WO2023226241A1 - 一种苯乙酰胺类化合物及其制备方法与应用 - Google Patents

一种苯乙酰胺类化合物及其制备方法与应用 Download PDF

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WO2023226241A1
WO2023226241A1 PCT/CN2022/118389 CN2022118389W WO2023226241A1 WO 2023226241 A1 WO2023226241 A1 WO 2023226241A1 CN 2022118389 W CN2022118389 W CN 2022118389W WO 2023226241 A1 WO2023226241 A1 WO 2023226241A1
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compound
phenylacetamide
reaction
binding agent
solvent
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French (fr)
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李祖任
柏连阳
罗丁峰
柏振东
刘娜
柏浩东
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湖南省农业生物技术研究所
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • 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
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the invention belongs to the technical fields of organic synthesis and pesticides, and specifically relates to a phenylacetamide compound and its preparation method and application.
  • Herbicides are chemicals that can completely or selectively kill weeds, also known as herbicides, a class of substances used to destroy or inhibit plant growth. Chemical control has always been an effective means of controlling weeds in farmland, but the extensive use of chemicals has also caused a series of problems, such as the emergence of herbicide-resistant weed plants, environmental pollution caused by herbicide residues, and the impact on non-weeds. The harm of grass organisms, etc. is not conducive to farmland weeding. Moreover, the dosage and cost of chemical herbicides in the existing technology are relatively high, and the cost of prevention and control is relatively high.
  • Amide herbicides are a new type of herbicides that develop rapidly, have high herbicidal effects and strong selectivity. Their market sales are second only to amino acids and sulfonylureas, accounting for 4.5% of the entire pesticide market and 1% of the herbicide market. 9.0%. Since the 1960s, this type of herbicide has made great progress, and 63 types have been developed so far. The mechanism of action of most varieties is to inhibit seed germination and sprout growth, causing the sprouts to become severely dwarfed and eventually die; to inhibit the biosynthesis of fatty acids, including the biosynthesis of soft fats and oleic acid. Most varieties are soil treatment agents, special herbicides for controlling annual grass weeds, but have relatively poor control effects on broadleaf weeds. The development of amide herbicides that reduce phytotoxicity and have good broadleaf control effects will have great practical value in enriching the product types and application scope of this type of herbicides.
  • the object of the present invention is to provide a phenylacetamide compound with excellent control effect, low herbicide dosage, low cost, simple synthesis process and environmental protection, and a preparation method and application.
  • R 1 and R 2 are any one of -H, -OCH 3 , -NO 2 , -COOCH 3 , -CONH 2 and -COOH respectively;
  • R 3 and R 4 are respectively -H, -CH 3 , Any one of -C 2 H 5 , -OCH 3 , -NO 2 , -Br, -Cl, -F and -CN.
  • the preparation method of this phenylacetamide compound provided by the invention includes the following steps:
  • step (3) Dissolve compound 2 obtained in step (1) and compound 4 obtained in step (2) in a solvent, add an acid binding agent, heat to the set temperature and stir the reaction. After the reaction is completed, extract, wash, dry and filter , rotary evaporation to obtain phenylacetamide compounds;
  • the molar ratio of compound 1, acid binding agent and 2-bromoacetyl chloride in step (1) is 1:3 ⁇ 5:1 ⁇ 2;
  • the acid binding agent is potassium carbonate, sodium carbonate, triethylamine, At least one of potassium bicarbonate and sodium bicarbonate;
  • the solvent is at least one of acetonitrile, acetone, tetrahydrofuran, dichloromethane and chloroform.
  • the stirring rate in step (1) is 500-600 rpm; the reaction time is 2-6 hours.
  • the molar ratio of compound 3, piperazine and acid binding agent in step (2) is 1:1 ⁇ 2:3 ⁇ 6;
  • the acid binding agent is potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate and at least one of triethylamine;
  • the solvent is at least one of acetonitrile, chloroform, dichloromethane and tetrahydrofuran.
  • the stirring rate in step (2) is 500-600 rpm; the reaction progress is monitored by thin layer chromatography.
  • the molar ratio of compound 2, compound 4 and acid binding agent is 1:1 ⁇ 1.5:3 ⁇ 6;
  • the acid binding agent is potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate and at least one of triethylamine;
  • the solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran.
  • the temperature is set to 40-60°C
  • the stirring rate is 500-600 rpm
  • the reaction time is 2-6 hours.
  • the phenylacetamide compound provided by the invention is used as a herbicidal active substance in suppressing annual and perennial weeds in corn fields.
  • the weeds are mainly broadleaf weeds.
  • the phenylacetamide compound provided by the invention has excellent herbicidal activity, and is particularly effective in preventing and controlling annual and perennial weeds in corn fields.
  • the plant control effect on total grass reached at least 86.22% 15 days after treatment, and the fresh weight control effect It reaches at least 83.39% and is safe and harmless to corn.
  • This compound can also effectively reduce the dosage and cost of herbicides, reduce residues, and reduce the potential threat of pesticides to the environment.
  • the synthesis method is simple and economical. It can be used as a lead compound to provide new fields for the development of new safe, efficient, and environmentally friendly herbicides.
  • step (3) Combine 0.70g (3mmol) 2-(m-tolyloxy)-1-(piperazin-1-yl)acetamide obtained in step (2) and 0.99g (3mmol) 2- obtained in step (1) Dissolve bromoacetamide methyl phthalate in 50 mL of N,N-dimethylformamide, add 0.83g (6mmol) potassium carbonate to the above solution, stir, and react at 55°C for 5 hours. After the reaction is completed, use Extract with ethyl acetate (3*70 mL), combine the organic phases, wash with brine three times, dry over anhydrous magnesium sulfate, filter, and rotary evaporate the solvent to obtain the target compound, weigh 1.26g, and the calculated yield is: 86.7%.
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 2 This example prepares a phenylacetamide compound: N-(3,5-methoxybenzene)-2-(4-(2-(4-fluorobenzene)acetyl)piperazine-1- base) acetamide (wherein, R 1 and R 2 are -OCH 3 , R 3 is -H, and R 4 is -F), the specific steps are as follows:
  • step (3) Combine 0.71g (3mmol) 2-(p-fluorophenoxy)-1-(piperazin-1-yl)acetamide obtained in step (2) and 0.82g (3mmol) 2 obtained in step (1) -N-(3,5-methoxybenzene)acetamide was dissolved in 50 mL dimethyl sulfoxide, then 0.60 g (6 mmol) potassium bicarbonate was added, stirred, and reacted at 60°C for 4 hours.
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 3 This example prepares a phenylacetamide compound: 4-(2-(4-(2-(4-bromo-2-chlorobenzene)acetyl)piperazin-1-yl)acetamide)benzene
  • R 1 is -H
  • R 2 is -COOH
  • R 3 is -Cl
  • R 4 is -Br
  • step (3) Combine 1.00g (3mmol) 2-(4-bromo-2-chlorophenoxy)-1-(piperazin-1-yl)acetamide obtained in step (2) and 1.03 obtained in step (1) Dissolve g (3mmol) 4-(2-bromoacetamide) benzoic acid into 50mL tetrahydrofuran, then add 1.03g (6mmol) potassium carbonate, stir, and react at 50°C for 5h. After the reaction is completed, use ethyl acetate (3 *70 mL), combine the organic phases, wash with brine three times, dry over anhydrous magnesium sulfate, filter, and rotary evaporate to obtain the target compound, weigh 1.36 g, and calculate the yield: 88.7%.
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 4 This example prepares a phenylacetamide compound: 2-(4-(2-(3-cyano-5-methoxyphenyl)acetyl)piperazin-1-yl)-N-( 2-Methoxy-4-nitrobenzene)acetamide (where R 1 is -OCH 3 , R 2 is -NO 2 , R 3 is -CN, R 4 is -OCH 3 ), the specific steps are as follows:
  • step (3) Combine 0.83g (3mmol) 3-methoxy-5-(2-oxo-2-(piperazin-1-yl)ethoxy)benzene cyanide obtained in step (2) and step (1) to obtain Dissolve 0.87g (3mmol) 2-bromo-N-(2-methoxy-4-nitrobenzene)acetamide into 50mL N,N-dimethylformamide, then add 0.64g (6mmol) sodium carbonate , stir, react at 60°C for 5 hours, extract with chloroform (3*70mL), combine the organic phases, wash with brine three times, dry with anhydrous magnesium sulfate, filter, and rotary evaporate to obtain the target compound, weigh 1.31g, calculate Yield: 90.3%;
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 5 This example prepares a phenylacetamide compound: 4-(2-(4-(2-phenylacetyl)piperazin-1-yl)acetamide)benzamide (where R 1 is H, R 2 is -CONH 2 , R 3 is -H, R 4 is -H), the specific steps are as follows:
  • step (3) Combine 0.66g (3mmol) 2-phenoxy-1-(piperazin-1-yl)ethyl-1-one obtained in step (2) and 0.87g (3mmol) 4 obtained in step (1) -(2-Bromoacetamide)benzamide was dissolved in 50 mL of dimethyl sulfoxide, then 0.61g (6 mmol) triethylamine was added, stirred, and reacted for 5 hours at 50°C. After the reaction was completed, ethyl acetate (3 *70mL), combine the organic phases, wash with brine three times, dry with anhydrous magnesium sulfate, filter, and rotary evaporate to obtain the target compound, weighing 0.79g, yield: 89.7%;
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 6 This example prepares a phenylacetamide compound: 4-(2-(4-(2-(2-chloro-4-methoxyphenoxy)acetyl)piperazin-1-yl) Acetamide)-2-methoxybenzoic acid methyl ester (where R 1 is -OCH 3 , R 2 is -COOCH 3 , R 3 is -Cl, R 4 is -OCH 3 ), the specific steps are as follows:
  • step (3) Combine 0.86g (3mmol) 2-(2-chloro-4-methoxyphenoxy)-1-(piperazin-1-yl)ethyl-1-one obtained in step (2) with the step (1)
  • 0.91g (3mmol) 4-(2-bromoacetamide)-2-methoxybenzoic acid methyl ester was dissolved in 50mL tetrahydrofuran, then 0.61g (6mmol) triethylamine was added, stirred, 60°C React under the conditions for 5 hours, extract with ethyl acetate (3*70mL), combine the organic phases, wash with brine three times, dry with anhydrous magnesium sulfate, filter and rotary evaporate to obtain the target compound, weigh 1.36g, and calculate the yield :89.7%;
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • Example 7 This example prepares a phenylacetamide compound: 2-(2-(4-(2-(3-ethyl-5-nitrobenzene)acetyl)piperazin-1-yl)acetamide ) Dimethyl terephthalate (where R 1 and R 2 are both -COOCH 3 , R 3 is -C 2 H 5 , and R 4 is -NO 2 ), the specific steps are as follows:
  • step (3) Combine 0.88g (3mmol) 2-(3-ethyl-5-nitrobenzene)-1-(piperazin-1-yl)acetamide obtained in step (2) and 0.99 obtained in step (1) Dissolve g (3mmol) methyl 2-bromoacetamide phthalate in 50mL of N,N-dimethylformamide. Add 0.83g (6mmol) potassium carbonate to the above solution, stir, and react at 60°C for 5 hours. , after the reaction is completed, extract with ethyl acetate (3*70mL), combine the organic phases, wash with brine three times, dry with anhydrous magnesium sulfate, filter, and rotary evaporate the solvent to obtain the target compound, weigh 1.38g, and calculate Yield: 84.7%.
  • the target compound in this example was subjected to melting point testing and nuclear magnetic characterization.
  • the results are as follows:
  • the stem and leaf spray method (NY/T 1155.4-2006) was used to conduct an indoor toxicity test on the phenylacetamide compounds prepared in Examples 1 to 6.
  • Test medicaments (a) Example 1; (b) Example 2; (c) Example 3; (d) Example 4; (e) Example 5; (f) Example 6; (g) Control Agent acetochlor; (h) control agent 2,4-D butyl ester; (f) water control.
  • E is the fresh weight control effect
  • C is the fresh weight of the above-ground part in the control
  • T is the fresh weight of the above-ground part in the treatment.
  • the stem and leaf spray method was used to conduct crop safety tests on the phenylacetamide compounds prepared in Examples 1 to 6.
  • Test medicaments (a) Example 1; (b) Example 2; (c) Example 3; (d) Example 4; (e) Example 5; (f) Example 6; (g) Control Agent acetochlor; (h) control agent 2,4-D butyl ester; (i) water control.
  • Test material corn.
  • Corn seeds are soaked and germinated, then sown on demand in plastic pots with a cross-sectional area of 0.25m2 filled with soil. 10 seeds are sown in each pot, and they are cultured in the greenhouse to the 2-leaf stage for processing.
  • the pesticide solution is sprayed with a hand-held compression sprayer (3NY-1.2) at a dosage of 50g/acre of active ingredient.
  • the spray volume is 50mL per treatment. Keep the soil moist after spraying. Each treatment was repeated 4 times.
  • the fresh weight of the above-ground parts of each treatment was weighed 20 days after treatment, and the fresh weight control effect (%) of each treatment was calculated according to the following formula:
  • E is the fresh weight control effect
  • C is the fresh weight of the above-ground parts in the control
  • T is the fresh weight of the above-ground parts in the treatment.
  • Example 1 was sprayed diluted with water at 850g.a.i/ha, and the plant control effect on total weeds 15 days after spraying was: The fresh weight control effect is 90.76% and 93.17%.
  • Examples 2, 3 and 4 were diluted and sprayed with water at 1025.5g.a.i/ha respectively.
  • the plant control effects on total grass 15 days after spraying were 86.22%, 90.79% and 88.53% respectively; the fresh weight control effects were 83.39% and 87.85% respectively. and 85.64%.
  • the control chemicals acetochlor and 2,4-D butyl ester were diluted with water at 1025.5g.a.i/ha and sprayed respectively.
  • the plant control effects on total grass 15 days after application were 51.21% and 73.88% respectively.
  • visual inspection revealed that the control agent 2,4-D butyl ester was seriously harmful to corn, while Examples 1 to 4 and acetochlor were safe to corn.
  • the phenylacetamide compound provided by the present invention has obvious control effects on annual and perennial weeds in corn fields, and its herbicidal spectrum is further expanded. It not only has the potential to be developed into a herbicide, but also has low cost and environmental protection. advantage.

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Abstract

本发明公开了一种苯乙酰胺类化合物及其制备方法与应用。该化合物的结构通式为（aa）。其中，R1和R2分别为-H、-OCH3、-NO2、-COOCH3、-CONH2和-COOH中的任意一种；R3和R4分别为-H、-CH3、-C2H5、-OCH3、-NO2、-Br、-Cl、-F和-CN中的任意一种。该类化合物具有优良的除草活性，尤其对玉米地防治一年生和多年生杂草效果显著，药后15天对总草的株防效至少达到86.22％，鲜重防效至少达到83.39％，且对玉米安全无害。该类化合物还可以有效降低除草剂用量及成本，减少残留，减轻农药对环境的潜在威胁，并且合成方法简单、经济，可以作为先导化合物，为开发安全高效环保的新型除草剂提供新的领域。

Description

一种苯乙酰胺类化合物及其制备方法与应用 技术领域
本发明属于有机合成和农药技术领域，具体涉及一种苯乙酰胺类化合物及其制备方法与应用。
背景技术
除草剂是指可使杂草彻底地或选择性地发生枯死的药剂，又称除莠剂，用以消灭或抑制植物生长的一类物质。一直以来，化学防除是防除农田杂草的有效手段，但化学药剂的大量使用也引发了一系列的问题，诸如除草剂抗性杂草植株的出现、除草剂残留造成的环境污染以及对非杂草生物的危害等，不利于农田除草。而且现有技术中的化学类除草剂用量及成本较高，防治成本相对较高。
酰胺类除草剂是一类发展较快、除草效果高、选择性强的新型除草剂，市场销售额仅次于氨基酸类、磺酰脲类，占整个农药市场的4.5％，占除草剂市场的9.0％。自60年代以来，该类除草剂取得了较大发展，目前已开发出63种。多数品种的作用机制是抑制种子发芽和幼芽生长，使幼芽严重矮化而最终死亡；抑制脂肪酸的生物合成，包括对软脂肪和油酸的生物合成。大多数品种都是土壤处理剂，防治一年生禾本科杂草的特效除草剂，对阔叶杂草的防效相对较差。研发药害降低、阔叶草防治效果好的酰胺类除草剂，对丰富该类除草剂的产品类型和使用范围具有较大的实用价值。
发明内容
本发明的目的是提供一种防治效果优良、除草剂用量少、成本低、合成工艺简单环保的苯乙酰胺类化合物及制备方法与应用。
为达到上述目的，本发明提供以下技术方案：
本发明提供的这种苯乙酰胺类化合物的结构通式为：
Figure PCTCN2022118389-appb-000001
其中，R 1和R 2分别为-H、-OCH 3、-NO 2、-COOCH 3、-CONH 2和-COOH中的任意一种；R 3和R 4分别为-H、-CH 3、-C 2H 5、-OCH 3、-NO 2、-Br、-Cl、-F和-CN中的任意一种。
本发明提供的这种苯乙酰胺类化合物的制备方法，包括以下步骤：
(1)将化合物1和2-溴乙酰氯溶解于溶剂，加入缚酸剂，室温搅拌反应，萃取、洗涤、干燥、过滤、旋蒸，得到化合物2；
(2)将化合物3和哌嗪溶解于溶剂，加入缚酸剂，室温搅拌反应，萃取、洗涤、干燥、过滤、旋蒸，得到化合物4；
(3)将步骤(1)得到的化合物2和步骤(2)得到的化合物4溶解于溶剂，加入缚酸剂，加热至设定温度并搅拌反应，反应结束后，萃取、洗涤、干燥、过滤、旋蒸，得到苯乙酰胺类化合物；
其合成路线如下：
Figure PCTCN2022118389-appb-000002
作为优选，所述步骤(1)中化合物1、缚酸剂和2-溴乙酰氯的摩尔比为1:3～5:1～2；缚酸剂为碳酸钾、碳酸钠、三乙胺、碳酸氢钾和碳酸氢钠中的至少一种；溶剂为乙腈、丙酮、四氢呋喃、二氯甲烷和氯仿中的至少一种。
作为优选，所述步骤(1)中搅拌速率为500～600rpm；反应时间为2～6h。
作为优选，所述步骤(2)中化合物3、哌嗪和缚酸剂的摩尔比为1:1～2:3～6；缚酸剂为碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠和三乙胺中的至少一种；溶剂为乙腈、氯仿、二氯甲烷和四氢呋喃中的至少一种。
作为优选，所述步骤(2)中搅拌速率为500～600rpm；反应进程用薄层色谱监测。
所述步骤(3)中化合物2、化合物4和缚酸剂的摩尔比为1:1～1.5:3～6；缚酸剂为碳酸钾、碳酸钠、碳酸铯、碳酸氢钾、碳酸氢钠和三乙胺中的至少一种；溶剂为N,N-二甲基甲酰胺、二甲基亚砜和四氢呋喃中的至少一种。
所述步骤(3)中设定温度为40～60℃，搅拌速率为500～600rpm，反应时间为2～6h。
本发明提供的这种苯乙酰胺类化合物作为除草活性物质在抑制玉米田一年生和多年生杂草中的应用。
优选地，所述杂草主要为阔叶杂草。
本发明的有益效果:
本发明提供的这种苯乙酰胺类化合物具有优良的除草活性，尤其对玉米地防治一年生和多年生杂草效果显著，药后15天对总草的株防效至少达到86.22％，鲜重防效至少达到83.39％，且对玉米安全无害。该化合物还可以有效降低除草剂用量及成本，减少残留，减轻农药对环境的潜在威胁，并且合成方法简单、经济，可以作为先导化合物，为开发安全高效环保的新型除草剂提供新的领域。
具体实施方式
下面结合具体实施例对本发明的实施方式作进一步详细描述。以下实施例，用于说明本发明，但不能用来限制本发明的范围。
实施例1
本实施例制备一种苯乙酰胺类化合物：2-(2-(4-(2-(间-甲苯)乙酰基)哌嗪-1-基)乙酰胺)对苯二甲酸二甲酯(其中，R 1和R 2都为-COOCH 3，R 3为-CH 3，R 4为-H)，具体步骤如下：
(1)将1.05g(5mmol)1,4-二甲酸二甲酯苯胺溶解于50mL四氢呋喃中，室温搅拌，向其中加入1.52g(15mmol)三乙胺，继续搅拌，接着滴加入10mL溶有0.94g(6mmol)2-溴乙酰氯的四氢呋喃溶液，室温下搅拌反应4h，反应结束后，用乙酸乙酯(3*70mL)萃取，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-溴乙酰胺苯二甲酸甲酯，称重1.52g，计算得产率：92％；
(2)将0.74g(4mmol)2-(间甲苯氧基)乙酰氯溶解于10mL二氯甲烷中，再将上述溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的二氯甲烷中，室温搅拌反应，薄层色谱监测直至反应完全，再加入二氯甲烷(2*50mL)，用食盐水洗涤三次，再用无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-(间甲苯氧基)-1-(哌嗪-1-基)乙酰胺，称重0.85g，计算得产率：91％；
(3)将步骤(2)得到的0.70g(3mmol)2-(间甲苯氧基)-1-(哌嗪-1-基)乙酰胺和步骤(1)得到的0.99g(3mmol)2-溴乙酰胺苯二甲酸甲酯溶解于50mL的N,N-二甲基甲酰胺中，向上述溶液中加入0.83g(6mmol)碳酸钾，搅拌，55℃条件下反应5h，反应结束后，用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到目标化合物， 称重1.26g，计算得产率：86.7％。
其合成路线为：
Figure PCTCN2022118389-appb-000003
对本实施例的目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：140.3～141.2℃； 1H NMR(400MHz,CDCl 3,δppm):12.10(s,1H,NH),9.39(s,1H,Ar-H),8.10(d,J＝5.6Hz,1H,Ar-H),7.76(d,J＝5.6Hz,1H,Ar-H),6.81(d,J＝4.8Hz,2H,Ar-H),6.78(s,1H,Ar-H),6.75(d,J＝5.6Hz,1H,Ar-H),4.69(s,2H,CH 2O),3.93(s,6H,OCH 3),3.83(s,2H,NCH 2),3.78(s,2H,NCH 2),3.23(s,2H,CH 2N),2.65(s,4H,NCH 2),2.33(s,3H,CH 3). 13C NMR(100MHz,CDCl 3,δppm):167.33,166.22,166.14,154.70,147.49,140.59,135.25,130.96,123.53,121.54,119.10,116.26,115.18,113.00,69.56,55.86,53.66,53.14,52.61,52.56,45.24,42.63.HRMS(ESI)C 25H 29N 3O 7[M+H]+:calcd.484.2078,found484.2083.
实施例2本实施例制备一种苯乙酰胺类化合物：N-(3,5-甲氧基苯)-2-(4-(2-(4-氟苯)乙酰基)哌嗪-1-基)乙酰胺(其中，R 1和R 2为-OCH 3，R 3为-H，R 4为-F)，具体步骤如下：
(1)将0.77g(5mmol)3,5-二甲氧基苯胺溶解在50mL乙腈溶剂中，室温搅拌，向该溶液中加入1.52g(15mmol)三乙胺，继续搅拌，再将10mL溶有0.94g(6mmol)2-溴乙酰氯的乙腈溶液滴加入上述溶液中，搅拌反应3h，反 应结束后，用二氯甲烷(2*70mL)萃取，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-N-(3,5-甲氧基苯)乙酰胺，称重1.21g，计算得产率：88.3％；
(2)将0.75g(4mmol)2-(对氟苯氧基)乙酰氯溶解于10mL氯仿中，再将该溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的氯仿溶液中，室温搅拌反应，薄层色谱监测直到反应完全，再加入氯仿(2*50mL)，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发，得到2-(对氟苯氧基)-1-(哌嗪-1-基)乙酰胺，称重0.83g，计算得产率：87.3％；
(3)将步骤(2)得到的0.71g(3mmol)2-(对氟苯氧基)-1-(哌嗪-1-基)乙酰胺和步骤(1)得到的0.82g(3mmol)2-N-(3,5-甲氧基苯)乙酰胺溶解于50mL二甲基亚砜，接着加入0.60g(6mmol)碳酸氢钾，搅拌，60℃条件下反应4h，反应结束后用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到目标化合物，称重1.16g，计算得产率：89.7％；
其合成路线为：
Figure PCTCN2022118389-appb-000004
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：130.6～132.2℃； 1H NMR(400MHz,CDCl 3,δppm):12.10(s,1H,NH),7.38(s,1H,Ar-H),7.25(d,J＝6.0Hz,2H,Ar-H),7.10(s,2H,J＝1.6Hz,Ar-H),6.90(d,J＝6.0Hz,2H,Ar-H),4.71(s,2H,CH 2O),3.86(s,6H,OCH 3),3.83(s, 2H,NCH 2),3.77(s,2H,NCH 2),3.24(s,2H,CH 2N),2.65(s,4H,NCH 2). 13C NMR(100MHz,CDCl 3,δppm):166.13,156.44,140.58,135.27,130.97,129.57,126.74,123.60,121.51,119.05,115.96,67.97,53.55,53.10,52.60,52.57,45.13,41.93.HRMS(ESI)C 22H 26FN 3O 5[M+H] +:calcd.432.1579,found 432.1575.
实施例3本实施例制备一种苯乙酰胺类化合物：4-(2-(4-(2-(4-溴-2-氯苯)乙酰基)哌嗪-1-基)乙酰胺)苯甲酸(其中，R 1为-H，R 2为-COOH，R 3为-Cl，R 4为-Br)，具体步骤如下：
(1)将0.69g(5mmol)对氨基苯甲酸溶解在50mL二氯甲烷中，室温搅拌，向其中加入1.52g(15mmol)三乙胺，继续搅拌，接着滴加入10mL溶有0.94g(6mmol)2-溴乙酰氯的二氯甲烷溶液，室温搅拌反应5h，反应结束后，再加入二氯甲烷(2*70mL)，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到4-(2-溴乙酰胺)苯甲酸，称重1.19g，计算得产率：92.2％；
(2)将1.14g(4mmol)2-(4-溴-2-氯苯氧基)乙酰氯溶解于10mL丙酮中，再将该溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的丙酮溶液中，室温搅拌反应，薄层色谱监测直到反应完全，用乙酸乙酯(2*50mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发，得到2-(4-溴-2-氯苯氧基)-1-(哌嗪-1-基)乙酰胺，称重1.16g，计算得产率：86.5％；
(3)将步骤(2)得到的1.00g(3mmol)2-(4-溴-2-氯苯氧基)-1-(哌嗪-1-基)乙酰胺和步骤(1)得到的1.03g(3mmol)4-(2-溴乙酰胺)苯甲酸溶解到50mL四氢呋喃中，接着加入1.03g(6mmol)碳酸钾，搅拌，50℃条件下反应5h，反应结束后，用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到目标化合物，称重1.36g，计算得产率：88.7％。
其合成路线为：
Figure PCTCN2022118389-appb-000005
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：190.1-192.6℃； 1H NMR(400MHz,CDCl 3,δppm):12.30(s,1H,OH),12.11(s,1H,NH),7.88(d,J＝6.0Hz,2H,Ar-H),7.75(d,J＝6.0Hz,2H,Ar-H),7.51(s,1H,Ar-H),7.35(d,J＝6.0Hz,1H,Ar-H),7.09(s,1H,Ar-H),4.81(s,2H,CH 2O),3.37(s,2H,NCH 2),3.24(s,4H,CH 2N),2.65(s,4H,NCH 2). 13C NMR(100MHz,CDCl 3,δppm):170.11,166.15,166.06156.49,141.38,135.13,130.91,129.57,126.34,123.42,121.53,119.15,115.16,67.97,53.75,53.30,52.63,52.32,45.11.HRMS(ESI)C 21H 21BrClN 3O 5[M+H] +:calcd.510.0638,found 510.0635.
实施例4本实施例制备一种苯乙酰胺类化合物：2-(4-(2-(3-氰基-5-甲氧基苯)乙酰基)哌嗪-1-基)-N-(2-甲氧基-4-硝基苯)乙酰胺(其中，R 1为-OCH 3，R 2为-NO 2，R 3为-CN，R 4为-OCH 3)，具体步骤如下：
(1)将1.38g(10mmol)2-甲氧基-4-硝基苯胺溶解在100mL四氢呋喃中，室温搅拌，向该溶液中加入3.04g(30mmol)三乙胺，继续搅拌，再将20mL溶有1.88g(12mmol)2-溴乙酰氯的四氢呋喃溶液滴加入上述溶液中，搅拌反应4h，反应结束后，用乙酸乙酯(2*70mL)萃取，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-溴-N-(2-甲氧基-4-硝基苯)乙酰胺，称重1.54g，计算得产率：89.1％；
(2)将0.91g(4mmol)2-(3-氰基-5-甲氧基苯氧基)乙酰氯溶解于10mL氯仿溶液中，将该溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的二氯甲 烷溶液中，室温搅拌反应，薄层色谱监测直到反应完全，再加入氯仿(2*50mL)，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发，得到3-甲氧基-5-(2-氧-2-(哌嗪-1-基)乙氧基)苯氰，称重1.01g，计算得产率：90.9％；
(3)将步骤(2)得到的0.83g(3mmol)3-甲氧基-5-(2-氧-2-(哌嗪-1-基)乙氧基)苯氰和步骤(1)得到的0.87g(3mmol)2-溴-N-(2-甲氧基-4-硝基苯)乙酰胺溶解到50mL N,N-二甲基甲酰胺中，接着加入0.64g(6mmol)碳酸钠，搅拌，60℃条件下反应5h，用氯仿(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到目标化合物，称重1.31g，计算得产率：90.3％；
其合成路线为：
Figure PCTCN2022118389-appb-000006
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：178.3-179.2℃； 1H NMR(400MHz,CDCl 3,δppm):12.08(s,1H,NH),8.31(s,1H,6.0Hz,Ar-H),8.26(d,J＝6.0Hz,1H,Ar-H),8.13(d,J＝6.0Hz,1H,Ar-H),7.51(s,1H,Ar-H),7.42(s,1H,Ar-H),6.89(s,1H,Ar-H),4.81(s,2H,CH 2O),3.86(s,3H,CH 3O),3.81(s,3H,CH 3O),3.35(s,2H,NCH 2),3.22(s,4H,CH 2N),2.75(s,4H,NCH 2). 13C NMR(100MHz,CDCl 3,δppm):166.11,166.06,156.13,135.17,131.38,130.75,129.42,125.94,122.31,118.69,119.15,115.16,66.98,62.03,53.27,53.10,53.00,44.59,41.69.HRMS(ESI)C 23H 25N 5O 7[M+H] +:calcd.484.2103,found484.2106.
实施例5本实施例制备一种苯乙酰胺类化合物：4-(2-(4-(2-苯基乙酰基)哌 嗪-1-基)乙酰胺)苯甲酰胺(其中，R 1为H，R 2为-CONH 2，R 3为-H，R 4为-H)，具体步骤如下：
(1)将0.68g(5mmol)4-氨基苯甲酰胺溶解在50mL丙酮中，室温搅拌，向该溶液中加入1.52g(15mmol)三乙胺，继续搅拌，再将10mL溶有0.94g(6mmol)2-溴乙酰氯的丙酮溶液滴加入上述溶液，搅拌反应4h，反应结束后，用乙酸乙酯(2*70mL)萃取，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到4-(2-溴乙酰胺)苯甲酰胺，称重1.12g，计算得产率：86.8％；
(2)将0.68g(4mmol)2-苯氧基乙酰氯溶解在10mL二氯甲烷中，将该溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的二氯甲烷溶液中，室温搅拌反应，薄层色谱监测直到反应完全，再加入二氯甲烷(2*50mL)，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发，得到2-苯氧基-1-(哌嗪-1-基)乙基-1-酮，称重0.79g，计算得产率：89.7％；
(3)将步骤(2)得到的0.66g(3mmol)2-苯氧基-1-(哌嗪-1-基)乙基-1-酮和步骤(1)得到的0.87g(3mmol)4-(2-溴乙酰胺)苯甲酰胺溶解到50mL二甲基亚砜中，接着加入0.61g(6mmol)三乙胺，搅拌，50℃条件下反应5h，反应结束后用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到目标化合物，称重0.79g，产率：89.7％；
其合成路线为：
Figure PCTCN2022118389-appb-000007
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：178.3～179.2℃； 1H NMR(400MHz,CDCl 3,δppm):12.09(s, 1H,NH),11.51(br,2H,NH 2),8.10(d,J＝5.6Hz,2H,Ar-H),7.86(d,J＝5.6Hz,2H,Ar-H),7.30(t,J＝4.8Hz,2H,Ar-H),7.00(d,J＝5.2Hz,1H,Ar-H),6.96(d,J＝5.2Hz,2H,Ar-H),4.72(s,2H,CH 2O),3.83(s,2H,NCH 2),3.79(s,2H,NCH 2),3.23(s,2H,CH 2N),2.65(s,4H,NCH 2). 13C NMR(100MHz,CDCl 3,δppm):170.03,166.58,157.79,140.59,135.25,130.96,129.68,123.58,121.76,121.52,119.08,114.60,67.85,53.58,53.12,52.61,52.56.HRMS(ESI)C 21H 24N 4O 4[M+H] +:calcd.397.1903,found 397.1908.
实施例6本实施例制备一种苯乙酰胺类化合物：4-(2-(4-(2-(2-氯-4-甲氧基苯氧基)乙酰基)哌嗪-1-基)乙酰胺)-2-甲氧基苯甲酸甲酯(其中，R 1为-OCH 3，R 2为-COOCH 3，R 3为-Cl，R 4为-OCH 3)，具体步骤如下：
(1)将0.91g(5mmol)4-氨基-2-甲氧基苯甲酸甲酯溶解在50mL丙酮中，室温搅拌，向上述溶液中加入三乙胺1.52g(15mmol)，继续搅拌，再将10mL溶有0.94g(6mmol)2-溴乙酰氯的丙酮溶液滴加到上述溶液，室温搅拌反应4h，反应结束后用乙酸乙酯(2*70mL)萃取，食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到4-(2-溴乙酰胺)-2-甲氧基苯甲酸甲酯，称重1.42g，计算得产率：93.4％；
(2)将0.93g(4.4mmol)2-(2-氯-4-甲氧基苯氧基)乙酰氯溶解于10mL氯仿中，将该溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的氯仿溶液中，室温搅拌反应，薄层色谱监测直到反应完全，再加入氯仿(2*50mL)，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到2-(2-氯-4-甲氧基苯氧基)-1-(哌嗪-1-基)乙基-1-酮，称重1.04g，计算得产率：91.2％；
(3)将步骤(2)得到的0.86g(3mmol)2-(2-氯-4-甲氧基苯氧基)-1-(哌嗪-1-基)乙基-1-酮和步骤(1)得到的0.91g(3mmol)4-(2-溴乙酰胺)-2-甲氧基苯 甲酸甲酯溶解到50mL四氢呋喃中，接着加入0.61g(6mmol)三乙胺，搅拌，60℃条件下反应5h，用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发得到目标化合物，称重1.36g，计算得产率：89.7％；
其合成路线为：
Figure PCTCN2022118389-appb-000008
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体，熔点：178.3～179.2℃； 1H NMR(400MHz,CDCl 3,δppm):12.09(s,1H,NH),8.36(d,J＝5.6Hz,1H,Ar-H),7.92(d,J＝5.6Hz,1H,Ar-H),7.43(s,1H,Ar-H),6.99(d,J＝6.0Hz,1H,Ar-H),6.95(d,J＝2.0Hz,1H,Ar-H),6.75-6.77(m,1H,Ar-H),4.74(s,2H,CH 2O),3.94(s,3H,OCH 3),3.87(s,2H,NCH 2),3.83(s,2H,NCH 2),3.76(s,3H,OCH 3),3.71(s,3H,OCH 3),3.24(s,2H,CH 2N),2.67(s,4H,NCH 2). 13C NMR(100MHz,CDCl 3,δppm):167.33,166.22，166.14，154.70,147.49,140.59,135.25,130.96,132.53,121.54,119.10,116.26,115.18,113.00,69.56,55.86,53.66,52.61,52.56,45.91,40.69.HRMS(ESI)C 24H 28ClN 3O 7[M+H] +:calcd.506.1638,found 506.1642.
实施例7本实施例制备一种苯乙酰胺类化合物：2-(2-(4-(2-(3-乙基-5-硝基苯)乙酰基)哌嗪-1-基)乙酰胺)对苯二甲酸二甲酯(其中，R 1和R 2都为-COOCH 3，R 3为-C 2H 5，R 4为-NO 2)，具体步骤如下：
(1)将1.05g(5mmol)1,4-二甲酸二甲酯苯胺溶解于50mL二氯甲烷中，室温搅拌，向其中加入1.52g(15mmol)三乙胺，继续搅拌，接着滴加入10mL 溶有0.94g(6mmol)2-溴乙酰氯的二氯甲烷溶液，室温下搅拌反应4h，反应结束后，再加二氯甲烷(2*70mL)，用食盐水洗涤三次，无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-溴乙酰胺苯二甲酸甲酯，称重1.52g，计算得产率：92％；
(2)将0.97g(4mmol)2-(3-乙基-5-硝基苯)乙酰氯溶解于10mL四氢呋喃中，再将上述溶液缓慢滴加到10mL溶有0.34g(4mmol)哌嗪的四氢呋喃中，室温搅拌反应，薄层色谱监测直至反应完全，加入二氯甲烷(3*50mL)，用食盐水洗涤三次，再用无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到2-(3-乙基-5-硝基苯)-1-(哌嗪-1-基)乙酰胺，称重1.05g，计算得产率：89.7％；
(3)将步骤(2)得到的0.88g(3mmol)2-(3-乙基-5-硝基苯)-1-(哌嗪-1-基)乙酰胺和步骤(1)得到的0.99g(3mmol)2-溴乙酰胺苯二甲酸甲酯溶解于50mL的N,N-二甲基甲酰胺中，向上述溶液中加入0.83g(6mmol)碳酸钾，搅拌，60℃条件下反应5h，反应结束后，用乙酸乙酯(3*70mL)萃取，合并有机相，用食盐水洗涤三次，用无水硫酸镁干燥，过滤、旋转蒸发溶剂，得到目标化合物，称重1.38g，计算得产率：84.7％。
其合成路线为：
Figure PCTCN2022118389-appb-000009
对本实施例目标化合物进行熔点测试和核磁表征，其结果如下：
白色固体,熔点：193.3～195.6℃； 1H NMR(400MHz,CDCl 3,δppm):12.10(s,1H,NH),9.39(s,1H,Ar-H),8.11(d,J＝5.6Hz,1H,Ar-H),7.86(d,J＝5.6Hz,1H, Ar-H),7.70(s,1H,Ar-H),7.38(s,1H,Ar-H),7.05(s,1H,Ar-H),4.69(s,2H,CH 2O),3.94(s,6H,OCH 3),3.80(s,2H,NCH 2),3.74(s,2H,NCH 2),3.20(s,2H,CH 2N),2.63(s,4H,NCH 2),2.73(m,2H,CH 2),1.43(t,J＝5.2Hz，3H,CH 3). 13C NMR(100MHz,CDCl 3,δppm):171.13,167.37,166.27,166.11,154.71,147.45,140.65,135.15,130.99,123.51,121.58,119.13,116.20,115.18,113.10,69.58,55.81,53.70,53.10,52.61,52.56,45.29,42.60,27.11,18.93.HRMS(ESI)C 26H 30N 4O 9[M+H]+:calcd.543.1872,found 543.1883.
实施例8室内生测
采用茎叶喷雾法(NY/T 1155.4-2006)对实施例1～6中制得的苯乙酰胺类化合物进行室内毒力测定试验。
供试药剂：(a)实施例1；(b)实施例2；(c)实施例3；(d)实施例4；(e)实施例5；(f)实施例6；(g)对照药剂乙草胺；(h)对照药剂2,4-D丁酯；(f)清水对照。
供试材料：小飞蓬、反枝苋、生菜种子。
小飞蓬、反枝苋、生菜种子浸种催芽后点播于装有泥土的截面积0.25m 2的塑料盆内，每盆播20粒，温室内培养至2叶期进行处理。按设计的剂量浓度梯度(1mg/L,5mg/L,10mg/L,15mg/L,20mg/L,25mg/L,30mg/L,50mg/L,60mg/L)，用手持压缩式喷雾器(3NY-1.2)喷施药液，喷液量为每处理50mL，药后保持土壤湿润。每处理重复4次，药后20天称取各处理地上部分鲜重，按以下公式计算各处理的鲜重防效(％)：
E＝100×(C-T)/C
式中，E为鲜重防效；C为对照地上部分鲜重；T为处理地上部分鲜重。
试验结果见表1～3。
表1苯乙酰胺类化合物对小飞蓬毒力测定结果
Figure PCTCN2022118389-appb-000010
从表1可以看出，实施例1～6苯乙酰胺类化合物的EC 50值均比对照例乙草胺(28.77mg/L)、2,4-D丁酯(24.78mg/L)值低，表明实施例1～6苯乙酰胺类化合物相比乙草胺和2,4-D丁酯对小飞蓬的毒力更高，具有较高的除草活性。
表2苯乙酰胺类化合物对反枝苋毒力测定结果
Figure PCTCN2022118389-appb-000011
从表2可以看出，实施例1～6苯乙酰胺类化合物的EC 50值均比对照例乙草胺(27.55mg/L)值低，实施例1和4苯乙酰胺类化合物的EC 50值均比对照例2,4-D丁酯(11.86mg/L)值低，表明实施例1和4苯乙酰胺类化合物相比乙草胺和2,4-D丁酯对反枝苋的毒力更高，具有较高的除草活性。
表3苯乙酰胺类化合物对生菜毒力测定结果
Figure PCTCN2022118389-appb-000012
从表3可以看出，实施例1～6苯乙酰胺类化合物的EC 50值均比对照例乙草胺(33.08mg/L)和对照例2,4-D丁酯(17.66mg/L)值低，表明实施例1～6苯乙酰胺类化合物相比乙草胺和2,4-D丁酯对生菜的毒力更高，具有较高的除草活性。
实施例9作物安全性试验
采用茎叶喷雾法对实施例1～6中制得的苯乙酰胺类化合物进行作物安全性试验。
供试药剂：(a)实施例1；(b)实施例2；(c)实施例3；(d)实施例4；(e)实施例5；(f)实施例6；(g)对照药剂乙草胺；(h)对照药剂2,4-D丁酯；(i)清水对照。
供试材料：玉米。
玉米种子浸种催芽后点播于装有泥土的截面积0.25m 2的塑料盆内，每盆播10粒，温室内培养至2叶期进行处理。均按有效成分50g/亩施药量，用手持压缩式喷雾器(3NY-1.2)喷施药液，喷液量为每处理50mL，药后保持土壤湿润。每处理重复4次，药后20天称取各处理地上部分鲜重，按以下公式计算各处理 的鲜重防效(％)：
E＝100×(C-T)/C
式中：E为鲜重防效；C为对照地上部分鲜重；T为处理地上部分鲜重。
试验结果见表4。
表4苯乙酰胺类化合物对玉米安全性测定结果
Figure PCTCN2022118389-appb-000013
从表4可以看出，实施例1、2、4、5苯乙酰胺类化合物的减重比例均比对照药剂乙草胺(0.25％)和对照例2,4-D丁酯(63.70％)值低，表明实施例1、2、4、5苯乙酰胺类化合物相比乙草胺和2,4-D丁酯对玉米安全性更高。
实施例10田间试验
将实施例1～4制得的苯乙酰胺类化合物应用于玉米地防治一年生和多年生杂草：实施例1按850g.a.i/ha加水稀释喷雾，药后15天对总草的株防效为90.76％、鲜重防效为93.17％。实施例2、3和4按1025.5g.a.i/ha分别加水稀释喷雾，药后15天对总草的株防效分别为86.22％、90.79％和88.53％；鲜重防效分别为83.39％、87.85％和85.64％。对照药剂乙草胺、2,4-D丁酯按1025.5g.a.i/ha分别兑水稀释喷雾，药后15天对总草的株防效分别为51.21％、73.88％。同时目测法发现对照药 剂2,4-D丁酯对玉米药害严重，实施例1～4和乙草胺对玉米安全。由此可知，本发明提供的这种苯乙酰胺类化合物对玉米地一年生和多年生杂草防治效果明显，杀草谱进一步扩宽，不但具备开发成除草剂的潜力，而且具有低成本和环保的优点。
以上实施方式仅用于说明本发明，而非对本发明的限制。尽管参照实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，对本发明的技术方案进行各种组合、修改或者等同替换尤其是将苯环替换成杂环和稠环，都不脱离本发明技术方案的精神和范围，均应涵盖在本发明的权利要求范围当中。

Claims (10)

  1. 一种苯乙酰胺类化合物，结构通式为：
    Figure PCTCN2022118389-appb-100001
    其中，R 1和R 2分别为-H、-OCH 3、-NO 2、-COOCH 3、-CONH 2和-COOH中的任意一种；R 3和R 4分别为-H、-CH 3、-C 2H 5、-OCH 3、-NO 2、-Br、-Cl、-F和-CN中的任意一种。
  2. 根据权利要求1所述的苯乙酰胺类化合物的制备方法，包括以下步骤：
    (1)将化合物1和2-溴乙酰氯溶解于溶剂，加入缚酸剂，室温搅拌反应，萃取、洗涤、干燥、过滤、旋蒸，得到化合物2；
    (2)将化合物3和哌嗪溶解于溶剂，加入缚酸剂，室温搅拌反应，萃取、洗涤、干燥、过滤、旋蒸，得到化合物4；
    (3)将步骤(1)得到的化合物2和步骤(2)得到的化合物4溶解于溶剂，加入缚酸剂，在设定温度下搅拌反应，反应结束后，萃取、洗涤、干燥、过滤、旋蒸，得到苯乙酰胺类化合物；
    其合成路线如下：
    Figure PCTCN2022118389-appb-100002
  3. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(1)中化合物1、2-溴乙酰氯和缚酸剂的摩尔比为1:1～2:3～5；缚酸剂为碳酸钾、碳酸钠、三乙胺、碳酸氢钾和碳酸氢钠中的至少一种；溶剂为乙腈、丙酮、四氢呋喃、二氯甲烷和氯仿中的至少一种。
  4. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(1)中搅拌速率为500～600rpm，反应时间为2～6h。
  5. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(2)中化合物3、哌嗪和缚酸剂的摩尔比为1:1～2:3～6；缚酸剂为碳酸钾、碳酸钠、碳酸氢钾、碳酸氢钠和三乙胺中的至少一种；溶剂为乙腈、氯仿、二氯甲烷和四氢呋喃中的至少一种。
  6. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(2)中搅拌速率为500～600rpm，反应进程用薄层色谱监测。
  7. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(3)中化合物2、化合物4和缚酸剂的摩尔比为1:1～1.5:3～6；缚酸剂为碳酸钾、碳酸钠、碳酸铯、碳酸氢钾、碳酸氢钠和三乙胺中的至少一种；溶剂为N,N-二甲基甲酰胺、二甲基亚砜和四氢呋喃中的至少一种。
  8. 根据权利要求2所述的苯乙酰胺类化合物的制备方法，其特征在于，所述步骤(3)中设定温度为40～60℃，搅拌速率为500～600rpm，反应时间为2～6h。
  9. 根据权利要求1所述的苯乙酰胺类化合物作为除草活性物质在抑制玉米田一年生和多年生杂草中的应用。
  10. 根据权利要求1所述的苯乙酰胺类化合物作为除草活性物质在抑制玉米田阔叶杂草中的应用。
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