WO2023083161A1 - 一种联苯类杂环化合物、其合成方法及其应用 - Google Patents

一种联苯类杂环化合物、其合成方法及其应用 Download PDF

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WO2023083161A1
WO2023083161A1 PCT/CN2022/130543 CN2022130543W WO2023083161A1 WO 2023083161 A1 WO2023083161 A1 WO 2023083161A1 CN 2022130543 W CN2022130543 W CN 2022130543W WO 2023083161 A1 WO2023083161 A1 WO 2023083161A1
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acid
biphenyl
general formula
heterocyclic compound
compound
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French (fr)
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郑绍军
姜乔榉
武文斌
谈祎
杨程
韩珂
朱瑞
陈立庄
李照磊
宋恒
蒋春辉
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江苏科技大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A01N37/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof the nitrogen atom being directly attached to an aromatic ring system, e.g. anilides
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A01N37/38—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system
    • A01N37/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system having at least one carboxylic group or a thio analogue, or a derivative thereof, and one oxygen or sulfur atom attached to the same aromatic ring system
    • 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
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/66—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the invention belongs to the technical field of marine pollution prevention and control, and in particular relates to the synthesis and antifouling technology of biphenyl heterocyclic compounds.
  • Marine biofouling refers to the undesirable deposition of harmful micro or large organisms in seawater on the surface of objects. It is a biological hazard that humans have encountered since they began to engage in marine activities.
  • the hazards of marine biofouling are mainly manifested in the following aspects: (1 ) increases the navigation resistance of the ship, resulting in an increase in power consumption. According to statistics, the additional consumption caused by biofouling reaches 60 billion U.S. dollars every year, while the annual consumption for cleaning and preventing marine biofouling reaches 5.7 billion U.S. dollars. (2) Increased fuel combustion due to biofouling is expected to increase CO 2 and SO 2 emissions by 38% to 72% by 2020, aggravating global warming.
  • the most common is to use a paint containing a biocide to drive and kill the attached marine organisms by means of the release of the biocide and its toxicity to marine organisms.
  • Biphenyl heterocyclic compounds have various biological activities and can be widely used in the fields of medicine, biological pesticides, food and health care, chemical industry and military affairs, and can also be used as antifouling coatings.
  • the antifouling paint can not only effectively inhibit and repel marine organisms and barnacles from attaching to the bottom of the ship, but also has certain inhibitory effect on other fouling organisms.
  • the inventor's application number is 2018104212515 invention patent, which discloses a preparation method of 2-(3,4)-dichlorophenyl-4-fluoroaniline, which uses copper reagent to replace the more toxic Pd reagent, and completes the joint
  • the synthesis of benzene; the process is simple, environmentally friendly and pollution-free.
  • the present invention is a further improvement of the preparation method.
  • the object of the present invention is to provide a biphenyl heterocyclic compound, its synthesis method and its antifouling application, using cheap and low-toxic magnesium chloride reagent as a catalyst, replacing the highly toxic and expensive The metal palladium, platinum and other precious metals; the synthesis process is simple, the synthesis cost is low, and it is environmentally friendly and pollution-free.
  • the R is any one of the following groups:
  • the organic solvent used in this step is any one selected from diethyl ether, tetrahydrofuran, dioxane, N,N-dimethylamide, acetone, m-xylene, dichloromethane, and dimethylacetamide.
  • the catalyst magnesium chloride reagent used in this step is cheap, low-toxic and meets environmental protection requirements.
  • the molar ratio of the magnesium chloride reagent to the oxidizing agent BQ is 0.1-0.5:0.2-1.5.
  • the acid is a heterocyclic acid, p-methoxybenzoic acid, 1-naphthoic acid, 3-chloroisonicotinic acid, 5,6-dichloronicotinic acid, isonicotinic acid, 5-methylpyrazine-2 -Carboxylic acid, 2-carboxypyrazine, 5-chloropyrazine-2-carboxylic acid, 2-chloropyridine-6-carboxylic acid, 2-aminonicotinic acid, 2-fluoronicotinic acid, 2-chloronicotinic acid, 2-chloroisonicotinic acid, pyridine-2-carboxylic acid, 6-chloronicotinic acid, 6-methylnicotinic acid, 5-methylnicotinic acid, nicotinic acid, 2-hydroxynicotinic acid, o-aldobenzoic acid.
  • the biphenyl heterocyclic compound with the general formula (I) has good bactericidal activity, and the fungi are Staphylococcus aureus and Escherichia coli.
  • the present invention has the following advantages:
  • the biphenyl synthesis method provided by the present invention adopts cheap and low-toxic magnesium chloride reagent, which replaces toxic and expensive metal palladium, precious metals such as platinum, and meets the requirements of environmental protection.
  • the oxidant BQ can be purchased directly, and the price is low, avoiding artificial synthesis, and saving manpower and financial resources.
  • the biphenyl compound provided by the present invention has simple structure, easy-to-obtain raw materials, mild reaction conditions, simple process, and is suitable for antifouling purposes.
  • the four biphenyl compounds provided by the present invention have higher antifouling activity than commercial TBT, and have a price advantage.
  • Step 2 Weigh 0.20 g (0.78 mmol, 1 equiv) of intermediate 3 and dissolve it in 10 mL of anhydrous dichloromethane, add 0.12 mL (1.16 mmol, 1.5 equiv) of Et 3 N, and place the reaction system in an ice bath. Mix 10 mL of anhydrous dichloromethane with the prepared acid chloride evenly, and slowly add it dropwise to the reaction system. At this time, white smoke is generated, and then react at room temperature for 2 hours. Use TLC to monitor whether the raw material point disappears.
  • Embodiment 21 Determination of the antifouling activity of the compound obtained in Examples 1-20
  • the concentration of the synthesized biphenyl heterocyclic compound was diluted sequentially twice, and then the diluted bacterial solution was added to the diphenyl heterocyclic compound dilution for cultivation, Escherichia coli and Staphylococcus aureus were shaken Cultivate for 24 hours, observe with the naked eye that the positive control tube (the test tube inoculated without the test compound) has bacterial growth and appears turbid, and the negative control tube (the test tube without the test compound and inoculated bacteria) grows sterile and appears transparent , so as to determine the minimum inhibitory concentration of the test substance to the two test strains. According to this judgment, the detection results of biphenyl-containing heterocyclic compounds against two kinds of bacteria are shown in Table 2.
  • Example 1 2 3 4 5 6 7 8 9 10 golden grapes 0.125 0.016 0.25 0.125 0.016 0.125 0.25 0.016 0.25 0.125 Escherichia coli 0.125 0.016 0.125 0.25 0.016 0.125 0.25 0.016 0.125 0.25 0.016 0.125 0.25 0.016 0.125 0.25 0.016 0.125 0.25
  • the synthesized compounds all showed certain antifouling activity, among which compound 2, compound 5, compound 8 and compound 14 showed outstanding antifouling activity, and the MICs for Staphylococcus aureus and Escherichia coli All reached 0.016mg/mL, which is superior to commercial tributyltin (TBT) antifouling agent.
  • TBT tributyltin

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  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
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Abstract

本发明提供了一种联苯类杂环化合物、其合成方法及其应用。所述的联苯类杂环化合物的通式(I)是合成工艺简单、采用廉价且低毒的镁试剂作为催化剂，替代了毒性较大，价格昂贵的金属钯，铂等贵金属，产品纯度高，该类化合物具有杀菌活性，对金黄色葡萄球菌和大肠杆菌均具有很高的杀菌活性，具有优良的防污应用前景。

Description

一种联苯类杂环化合物、其合成方法及其应用 技术领域
本发明属于海洋污损防治技术领域，具体涉及一种联苯类杂环化合物的合成及防污技术。
背景技术
海洋生物污损是指海水中有害的微型或大型生物在物体表面的不良沉积，是人类开始从事海洋活动就遇到的生物危害，海洋生物污损的危害主要表现在以下几个方面：(1)增大了船舶的航行阻力，造成动力消耗增加。据统计，每年因为生物污损引起的额外消耗就达600亿美元，而每年用于清除和防止海洋生物污损的消耗达57亿美元。(2)由于生物污损所增加的燃料燃烧预计到2020年将增加38％～72％的CO 2和SO 2排放量，加剧地球变暖。(3)加剧海洋工程材料的腐蚀破坏，降低海洋设施性能。(4)将新的物种带到异地，威胁当地的生态系统。目前最行之有效的防污方法就是涂刷含有机锡等有毒防污剂的防污涂料，然而这种防污涂料在防污的同时严重危害海洋生态环境。国际海事组织(IMO)明确规定，自2008年1月1日起，全球禁止使用含有机锡防污涂料。因此替代有机锡的无毒防污剂的研究开发成为当今海洋科学技术中亟待解决的重大技术问题之一。
在对付这些海洋生物污损的方法中，最普通的是使用一种内含杀生剂的涂料，借助杀生剂的释放及其对海洋生物的毒性，驱赶并杀死附着的海洋生物。联苯类杂环化合物的具有多种生物活性，可广泛的用于医药、生物农药、饮食保健、化工以及军事等领域，还可用作防污涂料。其作为防污剂的防污涂料不仅能有效地抑制和驱避海洋生物、藤壶对船底的附着污损，并且对其他污损生物也有一定抑制作用。发明人所拥有的申请号为2018104212515发明专利，公开了一种2-(3,4)-二氯苯基-4-氟苯胺的制备方法，利用铜试剂替代毒性较大的Pd试剂，完成联苯的合成；工艺简便，环保无污染。本发明是对该制备方法的进一步改进。
发明内容
针对现有问题的不足，本发明的目的是提供一种联苯类杂环化合物、其合成方法及其防污应用，采用廉价且低毒的氯化镁试剂作为催化剂，替代了毒性较大，价格昂贵的金属钯，铂等贵金属；合成工艺简便，合成成本低，环保无污染。
为了实现上述发明目的，本发明采用的技术方案是：
具有通式(I)的联苯类杂环化合物：
Figure PCTCN2022130543-appb-000001
上述联苯类杂环化合物的合成路线如下：
Figure PCTCN2022130543-appb-000002
所述的R为以下基团之任意一种：
Figure PCTCN2022130543-appb-000003
具体来说，一种联苯类杂环化合物的合成方法，步骤如下：
(1)2-溴-4-氟苯胺与酸酐在室温下反应2～3h，发生酰化反应，生成所需要的酰胺化合物，目的是保护胺基，以免发生副反应。
(2)胺基保护后的2-溴-4-氟乙酰苯胺，在氯化镁试剂以及溴化亚铁和氧化剂BQ的共同 作用下，发生联苯反应，生成了联苯化合物，这是本发明的关键反应。
该步骤所采用的有机溶剂选自乙醚，四氢呋喃、二氧六烷、N,N-二甲基酰胺、丙酮、间二甲苯、二氯甲烷、二甲基乙酰胺中的任意一种。
该步骤所采用的催化剂氯化镁试剂，廉价、低毒，符合环保要求。
加入氧化剂BQ
Figure PCTCN2022130543-appb-000004
的反应温度为r.t～50℃，反应时间20～90min。
氯化镁试剂与氧化剂BQ的摩尔比为0.1～0.5:0.2～1.5。
(3)然后2-(3,4-二氯苯基)-4-氟乙酰苯胺发生水解反应，得到关键中间体，为联苯类化合物的合成提供了关键合成骨架。
(5)关键骨架2-(3,4-二氯苯基)-4-氟苯胺与不同的酸反应，生成20个目标化合物。
所述的酸为杂环的酸，对甲氧基苯甲酸，1-萘酸，3-氯异烟酸，5,6-二氯烟酸，异烟酸，5-甲基吡嗪-2-羧酸，2-羧酸吡嗪，5-氯吡嗪-2-羧酸，2-氯吡啶-6-羧酸，2-氨基烟酸，2-氟烟酸，2-氯烟酸，2-氯异烟酸，吡啶-2-羧酸，6-氯烟酸，6-甲基烟酸，5-甲基烟酸，烟酸，2-羟基烟酸，邻醛基苯甲酸。
具有通式(I)的联苯类杂环化合物具有良好的杀菌活性，所述的菌类是金黄色葡萄球菌和大肠杆菌。
有益效果：与现有技术相比，本发明具有下述优点：
(1)本发明提供的联苯合成方法，采用的廉价且低毒的氯化镁试剂，替代了毒性较大，价格昂贵的金属钯，铂等贵金属，符合环保的要求。
(2)氧化剂BQ可以直接购买，且价格低廉，避免了人工合成，节约了人力和财力。
(3)本发明提供的联苯类化合物具有结构简单，原料易得，反应条件温和，工艺简单，适合作为防污用途。
(4)本发明提供的4个联苯类化合物,比商业化的TBT具有更高的防污活性，且具有价格优势。
具体实施方式
以下结合实施例对本发明做进一步详细说明。所用试剂或者仪器设备未注明生产厂商的，均视为可以通过市场购买的常规产品。
实施例1
Figure PCTCN2022130543-appb-000005
的合成工艺，步骤如下：
(1)向250mL三口烧瓶中加入20mL二氯乙烷和5.2g(0.03mol)2-溴-4-氟苯胺，室温下滴加3.1g(0.03mol)醋酸酐，20min滴加完毕。取样检测，得到中间体1(乙酰苯胺)，产率99％。
(2)室温下，将化合物2-溴-4-氟乙酰苯胺(3.7g,16mmol)和3,4-二氯溴苯(3.6g,16mmol)溶于THF(50mL)中，电磁搅拌，然后逐滴加入氯化镁试剂(4.9g，24mmol)，在50℃下反应2h。在另一个三颈烧瓶中，将加入FeBr 2(1.16g,10mmol)于THF(50mL)中，搅拌30min后，将上述混合物加入此溶液中，继续反应20min后，加入氧化剂BQ(2.16g，20mmol)，室温下反应30min，将反应液经过一小段硅胶过滤，减压蒸馏，经柱层析得中间体2共3.23g,收率为68％。
(3)取一个1.0L的单口圆底烧瓶,向其中加入2.97g(10mmol)2-(3,4-二氯苯基)-4-氟乙酰苯胺，再向其中加入乙醇，充分溶解后，加入30mL浓盐酸。在90℃下回流3小时，利用TLC对反应进行跟踪，当原料彻底反应完后，停止反应，并趁热将混合液倒入到冰水中淬灭，得到中间体3，其为固体，共2.35g，收率为92％。
(4)制酰氯。制备方法如下：
首先准确称量对甲氧基苯甲酸0.27g(2mmol)于50mL的圆底烧瓶中，加入10mL无水二氯甲烷，随后用1mL注射器取0.31mL(4mmol)的氯化亚砜注入反应体系中，在设定为55℃的油浴锅中回流2h，用旋转蒸发仪除去氯化亚砜和二氯甲烷。
第二步：称取0.20g(0.78mmol,1equiv)中间体3，并用10mL无水二氯甲烷溶解，加入0.12mL(1.16mmol,1.5equiv)Et 3N，将反应体系置于冰浴中。用10mL无水二氯甲烷与制好的酰氯混合均匀，缓慢的滴加至反应体系中，此时伴随白烟产生，随后在室温下反应2h，用TLC监测原料点是否消失。
加入3mL饱和碳酸氢钠溶液淬灭反应，搅拌10min，用二氯甲烷(30mL×3)萃取，饱和NaCl溶液洗涤，干燥、浓缩、层析柱纯化(石油醚∶乙酸乙酯＝4∶1)，得到化合物1，白色固体(0.27g,89％)。
化合物1.1H-NMR(400MHz,)δ8.20(dd,J＝9.0,5.3Hz,1H),8.20(dd,J＝9.0,5.3Hz, 1H),7.63–7.57(m,2H),7.68–7.51(m,5H),7.57–7.52(m,2H),7.30–7.23(m,1H),7.28–7.24(m,1H),8.43–3.69(m,15H),7.13(ddd,J＝8.8,8.0,2.9Hz,1H),7.13(ddd,J＝8.8,8.0,2.9Hz,1H),6.99(dd,J＝8.7,2.9Hz,1H),6.99(dd,J＝8.7,2.9Hz,1H),6.97–6.86(m,2H),6.93–6.88(m,2H),3.85(s,3H),3.85(s,3H)。
(R＝基团1～20的产物)为联苯类杂环化合物，合成方法与上述方法相同，区别在于加入不同的酸，反应条件和性状如表1所示，鉴定如实施例2-20：
表1 防污化合物的理化性质
Figure PCTCN2022130543-appb-000006
实施例2
Figure PCTCN2022130543-appb-000007
的鉴定
化合物2. 1H-NMR(400MHz,)δ8.30–8.15(m,2H),8.39–8.09(m,2H),7.93(d,J＝8.1Hz,1H),8.02–7.76(m,2H),7.87(dd,J＝5.9,3.2Hz,1H),8.79–6.57(m,16H),7.50(ddd,J＝25.6,11.8,5.5Hz,8H),7.50(ddd,J＝25.6,11.8,5.5Hz,7H),7.22–7.13(m,1H),7.38–7.14(m,3H),7.14–6.94(m,1H),7.07–6.99(m,1H)。
实施例3
Figure PCTCN2022130543-appb-000008
的鉴定
化合物3. 1H-NMR(400MHz,)δ7.83(d,J＝7.6Hz,1H),7.83(d,J＝7.6Hz,1H),7.66(td,J＝7.4,0.8Hz,1H),7.66(td,J＝7.4,0.8Hz,1H),7.56(d,J＝7.5Hz,1H),7.50(d,J＝2.0Hz,1H),7.59–7.38(m,5H),7.47(d,J＝7.7Hz,1H),7.44–7.40(m,1H),8.22–6.22(m,14H),7.19(ddd,J＝5.7,3.7,2.1Hz,3H),7.19(ddd,J＝5.7,3.7,2.1Hz,2H),7.07–6.96(m,1H),7.06–6.97(m,1H),6.84(dd,J＝8.7,2.9Hz,1H),6.84(dd,J＝8.7,2.9Hz,1H),6.65(d,J＝11.0Hz,1H),6.65(d,J＝11.0Hz,1H)。
实施例4
Figure PCTCN2022130543-appb-000009
的鉴定
化合物4. 1H-NMR(400MHz,)δ8.40(d,J＝1.4Hz,1H),8.40(d,J＝1.4Hz,1H),8.11(d,J＝1.0Hz,1H),8.11(d,J＝1.0Hz,1H),8.00(dd,J＝8.7,5.2Hz,1H),8.00(dd,J＝8.7,5.2Hz, 1H),7.85(s,1H),7.85(s,1H),7.55–7.51(m,1H),7.56–7.43(m,2H),8.77–6.62(m,10H),7.47(d,J＝1.8Hz,1H),7.22(dd,J＝8.2,2.0Hz,1H),7.22(dd,J＝8.2,2.0Hz,1H),7.16–7.09(m,1H),7.18–7.08(m,1H),7.02(dd,J＝8.6,2.9Hz,1H),7.02(dd,J＝8.6,2.9Hz,1H)。
实施例5
Figure PCTCN2022130543-appb-000010
的鉴定
化合物5. 1H-NMR(400MHz,)δ8.57(d,J＝2.0Hz,1H),8.57(d,J＝2.0Hz,1H),8.14(dd,J＝8.8,5.2Hz,1H),8.14(dd,J＝8.8,5.2Hz,1H),8.00(dd,J＝8.3,2.3Hz,1H),8.00(dd,J＝8.3,2.3Hz,1H),7.74(s,1H),7.74(s,1H),8.83–6.75(m,11H),7.55(d,J＝8.2Hz,1H),7.53(dd,J＝15.8,5.1Hz,2H),7.51(d,J＝1.9Hz,1H),7.43(d,J＝8.3Hz,1H),7.43(d,J＝8.3Hz,1H),7.26(s,1H),7.16(ddd,J＝8.8,8.0,2.9Hz,1H),7.16(ddd,J＝8.8,8.0,2.9Hz,1H),7.03(dd,J＝8.6,2.9Hz,1H),7.03(dd,J＝8.6,2.9Hz,1H)。
实施例6
Figure PCTCN2022130543-appb-000011
的鉴定
化合物6. 1H-NMR(400MHz,)δ9.71(s,1H),9.71(s,1H),9.31(d,J＝1.0Hz,1H),9.31(d,J＝1.0Hz,1H),8.47(dd,J＝9.1,5.3Hz,1H),8.47(dd,J＝9.1,5.3Hz,1H),8.30(d,J＝1.0Hz,1H),8.30(d,J＝1.0Hz,1H),7.56(dd,J＝5.2,3.0Hz,2H),7.56(dd,J＝5.2,3.0Hz,2H),10.31–2.21(m,12H),7.27(dd,J＝8.0,1.7Hz,1H),7.27(dd,J＝8.0,1.7Hz,1H),7.19–7.12(m,1H),7.21–7.11(m,1H),7.02(dd,J＝8.7,2.9Hz,1H),7.02(dd,J＝8.7,2.9Hz,1H),2.65(s,3H),2.65(s,3H)。
实施例7
Figure PCTCN2022130543-appb-000012
的鉴定
化合物7. 1H-NMR(400MHz,)δ9.76(s,1H),9.76(s,1H),9.47(d,J＝1.3Hz,1H),9.47(d,J＝1.3Hz,1H),8.77(d,J＝2.4Hz,1H),8.77(d,J＝2.4Hz,1H),8.49(dd,J＝9.1,5.3Hz,1H),8.53–8.43(m,2H),8.47–8.45(m,1H),10.20–6.37(m,11H),7.58(d,J＝5.4Hz,1H),7.61–7.54(m,2H),7.57(s,1H),7.28(dd,J＝8.3,2.1Hz,1H),7.32–7.24(m,2H),7.23–7.13(m,1H),7.22–7.14(m,1H),7.04(dd,J＝8.7,3.0Hz,1H),7.04(dd,J＝8.7,3.0Hz,1H)。
实施例8
Figure PCTCN2022130543-appb-000013
的鉴定
化合物8. 1H-NMR(400MHz,)δ8.59(s,1H),8.63–8.50(m,2H),8.55(d,J＝4.9Hz,1H),8.21(dd,J＝9.0,5.2Hz,1H),8.21(dd,J＝9.0,5.2Hz,1H),7.89(s,1H),7.89(s,1H),7.57(d,J＝4.9Hz,1H),7.61–7.48(m,3H),7.54(d,J＝8.2Hz,1H),8.91–6.86(m,11H),7.51(d,J＝2.1Hz,1H),7.23(dd,J＝8.2,2.1Hz,1H),7.29–7.13(m,3H),7.18(ddd,J＝8.9,7.9,2.9Hz,1H),7.01(dd,J＝8.6,2.9Hz,1H),7.01(dd,J＝8.6,2.9Hz,1H)。
实施例9
Figure PCTCN2022130543-appb-000014
的鉴定
化合物9. 1H-NMR(400MHz,)δ9.93(s,1H),9.93(s,1H),8.52(dd,J＝9.1,5.3Hz,1H),8.52(dd,J＝9.1,5.3Hz,1H),8.17–8.10(m,1H),8.18–8.10(m,1H),7.84(t,J＝7.8Hz,1H),7.84(t,J＝7.8Hz,1H),10.25–6.68(m,11H),7.63(d,J＝8.2Hz,1H),7.63(d,J＝8.2Hz,1H),7.55(d,J＝2.1Hz,1H),7.55(d,J＝2.1Hz,1H),7.49–7.43(m,1H),7.49–7.42(m,1H),7.31 (dd,J＝8.2,2.0Hz,1H),7.34–7.23(m,2H),7.20–7.12(m,1H),7.21–7.11(m,1H),7.04(dd,J＝8.7,3.0Hz,1H),7.04(dd,J＝8.7,3.0Hz,1H)。
实施例10
Figure PCTCN2022130543-appb-000015
的鉴定
化合物10. 1H-NMR(400MHz,)δ9.96(s,1H),9.96(s,1H),8.08(dd,J＝4.6,1.2Hz,1H),8.08(dd,J＝4.6,1.2Hz,1H),7.86(dd,J＝7.7,1.5Hz,1H),7.86(dd,J＝7.7,1.5Hz,1H),7.72(d,J＝2.0Hz,1H),7.72(d,J＝2.0Hz,1H),7.64(d,J＝8.3Hz,1H),7.64(d,J＝8.3Hz,1H),10.33–6.31(m,13H),7.44(ddd,J＝10.3,8.5,3.8Hz,2H),7.51–7.25(m,4H),7.37–7.28(m,2H),6.93(s,2H),6.93(s,2H),6.60(dd,J＝7.7,4.8Hz,1H),6.60(dd,J＝7.7,4.8Hz,1H),2.50(s,3H)。
实施例11
Figure PCTCN2022130543-appb-000016
的鉴定
化合物11. 1H-NMR(400MHz,)δ8.65–8.59(m,1H),8.60(ddd,J＝9.8,7.6,2.0Hz,1H),8.59–8.36(m,2H),8.46(d,J＝14.9Hz,1H),8.34(ddd,J＝6.1,5.6,3.4Hz,3H),8.36–8.30(m,2H),9.12–6.30(m,14H),7.57(d,J＝8.2Hz,1H),7.57(d,J＝8.2Hz,1H),7.51(d,J＝2.0Hz,1H),7.51(d,J＝2.0Hz,1H),7.40(ddd,J＝7.4,4.8,2.4Hz,1H),7.40(ddd,J＝7.4,4.8,2.4Hz,1H),7.25(dd,J＝8.0,2.3Hz,2H),7.25(dd,J＝8.0,2.3Hz,2H),7.16(ddd,J＝9.0,8.0,3.0Hz,1H),7.16(ddd,J＝9.0,8.0,3.0Hz,1H),7.01(dd,J＝8.6,3.0Hz,1H),7.01(dd,J＝8.6,3.0Hz,1H)。
实施例12
Figure PCTCN2022130543-appb-000017
的鉴定
化合物12. 1H-NMR(400MHz,)δ8.44(dd,J＝4.7,1.9Hz,1H),8.44(dd,J＝4.7,1.9Hz,1H),8.23(dd,J＝9.0,5.2Hz,1H),8.23(dd,J＝9.0,5.2Hz,1H),8.11(dd,J＝7.7,1.9Hz,1H),8.11(dd,J＝7.7,1.9Hz,1H),8.83–6.60(m,11H),7.52(dd,J＝10.6,5.1Hz,2H),7.52(dd,J＝10.6,5.1Hz,2H),7.36(dd,J＝7.7,4.7Hz,1H),7.36(dd,J＝7.7,4.7Hz,1H),7.24(dd,J＝8.2,2.0Hz,1H),7.29–7.12(m,2H),7.20–7.14(m,1H),7.01(dd,J＝8.6,3.0Hz,1H),7.01(dd,J＝8.6,3.0Hz,1H)。
实施例13
Figure PCTCN2022130543-appb-000018
的鉴定
化合物13. 1H-NMR(400MHz,)δ8.41(d,J＝5.0Hz,1H),8.41(d,J＝5.0Hz,1H),8.04(dd,J＝8.9,5.2Hz,1H),8.04(dd,J＝8.9,5.2Hz,1H),7.93(s,1H),7.93(s,1H),7.59–7.51(m,2H),7.59–7.45(m,3H),7.48(d,J＝1.9Hz,1H),9.49–5.93(m,11H),7.35(d,J＝4.4Hz,1H),7.35(d,J＝4.4Hz,1H),7.22(dd,J＝8.2,1.9Hz,1H),7.29–7.09(m,2H),7.18–7.10(m,1H),7.07–6.99(m,1H),7.07–6.99(m,1H)。
实施例14
Figure PCTCN2022130543-appb-000019
的鉴定
化合物14. 1H-NMR(400MHz,)δ10.16(s,1H),10.16(s,1H),8.51(dd,J＝9.1,5.3Hz,1H),8.49(ddd,J＝6.7,5.1,4.4Hz,2H),8.46(dd,J＝3.0,2.1Hz,1H),8.24(d,J＝7.8Hz,1H),8.24(d, J＝7.8Hz,1H),7.88(td,J＝7.7,1.6Hz,1H),7.88(td,J＝7.7,1.6Hz,1H),10.50–6.66(m,12H),7.59(d,J＝2.1Hz,1H),7.62–7.53(m,2H),7.58–7.54(m,1H),7.44(ddd,J＝7.4,4.7,1.0Hz,1H),7.44(ddd,J＝7.4,4.7,1.0Hz,1H),7.30(dd,J＝8.2,2.2Hz,1H),7.34–7.23(m,2H),7.19–7.12(m,1H),7.21–7.10(m,1H),7.03(dd,J＝8.8,3.0Hz,1H),7.03(dd,J＝8.8,3.0Hz,1H)。
实施例15
Figure PCTCN2022130543-appb-000020
的鉴定
化合物15. 1H-NMR(400MHz,)δ10.43(s,1H),10.43(s,1H),8.99(s,1H),8.99(s,1H),8.86(d,J＝1.0Hz,1H),8.86(d,J＝1.0Hz,1H),11.20–6.08(m,11H),7.75(d,J＝1.9Hz,1H),7.78–7.59(m,4H),7.68(ddd,J＝8.4,6.2,3.5Hz,2H),7.63(d,J＝8.3Hz,1H),7.44(dd,J＝8.4,2.0Hz,1H),7.44(dd,J＝8.4,2.0Hz,1H),7.39–7.32(m,2H),7.40–7.30(m,2H),2.50(s,6H)。
实施例16
Figure PCTCN2022130543-appb-000021
的鉴定
化合物16. 1H-NMR(400MHz,)δ8.71(d,J＝1.2Hz,1H),8.71(d,J＝1.2Hz,1H),8.12(dd,J＝8.9,5.3Hz,1H),8.12(dd,J＝8.9,5.3Hz,1H),7.94(dd,J＝7.9,1.8Hz,2H),7.94(dd,J＝7.9,1.8Hz,2H),7.52(d,J＝8.2Hz,1H),7.51(dd,J＝8.8,5.1Hz,2H),7.50(d,J＝2.0Hz,1H),8.85–2.42(m,14H),7.28–7.25(m,1H),7.29–7.21(m,2H),7.24(d,J＝2.2Hz,1H),7.13(ddd,J＝8.9,8.2,3.0Hz,1H),7.13(ddd,J＝8.9,8.2,3.0Hz,1H),7.01(dd,J＝8.7,2.9Hz,1H),7.01(dd,J＝8.7,2.9Hz,1H),2.59(s,3H),2.59(s,3H)。
实施例17
Figure PCTCN2022130543-appb-000022
的鉴定
化合物17. 1H-NMR(400MHz,)δ8.31(d,J＝1.1Hz,1H),8.31(d,J＝1.1Hz,1H),8.19(d,J＝1.8Hz,1H),8.19(d,J＝1.8Hz,1H),7.87(s,1H),7.87(s,1H),7.78(dd,J＝8.9,5.3Hz,1H),7.78(dd,J＝8.9,5.3Hz,1H),7.58(s,1H),7.58(s,1H),7.24(d,J＝3.1Hz,1H),7.24(d,J＝3.1Hz,2H),8.68–1.88(m,14H),7.04–6.94(m,1H),7.02–6.96(m,1H),6.92–6.82(m,1H),6.91–6.83(m,1H),6.76(dd,J＝8.7,2.9Hz,1H),6.76(dd,J＝8.7,2.9Hz,1H),2.10(s,3H),2.10(s,3H)。
实施例18
Figure PCTCN2022130543-appb-000023
的鉴定
化合物18. 1H-NMR(400MHz,)δ8.79(s,1H),8.79(s,1H),8.62(d,J＝3.8Hz,1H),8.62(d,J＝3.8Hz,1H),8.21(s,1H),8.21(s,1H),8.00(d,J＝6.0Hz,2H),8.00(d,J＝6.0Hz,2H),7.48(d,J＝8.3Hz,1H),7.47(dd,J＝7.2,5.1Hz,2H),8.99–6.56(m,12H),7.47(d,J＝1.9Hz,1H),7.35(dd,J＝7.9,4.9Hz,1H),7.35(dd,J＝7.9,4.9Hz,1H),7.22(dd,J＝8.2,2.0Hz,1H),7.22(dd,J＝8.2,2.0Hz,1H),7.15–7.07(m,1H),7.16–7.05(m,1H),7.00(dd,J＝8.7,3.0Hz,1H),7.00(dd,J＝8.7,3.0Hz,1H)。
实施例19
Figure PCTCN2022130543-appb-000024
的鉴定
化合物19. 1H-NMR(400MHz,)δ11.41(s,1H),11.41(s,1H),8.69(dd,J＝7.3,2.1Hz,1H),8.69(dd,J＝7.3,2.1Hz,1H),8.38(dd,J＝9.1,5.4Hz,1H),8.38(dd,J＝9.1,5.4Hz,1H),11.66–6.34(m,10H),7.59(d,J＝2.0Hz,1H),7.59(d,J＝2.0Hz,1H),7.50(d,J＝8.2Hz,1H),7.50(d,J＝8.2Hz,1H),7.33(dd,J＝8.2,2.0Hz,1H),7.33(dd,J＝8.2,2.0Hz,1H),7.30–7.08(m,4H),7.20–7.09(m,2H),6.98(dd,J＝8.8,3.0Hz,1H),6.98(dd,J＝8.8,3.0Hz,1H),6.62(t,J＝6.7Hz,1H),6.62(t,J＝6.7Hz,1H)。
实施例20
Figure PCTCN2022130543-appb-000025
的鉴定
化合物20. 1H-NMR(400MHz,)δ8.60(d,J＝3.6Hz,2H),8.60(d,J＝3.6Hz,2H),8.23(s,1H),8.23(s,1H),8.03(dd,J＝8.9,5.2Hz,1H),8.03(dd,J＝8.9,5.2Hz,1H),7.50(d,J＝8.2Hz,1H),7.54–7.41(m,4H),7.46(t,J＝3.6Hz,3H),8.82–6.72(m,12H),7.29–7.17(m,1H),7.21(dd,J＝8.2,2.1Hz,1H),7.17–7.07(m,1H),7.16–7.09(m,1H),7.01(dd,J＝8.7,2.9Hz,1H),7.01(dd,J＝8.7,2.9Hz,1H)。
实施例21：实施例1～20所得化合物的防污活性测定
最小抑菌浓度(MIC)的测定方法
采用试管二倍稀释法，将合成的联苯类杂环化合物的浓度依次二倍稀释，然后将稀释菌液加入到联苯类杂环化合物稀释液中进行培养，大肠杆菌与金黄色葡萄球菌震荡培养24h，肉眼观察阳性对照管(不加受试化合物而接种菌的试管)有菌生长，出现混浊，阴性对照管(不加受试化合物也不接种菌的试管)无菌生长，呈现透明状态，以此确定待测物对2种试验菌株的最小抑菌浓度。据此判断，含联苯类杂环化合物对两种细菌的检测结果见表2。
表2 化合物对2种菌的MIC
实施例 1 2 3 4 5 6 7 8 9 10
金黄色葡萄球 0.125 0.016 0.25 0.125 0.016 0.125 0.25 0.016 0.25 0.125
大肠杆菌 0.125 0.016 0.125 0.25 0.016 0.125 0.25 0.016 0.125 0.25
实施例 11 12 13 14 15 16 17 18 19 20
金黄色葡萄球 0.25 0.125 0.125 0.016 0.25 0.125 0.25 0.125 0.25 0.25
大肠杆菌 0.25 0.063 0.125 0.016 0.125 0.25 0.25 0.063 0.125 0.125
根据防污活性筛选，所合成的化合物均表现出了一定的防污活性，其中化合物2，化合物5，化合物8和化合物14表现出突出的防污活性，对金黄色葡萄球菌和大肠杆菌的MICs均达到了0.016mg/mL，优异于商品化的三丁基锡(TBT)防污剂。

Claims (8)

  1. 具有通式(I)的联苯类杂环化合物：
    Figure PCTCN2022130543-appb-100001
    所述的R为以下基团之任意一种：
    Figure PCTCN2022130543-appb-100002
  2. 权利要求1所述的具有通式(I)的联苯类杂环化合物的合成方法，其特征在于，反应式如下：
    Figure PCTCN2022130543-appb-100003
  3. 权利要求1所述的具有通式(I)的联苯类杂环化合物的合成方法，其特征在于，步骤如下：
    (1)2-溴-4-氟苯胺与酸酐反应，发生酰化反应，生成所需要的酰胺化合物，目的是保护胺基，以免发生副反应；
    (2)胺基保护产生的2-溴-4-氟乙酰苯胺，在氯化镁试剂以及溴化亚铁和氧化剂BQ的共同作用下，发生偶联反应；
    (3)2-(3,4-二氯苯基)-4-氟乙酰苯胺发生水解反应，得到关键中间体，为联苯类化合物的合成提供了关键合成骨架。关键骨架2-(3,4-二氯苯基)-4-氟苯胺与不同的酸反应，生成20个目标化合物。
  4. 根据权利要求3所述的具有通式(I)的联苯类杂环化合物的合成方法，其特征在于，步骤(1)中，反应条件是：室温反应2～3h。
  5. 根据权利要求3所述的具有通式(I)的联苯类杂环化合物的合成方法，其特征在于，步骤(2)中，所采用的有机溶剂选自乙醚，四氢呋喃、二氧六烷、N,N-二甲基酰胺、丙酮、间二甲苯、二氯甲烷、二甲基乙酰胺中的任意一种；
    加入氧化剂BQ的反应温度为r.t～50℃，反应时间20～90min；
    氯化镁试剂与氧化剂BQ的摩尔比为0.1～0.5:0.2～1.5。
  6. 根据权利要求3所述的具有通式(I)的联苯类杂环化合物的合成方法，其特征在于，步骤(3)中，所述的酸为杂环的酸，对甲氧基苯甲酸，1-萘酸，3-氯异烟酸，5,6-二氯烟酸，异烟酸，5-甲基吡嗪-2-羧酸，2-羧酸吡嗪，5-氯吡嗪-2-羧酸，2-氯吡啶-6-羧酸，2-氨基烟酸，2-氟烟酸，2-氯烟酸，2-氯异烟酸，吡啶-2-羧酸，6-氯烟酸，6-甲基烟酸，5-甲基烟酸，烟酸，2-羟基烟酸或者邻醛基苯甲酸。
  7. 权利要求1所述的具有通式(I)的联苯类杂环化合物用于船舶防污的用途。
  8. 权利要求7所述用于船舶防污的用途，其特征在于，所涉及杀灭的菌类是金黄色葡萄球菌和大肠杆菌。
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