WO2021017597A1 - 嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用 - Google Patents

嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用 Download PDF

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WO2021017597A1
WO2021017597A1 PCT/CN2020/092353 CN2020092353W WO2021017597A1 WO 2021017597 A1 WO2021017597 A1 WO 2021017597A1 CN 2020092353 W CN2020092353 W CN 2020092353W WO 2021017597 A1 WO2021017597 A1 WO 2021017597A1
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oxime
thio
chloro
dimethoxypyrimidin
ethan
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PCT/CN2020/092353
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French (fr)
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徐德锋
徐祥建
胡航
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常州大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • 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
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P13/00—Herbicides; Algicides

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  • the invention belongs to the technical field of herbicides, and relates to the use of herbicides to selectively control gramineous weeds and broadleaf weeds in crops.
  • the invention specifically relates to a preparation method of a pyrimidine salicylic acid oxime ester compound and its application as a herbicide.
  • Acetolactate synthase (ALS) inhibitor is a new type of herbicide developed in the 1980s, that is, to prevent weeds by preventing the biosynthesis of amino acids. It has the characteristics of broad-spectrum, high efficiency, low toxicity, etc., and has been widely used in field weed control. In recent years, a large number of inhibitors based on acetolactate synthase as a target have been developed. In terms of chemical structure, such herbicides mainly include sulfonylureas, imidazolinones, pyrimidotriazoles, and pyrimidine salicylic acids. Compared with several other ALS inhibitors, pyrimidine salicylic acids are more flexible in structural changes.
  • Pyrimidine salicylic acid herbicides are the first new herbicides developed by Japan Combinatorial Chemical Company. The agent has a significant effect on a wide range of gramineous weeds and broad-leaved weeds in rice fields. Its greatest commercial potential is the selective control of barnyardgrass, with extremely low dosage and wide application range, which has attracted more and more attention.
  • the commercial varieties of pyrimidine salicylic acid herbicides mainly include: bispyribac-methyl, saflufenacil, saflufenacil, saflufenacil, and cyflufenpyr.
  • pyrithione is the first commercialized variety of this type of herbicide, and it is also a special herbicide for cotton fields, which is highly safe to cotton. It can control annual and perennial grass weeds and most broad-leaved weeds. It has a good control effect on difficult weeds, such as all kinds of morning glory, cocklebur, abutilon, thorny yellow flower, Tianpu, Arabian sorghum, etc.
  • One of the objectives of the present invention is to provide a new type of pyrimidine salicylic acid compound with high herbicidal activity in response to the emergence of resistance to the herbicide pyrithione in cotton fields.
  • Another object of the present invention is to provide a method for preparing a novel pyrimidine salicylic acid compound with high herbicidal activity.
  • the third object of the present invention is to provide the application of pyrimidine salicylic acid compounds in the preparation of herbicides.
  • R is ortho, meta, and para methyl, trifluoromethyl, nitro, fluoro or 2,4-dimethoxy.
  • a novel pyrimidine salicylic compound with high herbicidal activity preferably its chemical name and chemical structural formula are as follows:
  • Step A Preparation of substituted acetophenone oxime: take hydroxylamine hydrochloride and substituted acetophenone as raw materials, add alcohol as solvent, and react at 0-80°C for 1-5 hours under alkaline conditions. After treatment, substituted acetophenone is obtained.
  • Step B Preparation of the compound of formula (I): starting from 2-chloro-6-((4,6-dimethoxypyrimidin-2-yl)thio)benzoic acid and substituted acetophenone oxime, Under the action of solvent, dehydrating agent and catalyst, react at 25°C for 6-24 hours. After the reaction is finished, suction filtration, the filtrate is distilled under reduced pressure and recrystallized to obtain the compound of formula (I).
  • the solvent alcohol in step A is methanol, ethanol, and isopropanol.
  • the base described in step A is sodium hydroxide, sodium carbonate, sodium acetate, triethylamine, and pyridine.
  • the molar ratio of the substituent acetophenone, hydroxylamine hydrochloride, base, and alcohol in step A is 1:1.5:1.5:8.
  • the organic solvent in step B is dichloromethane.
  • the dehydrating agent described in step B is N,N'-dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) , N,N'-Diisopropylcarbodiimide (DIC).
  • DCC N,N'-dicyclohexylcarbodiimide
  • EDCI 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
  • DIC N,N'-Diisopropylcarbodiimide
  • the catalyst described in step B is 4-dimethylaminopyridine (DMAP), 4-(1'-tetrahydropyrrole)pyridine (4-PPY), and 1-hydroxybenzotriazole (HOBt).
  • step B The molar ratio of 2-chloro-6-((4,6-dimethoxypyrimidin-2-yl)thio)benzoic acid, substituted acetophenone oxime, dehydrating agent, catalyst, and organic solvent described in step B is :1:1:1.2:0.06:9.
  • the reaction formula of the preparation method is as follows:
  • the technical solution adopted by the present invention is the application of the novel pyrimidine salicylic acid compound in the control of weeds.
  • the herbicide is used for the control of Echinochloa crusgalli, Eleusine indica, Setaria viridis, Amaranthus retroflexus, Portulaca oleracea, Chenopodium album .
  • the present invention provides a series of novel pyrimidine salicylic oxime ester compounds with high-efficiency and safe herbicidal activity, which are very effective in controlling weeds such as barnyardgrass, goosegrass, setaria, amaranthus retroflexus, purslane, quinoa, etc.
  • the dosage is low, it has a broad-spectrum effect, is environmentally friendly, has low toxicity, and is highly safe to crop cotton.
  • the pyrimidine salicylic acid compound of the present invention has good herbicidal activity and can be used as an effective active ingredient of herbicides to prepare various pesticide formulations, such as wettable powders, emulsions, water dispersible granules, tablets, granules and the like.
  • the herbicide prepared by the present invention is used to test the herbicidal activity, and the results are as follows:
  • test soil is quantitatively filled to 4/5 of the pot, and the bottom of the pot is infiltrated to make the soil moist.
  • the test weed seeds were sown on the soil surface and cultivated in a greenhouse. When the gramineous weeds grow to the 3 to 4 leaf stage and the broad-leaved weeds grow to the 4 to 6 leaf stage, use the stem and leaf spray method. On the 21st day after application, the above-ground part was taken to weigh the fresh weight, and the fresh weight inhibition rate was calculated according to the formula.
  • Fresh weight inhibition rate (%) (control fresh weight-treated fresh weight) / control fresh weight ⁇ 100%
  • pyrimazine sulfide As a positive control, pyrimazine sulfide. Through the general sieve for the herbicidal activity of the target compound; the dosage refers to the application dosage of pyrithione in the cotton field, when it is 45g ai/hm 2 , the stems and leaves are sprayed. The results are shown in Table 1.
  • pyrimidine salicylic acid compounds have a good inhibitory activity on barnyardgrass, goosegrass, amaranthus, purslane, quinoa and other weeds, and can inhibit setaria Not obvious. Its activity on broadleaf weeds is generally better than gramineous weeds. The inhibition rate of J, K, L and M on broadleaf weeds is higher than 90%, which is better than that of pyrithiopyr.
  • the pyrimidine salicylic acid herbicide compounds of the present invention are all new and unreported compounds, and their inhibitory activity on weeds such as barnyardgrass, goosegrass, amaranthus retroflexus, portulaca oleracea, and Chenopodium quinquefolia has been determined. Fluorine, nitro and 2,4-dimethoxy compounds have good inhibitory activity on weeds, and the inhibitory activity reaches more than 85%, or even 100% (except for setaria), and they are all higher than the commercial herbicide pyrithione Glyoxyfen, showing excellent herbicidal efficacy.
  • the present invention has conducted extensive research on pyrimidine salicylic acid compounds, with the purpose of studying a compound with high efficiency, broad spectrum and safety. The result is that the introduction of functional groups fluorine, nitro, and m-trifluoromethyl are all effective for the test compound. Grass has good control effect and can be used as a candidate compound for herbicide.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Environmental Sciences (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

本发明公开了嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用，属于除草剂技术领域，涉及除草剂在作物中选择性防治禾本科杂草和阔叶杂草的用途。所述化合物为嘧硫草醚肟酯类化合物，其制备方法包括将嘧硫草醚的酸在有机溶剂，缩合剂，与取代苯乙酮肟缩合，制备得到(I)化合物。所述化合物在45g a.i./hm 2能有效防除稗草、牛筋草、狗尾草、反枝苋、马齿苋、藜等多数禾本科杂草和阔叶杂草，可作为棉花田的候选除草剂，具有潜在的产业化应用。同时对环境友好，低毒，对农作物棉花高度安全。本发明提供了一种高效安全具有除草活性的新型嘧啶水杨酸类化合物的制备技术，能大量制备本发明的嘧啶水杨酸类化合物，收率高，纯度好。

Description

嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用 技术领域
本发明属于除草剂技术领域，涉及除草剂在作物中选择性防治禾本科杂草和阔叶杂草的用途。本发明具体涉及一种嘧啶水杨酸肟酯类化合物的制备方法及其作为除草剂的应用。
背景技术
乙酰乳酸合成酶(ALS)抑制剂是上世纪80年代开发兴起的一种新型除草剂，即通过阻止氨基酸的生物合成而达到防除杂草的作用。其具有广谱、高效、低毒等特点，现已被广泛应用于田间的杂草防治。近年来，基于乙酰乳酸合成酶为靶标的抑制剂被大量开发。从化学结构分此类除草剂主要有磺酰脲类、咪唑啉酮类、嘧啶并三唑类、嘧啶水杨酸类等。与其它几种ALS抑制剂相比，嘧啶水杨酸类结构变化更为灵活。
嘧啶水杨酸类除草剂为日本组合化学公司首先开发的新型除草剂。该药剂对稻田中广范围的禾本科杂草和阔叶杂草有显著效果。其最大的商业潜力是能选择性地防除稗草，且用量极低，应用范围广，从而越来越引起人们的重视。嘧啶水杨酸类除草剂的商品化品种主要有：双草醚，嘧草醚，嘧啶肟草醚，嘧硫草醚和环酯草醚。其中，嘧硫草醚是该类除草剂第一个商品化品种，也是棉花田专用除草剂，对棉花高度安全。它可以防除一年生和多年生禾本科杂草和大多数阔叶杂草。对难除杂草如各种牵牛、苍耳、苘麻、刺黄花禾念，田普、阿拉伯高粱等都有很好的防除效果。
由于ALS抑制剂的作用靶标单一，连续使用易诱发杂草产生抗药性，随着除草剂嘧硫草醚的广泛使用，杂草抗药性问题越来越突出，针对这一问题，发 现并开发使用剂量低、活性更高的新型嘧啶水杨酸类衍生物具有重要意义，可以为除草剂提供更多的选择。
发明内容
本发明的目的之一是针对棉花田除草剂嘧硫草醚出现的抗药性，提供一种新型嘧啶水杨酸类化合物，其具有高除草活性。
本发明另一目的是提供一种具有高除草活性的新型嘧啶水杨酸类化合物的制备方法。
本发明第三目的是提供嘧啶水杨酸类化合物在制备除草剂方面的应用。
为实现上述目的之一，本实验采取的技术方案是：一种具有高除草活性的新型嘧啶水杨类化合物，其化学结构式如下通式(I)所示：
Figure PCTCN2020092353-appb-000001
R＝o,m,p-CH 3,CF 3,NO 2,F或2,4-2OCH 3  (I)
-其中R为邻、间、对位甲基，三氟甲基，硝基，氟或2,4-二甲氧基。
一种具有高除草活性的新型嘧啶水杨类化合物，优选其化学名称和化学结构式分别如下：
A：(E)-1-(邻甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000002
B：(E)-1-(间甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000003
C：(E)-1-(对甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000004
D：(E)-1-(2-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000005
E：(E)-1-(3-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000006
F：(E)-1-(4-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000007
G：(E)-1-(2-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000008
H：(E)-1-(3-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000009
I:(E)-1-(4-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000010
J：(E)-1-(2-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000011
K：(E)-1-(3-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000012
L：(E)-1-(4-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000013
M：(E)-1-(2,4-二甲氧基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
Figure PCTCN2020092353-appb-000014
为实现上述第二个目的，本实验采取的技术方案是：嘧啶水杨酸类化合物的制备方法，按照下述步骤进行：
步骤A：取代苯乙酮肟的制备：以盐酸羟胺和取代基苯乙酮为原料，加入醇作溶剂，碱性条件下在0-80℃下反应1-5小时，经处理得取代苯乙酮肟；
步骤B：式(I)化合物的制备：以2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸和取代苯乙酮肟为原料，在有机溶剂，脱水剂和催化剂的作用下，25℃反应6-24小时。反应结束后抽滤，滤液减压蒸馏后重结晶得式(I)化合物。
步骤A所述的溶剂醇为甲醇、乙醇、异丙醇。
步骤A所述的碱为氢氧化钠、碳酸钠、乙酸钠、三乙胺、吡啶。
步骤A所述的取代基苯乙酮、盐酸羟胺、碱、醇的摩尔比为：1:1.5:1.5:8。
步骤B所述的有机溶剂为二氯甲烷。
步骤B所述的脱水剂为N,N'-二环己基碳二亚胺(DCC)，1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI)，N,N'-二异丙基碳二亚胺(DIC)。
步骤B所述的催化剂为4-二甲氨基吡啶(DMAP)，4-(1'-四氢吡咯)吡啶(4-PPY)、1-羟基苯并三唑(HOBt)。
步骤B所述的2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸、取代苯乙酮肟、脱水剂、催化剂、有机溶剂的摩尔比为：1:1:1.2:0.06:9。
该制备方法反应式如下所示：
Figure PCTCN2020092353-appb-000015
为实现上述第三个目的，本发明采取的技术方案是：所述的新型嘧啶水杨酸类化合物在杂草防治中的应用。
所述的除草剂用于防除稗草(Echinochloa crusgalli)、牛筋草(Eleusine indica)、狗尾草(Setaria viridis)、反枝苋(Amaranthus retroflexus)、马齿苋(Portulaca oleracea)、藜(Chenopodium album)。
本发明优点在于：
1.本发明提供了一系列具有高效安全除草活性的新型嘧啶水杨肟酯酸类化合物，对防除稗草、牛筋草、狗尾草、反枝苋、马齿苋、藜等杂草非常有效，使用剂量低，具有广谱效果，同时对环境友好，低毒，对农作物棉花高度安全。
2.提供了一种高效安全具有除草活性的新型嘧啶水杨酸类化合物的制备技术，能大量制备本发明的嘧啶水杨酸类化合物，收率高，纯度好。
具体实施方式
下面对本发明提供的具体实施方式做详细说明。
实施例1：2-甲基苯乙酮肟的制备
在250mL反应瓶中加入2-甲基苯乙酮(10.0g，74.5mmol)，盐酸羟胺(7.8g，112mmol)，甲醇80mL，然后滴加20％氢氧化钠水溶液(22.4g，112mmol)，65℃回流反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体2-甲基苯乙酮肟10.2g，收率91.8％。
实施例2：(E)-1-(邻甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(A)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，EDCI(7.0g，36.7mmol)，HOBt(0.21g，1.5mmol)，二氯甲烷90mL，滴加2-甲基苯乙酮肟(4.6g，30.6mmol)的二氯甲烷溶液，25℃反应6小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(邻甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟10.5g，收率77.26％，熔点：108-111℃。
1H NMR(400MHz,CDCl 3):δ7.64(d,J＝7.7Hz,1H),7.50(d,J＝8.0Hz,1H),7.41(t,J＝7.9Hz,1H),7.27(d,J＝7.2Hz,1H),7.23(d,1H),7.21–7.15(m,2H),5.68(s,1H),3.68(s,6H),2.31(s,3H),2.18(s,3H).
13C NMR(75MHz,CDCl 3):δ180.88,169.18,166.61,163.65,138.34,136.16,135.90,135.23,131.44,130.80,130.39,130.37,129.45,129.34,128.23,125.84,86.56,54.07,20.10,17.99.
实施例3：3-甲基苯乙酮肟的制备
在250mL反应瓶中加入3-甲基苯乙酮(10.0g，74.5mmol)，盐酸羟胺(7.8g，112mmol)，乙醇80mL，然后滴加20％碳酸钠水溶液(59.0g，112mmol)，25℃反应4小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体3-甲基苯乙酮肟10.4g，收率93.6％。
实施例4：(E)-1-(间甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(B)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加3-甲基苯乙酮肟(4.6g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(间甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟10.8g，收率79.5％，熔点84-88℃。
1H NMR(400MHz,CDCl 3):δ7.65(d,J＝7.3Hz,1H),7.57(s,1H),7.51(d,J＝7.6Hz,1H),7.49–7.39(m,2H),7.29–7.22(m,2H),5.68(s,1H),3.69(s,6H),2.35(s,3H),2.23(s,3H).
13C NMR(75MHz,CDCl 3):δ180.87,169.15,164.41,163.34,138.32,138.21,136.15,134.36,131.60,131.58,130.42,130.40,129.47,128.43,127.72,124.36,86.59,54.10,21.38,14.58.
实施例5：4-甲基苯乙酮肟的制备
在250mL反应瓶中加入4-甲基苯乙酮(10.0g，74.5mmol)，盐酸羟胺(7.8g，112mmol)，乙醇80mL，然后滴加20％乙酸钠水溶液(59g，112mmol)，25℃反应3小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体4-甲基苯乙酮肟10.3g，收率92.7％。
实施例6：(E)-1-(对甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(C)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DIC(4.6g，36.7mmol)，4-PPY(0.22g，1.5mmol)， 二氯甲烷90mL，滴加4-甲基苯乙酮肟(4.6g，30.6mmol)的二氯甲烷溶液，25℃反应20小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(对甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟10.6g，收率78.0％，熔点115-119℃。
1H NMR(400MHz,CDCl 3):δ7.66(dd,J＝7.7,1.0Hz,1H),7.62(d,J＝8.2Hz,2H),7.52(dd,J＝8.1,1.1Hz,1H),7.43(t,J＝7.9Hz,1H),7.19(d,J＝8.1Hz,2H),5.69(s,1H),3.80(s,6H),2.37(s,3H),2.24(s,3H).
13C NMR(75MHz,CDCl 3):δ180.87,169.14,164.01,163.48,141.13,138.26,136.1,131.53,131.51,130.41,130.38,129.40,129.25,127.09,86.59,54.09,21.42,14.35.
实施例7：2-三氟甲基苯乙酮肟的制备
在250mL反应瓶中加入2-三氟甲基苯乙酮(10.0g，53.1mmol)，盐酸羟胺(5.5g，79.7mmol)，甲醇80mL，然后滴加20％氢氧化钠水溶液(15.9g，79.7mmol)，65℃回流反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体2-三氟甲基苯乙酮肟10.2g，收率94.4％。
实施例8：(E)-1-(2-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(D)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，EDCI(7.0g，36.7mmol)，HOBt(0.21g，1.5mmol)，二氯甲烷90mL，冰浴滴加2-三氟甲基苯乙酮肟(6.2g，30.6mmol)的二氯甲烷溶液，25℃反应6小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(2-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟12.0g，收率76.9％，熔点82-85℃。
1H NMR(400MHz,CDCl 3):δ7.84(d,J＝7.7Hz,1H),7.76-7.69(m,2H),7.62-7.54(m,2H),7.36(t,J＝8.3Hz,1H),7.21(d,J＝7.9Hz,1H),5.80(s,1H),3.80(s,6H),2.29(s,3H).
13C NMR(75MHz,CDCl 3):δ180.90,169.02,163.14,162.86,137.90,137.68,136.20,132.73,131.82,131.02(q,J＝3.8Hz),130.18,129.60,128.64(d,J＝2.4Hz),127.46(d,J＝2.8Hz),126.24(q,J＝27.1Hz),124.10(q,J＝4.0Hz),123.43(q,J＝14.6Hz),86.62,54.12,13.46.
实施例9：3-三氟甲基苯乙酮肟的制备
在250mL反应瓶中加入3-三氟甲基苯乙酮(10.0g，53.1mmol)，盐酸羟胺(5.5g，79.7mmol)，甲醇80mL，然后滴加20％氢氧化钠水溶液(15.9g，79.7mmol)，25℃反应4小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体3-三氟甲基苯乙酮肟10.1g，收率93.5％。
实施例10：(E)-1-(3-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(E)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，EDCI(7.0g，36.7mmol)，HOBt(0.21g，1.5mmol)，二氯甲烷90mL，冰浴滴加3-三氟甲基苯乙酮肟(6.2g，30.6mmol)的二氯甲烷溶液，25℃反应6小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(3-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟11.6g，收率74.3％，熔点81-86℃。
1H NMR(400MHz,CDCl 3):δ7.95(d,J＝7.1Hz,2H),7.73–7.66(m,2H),7.54(dd,J＝11.1,4.0Hz,2H),7.46(t,J＝7.9Hz,1H),5.80(s,1H),3.80(s,6H),2.30(s,3H).
13C NMR(75MHz,CDCl 3):δ180.90,169.02,163.12,162.86,137.90,136.18,135.35,131.75,131.66(d,J＝13.0Hz),131.10(d,J＝32.47Hz),130.58,130.44(d,J＝2.4Hz),129.49,129.19,127.36(q,J＝3.7Hz),124.00(q,J＝3.9Hz),123.76(q,J＝27.1Hz),86.62,54.08,14.43.
实施例11：4-三氟甲基苯乙酮肟的制备
在250mL反应瓶中加入4-三氟甲基苯乙酮(10.0g，53.1mmol)，盐酸羟胺(5.5g，79.7mmol)，异丙醇80mL，20mL水和10mL吡啶，80℃回流反应1小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体4-三氟甲基苯乙酮肟10.3g，收率95.5％。
实施例12：(E)-1-(4-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(F)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，EDCI(7.0g，36.7mmol)，HOBt(0.21g，1.5mmol)，二氯甲烷90mL，滴加3-三氟甲基苯乙酮肟(6.2g，30.6mmol)的二氯甲烷溶液，25℃反应6小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(4-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟12.1g，收率77.3％，熔点：86-90℃。
1H NMR(400MHz,CDCl 3):δ7.84(d,J＝8.2Hz,2H),7.72–7.61(m,3H),7.57–7.49(m,1H),7.47(d,J＝7.9Hz,1H),5.80(s,1H),3.80(s,6H),2.29(s,3H).
13C NMR(75MHz,CDCl 3):δ180.89,169.01,163.19,162.86,137.89,137.88,136.20,132.46(t,J＝32.47Hz),131.54(d,J＝9.8Hz),129.43,129.15,127.56,125.53(q,J＝3.7Hz),125.45,121.97,86.62,54.11,14.46.
实施例13：2-硝基苯乙酮肟的制备
在250mL反应瓶中加入2-硝基苯乙酮(10.0g，60.5mmol)，盐酸羟胺(6.3g，90.8mmol)，甲醇80mL，然后滴加20％氢氧化钠水溶液(18.2g，90.8mmol)，65℃回流反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体2-硝基苯乙酮肟10.1g，收率92.7％。
实施例14：(E)-1-(2-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(G)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加2-硝基苯乙酮肟(5.5g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(2-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟11.8g，收率：78.9％，熔点：130-134℃。
1H NMR(400MHz,CDCl 3):δ8.15(d,J＝8.1Hz,1H),7.68(ddd,J＝15.6,7.8,1.0Hz,2H),7.60(td,J＝8.1,1.4Hz,1H),7.52(m,2H),7.44(t,J＝7.9Hz,1H),5.70(s,1H),3.71(s,6H),2.19(s,3H).
13C NMR(75MHz,CDCl 3):δ170.90,169.10,165.15,162.98,147.00,137.75,136.19,134.07,131.70,131.65,130.86,130.64,130.63,130.49,129.54,124.95,86.57,54.10,18.17.
实施例15：3-硝基苯乙酮肟的制备
在250mL反应瓶中加入3-硝基苯乙酮(10.0g，60.5mmol)，盐酸羟胺(6.3g，90.8mmol)，甲醇80mL，然后滴加20％乙酸钠水溶液(37.2g，90.8mmol)，25℃反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体3-硝基苯乙酮肟10.4g，收率95.4％。
实施例16：(E)-1-(3-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(H)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加3-硝基苯乙酮肟(5.5g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(3-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟11.4g，收率76.2％，熔点：155-159℃。
1H NMR(400MHz,CDCl 3):δ8.50(s,1H),8.28(d,J＝7.9Hz,1H),8.13(d,J＝7.8Hz,1H),7.67(d,J＝7.6Hz,1H),7.62–7.51(m,2H),7.46(t,J＝7.9Hz,1H),5.68(s,1H),3.69(s,6H),2.32(s,3H).
13C NMR(75MHz,CDCl 3):δ169.86,167.92,161.91,161.00,147.30,136.66,135.17,131.91,130.53,129.68,129.47,128.71,128.45,124.33,121.11,85.58,53.07,13.34.
实施例17：4-硝基苯乙酮肟的制备
在250mL反应瓶中加入4-硝基苯乙酮(10.0g，60.5mmol)，盐酸羟胺(6.3g，90.8mmol)，异丙醇80mL，然后滴加20％碳酸钠水溶液(48.1g，90.8mmol)，25℃反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体4-硝基苯乙酮肟10.2g，收率93.6％。
实施例18：(E)-1-(4-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(I)的制备
在250mL250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)， 二氯甲烷90mL，滴加4-硝基苯乙酮肟(5.5g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(4-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟12.4g，收率82.9％，熔点：153-157℃。
1H NMR(400MHz,CDCl 3):δ8.25(d,J＝8.9Hz,2H),7.92(d,J＝8.9Hz,2H),7.68(dd,J＝7.7,1.0Hz,1H),7.55(dd,J＝8.1,0.9Hz,1H),7.47(t,J＝7.9Hz,1H),5.70(s,1H),3.71(s,6H),2.32(s,3H).
13C NMR(75MHz,CDCl 3):δ170.90,168.95,162.94,162.19,149.09,140.44,137.65,136.22,131.57,130.74,130.52,129.47,128.20,123.74,86.62,54.13,14.49.
实施例19：2-氟苯乙酮肟的制备
在250mL反应瓶中加入2-氟苯乙酮(10.0g，72.4mmol)，盐酸羟胺(7.5g，108.6mmol)，乙醇80mL，然后滴加20％氢氧化钠水溶液(21.7g，108.6mmol)，25℃反应4小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体2-氟苯乙酮肟10.5g，收率94.7％。
实施例20：(E)-1-(2-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(J)的制备
在250mL250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加2-氟苯乙酮肟(4.7g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(2-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟9.7g，收率68.6％，熔点：87-91℃。
1H NMR(400MHz,CDCl 3):δ7.66(d,J＝7.7Hz,1H),7.59(s,1H),7.52(d,J＝7.4Hz,1H),7.46–7.36(m,2H),7.17–7.05(m,2H),5.70(s,1H),3.70(s,6H),2.26(d,J＝2.8Hz,3H).
13C NMR(75MHz,CDCl 3):δ170.89,169.08,163.21(d,J＝4.5Hz),162.47,159.14,137.92,136.17,132.14(d,J＝8.3Hz),131.59,130.45(d,J＝3.0Hz),130.24(d,J＝2.3Hz),129.51,124.34(d,J＝3.0Hz),123.30(d,J＝12.0Hz),116.36,116.07,86.62,54.00,16.98.
实施例21：3-氟苯乙酮肟的制备
在250mL反应瓶中加入3-氟苯乙酮(10.0g，72.4mmol)，盐酸羟胺(7.5g，108.6mmol)，乙醇80mL，然后滴加20％乙酸钠水溶液(44.5g，108.6mmol)，25℃反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体3-氟苯乙酮肟10.1g，收率91.1％。
实施例22：(E)-1-(3-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(K)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加3-氟苯乙酮肟(4.7g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(3-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟11.6g，收率82.0％，熔点：103-107℃。
1H NMR(400MHz,CDCl 3):δ7.67(dd,J＝7.7,1.0Hz,1H),7.52(dd,J＝8.1,1.0Hz,1H),7.49(d,J＝7.9Hz,1H),7.44(m,2H),7.35(td,J＝8.0,5.9Hz,1H),7.13(td,J＝8.3,1.8Hz,1H),5.69(s,1H),3.70(s,6H),2.25(s,3H).
13C NMR(75MHz,CDCl 3):δ176.83,173.41,163.79(d,J＝77.3Hz),162.94(d,J＝3.0Hz),161.04,137.99,136.55(d,J＝7.5Hz),136.18,131.51,130.49(d,J＝7.5Hz),130.23,130.12,129.42,122.90(d,J＝3.0Hz),117.75(d,J＝21.0Hz),114.13(d,J＝23.25Hz),86.59,54.22,14.29.
实施例23：4-氟苯乙酮肟的制备
在250mL反应瓶中加入4-氟苯乙酮(10.0g，72.4mmol)，盐酸羟胺(7.5g，108.6mmol)，甲醇80mL，然后滴加20％乙酸钠水溶液(44.5g，108.6mmol)，25℃反应2小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体4-氟苯乙酮肟10.0g，收率90.2％，
实施例24：(E)-1-(4-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(L)的制备
在250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加4-氟苯乙酮肟(4.7g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(4-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟11.6g，收率82.3％，熔点：102-105℃。
1H NMR(400MHz,CDCl 3):δ7.74(dd,J＝8.8,5.3Hz,2H),7.67(dd,J＝7.7,0.9Hz,1H),7.53(dd,J＝8.1,0.9Hz,1H),7.44(t,J＝7.9Hz,1H),7.07(t,J＝8.7Hz,2H),5.70(s,1H),3.70(s,6H),2.25(s,3H).
13C NMR(75MHz,CDCl 3):δ170.88,169.06,166.02,163.06,163.0(d,J＝45.7Hz),138.05,136.18,131.51,130.54,130.47(d,J＝5.1Hz),129.41,129.26(d,J＝8.6Hz),115.79,115.50,86.58,54.08,14.39.
实施例25：2,4-二甲氧基苯乙酮肟的制备
在250mL反应瓶中加入2,4-二甲氧基苯乙酮(10.0g，55.5mmol)，盐酸羟胺(5.8g，83.2mmol)，甲醇80mL，然后滴加20％氢氧化钠水溶液(16.6g，83.2mmol)，25℃反应5小时。反应结束后，减压蒸去溶剂，加水洗涤，抽滤，干燥，得白色固体2,4-二甲氧基苯乙酮肟10.2g，收率94.4％。
实施例26：(E)-1-(2,4-二甲氧基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟(M)的制备
在250mL250mL反应瓶中加入2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸(10.0g，30.6mmol)，DCC(7.6g，36.7mmol)，DMAP(0.18g，1.5mmol)，二氯甲烷90mL，滴加2，4-二甲氧基苯乙酮肟(4.7g，30.6mmol)的二氯甲烷溶液，25℃反应24小时。反应结束后，先抽滤，滤液减压蒸馏后重结晶得白色固体(E)-1-(2,4-二甲氧基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟12.2g，收率79.3％，熔点：125-129℃。
1H NMR(400MHz,CDCl 3):δ7.65(d,J＝7.7Hz,1H),7.51(d,J＝8.0Hz,1H),7.45–7.37(m,2H),6.49–6.40(m,2H),5.70(s,1H),3.80(d,J＝9.4Hz,6H),3.70(s,6H),2.17(s,3H).
13C NMR(75MHz,CDCl 3):δ170.85,169.23,166.28,163.54,162.63,159.04,138.39,136.13,131.52,131.11,130.36,130.25,129.39,117.49,104.37,98.81,86.53,55.48,55.44,54.06,17.42.
实施例27：除草活性测试
本发明的嘧啶水杨酸类化合物具有良好的除草活性，可用作除草剂的有效活性成分，制备各种农药剂型，例如可湿性粉末，乳剂，水分散颗粒剂，片剂，颗粒剂等。
使用本发明制备的除草剂进行除草活性测试，结果如下：
1.测试药剂及配制
用万分之一分析天平称取20mg的嘧啶水杨酸类化合物原药，用丙酮(或DMF或DMSO)溶解，用0.1％吐温80水溶液稀释成浓度为45g a.i/hm 2。
2.实验设计：
Figure PCTCN2020092353-appb-000016
3.试验方法
试验土壤定量装至盆钵的4/5处，采用盆钵底部渗灌方式，使土壤湿润。将测试杂草种子分别播种与土壤表面，于温室中培养。待禾本科杂草长到3～4叶期，阔叶杂草4～6叶期时，使用茎叶喷雾法处理。施药后第21天取地上部分称量鲜重，按照公式计算鲜重抑制率。
鲜重抑制率(％)＝(对照鲜重-处理鲜重)/对照鲜重×100％
嘧草硫醚作为阳性对照。通过对目标化合物的除草活性普筛；剂量参考嘧硫草醚在棉花田的施用剂量，为45g a.i/hm 2时，茎叶喷雾处理，结果见表1。
表1.嘧啶水杨酸类化合物的室内除草活性
Figure PCTCN2020092353-appb-000017
从上表1可以观察到，45g a.i./hm 2下，嘧啶水杨酸类化合物具有良好的抑制稗草、牛筋草、反枝苋、马齿苋、藜等杂草的活性，对狗尾草抑制不明显。其对阔叶科杂草活性普遍优于禾本科杂草，J、K、L和M对阔叶科杂草的抑制率高于90％，均优于嘧硫草醚。
本发明的嘧啶水杨酸类除草剂化合物均为新型、未报导的化合物，并测定了其对稗草、牛筋草、反枝苋、马齿苋、藜等杂草的抑制活性，其中含氟、硝基以及2,4-二甲氧基的化合物对杂草的抑制活性较好，抑制活性均达到85％以 上，甚至100％(除了狗尾草)，且均高于商品化除草剂嘧硫草醚，显示出优秀的除草效能。
4.结论
本发明对嘧啶水杨酸类化合物进行了广泛的研究，目的在于研究一种具有高效、广谱、安全的化合物，结果发现，引入官能团氟、硝基、间三氟甲基均对供试杂草有较好的防治效果，可作为除草剂的候选化合物。
以上所述仅是本发明的优选实验方式，应当指出，对于本技术领域的普通技术人员，在不脱离本发明的前提下，还可以做出若干改进和补充，这些改进和补充也应视为本发明的保护范围。

Claims (6)

  1. 一种具有高除草活性的新型嘧啶水杨酸类化合物，其特征在于，其化学结构式如下通式(I)所示：
    Figure PCTCN2020092353-appb-100001
    R＝o,m,p-CH 3,CF 3,NO 2,F或2,4-2OCH 3  (I)
    -其中R为邻、间、对位甲基，三氟甲基，硝基，氟或2,4-二甲氧基。
  2. 根据权利要求1所述的一种具有高除草活性的新型嘧啶水杨酸类化合物，其特征在于，其化学名称和化学结构式分别如下：
    A：(E)-1-(邻甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100002
    B：(E)-1-(间甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100003
    C：(E)-1-(对甲苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100004
    D：(E)-1-(2-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100005
    E：(E)-1-(3-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100006
    F：(E)-1-(4-(三氟甲基)苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100007
    G：(E)-1-(2-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100008
    H：(E)-1-(3-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100009
    I:(E)-1-(4-硝基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100010
    J：(E)-1-(2-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100011
    K：(E)-1-(3-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100012
    L：(E)-1-(4-氟苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100013
    M：(E)-1-(2,4-二甲氧基苯基)乙-1-酮O-(2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酰基)肟
    Figure PCTCN2020092353-appb-100014
  3. 权利要求1或2所述的一种具有高除草活性的新型嘧啶水杨酸类化合物的制备方法，其特征在于，按照下述步骤进行：
    步骤A：取代苯乙酮肟的制备：以盐酸羟胺和取代基苯乙酮为原料，加入醇作溶剂，碱性条件下在0-80℃下反应1-5小时，经处理得取代苯乙酮肟；
    步骤B：式(I)化合物的制备：以2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸和取代苯乙酮肟为原料，在有机溶剂，脱水剂和催化剂的作用下，25℃反应6-24小时；反应结束后抽滤，滤液减压蒸馏后重结晶得式(I)化合物。
  4. 根据权利要求3所述的一种具有高除草活性的新型嘧啶水杨酸类化合物的制备方法，其特征在于，步骤A所述的溶剂醇为甲醇、乙醇、异丙醇；
    步骤A所述的碱为氢氧化钠、碳酸钠、乙酸钠、三乙胺、吡啶；
    步骤A所述的取代基苯乙酮、盐酸羟胺、碱、醇的摩尔比为：1:1.5:1.5:8。
  5. 根据权利要求3所述的一种具有高除草活性的新型嘧啶水杨酸类化合物的制备方法，其特征在于，步骤B所述的有机溶剂为二氯甲烷；
    步骤B所述的脱水剂为N,N'-二环己基碳二亚胺(DCC)，1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI)，N,N'-二异丙基碳二亚胺(DIC)；
    步骤B所述的催化剂为4-二甲氨基吡啶(DMAP)，4-(1'-四氢吡咯)吡啶(4-PPY)、1-羟基苯并三唑(HOBt)；
    步骤B所述的2-氯-6-((4,6-二甲氧基嘧啶-2-基)硫代)苯甲酸、取代苯乙酮肟、脱水剂、催化剂、有机溶剂的摩尔比为：1:1:1.2:0.06:9。
  6. 根据权利要求1所述的一种具有高除草活性的新型嘧啶水杨酸类化合物的应用，其特征在于，所述的新型嘧啶水杨酸类化合物用于防除稗草、牛筋草、狗尾草、反枝苋、马齿苋、藜。
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1931846A (zh) * 2006-09-30 2007-03-21 中国科学院上海有机化学研究所 羟酰胺缩合酯类化合物、制备方法及其用途
CN103333121A (zh) * 2013-07-22 2013-10-02 金坛市信德农业科技有限公司 具有除草活性的氟嘧肟草醚类化合物及其制备方法
CN104302629A (zh) * 2013-12-03 2015-01-21 南京慧博生物科技有限公司 新型除草活性的嘧啶水杨酸类化合物、其制备方法及其作为除草剂的用途
CN110317177A (zh) * 2019-07-30 2019-10-11 常州大学 嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0608862A1 (en) * 1993-01-27 1994-08-03 Lucky Ltd. Novel 6-chloro-2-(4,6-dimethoxypyrimidin-2-yl) oxybenzoic acid ester derivatives, processes for their production an a method for their application as herbicides

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1931846A (zh) * 2006-09-30 2007-03-21 中国科学院上海有机化学研究所 羟酰胺缩合酯类化合物、制备方法及其用途
CN103333121A (zh) * 2013-07-22 2013-10-02 金坛市信德农业科技有限公司 具有除草活性的氟嘧肟草醚类化合物及其制备方法
CN104302629A (zh) * 2013-12-03 2015-01-21 南京慧博生物科技有限公司 新型除草活性的嘧啶水杨酸类化合物、其制备方法及其作为除草剂的用途
CN110317177A (zh) * 2019-07-30 2019-10-11 常州大学 嘧啶水杨酸肟酯类化合物的制备方法及作为除草剂的应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
XU, XIANGJIAN ET AL.: "Synthesis and Herbicidal Activities of Novel Substituted Acetophenone Oxime Esters of Pyrithiobac", CHEMISTRYSELECT, vol. 5, no. 1, 9 January 2020 (2020-01-09), pages 69 - 74, XP055777166, DOI: 10.1002/slct.201903927 *
ZHANG, TE ET AL.: "Advances in pyrimidinyl(oxy)thiobenzoic acid herbicides", PLANT PROTECTION, vol. 44, no. 2, 31 December 2018 (2018-12-31), pages 22 - 28, XP055777175, DOI: 10.16688/j.zwbh.2017205 *

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