CN115246826A - 季铵盐类异噁唑啉化合物及其制备和作为杀虫、杀菌剂的应用 - Google Patents

季铵盐类异噁唑啉化合物及其制备和作为杀虫、杀菌剂的应用 Download PDF

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CN115246826A
CN115246826A CN202110454200.4A CN202110454200A CN115246826A CN 115246826 A CN115246826 A CN 115246826A CN 202110454200 A CN202110454200 A CN 202110454200A CN 115246826 A CN115246826 A CN 115246826A
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汪清民
黄世盛
刘爱玲
王兹稳
李守军
李永强
李亚玲
刘玉秀
张朋丽
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Nankai University
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Abstract

本发明涉及一类新型季铵盐类异噁唑啉化合物及其制备方法和在防治害虫及植物病菌方面的应用。本发明的季铵盐类异噁唑啉化合物显示出很好的杀小菜蛾、东方粘虫、草地贪夜蛾、棉铃虫、玉米螟、蚊幼虫活性及抑制植物病菌活性。

Description

季铵盐类异噁唑啉化合物及其制备和作为杀虫、杀菌剂的 应用
技术领域
本发明涉及一类新型季铵盐类异噁唑啉化合物及其制备和在防治害虫及植物病菌方面的应用，属于农业防护及害虫防治技术领域。
背景技术
联合国粮农组织(FAO)统计数据显示，因病虫草害每年造成的世界粮食损失约占总产量的1/3。农药的应用大大减少了农田疾病、病虫害和杂草的破坏，减轻了全球饥荒。害虫为近几十年来农作物减产的最重要原因，然而，随着杀虫剂的广泛使用，对各种杀虫剂具有抗性的昆虫的出现成为世界范围内的严重问题。为促进农业中的杀虫剂抗性管理并满足快速增长的人口的食品需求，迫切需要开发作用于新靶标或靶标中新位点的绿色杀虫剂(Org.ProcessRes.Dev.2020,24,1024–1031)。
自2005年日本日产化学株式会社报道了异噁唑啉类化合物作为杀虫剂后(W.O.2005085216)，作为21世纪发现的一类新型杀虫剂，由于其独特的杀虫机制、高选择性，与现有杀虫剂无显著交互抗性等特点，已成为杀虫剂研究领域的热点和前沿。众多研究机构对此异噁唑啉结构进行了大量的研究报道，在广泛筛选中发现了许多高活性化合物。目前已有四个异噁唑啉商品化兽用杀虫剂和二个异噁唑啉农用杀虫剂(结构式一)(ChemMedChem2016,11,270–276.)。因此，从异噁唑啉骨架出发，设计开发新的高效低毒异噁唑啉类杀虫剂具有重要意义。
Figure BDA0003039201810000011
季铵盐具有广泛的生物活性，如抗癌、抗菌、抗真菌、抗病毒、抗寄生虫等。且通常认为季铵盐与nAChRs具有显著的亲和力，且季铵盐杀虫剂可降低其穿透血脑屏障的能力，从而减少副作用(J.Agric.Food Chem.2014,62,3577–3583.)。
发明内容
本发明目的在于提供一类新型季铵盐类异噁唑啉化合物及其制备和在防治害虫及植物病菌方面的应用。结合“中间体衍生化法”，引入季铵盐结构，来研究其生物活性的变化。并首次发现了基于杜邦公司报道的异噁唑啉杀虫剂高活性分子DP-9而得到的季铵盐类异噁唑啉化合物具有很好的杀小菜蛾、东方粘虫、草地贪夜蛾、棉铃虫、玉米螟、蚊幼虫活性、跳蚤、蜱、螨虫及抑制植物病菌活性。本发明为创制新型、广谱、高效的杀虫药剂奠定了基础，具备很好的创造性。
本发明所述的季铵盐类异噁唑啉衍生物I为下述I-1～I-46所示的化合物(结构式二)
Figure BDA0003039201810000021
Figure BDA0003039201810000031
上述化学结构式I-1～I-9的合成方法如下：
季铵盐异噁唑啉衍生物I-1～I-9的合成：按照方程式一所示的方法制备，首先以3,5-二氯苯硼酸(1)和2-溴-3,3-三氟丙烯(2)为原料，碳酸钠为碱，双三苯基膦基氯化钯为催化剂，在四氢呋喃和水中回流得到偶联产物3,5-二氯-1-(1-三氟甲基乙烯基)苯(3)。以2-氟-5-甲酰基苯腈(4)为原料，在甲醇和水中，碳酸钠催化下，与盐酸羟胺反应生成肟(5)，然后与上面合成的3在水中，KCl存在下，Oxone氧化环化生成5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-氟苯甲腈(6)。再以碳酸钾为碱，碘化亚铜催化下与1,2,3-三氮唑亲核取代得到化合物DP-9。最后与溴化物或碘化物在110℃下进行季铵化反应生成I-1～I-9。
Figure BDA0003039201810000041
上述方程式中R分别为I-1～I-9结构中所示基团。
季铵盐异噁唑啉衍生物I-10～I-46的合成：按照方程式二所示的方法制备，以乙腈做溶剂，4-唑基异噁唑啉DP-9和与溴化物在110℃下进行季铵化反应生成I-10～I-46。
Figure BDA0003039201810000042
上述方程式中R分别为I-10～I-46结构中所示基团。
本发明的季铵盐异噁唑啉衍生物I-1～I-46表现出广谱杀虫活性，部分化合物高于Fluralaner及DP-9的效果或者相当。整体来看，大部分化合物显示出了较好的杀小菜蛾活性，在0.1mg/L浓度下亦具有较好的活性。尤其是化合物I-31、I-34表现出优于fluralaner和DP-9的杀小菜蛾活性，对其它害虫如粘虫、草地贪夜蛾、棉铃虫、玉米螟、蚊幼虫、蚜虫、朱砂叶螨成螨、跳蚤、蜱、蠕形螨、疥螨、耳螨等亦具有很好的灭杀活性。
本发明的季铵盐异噁唑啉衍生物I-1～I-46表现出很好的抗植物病菌活性，能很好地抑制黄瓜枯萎，花生褐斑，苹果轮纹，小麦纹枯，玉米小斑，西瓜炭疽，水稻恶苗，番茄早疫，小麦赤霉，水稻稻瘟，辣椒疫霉，油菜菌核，黄瓜灰霉，水稻纹枯14种植物病菌。
具体实施方式
下述的实施例和生测试验结果可用来进一步说明本发明，但不意味着限制本发明。
实施例1：季铵盐异噁唑啉衍生物I-1的合成
第一步，3,5-二氯-1-(1-三氟甲基乙烯基)苯(3)的合成。将3,5-二氯苯基硼酸(1)(57.25g,300mmol)，二氯双(三苯基膦)钯(6.32g,9mmol)加入2L的干燥三口瓶中，氩气置换气三次，然后用注射器加入200mL 3.0M的碳酸钾水溶液及600mL四氢呋喃，随后加入2-溴-3,3,3-三氟丙烯(2)(37.4mL,360mmol)，加热回流搅拌4h。反应结束后，冷却至室温，加入冰水，水相用乙酸乙酯萃取3次，合并有机相经水洗2次，饱和氯化钠洗涤1次，无水硫酸钠干燥，减压浓缩，经PE柱层析得无色油状物45.92g，收率64％。
第二步，2-氟-5((羟基亚氨基)甲基)苯甲腈(5)的合成。将2-氟-5-甲酰基苄腈(14.91g,100mmol)和盐酸羟胺(10.43g,150mmol)溶解在含有200mL水和100mL甲醇的500mL烧瓶中，缓慢加入碳酸钠(19.08g,180mmol)，室温搅拌过夜。减压旋除大部分甲醇，随后将反应液倒入300mL冰水中，析出大量白色固体，抽滤得蓬松的白色粉末12.29g，收率75％。1HNMR(400MHz,CDCl3)δ8.10(s,1H),7.88–7.79(m,3H),7.25(t,J＝8.6Hz,1H).13C NMR(100MHz,CDCl3)δ163.7(d,J＝262.8Hz),147.3,133.4(d,J＝8.7Hz),132.0,129.7(d,J＝4.2Hz),117.2(d,J＝20.3Hz),113.5,102.4(d,J＝16.2Hz).
第三步，5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-氟苯甲腈(6)的合成。将3,5-二氯-1-(1-三氟甲基乙烯基)苯(3)(60.00g,250mmol)，2-氟-5((羟基亚氨基)甲基)苯甲腈(5)(16.4g,100mmol)和KCl(7.46g,100mmol)加入1L圆底烧瓶中，然后加入750mL水，最后在搅拌下加入Oxone(92.2g,150mmol)，室温搅拌4h。将混合物倒入分液漏斗中，水相用二氯甲烷萃取3次，合并有机相经水洗2次，饱和氯化钠洗涤1次，无水硫酸钠干燥，减压浓缩，经PE/EA＝10/1柱层析得白色固体5.40g，收率67％。1H NMR(400MHz,CDCl3)δ7.98(dd,J＝8.4,5.6Hz,1H),7.89(d,J＝5.6Hz,1H),7.49(s,2H),7.44(s,1H),7.32(t,J＝8.4Hz,1H),4.07(d,J＝17.2Hz,1H),3.70(d,J＝17.2Hz,1H).13C NMR(100MHz,CDCl3)δ164.3(d,J＝265.2Hz),153.7,138.5,135.9,133.4(d,J＝8.9Hz),132.1,130.1,125.4(d,J＝4.1Hz),125.3,123.7(q,J＝282.5Hz),117.7(d,J＝20.6Hz),112.9,102.8(d,J＝16.4Hz),88.0(q,J＝30.7Hz),43.8.
第四步，5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)的合成。将5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异恶唑-3-基)-2-氟苯甲腈(6)(33.78g,84mmol)，1,2,4-三唑(8.12g,117.6mmol)，CuI(3.20g,16.8mmol)和碳酸钾(23.22g,168mmol)加入含有160mLDMF干燥的250mL烧瓶中，氩气置换气三次，于120℃加热搅拌24h。将反应混合物冷却至室温，加入乙酸乙酯，用硅藻土过滤，加入300mL水，并用乙酸乙酯萃取3次，合并有机相经水洗多次，饱和氯化钠洗涤1次，无水硫酸钠干燥，减压浓缩，经PE/EA＝1/1柱层析得白色固体34.15g，收率90％。1H NMR(400MHz,CDCl3)δ8.86(s,1H),8.16(s,1H),8.11–8.04(m,2H),7.92–7.87(m,1H),7.48(d,J＝1.6Hz,2H),7.41(t,J＝1.6Hz,1H),4.13(d,J＝17.2Hz,1H),3.77(d,J＝17.2Hz,1H).13CNMR(100MHz,CDCl3)δ153.7,153.4,143.1,139.8,138.3,135.8,132.8,132.3,130.1,128.6,125.2,125.0,123.5(q,J＝282.7Hz),115.4,106.3,88.1(q,J＝30.8Hz),43.4.
第五步，I-1的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和碘甲烷(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体500.4mg，收率84％，熔点220-222℃；1H NMR(400MHz,DMSO-d6)δ10.90(s,1H),9.52(s,1H),8.50(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.10(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),4.56(d,J＝18.4Hz,1H),4.45(d,J＝18.4Hz,1H),4.06(s,3H).13C NMR(100MHz,DMSO-d6)δ156.1,146.2,145.2,138.4,136.9,134.7,134.4,132.9,130.3),129.7,126.3,125.6,123.7(q,J＝282.7Hz),114.5,107.6,87.5(q,J＝29.9Hz),42.6,34.7.19F NMR(376MHz,DMSO-d6)δ-78.84(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C20H13Cl2F3N5O[M-Br]+466.0444,found,466.0450.
实施例2：I-2的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴乙烷(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体459.7mg，收率82％，熔点222-224℃；1HNMR(400MHz,DMSO-d6)δ11.08(s,1H),9.67(s,1H),8.50(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.19(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),4.56(d,J＝18.4Hz,1H),4.50–4.40(m,3H),1.59(t,J＝7.2Hz,3H).13C NMR(100MHz,DMSO-d6)δ156.2,145.2,144.6,138.4,136.9,134.7,134.4,132.8,130.2,129.7,126.2,125.6,123.7(q,J＝282.6Hz),114.6,107.5,87.5(q,J＝29.9Hz),43.9,42.6,14.2.19F NMR(376MHz,DMSO-d6)δ-78.81(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C21H15Cl2F3N5O[M-Br]+480.0600,found,480.0605.
实施例3：I-3的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴丁烷(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体330.5mg，收率56％，熔点204-206℃；1HNMR(400MHz,DMSO-d6)δ11.06(s,1H),9.66(s,1H),8.49(d,J＝1.6Hz,1H),8.41(dd,J＝8.4,1.6Hz,1H),8.17(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),4.56(d,J＝18.4Hz,1H),4.49–4.38(m,3H),2.00–1.90(m,2H),1.46–1.36(m,2H),0.96(t,J＝7.2Hz,3H).13CNMR(100MHz,DMSO-d6)δ156.1,145.3,144.5,138.4,136.8,134.7,134.2,132.7,130.2,129.6,126.2,125.6,123.6(q,J＝282.6Hz),114.5,107.5,87.4(q,J＝30.0Hz),48.0,42.6,30.5,18.7,13.2.19F NMR(376MHz,DMSO-d6)δ-78.81(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C23H19Cl2F3N5O[M-Br]+508.0913,found,508.0918.
实施例4：I-4的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴庚烷(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体290.5mg，收率47％，熔点202-204℃；1H NMR(400MHz,DMSO-d6)δ11.10(s,1H),9.68(s,1H),8.50(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.6Hz,1H),8.19(d,J＝8.4Hz,1H),7.83(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),4.56(d,J＝18.4Hz,1H),4.46(d,J＝18.4Hz,1H),4.41(t,J＝7.2Hz,2H),2.01–1.91(m,2H),1.44–1.26(m,6H),0.89(t,J＝6.8Hz,3H).13C NMR(100MHz,DMSO-d6)δ156.1,145.3,144.6,138.4,136.9,134.7,134.3,132.7,130.2,129.7,126.2,125.6,123.7(q,J＝282.6Hz),114.5,107.5,87.5(q,J＝29.9Hz),48.2,42.6,30.6,28.6,25.1,21.8,13.8.19F NMR(376MHz,DMSO-d6)δ-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C25H23Cl2F3N5O[M-Br]+536.1226,found,536.1228.
实施例5：I-5的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴甲基环丙烷(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体399.0mg，收率68％，熔点213-214℃；1HNMR(400MHz,DMSO-d6)δ11.11(s,1H),9.72(s,1H),8.50(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.22(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),4.32(d,J＝7.6Hz,2H),1.52–1.40(m,1H),0.74–0.59(m,4H).13C NMR(100MHz,DMSO-d6)δ156.2,145.1,144.4,138.4,137.0,134.7,134.3,132.7,130.3,129.7,126.4,125.6,123.7(q,J＝282.6Hz),119.4,114.6,107.6,87.5(q,J＝29.3Hz),52.8,42.6,10.1,4.2.19FNMR(376MHz,DMSO-d6)δ-78.82(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C23H17Cl2F3N5O[M-Br]+506.0757,found,506.0763.
实施例6：I-6的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和3-溴丙烯(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体463.8mg，收率81％，熔点188-190℃；1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),9.67(s,1H),8.50(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.20(d,J＝8.4Hz,1H),7.83(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),6.18(ddt,J＝16.4,10.4,6.0Hz,1H),5.54(ddd,J＝13.6,11.2,0.8Hz,2H),5.11(d,J＝6.4Hz,2H),4.57(d,J＝18.4Hz,1H),4.46(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ156.6,145.2,144.8,138.4,136.9,134.7,134.3,132.7,130.3,130.0,129.7,126.4,125.6,123.7(q,J＝282.5Hz),122.1,114.5,107.6,87.5(q,J＝29.8Hz),50.2,42.6.19F NMR(376MHz,DMSO-d6)δ-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C22H15Cl2F3N5O[M-Br]+492.0600,found,492.0596.
实施例7：I-7的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-丁炔基溴(0.5mL)，于110℃下反应24h生成黑色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得黑色固体365.0mg，收率63％，熔点184-185℃；1HNMR(400MHz,DMSO-d6)δ11.12(s,1H),9.73(s,1H),8.50(d,J＝1.6Hz,1H),8.41(dd,J＝8.4,1.6Hz,1H),8.20(d,J＝8.4Hz,1H),7.83(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),5.40(d,J＝2.0Hz),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),1.95(t,J＝2.0Hz,3H).13CNMR(100MHz,DMSO-d6)δ156.2,144.9,144.7,138.4,136.9,134.7,134.2,132.7,130.4,129.7,126.7,125.6,123.7(q,J＝283.1Hz),114.5,107.9,87.5(q,J＝29.4Hz),86.0,70.1,42.6,38.8,3.4.19F NMR(376MHz,DMSO-d6)δ-78.86(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C23H15Cl2F3N5O[M-Br]+504.0600,found,504.0606.
实施例8：I-8的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴乙酸乙酯(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体489.9mg，收率81％，熔点189-191℃；1H NMR(400MHz,DMSO-d6)δ11.05–10.98(m,1H),9.68–9.61(m,1H),8.52(d,J＝1.6Hz,1H),8.40(dd,J＝8.4,1.6Hz,1H),8.20–8.14(m,1H),7.84(d,J＝0.8Hz,1H),7.62(d,J＝1.6Hz,2H),5.53(d,J＝2.4Hz,2H),4.56(d,J＝18.4Hz,1H),4.46(d,J＝18.4Hz,1H),4.29(q,J＝7.2Hz,2H),1.29(t,J＝7.2Hz,3H).13C NMR(100MHz,DMSO-d6)δ165.6,156.2,146.2,145.5,138.4,136.9,134.7,134.1,132.8,130.6,129.7,126.7,125.6,123.7(q,J＝282.9Hz),114.4,108.1,87.5(q,J＝29.9Hz),62.4,48.7,42.6,13.9.19F NMR(376MHz,DMSO-d6)δ-78.84(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C23H17Cl2F3N5O3[M-Br]+538.0655,found,538.0666.
实施例9：I-9的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴乙酰胺(0.5mL)，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体473.5mg，收率81％，熔点238-239℃；1HNMR(400MHz,DMSO-d6)δ11.00(s,1H),9.59(s,1H),8.50(d,J＝2.0Hz,1H),8.39(dd,J＝8.4,2.0Hz,1H),8.16(d,J＝8.4Hz,1H),8.10(s,1H),7.84(t,J＝1.6Hz,1H),7.78(s,1H),7.62(d,J＝1.6Hz,2H),7.18(s,2H),5.26(s,2H),4.56(d,J＝18.4Hz,1H),4.46(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ165.4,156.2,146.4,145.4,138.4,136.9,134.7,134.2,132.8,130.4,129.7,126.5,125.7,123.7(q,J＝285.6Hz),114.5,107.8,87.5(q,J＝30.0Hz),49.5,42.6.19F NMR(376MHz,DMSO-d6)δ-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C21H14Cl2F3N6O2[M-Br]+509.0502,found,509.0506.
实施例10：I-10的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和溴苄(342.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体435.2mg，收率70％，熔点200-203℃；1H NMR(400MHz,DMSO-d6)δ11.12(s,1H),9.73(s,1H),8.48(d,J＝2.0Hz,1H),8.40(dd,J＝8.4,2.0Hz,1H),8.17(d,J＝8.4Hz,1H),7.85(t,J＝1.6Hz,1H),7.65–7.59(m,4H),7.53–7.43(m,3H),5.69(s,2H),4.56(d,J＝18.4Hz,1H),4.45(d,J＝18.4Hz,1H).13CNMR(100MHz,DMSO-d6)δ156.2,145.2,144.8,138.4,136.9,134.7,134.3,133.0,132.7,130.2,129.7,129.2,129.1,129.0,126.3,125.6,123.7(q,J＝282.8Hz),114.6,107.6,87.5(q,J＝30.0Hz),51.2,42.6.19F NMR(376MHz,DMSO-d6)δ-78.82(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C26H17Cl2F3N5O[M-Br]+542.0757,found,542.0764.
实施例11：I-11的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和4-甲基溴苄(370.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体537.2mg，收率85％，熔点207-209℃；1H NMR(400MHz,DMSO-d6)δ11.12(s,1H),9.72(s,1H),8.48(d,J＝2.0Hz,1H),8.40(dd,J＝8.4,2.0Hz,1H),8.17(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),7.51(d,J＝8.0Hz,2H),7.29(d,J＝8.0Hz,2H),5.64(s,2H),4.56(d,J＝18.4Hz,1H),4.45(d,J＝18.4Hz,1H),2.33(s,3H).13C NMR(100MHz,DMSO-d6)δ156.2,145.1,144.6,138.8,138.4,136.9,134.7,134.2,132.7,130.2,123.0,129.7,129.6,129.2,126.4,125.6,123.7(q,J＝282.6Hz),114.6,107.6,87.5(q,J＝29.9Hz),51.0,42.6,20.8.19F NMR(376MHz,DMSO-d6)δ-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H19Cl2F3N5O[M-Br]+556.0913,found,556.0921.
实施例12：I-12的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和对三氟甲基溴苄(478.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体316.7mg，收率46％，熔点208-210℃；1H NMR(400MHz,DMSO-d6)δ11.13(s,1H),9.74(s,1H),8.49(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.16(d,J＝8.4Hz,1H),7.90–7.82(m,5H),7.62(d,J＝1.6Hz,2H),5.80(s,2H),4.56(d,J＝18.4Hz,1H),4.45(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ156.2,145.2,144.8,138.4137.5,136.8,134.7,134.3,132.7,130.3,130.1,129.7,129.4,126.3,125.9(q,J＝3.6Hz),125.6,124.0(q,J＝270.8Hz),123.7(q,J＝282.8Hz),114.6,107.5,87.5(q,J＝30.0Hz),50.5,42.6.19F NMR(376MHz,DMSO-d6)δ-61.72(s),-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H16Cl2F6N5O[M-Br]+610.0631,found,610.0640.
实施例13：I-13的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和4-叔丁基苄溴(454.3mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体640.0mg，收率95％，熔点199-200℃；1H NMR(400MHz,DMSO-d6)δ11.21–11.11(m,1H),9.79–9.72(m,1H),8.48(d,J＝2.0Hz,1H),8.40(dd,J＝8.4,2.0Hz,1H),8.21–8.15(m,1H),7.84(d,J＝1.6Hz,1H),7.62(d,J＝1.6Hz,2H),7.60–7.53(m,2H),7.52–7.47(m,2H),5.64(s,2H),4.56(d,J＝18.4Hz,1H),4.45(d,J＝18.4Hz,1H),1.28(s,9H).13C NMR(100MHz,DMSO-d6)δ156.1,151.8,145.1,144.7,138.4,136.9,134.7,134.2,132.7,130.2,130.1,129.0,126.3,125.8,125.6,123.7(q,J＝282.4Hz)，114.6,107.6,87.5(q,J＝30.0Hz),50.9,42.6,34.4,31.0.19F NMR(376MHz,DMSO-d6)δ-78.82(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C30H25Cl2F3N5O[M-Br]+598.1383,found,598.1395.
实施例14：I-14的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴苯乙酮(398.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体551.4mg，收率85％，熔点208-210℃；1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.60(s,1H),8.54(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.4Hz,1H),8.14(dd,J＝4.4,1.2Hz,1H),7.85(d,J＝1.6Hz,1H),7.82(dd,J＝12.8,1.2Hz,1H),7.69(t,J＝7.8Hz,2H),7.63(d,J＝1.6Hz,2H),6.34(s,2H2),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.8,156.2,146.5,145.5,138.4,137.0,134.9,134.7,134.1,133.3,132.8,130.5,129.7,129.2,128.4,126.8,125.7,123.7(q,J＝282.6Hz),114.4,108.1,87.51(q,J＝30.2Hz),54.4,42.6.19F NMR(376MHz,DMSO-d6)δ-78.85(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C27H17Cl2F3N5O2[M-Br]+570.0706,found,570.0717.
实施例15：I-15的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-氟苯乙酮(434.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体577.5mg，收率87％，熔点235-237℃；1H NMR(400MHz,DMSO-d6)δ11.00(s,1H),9.62(s,1H),8.54(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.2Hz,1H),8.28–8.19(m,3H),7.83(t,J＝1.6Hz,1H),7.63(d,J＝1.2Hz,2H),7.53(t,J＝8.4Hz,2H),6.36(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ188.6,165.9(d,J＝252.5Hz),156.2,146.4,145.6,138.4,137.0,134.7,134.1,132.8,131.6(d,J＝9.8Hz),130.5,130.1(d,J＝2.6Hz),129.7,126.8,125.7,123.7(q,J＝282.8Hz),116.43(d,J＝22.2Hz),114.5,108.1,87.5(q,J＝30.0Hz),54.4,42.6.19F NMR(376MHz,DMSO-d6)δ171.03(s),146.84(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C27H16Cl2F4N5O2[M-Br]+588.0612,found,588.0615.
实施例16：I-16的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-氯苯乙酮(467.0mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体612.9mg，收率90％，熔点247-248℃；1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.59(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.20(d,J＝8.4Hz,1H),8.16(d,J＝8.8Hz,2H),7.84(t,J＝1.6Hz,1H),7.77(d,J＝8.8Hz,2H),7.63(d,J＝1.6Hz,2H),6.33(s,2H),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.0,156.2,146.4,145.5,139.8,138.4137.0,134.7,134.1,132.8,132.1,130.5,130.3,129.7,129.4,126.8,125.6,123.7(q,J＝282.8Hz),114.4,108.1,87.5(q,J＝30.0Hz),54.4,42.6.19FNMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcd forC27H16Cl3F3N5O2[M-Br]+604.0316,found,604.0315.
实施例17：I-17的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-溴苯乙酮(555.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体652.0mg，收率90％，熔点235-237℃；1H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.58(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.20(d,J＝8.4Hz,1H),8.07(d,J＝8.8Hz,2H),7.91(d,J＝8.8Hz,2H),7.85(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.31(s,2H),4.57(d,J＝18.5Hz,1H),4.47(d,J＝18.5Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.3,156.2,146.5,145.6,138.4,137.0,134.7,134.1,132.8,132.4,132.3,130.5,130.3,129.8,129.1,126.8,125.7,123.7(q,J＝282.7Hz),114.5,108.1,87.5(q,J＝29.9Hz),54.4,42.6.19F NMR(376MHz,DMSO-d6)δ171.05(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C27H16BrCl2F3N5O2[M-Br]+647.9811,found,647.9815.
实施例18：I-18的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-(三氟甲基)苯乙酮(534.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体596.4mg，收率83％，熔点231-232℃；1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),9.60(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.34(d,J＝8.4Hz,2H),8.21(d,J＝8.4Hz,1H),8.07(d,J＝8.4Hz,2H),7.85(t,J＝2.0Hz,1H),7.63(d,J＝2.0Hz,2H),6.39(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.6,156.2,146.4,145.6138.4,137.0,136.6,134.7,134.1,133.9(q,J＝31.9Hz),132.8,130.5,129.7,129.3,126.8,126.2(q,J＝3.6Hz),125.7,123.7(q,J＝282.6Hz),123.6(q,J＝271.2Hz),114.4,108.2,87.5(q,J＝30.0Hz),54.7,42.6.19F NMR(376MHz,DMSO-d6)δ-61.74(s),-78.89(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H16Cl2F6N5O2[M-Br]+638.0580,found,638.0585.
实施例19：I-19的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-氰基苯乙酮(448.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体595.5mg，收率88％，熔点236-237℃；1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),9.60(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.29(d,J＝8.4Hz,2H),8.21(d,J＝8.4Hz,1H),8.18(d,J＝8.8Hz,2H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.38(s,2H),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.5,156.2,146.4,145.5,138.4,137.0,136.5,134.7,134.0,133.2,132.8,130.5,129.7,129.0,126.9,125.6,123.7(q,J＝282.7Hz),117.9,116.5,114.4,108.2,87.5(q,J＝30.0Hz),54.7,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H16Cl2F3N6O2[M-Br]+598.0658,found,598.0654.
实施例20：I-20的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-硝基苯乙酮(488.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体569.6mg，收率82％，熔点229-231℃；1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),9.61(s,1H),8.54(d,J＝1.6Hz,1H),8.49(d,J＝8.8Hz,2H),8.42(dd,J＝8.4,2.0Hz,1H),8.38(d,J＝8.8Hz,2H),8.22(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.2Hz,2H),6.42(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.3,156.2,150.7,146.4,145.6,138.4,138.0,137.0,134.7,134.0,132.8,130.5,129.9,129.7,126.9,125.6,124.2,123.7(q,J＝282.7Hz),114.4,108.2,87.5(q,J＝30.1Hz),54.8,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C27H16Cl2F3N6O4[M-Br]+615.0557,found,615.0557.
实施例21：I-21的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-1-(4-甲磺酰基)苯乙酮(554.3mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体621.8mg，收率86％，熔点238-239℃；1H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.63(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.38(d,J＝8.8Hz,2H),8.23(d,J＝8.0Hz,3H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.42(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),3.36(s,3H).13C NMR(100MHz,DMSO-d6)δ189.6,156.2,146.4,145.5,138.4,137.1,137.0,134.7,134.0,132.8,130.5,129.7,129.4,127.7,126.9,125.6,123.7(q,J＝282.7Hz),114.4,108.2,87.5(q,J＝30.1Hz),54.8,43.1,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H19Cl2F3N5O4S[M-Br]+648.0481,found,648.0482.
实施例22：I-22的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-甲基苯乙酮(426.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体455.4mg，收率69％，熔点234-235℃；1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.60(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.20(d,J＝8.4Hz,1H),8.04(d,J＝8.0Hz,2H),7.85(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.49(d,J＝8.0Hz,2H),6.31(s,2H),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),2.45(s,3H).13C NMR(100MHz,DMSO-d6)δ189.3,156.2,146.5,145.6,145.5,138.4,137.0,134.7,134.1,132.8,130.8,130.5,129.8129.7,128.5,126.8,125.7,123.7(q,J＝283.1Hz),114.4,108.1,87.5(q,J＝30.1Hz),54.3,42.6,21.4.19F NMR(376MHz,DMSO-d6)δ-78.85(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H19Cl2F3N5O2[M-Br]+584.0862,found,584.0871.
实施例23：I-23的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-1-(4-(叔丁基)苯基)乙酮(508.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体522.0mg，收率74％，熔点226-228℃；1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),9.61(s,1H),8.54(d,J＝1.6Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.4Hz,1H),8.07(d,J＝8.8Hz,2H),7.85(t,J＝1.6Hz,1H),7.70(d,J＝8.4Hz,2H),7.63(d,J＝1.2Hz,2H),6.32(s,2H),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),1.34(s,9H).13C NMR(100MHz,DMSO-d6)δ189.3,158.2,156.2,146.5,145.5,138.4,137.0,134.7,134.1,132.8,130.8,130.5,129.7,128.4,126.9,126.0,125.6,123.7(q,J＝282.8Hz),114.4,108.1,87.5(q,J＝30.1Hz),54.3,42.6,35.1,30.7.19F NMR(376MHz,DMSO-d6)δ171.05(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C31H25Cl2F3N5O2[M-Br]+626.1332,found,626.1328.
实施例24：I-24的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-1-(4-戊苯基)乙酮(508.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体516.0mg，收率73％，熔点203-204℃；1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),9.64(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.24(d,J＝8.4Hz,1H),8.06(d,J＝8.4Hz,2H),7.83(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.49(d,J＝8.4Hz,2H),6.36(s,2H),4.59(d,J＝18.4Hz,1H),4.49(d,J＝18.4Hz,1H),2.71(t,J＝7.6Hz,2H),1.65–1.54(m,2H),1.38–1.25(m,2H),0.90(t,J＝7.6Hz,3H).13C NMR(100MHz,DMSO-d6)δ189.3,156.2,150.2,146.4,145.5,138.4,137.0,134.7,134.1,132.8,131.1,130.5,129.7,129.1,128.6,126.8,125.7,123.7(q,J＝282.8Hz),114.5,108.1,87.5(q,J＝29.9Hz),54.3,42.6,34.9,32.7,21.7,13.7.19F NMR(376MHz,DMSO-d6)δ171.02(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C31H25Cl2F3N5O2[M-Br]+626.1332,found,626.1332.
实施例25：I-25的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-甲氧基苯乙酮(458.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体544.2mg，收率80％，熔点246-247℃；1H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.58(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.19(d,J＝8.4Hz,1H),8.11(dt,J＝9.2,2.0Hz,2H),7.85(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.20(dt,J＝9.2,2.0Hz,2H),6.27(s,2H),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),3.91(s,3H).13C NMR(100MHz,DMSO-d6)δ188.0,164.4,156.2,146.5145.5,138.4,137.0,134.7,134.1,132.8,130.9,130.5,129.7,126.8,126.1,125.7,123.7(q,J＝282.7Hz),122.3,114.5,114.4,108.1,87.5(q,J＝29.6Hz),55.8,54.0,42.6.19F NMR(376MHz,DMSO-d6)δ-78.84(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C28H19Cl2F3N5O3[M-Br]+600.0812,found,600.0819.
实施例26：I-26的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-4'-苯基苯乙酮(550.3mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体655.9mg，收率90％，熔点238-240℃；1H NMR(400MHz,DMSO-d6)δ11.03(s,1H),9.66(s,1H),8.55(d,J＝2.0Hz,1H),8.43(dd,J＝8.4,2.0Hz,1H),8.27–8.19(m,3H),8.00(d,J＝8.4Hz,2H),7.87–7.80(m,3H),7.64(d,J＝1.6Hz,2H),7.54(t,J＝7.6Hz,2H),7.47(tt,J＝7.6,1.6Hz,1H),6.42(s,2H),4.59(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.4,156.2,146.5,146.0,145.6,138.5,138.4,137.1,134.7,134.1,132.9,132.1,130.5,129.7,129.2,129.1,128.8127.3,127.1,126.8,125.7,123.7(q,J＝282.6Hz),114.5,108.1,87.5(q,J＝29.9Hz),54.4,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C33H21Cl2F3N5O2[M-Br]+646.1019,found,646.1015.
实施例27：I-27的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3'-三氟甲基苯乙酮(534.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体609.6mg，收率85％，熔点221-222℃；1H NMR(400MHz,DMSO-d6)δ11.00(s,1H),9.62(s,1H),8.54(d,J＝1.6Hz,1H),8.46–8.39(m,3H),8.23(d,J＝8.4Hz,1H),8.19(d,J＝7.6Hz,1H),7.95(t,J＝7.6Hz,1H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.43(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.3,156.2,146.4,145.6,138.4,137.0,134.7,134.3,134.1,132.8,132.4,131.0,130.7,130.5,129.8(q,J＝32.3Hz),129.7,126.9,125.7,124.9(q,J＝3.6Hz),123.7(q,J＝271.0Hz),123.6(q,J＝282.8Hz),114.5,108.2,87.5(q,J＝29.8Hz),54.6,42.6.19F NMR(376MHz,DMSO-d6)δ188.67(s),171.02(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H16Cl2F6N5O2[M-Br]+638.0580,found,638.0582.
实施例28：I-28的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-三氟甲基苯乙酮(534.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体510.6mg，收率71％，熔点237-239℃；1H NMR(400MHz,DMSO-d6)δ11.09(s,1H),9.70(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.33(d,J＝7.6Hz,1H),8.23(d,J＝8.4Hz,1H),8.00(t,J＝8.0Hz,2H),7.93(t,J＝7.6Hz,1H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.34(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ192.3,156.2,146.2,145.5,138.4,137.0,134.7,134.1,133.8(q,J＝1.5Hz),133.2,133.0,132.8,130.5,129.9,129.7,127.6(q,J＝5.4Hz),126.8,126.7(q,J＝31.9Hz),125.7,123.7(q,J＝282.6Hz),123.3(q,J＝272.1Hz),114.5,108.1,87.5(q,J＝29.9Hz),55.9,42.6.19F NMR(376MHz,DMSO-d6)δ192.90(s),171.04(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C28H16Cl2F6N5O2[M-Br]+638.0580,found,638.0580.
实施例29：I-29的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3'-氯苯乙酮(466.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体603.2mg，收率88％，熔点217-218℃；1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.59(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.8Hz,1H),8.18(t,J＝2.0Hz,1H),8.10(dt,J＝8.0,0.8Hz,1H),7.89(ddd,J＝8.0,2.0,0.8Hz,1H),7.85(t,J＝1.6Hz,1H),7.72(t,J＝8.0Hz,1H),7.63(d,J＝1.6Hz,2H),6.35(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13CNMR(100MHz,DMSO-d6)δ189.1,156.2,146.4145.6,138.4,137.0,135.2,134.7,134.5,134.1,134.0,132.8,131.3,130.5,129.7,128.1,127.1,126.9,125.7,123.7(q,J＝282.7Hz),114.5,108.2,87.5(q,J＝29.9Hz),54.5,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcd forC27H16Cl3F3N5O2[M-Br]+604.0316,found,604.0313.
实施例30：I-30的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-氯苯乙酮(466.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体395.4mg，收率58％，熔点205-207℃；1H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.64(s,1H),8.54(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.6Hz,1H),8.22(d,J＝8.4Hz,1H),8.15(dd,J＝8.0,1.2Hz,1H),7.84(t,J＝1.6Hz,1H),7.76–7.69(m,2H),7.67–7.61(m,3H),6.29(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ190.1,156.2,146.4,145.5,138.4,137.0,134.7,134.6,134.1,132.8,131.7,131.5,131.3,130.5,129.7,127.7,126.8,125.6,123.7(q,J＝282.6Hz),114.4,108.1,87.5(q,J＝29.9Hz),56.0,42.6.19F NMR(376MHz,DMSO-d6)δ171.05(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C27H16Cl3F3N5O2[M-Br]+604.0316,found,604.0319.
实施例31：I-31的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-溴苯乙酮(455.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体436.6mg，收率64％，熔点201-202℃。1H NMR(400MHz,DMSO-d6)δ11.04(s,1H),9.66(s,1H),8.54(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.6Hz,1H),8.23(d,J＝8.4Hz,1H),8.16(dd,J＝7.6,1.4Hz,1H),7.88(d,J＝7.6Hz,1H),7.84(t,J＝1.6Hz,1H),7.69(td,J＝7.6,1.2Hz,1H),7.66–7.60(m,3H),6.29(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ190.8,156.2,146.3,145.5,138.4,137.0,134.9,134.7,134.5,134.4,134.2,132.8,131.3,130.5,129.7,128.2,126.8,125.6,123.7(q,J＝282.7Hz),119.9,114.5,108.1,87.5(q,J＝29.8Hz),55.6,42.6.19F NMR(376MHz,DMSO-d6)δ-78.86(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C27H16BrCl2F3N5O2[M-Br]+647.9811,found,647.9813.
实施例32：I-32的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3'-甲氧基苯乙酮(458.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体548.9mg，收率81％，熔点221-223℃；1H NMR(400MHz,DMSO-d6)δ11.02(s,1H),9.65(s,1H),8.56(d,J＝2.0Hz,1H),8.44(dd,J＝8.4,2.0Hz,1H),8.24(d,J＝8.4Hz,1H),7.85(t,J＝1.6Hz,1H),7.76(d,J＝8.0Hz,1H),7.68–7.60(m,4H),7.41(dd,J＝8.0,2.0Hz,1H),6.39(s,2H),4.60(d,J＝18.4Hz,1H),4.50(d,J＝18.4Hz,1H),3.90(s,3H).13C NMR(100MHz,DMSO-d6)δ189.7,159.6,156.2,146.4,145.5,138.4,137.0,134.7,134.6,134.1,132.9,130.5,129.7,126.8,125.7,123.7(q,J＝282.8Hz),120.9,120.7,114.5,113.0,108.1,87.5(q,J＝29.9Hz),55.6,54.6,42.6.19F NMR(376MHz,DMSO-d6)δ171.03(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C28H19Cl2F3N5O3[M-Br]+600.0812,found,600.0811.
实施例33：I-33的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-甲氧基苯乙酮(458.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体447.6mg，收率66％，熔点214-215℃。1H NMR(400MHz,DMSO-d6)δ10.95(s,1H),9.58(s,1H),8.54(d,J＝1.6Hz,1H),8.41(dd,J＝8.4,1.4Hz,1H),8.20(d,J＝8.4Hz,1H),7.93(dd,J＝8.0,1.6Hz,1H),7.84(t,J＝1.6Hz,1H),7.76(td,J＝8.0,1.6Hz,1H),7.63(d,J＝1.6Hz,1H),7.37(d,J＝8.4Hz,1H),7.18(t,J＝7.6Hz,1H),6.09(s,1H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),4.06(s,1H).13CNMR(100MHz,DMSO-d6)δ189.2,160.0,156.2,146.5,145.5,138.4,137.0,136.5,134.7,134.1,132.9,130.5,129.7,126.7,125.6,123.7(q,J＝282.8Hz),122.7,121.1,114.4,113.2,108.1,87.5(q,J＝29.9Hz),57.8,56.4,42.6.19F NMR(376MHz,DMSO-d6)δ-78.87(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C28H19Cl2F3N5O3[M-Br]+600.0812,found,600.0814.
实施例34：I-34的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-羟基苯乙酮(430.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体559.5mg，收率84％，熔点203-205℃。1H NMR(400MHz,DMSO-d6)δ11.35(s,1H),11.00(s,1H),9.60(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.22(d,J＝8.4Hz,1H),7.88(dd,J＝8.0,1.6Hz,1H),7.82(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.59(td,J＝7.6,1.6Hz,1H),7.18(d,J＝8.0Hz,1H),7.01(td,J＝7.6,0.8Hz,1H),6.14(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.7,159.5,156.2,146.6,145.5,138.4,137.0,136.4,134.7,134.1,132.9,130.5,130.1,129.7,126.6,125.7,123.7(q,J＝282.6Hz),120.5,119.7,117.7,114.4,108.0,87.5(q,J＝29.8Hz),57.6,42.6.19F NMR(376MHz,DMSO-d6)δ-78.90(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H17Cl2F3N5O3[M-Br]+586.0655,found,586.0655.
实施例35：I-35的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-硝基苯乙酮(488.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体539.0mg，收率78％，熔点210-212℃。1H NMR(400MHz,DMSO-d6)δ11.12(s,1H),9.70(s,1H),8.54(s,1H),8.42(d,J＝8.4Hz,1H),8.27(d,J＝8.0Hz,1H),8.23(d,J＝8.4Hz,1H),8.11(t,J＝7.6Hz,1H),8.05(t,J＝7.6Hz,1H),7.95(t,J＝7.6Hz,1H),7.85(s,1H),7.63(s,2H),6.23(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ191.9,156.2,146.3,146.1,145.5,138.4,137.0,134.7,134.5,134.1,133.4,132.7,130.9,130.5,129.7,129.2,126.9,125.7,124.6,123.7(q,J＝282.5Hz),114.5,108.2,87.5(q,J＝29.7Hz),55.7,42.6.19F NMR(376MHz,DMSO-d6)δ-78.87(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C27H16Cl2F3N6O4[M-Br]+615.0557,found,615.0556.
实施例36：I-36的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-甲基苯乙酮(426.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体469.0mg，收率71％，熔点208-210℃。1H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.64(s,1H),8.54(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.6Hz,1H),8.24(d,J＝8.4Hz,1H),8.12(d,J＝7.6Hz,1H),7.84(t,J＝1.6Hz,1H),7.67–7.58(m,3H),7.51(t,J＝7.6Hz,1H),7.45(d,J＝7.6Hz,1H),6.29(s,1H),4.59(d,J＝18.4Hz,1H),4.49(d,J＝18.4Hz,1H),2.53(s,1H).13C NMR(100MHz,DMSO-d6)δ191.8,156.2,146.4,145.5,139.3,138.4,137.1,134.7,134.1,133.4,132.8,132.7,132.3,130.5,129.9,129.7,126.7,126.4,125.7,123.7(q,J＝282.7Hz),114.5,108.1,87.5(q,J＝29.8Hz),55.6,42.6,21.3.19F NMR(376MHz,DMSO-d6)δ-78.87(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H19Cl2F3N5O2[M-Br]+568.0862,found,568.0865.
实施例37：I-37的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3',4'-二氯苯乙酮(535.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体677.2mg，收率94％，熔点236-237℃；1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.58(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.39(d,J＝2.0Hz,1H),8.21(d,J＝8.8Hz,1H),8.09(dd,J＝8.4,2.0Hz,1H),7.98(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.34(s,2H),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13CNMR(100MHz,DMSO-d6)δ188.5,156.2,146.4,145.6,138.4,137.6,137.0,134.7,134.1,133.6,132.8,132.3,131.6,130.5,130.3,129.8,128.4,126.9,125.7,123.7(q,J＝282.9Hz),114.5,108.2,87.5(q,J＝29.9Hz),54.5,42.6.19F NMR(376MHz,DMSO-d6)δ171.05(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H15Cl4F3N5O2[M-Br]+637.9926,found,637.9923.
实施例38：I-38的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3',5'-二氯苯乙酮(535.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体651,1mg，收率91％，熔点221-223℃。1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),9.58(s,1H,NCH),8.53(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.4Hz,1H),8.15(d,J＝2.0Hz,2H),8.11(t,J＝2.0Hz,1H),7.85(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.34(s,2H),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ188.4,156.2,146.3,145.6,138.4,137.0,136.4,135.1,134.7,134.1,133.8,132.8,130.5,129.8,127.0,126.9,125.7,123.7(q,J＝282.7Hz),114.5,108.2,87.5(q,J＝29.8Hz),54.6,42.6.19F NMR(376MHz,DMSO-d6)δ-78.89(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H15Cl4F3N5O2[M-Br]+637.9926,found,637.9923.
实施例39：I-39的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2',4'-二氯苯乙酮(535.9mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体644.4mg，收率90％，熔点231-233℃。1H NMR(400MHz,DMSO-d6)δ11.01(s,1H),9.63(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.22(d,J＝8.4Hz,1H),8.18(d,J＝8.4Hz,1H),7.91(d,J＝2.0Hz,1H),7.84(t,J＝1.6Hz,1H),7.77(dd,J＝8.4,2.0Hz,1H),7.63(d,J＝1.6Hz,2H),6.28(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13CNMR(100MHz,DMSO-d6)δ189.3,156.2,146.3,145.5,138.6,138.4,137.0,134.7,134.1,133.0,132.8,132.7,131.6,131.1,130.5,129.7,127.9,126.3,125.6,123.7(q,J＝282.8Hz),114.4,108.1,87.5(q,J＝29.8Hz),56.0,42.6.19F NMR(376MHz,DMSO-d6)δ-78.88(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C27H15Cl4F3N5O2[M-Br]+637.9926,found,637.9925.
实施例40：I-40的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2'-氯-6'-氟苯乙酮(503.0mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体368.0mg，收率53％，熔点201-202℃。1H NMR(400MHz,DMSO-d6)δ11.15(s,1H),9.73(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.24(d,J＝8.4Hz,1H),7.84(t,J＝1.6Hz,1H),7.75(td,J＝8.4,6.0Hz,1H),7.63(d,J＝1.6Hz,2H),7.60–7.51(m,2H),6.18(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ189.6,160.0(d,J＝250.8Hz),156.2,146.3,145.7,138.4,136.9,134.9,134.7,134.2,132.8,131.6(d,J＝5.1Hz),130.5,129.7,127.1(d,J＝3.0Hz),126.7,125.7,123.7(q,J＝282.8Hz),123.2(d,J＝19.4Hz),115.8(d,J＝21.9Hz),114.5,108.0,87.5(q,J＝29.7Hz),57.2(d,J＝6.9Hz),42.6.19F NMR(376MHz,DMSO-d6)δ-78.89(s),-109.81(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C27H15Cl3F4N5O2[M-Br]+622.0222,found,622.0225.
实施例41：I-41的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-3',4'二甲氧基苯乙酮(518.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体585.8mg，收率83％，熔点214-216℃；1H NMR(400MHz,DMSO-d6)δ10.97(s,1H),9.61(s,1H),8.54(d,J＝1.6Hz,1H),8.42(dd,J＝8.4,1.6Hz,1H),8.21(d,J＝8.4Hz,1H),7.87–7.80(m,2H),7.63(d,J＝1.6Hz,2H),7.57(d,J＝2.0Hz,1H),7.23(d,J＝8.4Hz,1H),6.31(s,2H),4.58(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H),3.92(s,3H),3.87(s,3H).13C NMR(100MHz,DMSO-d6)δ188.1,156.2,154.4,148.9,146.5,145.5,138.4,137.0,134.7,134.1,132.8,130.5,129.7,126.8,126.0,125.6,123.7(q,J＝282.8Hz),123.6,114.4,111.3,110.3,108.1,87.5(q,J＝29.9Hz),56.0,55.8,54.1,42.6.19F NMR(376MHz,DMSO-d6)δ171.04(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C29H21Cl2F3N5O4[M-Br]+630.0917,found,630.0917.
实施例42：I-42的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2',5'二甲氧基苯乙酮(518.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体653.0mg，收率92％，熔点219-220℃。1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),9.59(s,1H),8.54(d,J＝2.0Hz,1H),8.42(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.4Hz,1H),7.83(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.41–7.30(m,3H),6.09(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),4.02(s,3H),3.78(s,3H).13C NMR(100MHz,DMSO-d6)δ189.0,156.2,154.4,153.2,146.5,145.5,138.4,137.0,134.7,134.1,132.9,130.5,129.7,126.7,125.7,123.7(q,J＝282.9Hz),122.9,122.8,114.8,114.4,113.5,108.1,87.5(q,J＝30.0Hz),57.8,56.8,55.7,42.6.19F NMR(376MHz,DMSO-d6)δ-78.90(s).MassSpectrometry:HRMS-ESI(m/z):calcd for C29H21Cl2F3N5O4[M-Br]+630.0917,found,630.0919.
实施例43：I-43的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-2',4'二甲氧基苯乙酮(518.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体619.3mg，收率87％，熔点226-228℃。1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),9.58(s,1H),8.54(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.21(d,J＝8.4Hz,1H),7.92(d,J＝8.8Hz,1H),7.83(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),6.82(d,J＝2.0Hz,1H),6.76(dd,J＝8.8,2.0Hz,1H),6.02(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),4.06(s,3H),3.92(s,3H).13C NMR(100MHz,DMSO-d6)δ187.2,166.2,162.2,156.2,146.6,145.5,138.4,137.0,134.7,134.1,132.9,132.5,130.4,129.7,126.6,125.6,123.7(q,J＝282.6Hz),115.9,114.4,108.0,107.5,98.5,87.5(q,J＝29.8Hz),57.6,56.5,56.0,42.6.19F NMR(376MHz,DMSO-d6)δ-78.90(s).Mass Spectrometry:HRMS-ESI(m/z):calcdfor C29H21Cl2F3N5O4[M-Br]+630.0917,found,630.0920.
实施例44：I-44的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和1-(1,3-苯并氧)2-溴乙酮(486.1mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体591.2mg，收率85％，熔点249-251℃；1H NMR(400MHz,DMSO-d6)δ10.93(s,1H),9.58(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.19(d,J＝8.4Hz,1H),7.85(t,J＝1.6Hz,1H),7.80(dd,J＝8.4,1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.61(d,J＝1.7Hz,1H),7.21(d,J＝8.4Hz,1H),6.29–6.18(m,4H),4.57(d,J＝18.4Hz,1H),4.47(d,J＝18.4Hz,1H).13C NMR(100MHz,DMSO-d6)δ187.8,156.2,152.9,148.2,146.5,145.5,138.4,137.0,134.7,134.1,132.8,130.5,129.8,127.7,126.8,125.7,125.5,123.7(q,J＝282.3Hz),114.5,108.6,108.1,107.5,102.6,87.5(q,J＝29.9Hz),54.1,42.6.19F NMR(376MHz,DMSO-d6)δ171.05(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C28H17Cl2F3N5O4[M-Br]+614.0604,found,614.0607.
实施例45：I-45的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和2-溴-1-(2,4-二甲基苯基)乙酮(454.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体601.9mg，收率89％，熔点229-230℃；1H NMR(400MHz,DMSO-d6)δ10.96(s,1H),9.61(s,1H),8.53(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.22(d,J＝8.4Hz,1H),8.03(d,J＝8.4Hz,1H),7.84(t,J＝2.0Hz,1H),7.63(d,J＝1.6Hz,2H),7.32(d,J＝8.0Hz,1H),7.27(s,1H),6.24(s,2H),4.58(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),2.51(s,3H),2.39(s,3H).13C NMR(100MHz,DMSO-d6)δ191.0,156.2,146.5,145.5,144.1,139.7,138.4,137.1,134.7,134.1,133.1,132.8,130.5,130.3,129.9,129.7,126.9,126.7,125.7,123.7(q,J＝282.8Hz),114.5,108.1,87.5(q,J＝29.9Hz),55.3,42.6,21.5,21.1.19F NMR(376MHz,DMSO-d6)δ171.05(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C29H21Cl2F3N5O2[M-Br]+598.1019,found,598.1015.
实施例46：I-46的合成。向耐压管中加入5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-(1H-1,2,4-三唑-1-基)苯甲腈(DP-9)(451.0mg,1mmol)和3-溴-1-苯基丙-1-酮(454.2mg,2mmol)，随后加入1mL乙腈，于110℃下反应24h生成白色固体。冷却至室温后，加入少量石油醚，抽滤，固体用THF/PE(1:1)洗涤并干燥，得白色固体612.5mg，收率90％，熔点218-220℃。1H NMR(400MHz,DMSO-d6)δ10.98(s,1H),9.56(s,1H),8.52(d,J＝2.0Hz,1H),8.41(dd,J＝8.4,2.0Hz,1H),8.20(d,J＝8.4Hz,1H),7.82(t,J＝1.6Hz,1H),7.63(d,J＝1.6Hz,2H),7.32–7.24(m,4H),7.19(tt,J＝6.4,2.0Hz,1H),5.70(s,2H),4.57(d,J＝18.4Hz,1H),4.48(d,J＝18.4Hz,1H),3.09(t,J＝7.6Hz,2H),2.91(t,J＝7.6Hz,2H).13C NMR(100MHz,DMSO-d6)δ200.0,156.2,146.1,145.3,140.5,138.4,137.0,134.7,134.1,132.8,130.5,129.7,128.4,128.3,126.7,126.1,125.7,123.7(q,J＝282.7Hz),114.5,108.0,87.5(q,J＝29.9Hz),55.8,42.6,40.6,28.3.19F NMR(376MHz,DMSO-d6)δ-78.89(s).Mass Spectrometry:HRMS-ESI(m/z):calcd for C29H21Cl2F3N5O2[M-Br]+598.1019,found,598.1018.
实施例47：季铵盐异噁唑啉类化合物I-1～I-46对小菜蛾(Plutellaxylostella)、粘虫(Mythimna separata)、草地贪夜蛾(Spodopterafrugiperda)、棉铃虫(Helicoverpa armigera)、玉米螟(0strinia nubilalis)、尖音库蚊淡色亚种(Culexpipienspallens)、蚜虫(Aphis laburniKaltenbach)的杀虫活性及朱砂叶螨成螨(Tetranychus cinnabarinus)的杀螨活性测定，测定程序如下：
草地贪夜蛾的活性测试：草地贪夜蛾Spodopterafrugiperda(J.E.Smith,1797)。试验方法：浸叶法。将大喇叭口期幼嫩玉米叶片剪为5cm叶段，浸渍药液10s,自然晾干后置于玻璃培养皿(直径75mm)中。选取发育整齐的2龄幼虫饥饿处理4h后接入处理后的叶片。以丙酮溶剂为对照。每处理幼虫10头,4次重复。处理后72h检查幼虫存活状态,以毛刷轻触幼虫体表，无反应判定为死亡，记录死亡数、存活数,计算死亡率及校正死亡率。
死亡率(％)＝(施药死亡虫数/施药总虫数)×100
校正死亡率(％)＝[(施药死亡率-空白死亡率)/(1-空白死亡率)]×100
粘虫的活性测试：粘虫(Mythimna separata Walker)，室内饲养的正常群体。试验方法：浸叶法，用玉米叶浸渍于丙酮配制的药液中，待药液干后接入10头3龄幼虫，主要为胃毒、触杀作用，同时观察幼虫取食现象。72h检查死亡率。每个化合物重复3次。
棉铃虫的活性测试：棉铃虫(Helicoverpa armigera)，室内饲养的正常群体。试验方法：浸叶法。用玉米叶浸渍于丙酮配制的药液中，待药液干后接入10头3龄幼虫，主要为胃毒、触杀作用，同时观察幼虫取食现象。72h后检查死亡率。每个化合物重复3次。
玉米螟的活性测试：玉米螟(0strinia nubilalis Hubner)，室内饲养的正常群体。试验方法：浸叶法。用玉米叶浸渍于丙酮配制的药液中，待药液干后接入10头3龄幼虫，主要为胃毒、触杀作用，同时观察幼虫取食现象。72小时后检查死亡率。每个化合物重复3次。
小菜蛾的活性测试：小菜蛾(Plutella xylostella)，室内饲养的正常群体。试验方法：浸叶法。用直头眼科镊子浸渍甘蓝叶片到合适浓度的药液中，时间3-5秒，甩掉余液。每次一片，每个样品3片，按样品标记顺序依次放在处理纸上。待药液干后，放入具有标记的10cm长的直行管内，接入10头二龄幼虫用纱布盖好管口。将实验处理置于标准室内，4天后检查结果。每个化合物重复3次。
库蚊幼虫的活性测试：尖音库蚊淡色亚种(Culexpipienspallens))，室内饲养的正常群体。选取10头3龄库蚊幼虫，置于配制好的所需浓度100mL烧杯中。将处理放入标准处理室内，72h后检查死亡率。以含有1mL试验溶剂的水溶液为空白对照。每个化合物重复3次。蚜虫的活性测试：蚜虫(Aphis laburniKaltenbach)，实验室蚕豆叶饲养的正常群体。称取药品，加1mLDMF溶解，加两滴吐温－20乳化剂，加入一定量的蒸馏水，搅拌均匀，配成所需浓度的药液。将带蚜虫(约60只)蚕豆叶片浸入药剂中5秒钟，拿出轻轻甩干，用滤纸吸干多余药剂，然后将蚕豆枝插入吸水海绵中，并用玻璃罩罩住枝条，用纱布封口，96h后检查结果，每个化合物重复3次。对照只向蒸馏水中加入乳化剂和溶剂，搅拌均匀。
朱砂叶螨成螨的活性测试：朱砂叶螨(Tetranychus cinnabarinus)供实验用的矮生菜豆长至两片真叶时，选择长势比较整齐、叶面积4-5平方厘米、株高10厘米左右的植株接虫，每株虫量控制在60-100头左右。接虫2h后，进行药剂处理。药剂处理采用植株浸渍法，浸渍时间5秒钟。植株从药液中取出后，轻轻抖动，甩掉多余药液，然后移入水培缸中，放置在室温下。处理后24h在双目镜下检查结果。每个化合物重复3次。
表1化合物I-1～I-46对小菜蛾的活性测试结果
Figure BDA0003039201810000211
Figure BDA0003039201810000221
表2化合物I-1～I-46对粘虫、草地贪夜蛾、棉铃虫、玉米螟的活性测试结果
Figure BDA0003039201810000222
Figure BDA0003039201810000231
aActivities at 200mg/L.bActivities at 100mg/L.cActivities at 25mg/LdActivities at 10mg/L,eActivities at 5mg/L.fActivities at 2.5mg/L.gActivitiesat 1mg/L.hActivities at 0.5mg/L,iActivities at 0.25mg/L.jActivities at 0.1mg/L.
表3化合物I-1～I-46对蚊幼虫、棉铃虫、玉米螟的活性测试结果
Figure BDA0003039201810000232
Figure BDA0003039201810000241
aActivities at 200mg/L.bActivities at 100mg/L.cActivities at 10mg/L.dActivities at 5mg/L,eActivities at 2.5mg/L.fActivities at 1mg/L.gActivitiesat 0.5mg/L,hActivities at 0.25mg/L.iActivities at 0.1mg/L.jActivitiesat0.05mg/L,kActivities at 0.025mg/L.lActivities at 0.01mg/L.mActivities at0.005mg/L,nActivities at 0.0025mg/L.oActivities at0.001 mg/L.
以商品化品种Fluralaner及DP-9为对照，对小菜蛾、粘虫、草地贪夜蛾、棉铃虫、玉米螟、尖音库蚊淡色亚种、蚜虫的杀虫活性及朱砂叶螨成螨杀螨活性进行了测试。
杀小菜蛾活性：从表1中可看出，大部分季铵盐类衍生物都表现出了较好的杀小菜蛾活性,一部分化合物在0.1mg/L浓度下对小菜蛾亦有100％的致死率；尤其是化合物II--30(93％,0.0001mg/L)、I-31(93％,0.00005mg/L)、I-33(90％,0.0001mg/L)、III-h34(80％,0.000001mg/L)、I-36(83％,0.00005mg/L)、I-38(50％,0.00005mg/L)、I-40(90％,0.00005mg/L)、I-42(60％,0.00005mg/L)表现出了优于对照样fluralaner(70％,0.0001mg/L)、DP-9(80％,0.0001mg/L)的杀小菜蛾活性。
杀粘虫活性：季铵盐类衍生物(I-1–I-13)大多在10mg/L下就并无杀粘虫活性，而化合物I-14–I-46表现出较好的杀粘虫活性，其中化合物I-18(50％,0.5mg/L)、I-31(70％,0.5mg/L)、I-34(40％,0.5mg/L)表现与DP-9(70％,0.5mg/L)相等的活性。
杀草地贪夜蛾活性：大部分具有较好的活性，尤其化合物I-31(20％,2.5mg/L)、I-34(40％,2.5mg/L)表现与DP-9(50％,2.5mg/L)相等的活性。
杀玉米螟、棉铃虫活性：季铵盐异噁唑啉衍生物在浓度600mg/L表现出一定的杀玉米螟、棉铃虫活性；其中衍生物I-18、I-20、I-27、I-28、I-31、I-34、I-40、I-42在浓度200mg/L表现出与对照样fluralaner相似的杀玉米螟和棉铃虫活性
杀蚊幼虫活性：大部分衍生物都表现出一定的杀蚊幼虫活性；化合物I-1、I-29、I-33对蚊幼虫表现出了较好的活性，特别是苯环3位被溴取代的化合物I-33在0.005mg/L浓度下仍具有一定的杀蚊幼虫活性
杀蚜虫和朱砂叶螨成螨活性：大部分化合物对蚜虫和朱砂叶螨成螨都无活性。
实施例48：抗菌活性测试，测定程序如下：
离体杀菌测试，菌体生长速率测定法(平皿法)：
将一定量药剂溶解在适量丙酮内，然后用含有200μg/mL乳化剂水溶液稀释至所需浓度，然后各吸取1mL药液注入培养皿内，再分别加入9mL培养基，摇匀后制成50μg/mL的含药平板，以添加1mL灭菌水的平板做空白对照。用直径4mm的打孔器沿菌丝外缘切取菌盘，移至含药平板上。每处理重复三次。将培养皿放在24±1℃恒温培养箱内培养。48小时后调查各处理菌盘扩展直径，求平均值，与空白对照比较计算相对抑菌率。
Figure BDA0003039201810000251
表4化合物I-1～I-46对植物病菌活性测试结果活性测试结果
Figure BDA0003039201810000252
Figure BDA0003039201810000261
以广谱性杀菌剂多菌灵、百菌清，Fluralaner及DP-9为对照，进行了对14种植物真菌活性测试，测试结果表明部分化合物在测试浓度为50mg/L的条件下对14种被测试菌都表现出广谱的抑制活性。其中衍生物I-1–I-7、I-10–I-13对花生褐斑病菌的抑制率优于DP-9(51％)、fluralaner(30％)、百菌清(44％)和乙胺嘧啶(18％)，其中大多数对小麦纹枯病菌的抑制率约为90％。I-1、I-2、I-5、I-7对番茄早疫病菌的杀菌活性高于或相当于对照样。I-2、I-10对苹果轮纹病菌的抑制率达90％以上。I-1、I-10、I-11对辣椒疫霉病菌的抑制率分别为61％、61％、61％。

Claims (5)

1.如下所示结构的季铵盐异噁唑啉衍生物I，具体为I-1～I-46所示的化合物：
Figure FDA0003039201800000011
Figure FDA0003039201800000021
2.权利要求1所述的季铵盐异噁唑啉衍生物I-1～I-9的制备方法：首先以3,5-二氯苯硼酸(1)和2-溴-3,3-三氟丙烯(2)为原料，碳酸钠为碱，双三苯基膦基氯化钯为催化剂，在四氢呋喃和水中回流得到偶联产物3,5-二氯-1-(1-三氟甲基乙烯基)苯(3)；以2-氟-5-甲酰基苯腈(4)为原料，在甲醇和水中，碳酸钠催化下，与盐酸羟胺反应生成肟(5)，然后与上面合成的3在水中，KCl存在下，Oxone氧化环化生成5-(5-(3,5-二氯苯基)-5-(三氟甲基)-4,5-二氢异噁唑-3-基)-2-氟苯甲腈(6)；再以碳酸钾为碱，碘化亚铜催化下与1,2,3-三氮唑亲核取代得到化合物DP-9；最后与溴化物或碘化物在110℃下进行季铵化反应生成I-1～I-9
Figure FDA0003039201800000022
R分别为I-1～I-9结构中所示基团。
3.权利要求1所述的季铵盐异噁唑啉衍生物I-10～I-46的制备方法：以乙腈做溶剂，4-唑基异噁唑啉DP-9和与溴化物在110℃下进行季铵化反应生成I-10～I-46
Figure FDA0003039201800000031
R分别为I-1～I-9结构中所示基团。
4.权利要求1所述的季铵盐类异噁唑啉衍生物I-1～I-46在害虫防治中的应用，其特征在于它们作为杀虫剂，能灭杀小菜蛾、粘虫、草地贪夜蛾、棉铃虫、玉米螟、蚊幼虫、蚜虫、朱砂叶螨成螨、跳蚤、蜱、蠕形螨、疥螨、耳螨。
5.权利要求1所述的季铵盐类异噁唑啉衍生物I-1～I-46在防治植物病菌病中的应用，其特征在于它作为抗植物病菌剂，能抑制黄瓜枯萎，花生褐斑，苹果轮纹，小麦纹枯，玉米小斑，西瓜炭疽，水稻恶苗，番茄早疫，小麦赤霉，水稻稻瘟，辣椒疫霉，油菜菌核，黄瓜灰霉，水稻纹枯14种植物病菌。
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Citations (2)

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Publication number Priority date Publication date Assignee Title
JP2007016017A (ja) * 2005-06-06 2007-01-25 Nissan Chem Ind Ltd 置換イソキサゾリン化合物及び有害生物防除剤
CN101331127A (zh) * 2005-12-16 2008-12-24 杜邦公司 用于防治无脊椎害虫的5-芳基异噁唑啉

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007016017A (ja) * 2005-06-06 2007-01-25 Nissan Chem Ind Ltd 置換イソキサゾリン化合物及び有害生物防除剤
CN101331127A (zh) * 2005-12-16 2008-12-24 杜邦公司 用于防治无脊椎害虫的5-芳基异噁唑啉

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