CN111592529A - 一种苯基吡唑酰胺类衍生物及其制备方法与应用 - Google Patents

一种苯基吡唑酰胺类衍生物及其制备方法与应用 Download PDF

Info

Publication number
CN111592529A
CN111592529A CN202010627754.5A CN202010627754A CN111592529A CN 111592529 A CN111592529 A CN 111592529A CN 202010627754 A CN202010627754 A CN 202010627754A CN 111592529 A CN111592529 A CN 111592529A
Authority
CN
China
Prior art keywords
compound
dmso
nmr
pyrazole
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202010627754.5A
Other languages
English (en)
Inventor
司伟杰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Anyang Normal University
Original Assignee
Anyang Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Anyang Normal University filed Critical Anyang Normal University
Priority to CN202010627754.5A priority Critical patent/CN111592529A/zh
Publication of CN111592529A publication Critical patent/CN111592529A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

本发明公开了一种苯基吡唑酰胺类衍生物及其制备方法与应用，所述衍生物的结构如式(I)所示：
Figure DDA0002567153860000011
本发明涉及的化合物制备方法简便，对番茄灰霉病菌、水稻纹枯病菌、小麦赤霉病菌和番茄早疫病菌具有抑制作用，可应用于防治植物真菌病害。

Description

一种苯基吡唑酰胺类衍生物及其制备方法与应用
技术领域
本发明涉及农药领域，具体来说涉及一种含苯并咪唑基团的苯基吡唑酰胺类衍生物，同时涉及该类衍生物的制备方法，还涉及该类衍生物在防治植物真菌病害方面的应用。
背景技术
农业病害，特别是真菌性病害，具有种类多、防治难的特点，一直是农业科学研究的重点和热点。有些种类病原真菌寄主范围广、危害时间长，不仅影响农作物的正常生长、产量和质量，还影响农产品的运输和存储，进而影响人们的生活和身体健康。合成杀菌剂在农作物病害的防治中一直发挥着重要作用，但是现有的一些杀菌剂作用靶标相对单一，加上农业生产者的不科学使用，使病原真菌的抗药性问题日益凸出，严重限制了杀菌剂的正常使用和农业的可持续发展。因此，研制高效、安全、经济、环保的新型杀菌候选物对防治农作物病害，保证农产品产量和质量，粮食安全具有重要意义。
苯并咪唑类化合物在杀菌剂的研究与应用领域中占有重要地位，如商品化杀菌剂多菌灵(Carbendazim)、噻菌灵(Thiabendazole)、麦穗宁(Fuberidazole)等都属于该类化合物。吡唑类化合物及其衍生物因其结构的可变性和高效广谱的生物活性，在农药领域也有着广泛的应用，主要表现在杀虫杀螨剂，杀菌剂及除草剂等方面，一直吸引着化学、药学和生物学领域研究者的兴趣。近年来，成为精细化工和农药领域研究的热点之一。苯基吡唑作为吡唑类化合物中的重要组成部分，在杀虫、杀菌领域发挥着重要作用。同时，在设计新型杀菌活性化合物时，人们经常将酰胺基团引入分子结构中，来合成、筛选高活性化合物。
发明内容
本发明采用活性片段拼接法，将苯并咪唑、苯基吡唑等活性基团通过酰胺键融合于同一个分子结构中，设计并合成一系列含有苯并咪唑基团的苯基吡唑酰胺类衍生物，该类衍生物对真菌具有明显的抑制作用
本发明一方面提供了一种具有通式(I)所示结构的化合物，为含苯并咪唑基团的苯基吡唑酰胺类衍生物，
Figure BDA0002567153840000011
其中，R1选自H、C1-6烷基、被1-3个卤素取代的甲基，R2选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，R3选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，Y(n)中，n＝1-5取代，Y(n)选自下列1-5个基团：H、卤素、C1-6烷基、C1-3烷氧基、NO2、被1-3个卤素取代的甲基。
优选地，R1选自H、F、Cl、CH3、CHF2、CF3，R2选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，R3选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，Y(n)中，n＝1-3取代，Y(n)选自下列1-3个基团：H、F、Cl、Br、CH3、C2H5、CH(CH3)2、OCH3、OC2H5、OCH(CH3)2、NO2、CF3、OCF3。
进一步优选地，R1选自CH3、CHF2、CF3，R2选自H、F、Cl、Br、CH3、CF3，R3选自H、F、Cl、Br、CH3、CF3，Y(n)选自H、2-Cl、3-Cl、4-Cl、4-F、4-Br、4-CH3、4-OCH3、4-NO2、2,4-Cl。
本发明还提供了式(I)化合物的制备方法：以式(II)2-(氨基苯基)-苯并咪唑化合物与式(III)取代苯基吡唑-4-甲酸反应，其反应方程式如下述通式(A)表示：
Figure BDA0002567153840000021
本发明的第三个方面涉及式(I)化合物作为杀菌剂的应用。
优选的，所得化合物作为杀菌剂或抑菌剂在防治或抑制植物病原真菌制剂的应用。
优选的，化合物作为杀菌剂或抑菌剂在制备抑制植物病原真菌制剂的应用。
进一步优选地，所述植物为农作物。
进一步优选地，所述化合物应用在制备抑制番茄灰霉病菌、水稻纹枯病菌、小麦赤霉病菌、番茄早疫病菌制剂。
进一步优选地，所述化合物应用在制备防治番茄灰霉病、水稻纹枯病、小麦赤霉病、番茄早疫病制剂。
有益效果：
1、本发明专利所述的式(I)的化合物为一种含苯并咪唑基团的苯基吡唑酰胺类衍生物，分子结构新颖，均为新化合物。化学结构特征鲜明，结构式中含有2-苯基苯并咪唑、苯基-5-(三氟甲基)-吡唑，苯环与吡唑环之间通过酰胺键相连接。
2、本发明所述的式(I)的化合物的制备方法简便，原料易得，反应条件易控。尤其是方法B使用缩合剂，使用缩合剂常温反应不需加热，产物经抽滤或者过滤即可得到。
3、本发明所述的式(I)的化合物表现出明显的抑制植物病原真菌的活性，具有防治农作物真菌病害的作用，能够作为农药杀菌剂应用。具体的说，化合物中含有苯并咪唑结构又含有(带三氟甲基的)吡唑结构，而且三氟甲基位于吡唑环的-5-位，与传统杀菌剂的三氟甲基位于3-位不同。苯并咪唑具有广谱杀菌活性，但长期使用导致真菌对其有抗药性，引入吡唑基团后，减缓抗性，同时使化合物具有新的双重作用机制---既具有苯并咪唑类化合物的作用机制，又具有吡唑酰胺类化合物的作用机制(SDHI抑制剂)，杀菌谱广、真菌抗药性小。
附图说明
附图1：在100μg/mL浓度下，化合物I14、恶霉灵和CK对番茄灰霉病菌的防护效果；
附图2：在100μg/mL浓度下，化合物I18、恶霉灵和CK对番茄灰霉病菌的防护效果。
具体实施方式
本发明的实质性特点可从下述实施例得以体现，但它不应视为是对本发明的任何限制。
制备实施例
实施例1：N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I4)的制备化合物(I4)由下式(A4)表示的方法制备：
Figure BDA0002567153840000022
1-(4-氯苯基)-5-(三氟甲基)-吡唑-4-甲酸(0.73g,2.5mmol)缓慢加入15mL氯化亚砜，回流4～6h，减压蒸去氯化亚砜，得到中间体(III4)。迅速加入20mL二氯甲烷，冷却至0～-5℃，分批缓慢加入2-(2-氨基苯基)-1-氢苯并咪唑(0.52g,2.5mmol)，加入三乙胺(0.50g,5mmol)，冰浴条件下搅拌反应1h，自然升温至室温，继续搅拌4～6h。反应液经过水洗，饱和食盐水洗涤，干燥，减压蒸去溶剂，经柱层析提纯即得I4。
实施例2：N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氟苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I16)的制备化合物(I16)由下式(A16)表示的方法制备：
Figure BDA0002567153840000031
1-(4-氟苯基)-5-(三氟甲基)-吡唑-4-甲酸(0.68g,2.5mmol)缓慢加入15mL氯化亚砜，回流4～6h，减压蒸去氯化亚砜，得到中间体(III6)。迅速加入20mL二氯甲烷，冷却至0～-5℃，分批缓慢加入2-(3-氨基苯基)-1-氢苯并咪唑(0.52g,2.5mmol)，加入三乙胺(0.50g,5mmol)，冰浴条件下搅拌反应1h，自然升温至室温，继续搅拌4～6h。反应液经过水洗，饱和食盐水洗涤，干燥，减压蒸去溶剂，经柱层析提纯即得I16。
实施例3：N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-溴苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I27)的制备化合物(I27)由下式(A27)表示的方法制备：
Figure BDA0002567153840000032
1-(4-溴苯基)-5-(三氟甲基)-吡唑-4-甲酸(0.83g,2.5mmol)缓慢加入15mL氯化亚砜，回流4～6h，减压蒸去氯化亚砜，得到中间体(III7)。迅速加入20mL二氯甲烷，冷却至0～-5℃，分批缓慢加入2-(4-氨基苯基)-1-氢苯并咪唑(0.52g,2.5mmol)，加入三乙胺(0.50g,5mmol)，冰浴条件下搅拌反应1h，自然升温至室温，继续搅拌4～6h。反应液经过水洗，饱和食盐水洗涤，干燥，减压蒸去溶剂，经柱层析提纯即得I27。
采用上述实施例1-3的方法(A)，制备了式(I)化合物I1-I30，亦可以采用如下方法(B)来制备上述化合物，将苯基吡唑-4-甲酸(2.5mmol)置于二氯甲烷中，加入1.5倍物质的量的TBTU(3.75mmol)，2倍物质的量的三乙胺(5mmol)，常温搅拌30min，加入等物质的量(2.5mmol)的式(II)的化合物，常温搅拌反应8～16h。反应混合液有大量固体生成，抽滤，固体经过水洗，干燥，即为式(I)的目标化合物I1-I30，化合物I1-I30图谱见其他文件：
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-苯基-5-(三氟甲基)-吡唑-4-甲酰胺(I1)
Figure BDA0002567153840000033
白色粉末，收率50.7％，mp 210-212℃；IR(KBr)(vmax/cm-1):3225,1662,1594,1542,1499,1431,1316,1287,1229,1189,1145,1035,973,863,765,741,694.1H NMR(400MHz,DMSO-d6)δ:13.98(s,1H),13.32(s,1H),8.83(d,J＝8.3Hz,1H),8.56(s,1H),8.22(d,J＝7.9Hz,1H),7.71(d,J＝7.4Hz,1H),7.63(d,J＝8.4Hz,6H),7.57(t,J＝7.8Hz,1H),7.34(m,3H).13C NMR(101MHz,DMSO-d6)δ:159.0,151.3,142.3,139.9,139.5,138.5,133.9,131.3,130.1(d,J＝19.2Hz),130.6,129.8,127.7,126.6,124.0,123.9,122.9,122.2,121.1,120.4,118.7,118.4,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–54.38.HRMS(ESI)Calcd for C24H17F3N5O[M+H]+:448.13797,found:448.13791.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(2-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I2)
Figure BDA0002567153840000041
浅黄色粉末，收率49.3％，mp 238-240℃；IR(KBr)(vmax/cm-1):3201,1700,1633,1595,1549,1498,1435,1314,1287,1222,1176,1154,1036,979,877,761,745,683.1H NMR(400MHz,DMSO-d6)δ:14.02(s,1H),13.33(s,1H),8.82(dd,J＝8.3Hz,1H),8.66(s,1H),8.22(d,J＝7.2Hz,1H),7.87(dd,J＝7.8,1.4Hz,1H),7.81(dd,J＝8.0,1.0Hz,1H),7.74–7.55(m,5H),7.33(m,3H).13C NMR(101MHz,DMSO-d6)δ:158.8,151.3,142.2,140.5,138.4,137.0,133.9,132.9,132.9(d,J＝39.6Hz),131.4,131.3,130.6,130.1,128.8,127.8,124.1,124.0,123.0,121.6,120.9,120.4,118.6,118.2,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–56.22.HRMS(ESI)Calcd for C24H15ClF3N5O[M+H]+:482.09900,found:482.09909.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(3-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I3)
Figure BDA0002567153840000042
浅黄色粉末，收率25.1％，mp 213-215℃；IR(KBr)(vmax/cm-1):3242,1664,1617,1592,1541,1485,1432,1315,1294 1227,1187,1148,1035,961,883,765,741,678.1H NMR(400MHz,DMSO-d6)δ:14.02(s,1H),13.32(s,1H),8.83(d,J＝8.2Hz,1H),8.59(s,1H),8.22(d,J＝7.8Hz,1H),7.86(s,1H),7.72(d,J＝7.5Hz,2H),7.65(d,J＝13.0Hz,3H),7.57(s,1H),7.46–7.20(m,3H).13C NMR(101MHz,DMSO-d6)δ:158.8,151.3,142.2,140.5,140.2,138.5,133.9,133.9,131.4,132.4(d,J＝39.4Hz),131.3,130.7,127.8,126.9,125.6,124.1,124.0,122.9,122.4,120.4 118.7,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–54.39.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09937.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I4)
Figure BDA0002567153840000051
浅黄色粉末，收率31.3％，mp 186-188℃；IR(KBr)(vmax/cm-1):3357,1631,1615,1592,1532,1457,1434,1318,1298,1226,1191,1133,1036,973,831,753,740.1H NMR(400MHz,DMSO-d6)δ:13.99(s,1H),13.32(s,1H),8.82(d,J＝8.1Hz,1H),8.57(s,1H),8.21(d,J＝7.8Hz,1H),7.75–7.68(m,5H),7.63(d,J＝7.3Hz,1H),7.57(t,J＝7.9Hz,1H),7.33(m,3H).13C NMR(101MHz,DMSO-d6)δ:158.8,151.3,142.2,140.2,138.5,138.3,135.3,133.8,131.3(t,J＝19.7Hz),129.9,128.5,127.7,124.0,123.9,122.9,122.4,120.4,118.7,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–54.39.HRMS(ESI)Calcd forC24H16ClF3N5O[M+H]+:482.09900,found:482.09912.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(2,4-二氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I5)
Figure BDA0002567153840000052
浅黄色粉末，收率22.1％，mp 213–215℃；IR(KBr)(vmax/cm-1):3442,1657,1629,1592,1566,1540,1495,1435,1373,1312,1285,1231,1181,1157,1110,1034,972,829,741.1H NMR(400MHz,DMSO-d6)δ:14.03(s,1H),13.33(s,1H),8.82(d,J＝8.3Hz,1H),8.68(s,1H),8.21(t,J＝9.7Hz,1H),8.06(d,J＝2.1Hz,1H),7.96(d,J＝8.5Hz,1H),7.75(dd,J＝8.5,2.3Hz,1H),7.68(d,J＝7.6Hz,1H),7.63(d,J＝7.4Hz,1H),7.58(t,J＝7.4Hz,1H),7.34(m,3H).13C NMR(101MHz,DMSO-d6)δ:158.6,151.3,142.2,140.7,138.4,136.8,136.0,133.9,132.7,132.3,131.4(d,J＝8.4Hz),130.3,129.0,127.8,124.1(d,J＝5.5Hz),123.0,121.8,120.8,120.4,118.6,118.1,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–56.22.HRMS(ESI)Calcd for C24H15Cl2F3N5O[M+H]+:516.06003,found:516.06012.N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氟苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I6)
Figure BDA0002567153840000061
浅黄色粉末，收率34.5％，mp 217-219℃；IR(KBr)(vmax/cm-1):3448,1672,1634,1618,1600,1516,1435,1403,1319,1291,1223,1139,1033,976,882,843,742.1H NMR(400MHz,DMSO-d6)δ:13.99(s,1H),13.32(s,1H),8.79(dd,J＝23.0,8.1Hz,1H),8.56(s,1H),8.21(d,J＝6.9Hz,1H),7.78–7.68(m,3H),7.63(d,J＝7.2Hz,1H),7.57(t,J＝7.3Hz,1H),7.49(t,J＝8.7Hz,2H),7.33(m,3H).13C NMR(101MHz,DMSO-d6)δ:164.2,161.8,159.0,151.3,142.3,140.0,138.5,135.8,133.8,131.4(q,J＝39.4Hz),131.3,129.2,129.1,127.8 124.1,124.0,122.9,122.1,121.0,120.4,118.7,118.3,116.9,116.6,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–54.47,-110.71.HRMS(ESI)Calcd for C24H16F4N5O[M+H]+:466.12855,found:466.12869.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-溴苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I7)
Figure BDA0002567153840000062
浅黄色粉末，收率22.4％，mp 198-200℃；IR(KBr)(vmax/cm-1):3450,1630,1601,1552,1496,1434,1400,1318,1299,1225,1190,1067,1036,972,827,760,730.1H NMR(400MHz,DMSO-d6)δ:13.99(s,1H),13.32(s,1H),8.79(dd,J＝23.0,8.1Hz,1H),8.56(s,1H),8.21(d,J＝6.9Hz,1H),7.78–7.68(m,3H),7.63(d,J＝7.2Hz,1H),7.57(t,J＝7.3Hz,1H),7.49(t,J＝8.7Hz,2H),7.38–7.29(m,3H).13C NMR(101MHz,DMSO-d6)δ:158.9,151.2,142.2,140.2,138.7,138.4,133.8,132.8,131.3,131.3(d,J＝39.4Hz),128.7,127.8,124.1,124.0,123.8,122.9,122.4,121.0,120.4,118.7,118.3,116.0,112.1.19F NMR(376MHz,DMSO-d6)δ:–54.38.HRMS(ESI)Calcd for C24H16BrF3N5O[M+H]+:526.04848,found:526.04871.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I8)
Figure BDA0002567153840000063
白色粉末，收率26.1％，mp 198-200℃；IR(KBr)(vmax/cm-1):3362,1673,1634,1600,1550,1490,1467,1435,1404,1319,1291,1224,1168,1137,1126,1088,1052,978,841,763,744.1H NMR(400MHz,DMSO-d6)δ:13.97(s,1H),13.36(s,1H),8.82(d,J＝8.4Hz,1H),8.53(s,1H),8.23(d,J＝7.9Hz,1H),7.67(s,2H),7.57(t,J＝7.9Hz,1H),7.52(d,J＝7.9Hz,2H),7.43(d,J＝7.9Hz,2H),7.39–7.26(m,3H),2.44(s,3H).13C NMR(101MHz,DMSO-d6)δ:159.1,151.3,142.2,140.4,139.8,138.5,137.0,134.0,131.3,131.2,130.4(t,J＝39.4Hz),127.9,126.3,124.0,124.0,122.9,122.1,121.1,120.3,118.6,116.0,112.2,21.2.19F NMR(376MHz,DMSO-d6)δ:–54.44.HRMS(ESI)Calcd for C25H19F3N5O[M+H]+:462.1536,found:462.1528.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲氧基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I9)
Figure BDA0002567153840000071
浅黄色粉末，收率27.3％，mp 234-235℃；IR(KBr)(vmax/cm-1):3450,1679,1631,1592,1545,1515,1486,1435,1408,1365,1307,1288,1222,1162,1137,1082,1050,975,840,744.1H NMR(400MHz,DMSO-d6)δ:13.95(s,1H),13.31(s,1H),8.82(d,J＝8.2Hz,1H),8.51(s,1H),8.21(d,J＝7.0Hz,1H),7.70(d,J＝7.2Hz,1H),7.63(d,J＝6.9Hz,1H),7.57(dd,J＝7.4,5.1Hz,3H),7.33(dd,J＝13.7,5.6Hz,3H),7.15(d,J＝8.9Hz,3H),3.87(s,3H).13C NMR(101MHz,DMSO-d6)δ:160.6,159.1,151.3,142.3,139.7,138.5,133.9,132.3,131.4,131.1(d,J＝39.2Hz),128.0,127.8,124.1,124.0,122.9,121.9,121.1,120.4,118.7,118.4,116.0,114.8,112.1,56.0.19F NMR(376MHz,DMSO-d6)δ:–54.56.HRMS(ESI)Calcd for C25H19F3N5O2[M+H]+:478.14854,found:478.14822.
N-(2-(1-氢-苯并咪唑-2-基)苯基)-1-(4-硝基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I10)
Figure BDA0002567153840000072
浅黄色粉末，收率51.8％，mp 264-266℃；IR(KBr)(vmax/cm-1):3350,1680,1617,1594,1565,1519,1490,1436,1399,1348,1311,1288,1227,1172,1146,1110,1033,973,858,742.1H NMR(400MHz,DMSO-d6)δ:14.05(s,1H),13.34(s,1H),8.82(d,J＝8.2Hz,1H),8.65(s,1H),8.48(d,J＝8.9Hz,2H),8.22(d,J＝7.1Hz,1H),7.99(d,J＝8.9Hz,2H),7.72(d,J＝7.7Hz,1H),7.63(d,J＝7.3Hz,1H),7.58(t,J＝7.8Hz,1H),7.41–7.29(m,3H).13CNMR(101MHz,DMSO-d6)δ:158.7,151.2,148.5 144.1,142.2,140.8,138.4,133.9,131.4(d,J＝39.4Hz),131.3,128.0 127.8,125.2,124.1,123.0,122.9,121.0,120.4,118.7,118.3,116.0,112.1,110.1.19F NMR(376MHz,DMSO-d6)δ:–54.15.HRMS(ESI)Calcd forC24H16F3N6O3[M+H]+:493.12305,found:493.12296.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-苯基-5-(三氟甲基)-吡唑-4-甲酰胺(I11)
Figure BDA0002567153840000081
白色粉末，收率39.5％，mp 235-237℃；IR(KBr)(vmax/cm-1):3436,1654,1570,1500,1449,1303,1244,1143,974,881,746,695.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.71(s,1H),8.69(s,1H),8.39(s,1H),7.90(d,J＝7.7Hz,1H),7.79(d,J＝8.3Hz,1H),7.69(d,J＝7.5Hz,1H),7.65–7.61(m,3H),7.60–7.52(m,4H),7.27–7.18(m,2H).13C NMR(101MHz,DMSO-d6)δ:159.6,151.5,140.4,139.8,139.2,131.3,130.6,130.5(d,J＝38.4Hz),129.9,126.5,123.1,122.3,121.8,121.7,121.2,119.3,118.6,118.5,111.9.19FNMR(376MHz,DMSO-d6)δ:–54.69.HRMS(ESI)Calcd for C24H17F3N5O[M+H]+:448.13797,found:448.13770.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(2-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I12)
Figure BDA0002567153840000082
白色粉末，收率25.7％，mp 209-212℃；IR(KBr)(vmax/cm-1):3449,1634,1572,1492,1473,1301,1234,1150,973,875,744,687.1H NMR(400MHz,DMSO-d6)δ:12.98(s,1H),10.71(s,1H),8.70(s,1H),8.51(s,1H),7.91(d,J＝7.7Hz,1H),7.80(t,J＝8.0Hz,2H),7.75(d,J＝7.7Hz,1H),7.73–7.66(m,1H),7.62–7.54(m,4H),7.22(dd,J＝5.9,3.1Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.2,151.6141.0,139.8,136.8,132.8,132.1(d,J＝39.3Hz),131.5,131.3 130.6,130.1,129.9,128.7,122.6,122.4,121.9,121.1,121.0,118.3.19F NMR(376MHz,DMSO-d6)δ:–56.38.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09918.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(3-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I13)
Figure BDA0002567153840000083
白色粉末，收率61.1％，mp 284-286℃；IR(KBr)(vmax/cm-1):3453,1658,1572,1489,1450,1299,1179,1145,989,882,745,688.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.71(s,1H),8.69(s,1H),8.43(s,1H),7.90(d,J＝7.7Hz,1H),7.79(d,J＝8.1Hz,1H),7.76–7.63(m,4H),7.61–7.51(m,3H),7.22(t,J＝6.9Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.3,151.5,140.7,140.3,139.7,134.0,131.6,131.2,130.8(t,J＝19.6Hz),129.9,126.6,125.5,122.3,121.9,121.8,121.3,121.1,120.6,118.7,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.64.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09894.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I14)
Figure BDA0002567153840000091
白色粉末，收率80.5％，mp 160-162℃；IR(KBr)(vmax/cm-1):3455,1618,1574,1500,1473,1305,1244,1133,977,837,737,683.1H NMR(400MHz,DMSO-d6)δ:13.00(s,1H),10.71(s,1H),8.69(s,1H),8.42(s,1H),7.90(d,J＝7.7Hz,1H),7.78(d,J＝8.2Hz,1H),7.70(d,J＝8.6Hz,2H),7.65–7.53(m,5H),7.22(dd,J＝5.8,3.0Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.4,151.5,140.6,139.7,138.0,135.2,131.3,130.7(d,J＝39.1Hz),130.0,128.3,122.7,122.4,121.99,121.8,121.1,118.7,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.68.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09897.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(2,4-二氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I15)
Figure BDA0002567153840000092
白色粉末，收率20.5％，mp 195-197℃；IR(KBr)(vmax/cm-1):3439,1661,1616,1569,1526,1492,1473,1449,1301,1244,1183,1153,1041,974,871,745,689.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.69(s,1H),8.69(s,1H),8.52(s,1H),8.03(s,1H),7.90(d,J＝7.6Hz,1H),7.82(t,J＝10.1Hz,2H),7.70(dd,J＝13.5,8.1Hz,2H),7.56(t,J＝8.4Hz,2H),7.30–7.11(m,2H).13C NMR(101MHz,DMSO-d6)δ:159.1,151.5,141.3,139.7,136.8,135.8,132.8,132.2(d,J＝39.2Hz),131.4,131.2,130.3,129.9,129.0,123.0,122.4,121.9,121.2,120.9,118.8,118.2.19F NMR(376MHz,DMSO-d6)δ:–56.37.HRMS(ESI)Calcd for C24H15Cl2F3N5O[M+H]+:516.06003,found:516.05988.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氟苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I16)
Figure BDA0002567153840000093
白色粉末，收率27.3％，mp 259-261℃；IR(KBr)(vmax/cm-1):3443,1655,1570,1514,1473,1301,1238,1181,1145,975,848,747,689.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.70(s,1H),8.68(s,1H),8.39(s,1H),7.90(d,J＝7.8Hz,1H),7.78(d,J＝8.0Hz,1H),7.71–7.61(m,3H),7.55(t,J＝7.9Hz,2H),7.47(t,J＝8.6Hz,2H),7.22(s,2H).13C NMR(101MHz,DMSO-d6)δ:164.2,161.7,159.5,151.54 140.4,139.8,135.6,131.3,130.7(d,J＝38.9Hz),129.9,129.1,129.0,122.6,122.4,121.8,121.1,118.7,118.4,117.0,116.7.19F NMR(376MHz,DMSO-d6)δ:–54.77,–110.75.HRMS(ESI)Calcd for C24H16F4N5O[M+H]+:466.12855,found:466.12863.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-溴苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I17)
Figure BDA0002567153840000101
白色粉末，收率36.3％，mp 164–166℃；IR(KBr)(vmax/cm-1):3468,1639,1572,1495,1449,1304,1183,1150,973,858,746,686.1H NMR(400MHz,DMSO-d6)δ:12.97(s,1H),10.71(s,1H),8.69(s,1H),8.42(s,1H),7.91(d,J＝7.7Hz,1H),7.84(d,J＝8.3Hz,2H),7.79(d,J＝8.1Hz,1H),7.61–7.54(m,5H),7.23(s,2H).13C NMR(101MHz,DMSO-d6)δ:159.4,151.5,140.7,139.7,138.5,132.9,131.3,130.6(d,J＝39.1Hz),129.9,128.5,123.8,122.4,122.0,121.8,121.1,119.3,118.7,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.65.HRMS(ESI)Calcd for C24H16BrF3N5O[M+H]+:526.04848,found:526.04851.N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I18)
Figure BDA0002567153840000102
白色粉末，收率38.4％，mp 149-151℃；IR(KBr)(vmax/cm-1):3463,1639,1572,1516,1491,1450,1303,1177,1150,1041,975,825,746,686.1H NMR(400MHz,DMSO-d6)δ:12.94(s,1H),10.69(s,1H),8.68(s,1H),8.36(s,1H),7.89(d,J＝7.7Hz,1H),7.77(d,J＝7.8Hz,1H),7.68(d,J＝7.0Hz,1H),7.55(t,J＝7.7Hz,2H),7.46–7.38(m,4H),7.25–7.18(m,2H),2.43(s,3H).13C NMR(101MHz,DMSO-d6)δ:159.6,151.5,140.4,140.2,139.8,136.8,131.3,130.6,130.3,129.9,126.2,122.7,122.3,121.7,121.2,118.6,21.2.19F NMR(376MHz,DMSO-d6)δ:–54.76.HRMS(ESI)Calcd for C25H19F3N5O[M+H]+:462.15362,found:462.15386.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲氧基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I19)
Figure BDA0002567153840000103
白色粉末，收率35.7％，mp 151-153℃；IR(KBr)(vmax/cm-1):3442,1685,1615,1568,1513,1492,1448,1305,1215,1182,1139,1042,980,837,741,686.1H NMR(400MHz,DMSO-d6)δ:13.12(s,1H),10.76(s,1H),8.32(s,1H),8.18(d,J＝8.6Hz,2H),7.90(d,J＝8.5Hz,2H),7.59(s,2H),7.47(d,J＝8.7Hz,2H),7.21(dd,J＝5.7,3.0Hz,2H),7.13(d,J＝8.8Hz,2H),3.86(s,3H).13C NMR(101MHz,DMSO-d6)δ:160.6,159.7,151.6 140.1,139.9,132.1,131.3,130.6(d,J＝38.8Hz),129.9,127.9 122.7,122.4,121.8,121.5,121.2,118.7,118.5,114.8,56.0.19F NMR(376MHz,DMSO-d6)δ:–54.89.HRMS(ESI)Calcd forC25H19F3N5O2[M+H]+:478.14854,found:478.14880.
N-(3-(1-氢-苯并咪唑-2-基)苯基)-1-(4-硝基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I20)
Figure BDA0002567153840000111
白色粉末，收率72.1％，mp 265-266℃；IR(KBr)(vmax/cm-1):3431,3226,1649,1577,1530,1491,1473,1450,1348,1295,1180,1135,1038,975,860,750,692.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.74(s,1H),8.69(s,1H),8.51(s,1H),8.47(d,J＝8.4Hz,2H),7.91(d,J＝8.3Hz,3H),7.79(d,J＝8.1Hz,1H),7.68(d,J＝7.2Hz,1H),7.56(t,J＝7.9Hz,2H),7.22(s,2H).13C NMR(101MHz,DMSO-d6)δ:159.2,151.5,148.3,143.9,141.4,139.7,131.3,130.9(d,J＝39.4Hz),129.9,127.6,125.3,122.7,122.6,122.4,121.0,121.0,118.7,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.42.HRMS(ESI)Calcd forC24H16F3N6O3[M+H]+:493.12305,found:493.12347.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-苯基-5-(三氟甲基)-吡唑-4-甲酰胺(I21)
Figure BDA0002567153840000112
浅黄色粉末，收率57.3％，mp 303-305℃；IR(KBr)(vmax/cm-1):3425,1665,1597,1537,1432,1400,1320,1298,1257,1228,1186,1139,1073,972,833,749,692.1H NMR(400MHz,DMSO-d6)δ:12.87(s,1H),10.78(s,1H),8.37(s,1H),8.18(d,J＝8.6Hz,2H),7.90(d,J＝8.6Hz,2H),7.64(dd,J＝9.1,5.9Hz,4H),7.57(d,J＝5.7Hz,2H),7.52(d,J＝7.3Hz,1H),7.25–7.15(m,2H).13C NMR(101MHz,DMSO-d6)δ:159.6,151.5,140.6,140.4 139.2,130.6,130.2,129.9,127.6,126.5 126.2,122.5,121.8,121.1,120.3,118.5.19F NMR(376MHz,DMSO-d6)δ:-54.77.HRMS(ESI)Calcd for C24H17F3N5O[M+H]+:448.13797,found:448.13828.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(2-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I22)
Figure BDA0002567153840000113
浅棕色粉末，收率48.9％，mp 305-307℃；IR(KBr)(vmax/cm-1):3442,1638,1497,1434,1384,1300,1239,1182,1158,1073,977,750,699.1H NMR(400MHz,DMSO-d6)δ:12.89(s,1H),10.78(s,1H),8.47(s,1H),8.19(d,J＝8.6Hz,2H),7.92(d,J＝8.5Hz,2H),7.79(d,J＝8.0Hz,1H),7.74(d,J＝7.6Hz,1H),7.70(t,J＝7.7Hz,1H),7.63(dt,J＝15.2,7.6Hz,2H),7.52(d,J＝7.2Hz,1H),7.19(dd,J＝13.5,6.1Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.2,151.5,141.0,140.6,136.7,132.9,131.9(d,J＝39.3Hz),131.5,130.6,130.1,128.8,127.6,126.2,122.5,121.1,120.9,120.5,118.2.19F NMR(376MHz,DMSO-d6)δ:–56.45.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09930.N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(3-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I23)
Figure BDA0002567153840000121
浅黄色粉末，收率57.1％，mp 298-300℃；IR(KBr)(vmax/cm-1):3438,1661,1606,1566,1480,1432,1384,1315,1228,1181,1133,1038,987,837,747,685.1H NMR(400MHz,DMSO-d6)δ:12.87(s,1H),10.79(s,1H),8.42(s,1H),8.20(d,J＝8.5Hz,2H),7.90(t,J＝12.7Hz,2H),7.74(d,J＝12.0Hz,2H),7.66(t,J＝7.8Hz,2H),7.58(d,J＝7.8Hz,1H),7.53(d,J＝6.8Hz,1H),7.21(s,2H).13C NMR(101MHz,DMSO-d6)δ:159.4,151.6,140.7,140.6,140.2,134.1,131.5 130.7(t,J＝19.6Hz),127.6,126.6126.2,125.4,122.7,122.0,121.1,120.4,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.72.HRMS(ESI)Calcd forC24H16ClF3N5O[M+H]+:482.09900,found:482.09912.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I24)
Figure BDA0002567153840000122
浅黄色粉末，收率40.2％，mp 307–309℃；IR(KBr)(vmax/cm-1):3462,1677,1607,1559,1480,1454,1437,1371,1324,1227,1180,1128,1037,975,836,743,653.1H NMR(400MHz,DMSO-d6)δ:12.95(s,1H),10.83(s,1H),8.40(s,1H),8.19(d,J＝8.0Hz,2H),7.92(t,J＝11.5Hz,2H),7.71(d,J＝8.6Hz,2H),7.66–7.54(m,4H),7.19(dd,J＝5.9,3.1Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.5,151.6,140.7,140.6 138.0,135.3,130.6(d,J＝39.1Hz),130.0,128.3,127.6,126.2,122.4,122.0,121.1,120.4,118.4.19F NMR(376MHz,DMSO-d6)δ:–54.75.HRMS(ESI)Calcd for C24H16ClF3N5O[M+H]+:482.09900,found:482.09915.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(2,4-二氯苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I25)
Figure BDA0002567153840000123
白色粉末，收率30.5％，mp 312-314℃；IR(KBr)(vmax/cm-1):3299,1665,1601,1526,1496,1429,1314,1298,1229,1153,1111,1036,973,816,747,669.1H NMR(400MHz,DMSO-d6)δ:12.86(s,1H),10.76(s,1H),8.50(s,1H),8.19(d,J＝8.4Hz,2H),8.04(d,J＝2.0Hz,1H),7.91(d,J＝8.4Hz,2H),7.83(d,J＝8.5Hz,1H),7.72(dd,J＝8.5,2.1Hz,1H),7.65(d,J＝7.3Hz,1H),7.52(d,J＝7.2Hz,1H),7.26–7.14(m,2H).13C NMR(101MHz,DMSO-d6)δ:159.1,151.6,141.3,140.6,136.9 135.7,132.8,130.9(t,J＝38.3Hz),131.3,130.4,129.0,127.6,126.2,122.5,121.3 120.5,118.2.19F NMR(376MHz,DMSO-d6)δ:–56.44.HRMS(ESI)Calcd for C24H15Cl2F3N5O[M+H]+:516.06003,found:516.06024.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-氟苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I26)
Figure BDA0002567153840000131
浅黄色粉末，收率28.1％，mp 315-317℃；IR(KBr)(vmax/cm-1):3405,1669,1605,1560,1539,1474,1448,1437,1315,1298,1225,1185,1133,1033,978,842,764,685.1H NMR(400MHz,DMSO-d6)δ:12.87(s,1H),10.78(s,1H),8.38(s,1H),8.20(d,J＝8.6Hz,2H),7.91(d,J＝8.5Hz,2H),7.78–7.59(m,3H),7.59–7.41(m,3H),7.28–7.07(m,2H).13C NMR(101MHz,DMSO-d6)δ:164.2,161.7,159.5,151.5,140.6,140.4,135.5,130.4(t,J＝39.4Hz),129.1,129.0,127.6,126.2,121.8,121.1,120.3,118.4,117.0 116.7.19F NMR(376MHz,DMSO-d6)δ:–54.85,–110.71.HRMS(ESI)Calcd for C24H16F4N5O[M+H]+:466.12855,found:466.12848.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-溴苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I27)
Figure BDA0002567153840000132
浅黄色粉末，收率44.6％，mp 307–308℃；IR(KBr)(vmax/cm-1):3358,1677,1607,1559,1480,1453,1428,1324,1297,1226,1181,1128,1033,974,835,745,652.1H NMR(400MHz,DMSO-d6)δ:12.94(s,1H),10.82(s,1H),8.40(s,1H),8.19(d,J＝8.6Hz,2H),7.90(d,J＝8.6Hz,2H),7.84(d,J＝8.6Hz,2H),7.64(s,1H),7.55(d,J＝8.5Hz,3H),7.20(d,J＝4.3Hz,2H).13C NMR(101MHz,DMSO-d6)δ:159.5,151.6,140.7,140.6,138.4,132.9,132.6,130.5(q,J＝39.0Hz),128.5,127.6,126.2,123.8,122.4,122.0,121.1,120.4,114.0.19FNMR(376MHz,DMSO-d6)δ:–54.73.HRMS(ESI)Calcd for C24H16BrF3N5O[M+H]+:526.04848,found:526.04800.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I28)
Figure BDA0002567153840000133
浅黄色粉末，收率43.5％，mp 317-319℃；IR(KBr)(vmax/cm-1):3246,1660,1606,1516,1478,1449,1432,1314,1298,1229,1190,1126,1084,974,822,748,681.1H NMR(400MHz,DMSO-d6)δ:12.87(s,1H),10.77(s,1H),8.34(s,1H),8.19(d,J＝8.3Hz,2H),7.89(t,J＝10.1Hz,2H),7.59(s,2H),7.48–7.35(m,4H),7.19(dt,J＝20.9,10.4Hz,2H),2.43(s,3H).13C NMR(101MHz,DMSO-d6)δ:159.7 151.5,140.7,140.4,140.2,136.8,130.3(t,J＝19.1Hz),130.3,127.6,126.2,126.1,121.7,121.2 120.3,118.5,21.2.19F NMR(376MHz,DMSO-d6)δ:–54.84.HRMS(ESI)Calcd for C25H19F3N5O[M+H]+:462.15362,found:462.15366.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-甲氧基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I29)
Figure BDA0002567153840000141
浅黄色粉末，收率34.3％，mp 296-298℃；IR(KBr)(vmax/cm-1):3241,1662,1600,1514,1475,1446,1430,1365,1299,1254,1182,1140,1036,973,833,748,683.1H NMR(400MHz,DMSO-d6)δ:12.86(s,1H),10.75(s,1H),8.32(s,1H),8.18(d,J＝8.7Hz,2H),7.89(d,J＝8.6Hz,2H),7.64(s,1H),7.51(d,J＝9.7Hz,1H),7.48(d,J＝8.8Hz,2H),7.20(d,J＝4.5Hz,2H),7.13(d,J＝8.9Hz,2H),3.86(s,3H).13C NMR(101MHz,DMSO-d6)δ:160.6,159.7,151.5,140.7 140.0,132.0 130.4(d,J＝38.8Hz),127.9,127.6,126.1,122.5,121.5,121.2,120.3,118.5,114.9,56.0.19F NMR(376MHz,DMSO-d6)δ:–54.97.HRMS(ESI)Calcdfor C25H19F3N5O2[M+H]+:478.14854,found:478.14862.
N-(4-(1-氢-苯并咪唑-2-基)苯基)-1-(4-硝基苯基)-5-(三氟甲基)-吡唑-4-甲酰胺(I30)
Figure BDA0002567153840000142
浅黄色粉末，收率55.1％，mp 316–318℃；IR(KBr)(vmax/cm-1):3286,1665,1597,1527,1499,1450,1431,1348,1294,1254,1191,1144,1037,972,854,746,690.1H NMR(400MHz,DMSO-d6)δ:12.87(s,1H),10.82(s,1H),8.47(d,J＝9.7Hz,3H),8.19(d,J＝8.3Hz,2H),7.90(d,J＝8.2Hz,4H),7.65(d,J＝7.1Hz,1H),7.53(d,J＝7.0Hz,1H),7.20(s,2H).13C NMR(101MHz,DMSO-d6)δ:159.2,151.5,148.4,143.8,141.4,140.5,130.7(q,J＝39.3Hz),127.6,126.3 125.4,122.7,122.4,121.0,120.4,118.3.19F NMR(376MHz,DMSO-d6)δ:–54.49.HRMS(ESI)Calcd for C24H16F3N6O3[M+H]+:493.12305,found:493.12283.
用途实施例实施例4：本发明的式(I)化合物I1-I30的杀菌活性
本发明的式(I)的化合物I1-I30的杀菌活性测定以植物病原真菌番茄灰霉病菌(Botrytis cinerea)、水稻纹枯病菌(Rhizoctonia solani)、小麦赤霉病菌(Fusariumgraminearum)、番茄早疫病菌(Alternaria solani)为供试菌，采用菌丝生长速率法进行测定。
测定方法如下：
称取18mg的本发明式(I)的化合物I1-I30分别溶于0.8mL DMSO中，配置成母液，取200μL母液加入到45mL熔融无菌状态的马铃薯葡萄糖琼脂(PDA)培养基中摇匀，得到100mg/L的含药培养基，趁热均匀倒入三个无菌培养皿中，冷却凝固，依次得对应实验组I1-I30。以等剂量DMSO作为空白对照组，以相同条件下的恶霉灵为对照药剂组。
在培养基中央接入直径0.5cm的菌饼。每个药剂做3次平行实验。置于25±1℃恒温培养箱中黑暗培养一段时间后检查并记录药剂对真菌菌丝生长的抑制情况，并进行统计分析，所述时间由不同菌种菌丝生长速率决定。
菌丝生长抑制率(％)＝(C-T)/(C-0.5)×100，C为空白对照菌落直径(cm)，T为药剂处理菌落直径(cm)。
实验组I1-I30以及对照药剂组的杀菌活性测定结果见表1，对水稻纹枯病菌的抑制率，实验组I1-I30为27.43％-56.11％，对照药剂组为72.82±0.61。对番茄灰霉病菌的抑制率，实验组I1-I30为29.22％-90.41％，其中实验组I16、I21的抑制率分别达到81.74％和90.41％，对照药剂组为100.00±0.00。对小麦赤霉病菌的抑制率，实验组I1-I30为12.89％-52.63％，，对照药剂组为68.16±0.64。对番茄早疫病菌的抑制率，实验组I1-I30为25.71％-60.00％，其中实验组I23、I24、I27、I29的抑制率达到55.43％-60.00％，对照药剂组为55.43±1.53。
由表中结果可见，实验条件下，化合物I1-I30对4种植物病原真菌显示出不同程度的抑菌活性，部分高于对照药剂恶霉灵。
表1式(I)化合物I1-I30的杀菌活性(抑制率，％)
Figure BDA0002567153840000151
Figure BDA0002567153840000161
实施例5：化合物I1-I30对灰霉病菌的EC50值的测定
鉴于目标化合物对灰霉病菌具有较好的抑制活性，测试了化合物对灰霉病菌的EC50值，结果如表2所示。从表中可以看出，化合物对番茄灰霉病菌的EC50值较大，即目标化合物对灰霉病菌的活性偏低。其中化合物I11、I14、I18和I21对灰霉病菌的EC50值低于30μg/mL，分别为26.23、19.16、18.27和29.68μg/mL。
表2式(I)化合物I1-I30对灰霉病菌的EC50值
Figure BDA0002567153840000162
实施例6：化合物室内活体杀菌活性测试
在100μg/mL浓度下，化合物I14和I18对番茄灰霉病菌的防护效果如附图1、附图2和表3所示。化合物I14和I18对番茄灰霉病菌的保护防效分别为33.63％和41.11％，高于对照药剂恶霉灵的30.83％。
表3化合物I14和I18对灰霉的防效
Figure BDA0002567153840000171
所属领域的普通技术人员应当理解：以上所述仅为本发明的具体实施例而已，并不用于限制本发明，凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (10)

1.一种如式(I)的化合物，
Figure FDA0002567153830000011
其中，R1选自H、C1-6烷基、被1-3个卤素取代的甲基，R2选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，R3选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，Y(n)中，n＝1-5取代，Y(n)选自下列1-5个基团：H、卤素、C1-6烷基、C1-3烷氧基、NO2、被1-3个卤素取代的甲基；
优选地，R1选自H、F、Cl、CH3、CHF2、CF3，R2选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，R3选自H、卤素、NO2、C1-6烷基、C1-3烷氧基、被1-3个卤素取代的甲基，Y(n)中，n＝1-3取代，Y(n)选自下列1-3个基团：H、F、Cl、Br、CH3、C2H5、CH(CH3)2、OCH3、OC2H5、OCH(CH3)2、NO2、CF3、OCF3；
优选地，R1选自CH3、CHF2、CF3，R2选自H、F、Cl、Br、CH3、CF3，R3选自H、F、Cl、Br、CH3、CF3，Y(n)选自H、2-Cl、3-Cl、4-Cl、4-F、4-Br、4-CH3、4-OCH3、4-NO2、2,4-Cl。
2.权利要求1所述的化合物，其特征在于：包括如下化合物
Figure FDA0002567153830000012
Figure FDA0002567153830000021
3.一种制备权利要求1或2中所述化合物的方法，其特征在于，化合物(II)和(III)经缩合反应得化合物(I)反应方程式如式(A)所示：
Figure FDA0002567153830000022
4.如权利要求3所述的方法，其特征在于，所述反应的条件为，将化合物(III)制成相应的酰氯，加入溶剂，冷却至0～-5℃，分批缓慢加入等当量化合物(II)，加入碱，冰浴条件下搅拌反应，自然升温至室温，继续搅拌4～6h，经纯化处理，既得；优选地，所述溶剂为二氯甲烷；优选地，所述碱为三乙胺；优选地，碱的加入量为2当量；优选地，搅拌反应时间为1h；优选地，所述纯化处理为将反应液经过水洗，饱和食盐水洗涤，干燥，减压蒸去溶剂，经柱层析提纯。
5.如权利要求3所述的方法，其特征在于，所述反应的条件为，将化合物(III)置于反应溶剂中，加入缩合剂，碱，常温搅拌一段时间，加入等当量的式(II)的化合物，常温搅拌反应8～16h，经后处理，既得；优选地，所述溶剂为二氯甲烷；优选地，所述碱为三乙胺，所述碱的加入量为2倍当量；优选地，所述缩合剂为TBTU，所述缩合剂加入量为1.5个当量；优选地，常温搅拌的时间为30min；所述纯化处理为抽滤得反应混合液中固体，水洗，干燥，既得。
6.如权利要求1或2所述的化合物或权利要求3-5任一项所述制备方法所得化合物作为杀菌剂或抑菌剂在防治或抑制植物病原真菌制剂的应用。
7.如权利要求6所述的应用，其特征在于，所述化合物作为杀菌剂或抑菌剂在制备抑制植物病原真菌制剂的应用。
8.如权利要求6或7所述的应用，其特征在于，所述植物为农作物。
9.如权利要求6或7所述的应用，其特征在于，所述化合物应用在制备抑制番茄灰霉病菌、水稻纹枯病菌、小麦赤霉病菌、番茄早疫病菌制剂。
10.如权利要求6或7所述的应用，其特征在于，所述化合物应用在制备防治番茄灰霉病、水稻纹枯病、小麦赤霉病、番茄早疫病制剂。
CN202010627754.5A 2020-07-02 2020-07-02 一种苯基吡唑酰胺类衍生物及其制备方法与应用 Pending CN111592529A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010627754.5A CN111592529A (zh) 2020-07-02 2020-07-02 一种苯基吡唑酰胺类衍生物及其制备方法与应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010627754.5A CN111592529A (zh) 2020-07-02 2020-07-02 一种苯基吡唑酰胺类衍生物及其制备方法与应用

Publications (1)

Publication Number Publication Date
CN111592529A true CN111592529A (zh) 2020-08-28

Family

ID=72191756

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010627754.5A Pending CN111592529A (zh) 2020-07-02 2020-07-02 一种苯基吡唑酰胺类衍生物及其制备方法与应用

Country Status (1)

Country Link
CN (1) CN111592529A (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114105971A (zh) * 2021-09-30 2022-03-01 南京林业大学 6-(苯并1,3二氧五环基）-4苯基-6h-1,3-噻嗪-2-胺衍生物和应用
CN116003323A (zh) * 2023-02-14 2023-04-25 西北农林科技大学 含氟吡唑苯乙酰胺类衍生物及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102993097A (zh) * 2012-11-09 2013-03-27 贵州大学 吡唑酰胺类化合物及其应用
CN110746407A (zh) * 2018-07-23 2020-02-04 南京农业大学 一种含苯并咪唑基团的酰胺类衍生物及其制备方法与应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102993097A (zh) * 2012-11-09 2013-03-27 贵州大学 吡唑酰胺类化合物及其应用
CN110746407A (zh) * 2018-07-23 2020-02-04 南京农业大学 一种含苯并咪唑基团的酰胺类衍生物及其制备方法与应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
STN REGISTRY DATABASE: "RN:2193376-60-0，2182796-54-7，2182475-32-5，2182205-31-6，2175526-64-2，1388315-32-9，1387484-72-1，1387477-35-1，1386552-53-9，1297693-05-0，1133429-50-1，956957-34-9", 《STN REGISTRY DATABASE》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114105971A (zh) * 2021-09-30 2022-03-01 南京林业大学 6-(苯并1,3二氧五环基）-4苯基-6h-1,3-噻嗪-2-胺衍生物和应用
CN114105971B (zh) * 2021-09-30 2024-04-09 南京林业大学 6-(苯并1,3二氧五环基）-4苯基-6h-1,3-噻嗪-2-胺衍生物和应用
CN116003323A (zh) * 2023-02-14 2023-04-25 西北农林科技大学 含氟吡唑苯乙酰胺类衍生物及其应用
CN116003323B (zh) * 2023-02-14 2023-12-08 西北农林科技大学 含氟吡唑苯乙酰胺类衍生物及其应用

Similar Documents

Publication Publication Date Title
US9554576B2 (en) Tetrazolinone compounds and their use as pesticides
KR101332900B1 (ko) 살진균성 카르복사미드
TW577883B (en) Tetrazoyloxime derivative and agricultural chemical comprising the same as active ingredient
WO1996019442A1 (fr) Derive de benzamidoxime, procede de production, et bactericide agrohorticole
JP5500582B2 (ja) ピラゾ−ル−４−カルボキサミド誘導体、それらの製造方法及びそれらを有効成分とする殺菌剤
TW200407073A (en) Benzanilide compound and preventing and eradiating agent for pest containing the same
JP2008044880A (ja) 殺虫性イソオキサゾリン類
BR112015012209B1 (pt) Composto de tetrazolinona, seu uso, agente e método para o controle de pragas
FR2812633A1 (fr) Derives de phenyl(thio)urees et phenyl(thio)carbamates fongicides
JPH10152476A (ja) １−アリールピラゾール誘導体、その製造法および用途
JPH08208620A (ja) アミノピラゾール誘導体、その製造法および用途
CN102428082A (zh) 嘧啶化合物和其在害虫控制上的用途
JPWO2019039429A1 (ja) 環状アミン化合物および有害生物防除剤
JP2009516647A (ja) 殺虫性２−アシルアミノチアゾール−４−カルボキサミド類
CN111875559B (zh) 一类噻唑酰肼衍生物及作为农用杀菌剂的用途
WO2021085370A1 (ja) アゾール誘導体及びその用途
CN111592529A (zh) 一种苯基吡唑酰胺类衍生物及其制备方法与应用
JPH0262876A (ja) ピラゾール類およびこれを有効成分とする殺虫、殺ダニ、殺菌剤
CN111362932A (zh) 一类异噻唑联噁二唑酰胺衍生物及其制备方法和用途
WO1995004724A1 (fr) Derive d'imidazole et son procede de production, et substance anti-nuisibles
JPS60166665A (ja) テトラヒドロ−２ｈ−インダゾ−ル誘導体、その製造法およびそれを有効成分とする除草剤
WO1994002471A1 (en) Triazole derivative, process for producing the same, pest control agent, and pest control method
JPH04316559A (ja) ピラゾールカルボキサニリド誘導体及び殺菌剤
TW201930277A (zh) 氟烯基化合物、製備方法及其用途
CN109232534B (zh) 含杂环二芳胺基吡唑甲酰胺类化合物及其制备方法与应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination