. [18]
  Meanwell, N. J. Med. Chem. 2011, 54, 2529. doi: 10.1021/jm1013693
19. [19]
  Lingaraju, G.; Balaji, K.; Jayarama, S.; Anil, S.; Kiran, K.; Sadashiva, M. Bioorg. Med. Chem. Lett. 2018, 28, 3606. doi: 10.1016/j.bmcl.2018.10.046
20. [20]
  Loh, B.; Vozzolo, L.; Mok, B.; Lee, C.-C.; Fitzmaurice, R.; Caddick, S.; Fassati, A. Chem. Biol. Drug. Des. 2010, 75, 461. doi: 10.1111/j.1747-0285.2010.00956.x
21. [21]
  Talley, J.; Brown, D.; Carter, J.; Graneto, M.; Koboldt, C.; Masferrer, J.; Perkins, W.; Rogers, R.; Shaffer, A.; Zhang, Y.-Y.; Zweifel, B.; Seibert, K. J. Med. Chem. 2000, 43, 775. doi: 10.1021/jm990577v
22. [22]
  Brahmayya, M.; Venkateswararao, B.; Krishnarao, D.; Durgarao, S.; Prasad, U.; Damodharam, T.; Mishra, R. J. Pharm. Res. 2013, 7, 516.
23. [23]
  方芳, 博士论文, 广西大学, 南宁, 2016.Fang, F. Ph. D. Dissertation, Guangxi University, Nanning, 2016 (in Chinese).
24. [24]
  Pascal, B.; Gopal, D.; Wolfgang, V.; Matthias, P.; Franz, J. B. WO 2016102482, 2016 [Chem. Abstr. 2016, 165, 152398].
25. [25]
  Shoop, W.; Hartline, E.; Gould, B.; Waddell, M.; McDowell, R.; Kinney, J.; Lahm, G.; Long, J.; Xu, M.; Wagerle, T.; Jones, G.; Dietrich, R.; Cordova, D.; Schroeder, M.; Rhoades, D.; Benner, E.; Confalone, P. Vet. Parasitol. 2014, 201, 179. doi: 10.1016/j.vetpar.2014.02.020
26. [26]
  Ishaaya, I.; Horowitz, A. R. In Insecticides with Novel Modes of Action: Mechanisms and Application, Eds.: Ishaaya, I.; Degheele, D., Springer, Berlin, 1998, p. 152.
27. [27]
  Semple, G.; Gharbaoui, T.; Shin, Y.; Decaire, M.; Averbuj, C.; Skinner, P. US 20070032537, 2007 [Chem. Abstr. 2007, 142, 219276].
28. [28]
  Martins, M.; Sinhorin, A.; Frizzo, C.; Buriol, L.; Scapin, E.; Zanatta, N.; Bonacorso, H. J. Heterocycl. Chem. 2013, 50, 71. doi: 10.1002/jhet.996
29. [29]
  Jagannath, M.; Madhavan, G.; Shanmugam, P. WO 2014202580, 2014[Chem. Abstr. 2014, 162, 137571].
30. [30]
  刘婷婷, 倪芸, 钟良坤, 黄红英, 胡伟群, 许天明, 谭成侠, 有机化学, 2015, 35, 422. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract344660.shtmlLiu, T.-T.; Ni, Y.; Zhong, L.-K.; Huang, H.-Y.; Hu, W.-Q.; Xu, T.-M.; Tan, C.-X. Chin. J. Org. Chem. 2015, 35, 422 (in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract344660.shtml

图 1 吡唑类衍生物

Figure 1 Pyrazole derivatives

下载: 全尺寸图片幻灯片

图式 1 目标化合物的设计策略

Scheme 1 Design strategy of the target compounds

下载: 全尺寸图片幻灯片

图式 2 目标化合物ZJ1~ZJ16的合成路线

Scheme 2 Synthetic routes of the target compounds ZJ1~ZJ16

下载: 全尺寸图片幻灯片

表 1 500 mg/L下目标化合物的杀虫活性(死亡率/%)

Table 1. Insecticidal activities (mortality/%) of title compounds at 500 mg/L

Compd.	Mythimna separate	Aphis craccivora	Tetranychus cinnabarinus
ZJ1	50	0	0
ZJ2	100	0	0
ZJ3	60	0	0
ZJ4	0	30	0
ZJ5	100	80	0
ZJ6	80	80	0
ZJ7	100	0	0
ZJ8	100	0	0
ZJ9	100	80	0
ZJ10	0	50	0
ZJ11	50	0	0
ZJ12	60	0	0
ZJ13	0	90	0
ZJ14	100	0	0
ZJ15	0	60	0
ZJ16	90	30	0
Avermectin	100	100	100
空白对照	0	0	0

下载: 导出CSV

表 2 目标化合物在100, 20 mg/L浓度下对粘虫和苜蓿蚜的杀虫活性(死亡率/%)

Table 2. Insecticidal activities (mortality/%) of title compounds against M. separate and A. craccivora at 100 and 20 mg/L

Compd.	Mythimna separate		Aphis craccivora
Compd.	100 mg/L	20 mg/L	100 mg/L
ZJ2	30	0	0
ZJ5	60	0	30
ZJ6	55	0	30
ZJ7	30	0	0
ZJ8	65	0	0
ZJ9	60	0	25
ZJ13	0	0	20
ZJ14	50	0	0
ZJ15	0	0	15
ZJ16	35	0	0
Avermectin	100	95	100
空白对照	0	0	0

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