CN115536543B - 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用 - Google Patents

一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用 Download PDF

Info

Publication number
CN115536543B
CN115536543B CN202211404321.9A CN202211404321A CN115536543B CN 115536543 B CN115536543 B CN 115536543B CN 202211404321 A CN202211404321 A CN 202211404321A CN 115536543 B CN115536543 B CN 115536543B
Authority
CN
China
Prior art keywords
triclosan
isopropanolamine
bacteria
compound
compounds
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202211404321.9A
Other languages
English (en)
Other versions
CN115536543A (zh
Inventor
杨松
张娇娇
张军荣
周翔
柳立伟
吴志兵
薛伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guizhou University
Original Assignee
Guizhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guizhou University filed Critical Guizhou University
Priority to CN202211404321.9A priority Critical patent/CN115536543B/zh
Publication of CN115536543A publication Critical patent/CN115536543A/zh
Application granted granted Critical
Publication of CN115536543B publication Critical patent/CN115536543B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08—Hydroxylamino compounds or their ethers or esters
    • C07C239/12—Hydroxylamino compounds or their ethers or esters having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen 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
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/16—Oxygen or sulfur directly attached to an aromatic ring system with two or more oxygen or sulfur atoms directly 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
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/08—Amines; Quaternary ammonium compounds containing oxygen or sulfur
    • A01N33/10—Amines; Quaternary ammonium compounds containing oxygen or sulfur having at least one oxygen or sulfur atom directly attached to an 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
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds containing nitrogen-to-oxygen bonds
    • A01N33/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds containing nitrogen-to-oxygen bonds only one oxygen atom attached to the nitrogen atom
    • 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
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • 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
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • 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
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-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
    • A01N43/34—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
    • 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
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • 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
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/04—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reaction of ammonia or amines with olefin oxides or halohydrins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
    • C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
    • C07C217/20—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D211/38—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • 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
    • C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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
    • 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
    • C07D295/20—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 carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205—Radicals derived from carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/27—Condensation of epihalohydrins or halohydrins with compounds containing active hydrogen atoms
    • C07D301/28—Condensation of epihalohydrins or halohydrins with compounds containing active hydrogen atoms by reaction with hydroxyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
    • C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
    • C07D303/24—Ethers with hydroxy compounds containing no oxirane rings with polyhydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms

Abstract

本发明公开了一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用，该类化合物具有如通式(Ⅰ)所示的结构：

Description

一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用
技术领域
本发明涉及有机合成技术领域，特别是涉及一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用。
背景技术
植物细菌性和真菌性病害，如水稻白叶枯病、辣椒青枯病、白菜叶斑病、烟草青枯病、柑桔溃疡病、猕猴桃溃疡病和黄瓜灰霉病、辣椒枯萎病、油菜菌核病、小麦赤霉病、马铃薯晚疫病、蓝莓根腐病、葡萄座腔菌、火龙果炭疽病、水稻纹枯病等，是由植物病原细菌和真菌引起并影响农作物生产的几种重要病害，主要表现为坏死、枯萎、腐烂等症状。由于传统杀菌剂的使用不仅增加了植物病原微生物的抗药性而且影响环境和危害农作物安全。因此，当前迫切需要开发具有高活性、高选择性的新型杀菌剂。
三氯生是一种广谱抗菌剂，可以抑制细菌、病毒和真菌等。三氯生类化合物的生物活性研究进展如下：
2001年，Herbert P.Schweizer[Herbert P.Schweizer.Triclosan:a widelyused biocide and its link to antibiotics[J].FEMS Microbiology Letters,2001,202:1-7.]发现三氯生和抗生素之间存在联系，广泛使用含三氯生的防腐剂和消毒剂可能有助于微生物耐药性的形成，特别是对抗生素的交叉耐药性。
2017年，Xuyun Yang等[Xuyun Yang,Junrui Lu,Ming Ying,Jiangbei Mu,Peichun Li,and Yue Liu.Docking and molecular dynamics studies on triclosanderivatives binding to FabI[J].J.Mol.Model.2017,23,25.]通过分子对接、分子动力学模拟和结合自由能计算等计算机辅助方法，阐明了三氯生衍生物与FabI蛋白的相互作用规律，指导了新衍生物的开发。
2019年，Gemma L.Howse等[Gemma L.Howse,Richard A.Bovill,PeterJ.Stephens,and Helen M.I.Osborn.Synthesis and antibacterial profiles oftargeted triclosan derivatives[J].Eur.J.Med.Chem.2019,162,51-58.]合成了一类糖苷衍生物，在所合成的三氯生糖苷衍生物对许多微生物都显示出较好的抗菌活性。尤其是化合物2a和2c对葡萄球菌(S.aureus)的MIC值均为0.5μg/mL。
因此，有必要寻找高效抗菌三氯生类活性化合物。
发明内容
为了寻找高效抗菌活性化合物，本发明以三氯生结构为基础，以异丙醇作为连接链，合成一系列含异丙醇胺结构的三氯生类化合物，并考察其抗植物病原微生物的生物活性，为新农药的研发和创制提供重要的科学基础。
因此，本发明的目的之一是提供一种含异丙醇胺结构的三氯生类化合物。
本发明的另一目的是提供制备上述含异丙醇胺结构的三氯生类化合物的中间体化合物及其制备方法。
本发明还有一目的是提供一种含有上述含异丙醇胺结构的三氯生类化合物的组合物。
本发明还有一目的是提供上述含异丙醇胺结构的三氯生类化合物或所述组合物的用途。
本发明另一目的是提供利用上述含异丙醇胺结构的三氯生类化合物或所述组合物防治农业病虫害的方法。
为实现上述目的，本发明提供了如下方案：
一种含异丙醇胺结构的三氯生类化合物，具有如通式(I)所示的结构：
其中，R1和R2各自独立的选自氢、氘、卤素、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的烷氧基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个、任意取代或未取代的苄基、任意取代或未取代的α-甲基苄基；或R1和R2相连构成任意取代的5-10元环或含杂原子的环，所述杂原子为N、O和S中的一个或多个。
优选地，R1和R2各自独立的选自氢、氘、卤素、任意取代或未取代的C1-6烷基、任意取代或未取代的C2-6烯基、任意取代或未取代的C2-6炔基、任意取代或未取代的C1-6烷氧基、任意取代或未取代的C5-10环烷基、任意取代或未取代的C5-10芳基、任意取代或未取代的C5-10杂芳基；或R1和R2相连构成任意取代的5-10元环或含杂原子的环，所述杂原子为N、O和S中的一个或多个。
优选地，R1和R2各自独立的选自氢、羟基、甲基、乙基、丙基、异丙基、丁基、叔丁基、正已基、丙炔基、苯基、氟苯基、甲氧基苯基、三氟苯基、氯苯基、 当R1和R2相连成环时为下述基团：/>
优选地，所述含异丙醇胺结构的三氯生类化合物，选自下述化合物：
一种用于制备所述含异丙醇胺结构的三氯生类化合物的中间体化合物，结构式如式(II)所示：
优选地，所述中间体化合物的制备方法为：步骤1-1、将三氯生和无水碳酸钾加入到二甲基甲酰胺(DMF)溶液中，搅拌溶解；然后加入环氧溴丙烷，加热搅拌，反应完成后，加入乙酸乙酯萃取。水洗，干燥，脱溶，采用柱层析纯化得2-((5-氯-2-(2,4-二氯苯氧基)苯氧基)甲基)环氧乙烷；
步骤1-2、将2-((5-氯-2-(2,4-二氯苯氧基)苯氧基)甲基)环氧乙烷加入到含有甲胺和异丙醇的溶液中，加热搅拌，反应完成后，反应液用水淬火，用二氯甲烷萃取，干燥，脱溶，采用柱层析纯化得到中间体化合物1-(5-氯-2-(2,4-二氯苯氧基)苯氧)-3-(甲氨基)-2-丙醇。
所述含异丙醇胺结构的三氯生类化合物的制备方法，合成路线如下：
其中，R1和R2各自独立的选自氢、氘、卤素、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的烷氧基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个、任意取代或未取代的苄基、任意取代或未取代的α-甲基苄基；或R1和R2相连构成任意取代的5-10元环或含杂原子的环，所述杂原子为N、O和S中的一个或多个。
一种组合物，含有所述含异丙醇胺结构的三氯生类化合物或其立体异构体、或其盐或其溶剂化物，以及农业上可用的助剂或杀菌剂、杀虫剂或除草剂。优选地，所述组合物的剂型选自乳油(EC)、粉剂(DP)、可湿性粉剂(WP)、颗粒剂(GR)、水剂(AS)、悬浮剂(SC)、超低容量喷雾剂(ULV)、可溶性粉剂(SP)、微胶囊剂(MC)、烟剂(FU)、水乳剂(EW)、水分散性粒剂(WG)。
所述含异丙醇胺结构的三氯生类化合物或所述组合物在防治农业病虫害方面的用途。优选地，所述农业病虫害为植物细菌性或真菌性病害；更优选地，所述农业病虫害为植物叶枯病和植物溃疡病；最优选地，所述农业病虫害为水稻白叶枯病、黄瓜白叶枯病、魔芋白叶枯病、柑橘溃疡病、葡萄溃疡病、番茄溃疡病、猕猴桃溃疡病、苹果溃疡病、黄瓜灰霉病菌、辣椒枯萎病菌、油菜菌核病菌、小麦赤霉病菌、马铃薯晚疫病菌、茄子黄萎病菌。
一种防治农业病虫害的方法，使所述含异丙醇胺结构的三氯生类化合物或所述组合物作用于有害物或其生活环境。优选地，所述农业病虫害为植物细菌性或真菌性病害；更优选地，所述农业病虫害为水稻白叶枯病、烟草青枯病菌、黄瓜白叶枯病、魔芋白叶枯病、柑橘溃疡病、葡萄溃疡病、番茄溃疡病、猕猴桃溃疡病、苹果溃疡病、黄瓜灰霉病菌、辣椒枯萎病原菌、油菜菌核病菌、小麦赤霉病菌、马铃薯晚疫病菌、茄子黄萎病菌。
用于保护植物免受农业病虫害侵害的方法，使所述任一项含异丙醇胺结构的三氯生类化合物或所述组合物作用于植物或其生活环境。
此处用到的术语“烷基”是包括具有特定数目碳原子的支链和直链饱和烃基。例如“C1-10烷基”(或亚烷基)目的是C1、C2、C3、C4、C5、C6、C7、C8、C9和C10烷基。另外，例如“C1-6烷基”表示具有1到6个碳原子的烷基。烷基可为非取代或取代的，以使一个或多个其氢原子被其它化学基团取代。烷基的实施例包括但不限于甲基(Me)、乙基(Et)、丙基(如正丙基和异丙基)、丁基(如正丁基、异丁基、叔丁基)、戊基(如正戊基、异戊基、新戊基)及其类似物。
“烯基”是既包括直链或支链结构的烃，且具有一个或多个出现在链中任何稳定点的碳-碳双键。例如“C2-6烯基”(或亚烯基)目的是包括C2、C3、C4、C5和C6烯基。烯基的实例包括但不限于乙烯基、1-丙烯基,2-丙烯基、2-丁烯基、3-丁烯基、2-戊烯基、3-戊烯基、4-戊烯基、2-己烯基、3-己烯基、4-己烯基、5-己烯基、2-甲基-2-丙烯基、4-甲基-3-戊烯基及其类似物。
“炔基”是既包括直链或支链结构的烃，且具有一个或多个出现在链中任何稳定点的碳-碳叁键。例如“C2-6炔基”(或亚炔基)目的是包括C2、C3、C4、C5和C6炔基；如乙炔基、丙炔基、丁炔基、戊炔基、己炔基及其类似物。
此处用到的术语“取代的”指的是在指定原子或基团上的任意一个或多个氢原子以选择的指定基团取代，前提是不超过指定原子的一般化合价。如果没有其它说明，取代基命名至中心结构。例如，可以理解的是当(环烷基)烷基是可能的取代基，该取代基至中心结构的连接点是在烷基部分中。此处使用的环双键是形成于两个临近环原子之间的双键(如C＝C、C＝N或N＝N)。当提到取代时，特别是多取代时，指的是多个取代基在指定基团上的各个位置上取代，如二氯苯基指的是1,2-二氯苯基、1,3-二氯苯基和1,4-二氯苯基。
取代基和或变量的组合是允许的，仅当这些组合产生稳定的化合物或有用的合成中间体。稳定的化合物或稳定结构暗示所述化合物以有用的纯度从反应混合物分离出来时是足够稳定的，随之配制形成有效的治疗试剂。优选地，目前所述化合物不包含N-卤素、S(O)2H或S(O)H基。
术语“芳基”指的是在环部分具有6到12个碳原子的单环或双环芳香烃基，如苯基和萘基，每个可被取代的。
术语“卤素”或“卤素原子”指的是氯、溴、氟和碘。
术语“卤代烷基”指的是具有一个或多个卤素取代基的取代烷基。例如“卤代烷基”包括单、双和三氟甲基；即便卤代烷基中的卤代被明确为氟、氯、溴、碘，同样指的是具有一个或多个氟、氯、溴、碘取代基的取代烷基。
术语“杂芳基”指的是取代和非取代芳香5或6元单环基团，9-或10-元双环基团，和11到14元三环基团，在至少一个环中具有至少一个杂原子(O，S或N)，所述含杂原子的环优选具有1、2或3个选自O、S和N中的杂原子。含杂原子的杂芳基的每个环可含一个或两个氧或硫原子和/或由1到4个氮原子，前提是每个环中杂原子的总数是4或更少，且每个环具有至少一个碳原子。完成双环和三环基团的稠合环可仅含有碳原子，并可以是饱和、部分饱和或不饱和。氮和硫原子可任选被氧化且氮原子可任选被季铵化。双环或三环的杂芳基必须包括至少一个全芳香环，氮其它稠合环可为芳香性或非芳香性的。杂芳基可在任何环的任何可利用氮或碳原子上连接。
示例性单环杂芳基包括吡咯基、吡唑基、吡唑啉基、咪唑基、噁唑基、异噁唑基、噻唑基、噻二唑基、呋喃基、噻吩基、噁二唑基、吡啶基、吡嗪基、嘧啶基、哒嗪基、三嗪基及其类似物。
示例性双环杂芳基包括吲哚基、苯并噻唑基、苯并二氧杂环戊烯基、苯并噁唑基、苯并噻吩基、喹啉基、四氢异喹啉基、异喹啉基、苯并咪唑基、苯并呋喃基、吲哚嗪基、苯并呋喃基、色酮基、香豆素基、苯并呋喃基、噌啉基、喹喔啉基、吲唑基、吡咯并吡啶基、氟代吡啶基、二氢异吲哚基、四氢喹啉基及其类似物。
如果没有其它说明，本发明的化合物理解为包括游离态和其盐。术语“盐”表示以无机和/或有机酸和碱形成酸式和/或碱式盐。另外，术语“盐可包括两性离子(内盐)，如当式I化合物含有碱性片段如胺或吡啶或咪唑环，和酸式片段如羧酸。药物上可接受的(即非毒性、生理学上可接受的)盐是优选的，如可接受的金属和胺盐，其中阳离子没有显著贡献毒性或盐的生物活性。然而，其它盐可是有用的，如在制备过程中采用分离或纯化步骤，因此也包含于本发明范围中。
优选地，C1-C10烷基指的是甲基、乙基、丙基、丁基、戊基、己基、庚基、辛基、壬基、癸基及其同分异构体；C2-C5烯基指的是乙烯基、丙烯基、烯丙基、丁烯基、戊烯基及其同分异构体。
当提到取代基为烯基、炔基、烷基、卤素、芳基、杂芳基、烷氧基、环烷基、羟基、氨基、巯基时，或这些取代基具体的为某个具体的烯基、炔基、烷基、卤素、芳基、杂芳基、烷氧基、环烷基、羟基、氨基、巯基时，指的是一个到三个上述取代基。
本发明公开了以下技术效果：
本发明以三氯生类化合物为基础，合成了一系列含异丙醇胺结构的三氯生类化合物，且发现该类化合物对致病病原细菌及真菌都具有良好的抑制作用，针对病原细菌[如水稻白叶枯病菌(Xanthomonas oryzae pv.oryzae,Xoo)、柑橘溃疡病菌(Xanthomonasaxonopodis pv.citri,Xac)和猕猴桃溃疡病菌(Pseudomonas syringae pv.actinidiae,Psa)等]均具有良好的抑制效果，针对病原真菌[如葡萄座腔菌(Botryosphaeriadothidea，B.d)、茄子黄萎病(Verticillium dahliae Kleb,V.d)、水稻纹枯病(Thanatephorus cucumeris,T.C)等]均具有良好的抑制效果，为新农药的研发和创制提供重要的科学基础。
具体实施方式
现详细说明本发明的多种示例性实施方式，该详细说明不应认为是对本发明的限制，而应理解为是对本发明的某些方面、特性和实施方案的更详细的描述。
应理解本发明中所述的术语仅仅是为描述特别的实施方式，并非用于限制本发明。另外，对于本发明中的数值范围，应理解为还具体公开了该范围的上限和下限之间的每个中间值。在任何陈述值或陈述范围内的中间值，以及任何其他陈述值或在所述范围内的中间值之间的每个较小的范围也包括在本发明内。这些较小范围的上限和下限可独立地包括或排除在范围内。
除非另有说明，否则本文使用的所有技术和科学术语具有本发明所述领域的常规技术人员通常理解的相同含义。虽然本发明仅描述了优选的方法和材料，但是在本发明的实施或测试中也可以使用与本文所述相似或等同的任何方法和材料。本说明书中提到的所有文献通过引用并入，用以公开和描述与所述文献相关的方法和/或材料。在与任何并入的文献冲突时，以本说明书的内容为准。
在不背离本发明的范围或精神的情况下，可对本发明说明书的具体实施方式做多种改进和变化，这对本领域技术人员而言是显而易见的。由本发明的说明书得到的其他实施方式对技术人员而言是显而易见得的。本发明说明书和实施例仅是示例性的。
关于本文中所使用的“包含”、“包括”、“具有”、“含有”等等，均为开放性的用语，即意指包含但不限于。
实施例1：中间体2-((5-氯-2-(2,4-二氯苯氧)苯氧基)甲基)环氧乙烷的制备
将三氯生(15.0mmol)加入到溶有碳酸钾(22.5mmol)和环氧溴丙烷(30.0mmol)的30mL DMF溶液中，加热至60℃反应3h后停止反应，乙酸乙酯萃取，干燥，脱溶，柱层析，得白色固体，收率81.7％。其核磁数据为：1H NMR(400MHz,CDCl3)δ7.43(d,J＝2.5Hz,1H,1-Ar-3-H),7.13–7.09(m,1H,1-Ar-5-H),7.03(d,J＝2.2Hz,1H,2-Ar-2-H),6.95(dd,J＝8.5,2.2Hz,1H,2-Ar-4-H),6.92–6.88(m,1H,1-Ar-6-H),6.70–6.66(m,1H,2-Ar-5-H),4.22(dd,J＝11.3,3.0Hz,1H,-O-CH2-),3.97(dd,J＝11.3,5.4Hz,1H,-O-CH2-),3.20(m,1H,epoxy-CH-),2.80(dd,J＝4.8,4.4Hz,1H,epoxy-CH2-),2.61(dd,J＝4.9,2.6Hz,1H,epoxy-CH2-)；13C NMR(101MHz,CDCl3)δ152.1,150.4,143.6,130.4,130.3,128.2,127.8,124.7,122.0,121.8,118.4,115.9,70.1,49.8,44.4.
实施例2：(1-(5-氯-2)–2,4-二氯苯氧)苯氧基)3-(甲胺基)丙-2-醇的制备
将2-((5-氯-2-(2,4-二氯苯氧)苯氧基)甲基)环氧乙烷(0.5mmol)加入到溶有甲胺(1.0mmol)的6mL异丙醇溶液中，加热至60℃反应12h后停止反应，30mL二氯甲烷萃取，干燥，脱溶，柱层析，得白色固体，收率63.8％。
采用中间体2-((5-氯-2-(2,4-二氯苯氧)苯氧基)甲基)环氧乙烷制备含异丙醇胺结构的三氯生类化合物，合成路线如下：
其中，R1和R2各自独立的选自氢、氘、卤素、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的烷氧基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个、任意取代或未取代的苄基、任意取代或未取代的α-甲基苄基；或R1和R2相连构成任意取代的5-10元环或含杂原子的环，所述杂原子为N、O和S中的一个或多个；
具体步骤如表1所示。
表1目标化合物的具体合成步骤
合成的含异丙醇胺结构的三氯生类化合物的结构及核磁共振氢谱、碳谱和高分辨质谱数据如表2所示，物化性质如表3所示。
表2化合物的核磁共振氢谱、碳谱和高分辨质谱数据
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
/>
表3目标化合物的理化性质
/>
药理实施例1
EC50(median effective concentration)是评价植物病原菌对化合物敏感性的重要指标，同时也是对目标化合物作用机制研究时，化合物浓度设置的重要参数。在浓度梯度实验中，采用二倍稀释法设定合适的5个浓度，最后将药剂对植物病原菌的抑制率、药剂浓度换算成对数值，通过SPSS软件回归分析得到毒力曲线，计算出EC50。
采用浊度法测试目标化合物对植物病原菌的有效中浓度EC50，试验对象为水稻白叶枯病菌(Xoo)、柑橘溃疡病菌(Xac)和猕猴桃溃疡病菌(Psa)。DMSO溶解在培养基中作为空白对照。将水稻白叶枯病菌(水稻白叶枯病原菌在M210固体培养基)放到NB培养基中，在28℃、180rpm恒温摇床中振荡培养到对数生长期备用；将柑橘溃疡病菌(在M210固体培养基上)放到NB培养基中，在28℃、180rpm恒温摇床中振荡培养到对数生长期备用。将药剂(化合物)配置成不同浓度(例：100,50,25,12.5,6.25μg/mL)的含毒NB液体培养基5mL加入到试管中，分别加入40μL含有植病细菌的NB液体培养基，在28℃、180rpm恒温摇床中振荡，其水稻白叶枯病原菌培养36h，柑橘溃疡病菌培养48h，猕猴桃溃疡病菌培养36h。将各个浓度的菌液在分光光度计上测定OD595值，并且另外测定对应浓度的含毒无菌NB液体培养基的OD595值。
校正OD值＝含菌培养基OD值－无菌培养基OD值
抑制率％＝[(校正后对照培养基菌液OD值－校正含毒培养基OD值)/校正后对照培养基菌液OD值]×100
本发明实施例辅以说明本发明的技术方案，但实施例的内容并不局限于此，目标化合物实验结果如表4所示。
表4含异丙醇胺结构的三氯生类化合物对植物病原细菌的EC50
/>
/>
/>
从表4中可以看出，在离体试验中，部分目标化合物对植物病原菌(如水稻白叶枯病菌、柑橘溃疡病菌和猕猴桃溃疡病菌)表现出了良好的抑制活性。其中，化合物38对水稻白叶枯病菌、柑橘溃疡病菌和猕猴桃溃疡病菌都具有极好的抑制活性，其EC50分别为0.34、2.11和2.93μg/mL，可用于防治植物细菌性病害。
药理实施例2
采用菌丝体生长速率抑制法在PDA培养基上测定了化合物对葡萄座腔菌(Botryosphaeriadothidea，B.d)、茄子黄萎病(Verticillium dahliae Kleb,V.d)、水稻纹枯病(Thanatephoruscucumeris,T.C)、油菜菌核病菌(Sclerotinia sclerotiorum,S.s.)、小麦赤霉病菌(Gibberellazeae,G.z.)和辣椒枯萎病菌(Fusarium oxysporum,F.o.)六种植物病原真菌的抗菌活性，菌种均提前活化。用万分之一天平称取待测化合物加入1mL DMSO溶解后在无菌操作台中转移至15mL灭菌的离心管中，加入9mL吐温水(Tween-20)定溶10mL，倒入培养基中，混匀后平均分装至9个培养皿中冷却备用；在无菌操作台内，以灭菌的打孔器(5mm)将生长正常的菌落制成菌饼，用接菌环将菌饼倒扣于培养基中央，于28℃条件下培养3～5天，待对照菌落生长至整个平板直径的2/3时用直尺按十字交叉法测量2次，以平均值计算菌落直径大小。初期我们选择100μg/mL为初筛浓度。根据下列公式求出菌丝生长抑制率。将多菌灵和嘧菌酯作为对照药剂一起参与测试。计算公式如下：抑制率(％)＝(C1-C2)/(C1-0.5)×100，公式中：
C1：对照菌落直径即DMSO处理的菌落直径；
C2：理菌落直径即加药处理的菌落直径；
0.5：菌饼的直径。
本发明实施例辅以说明本发明的技术方案，但实施例的内容并不局限于此，目标化合物实验结果如表5所示。
表5含异丙醇胺三氯生类化合物对植物病原真菌初筛
/>
/>
从表5中可以看出，大部分目标化合物在100μg/mL对葡萄座腔菌(B.d.)表现出较好的抗菌活性，抑制率为90％以上；化合物6,15,和43在100μg/mL对油菜菌核病菌(S.s.)表现出较好的抗菌活性，抑制率分别为95.3％、93.8％和91.9％；化合物3,7和42在100μg/mL对茄子黄萎病菌(V.d.)表现出较好的抗菌活性，抑制率分别为94.4％、95.9％和92.8％；化合物8在100μg/mL对水稻纹枯病菌(R.s.)表现出较好的抗菌活性，抑制率为92.3％。
以上所述的实施例仅是对本发明的优选方式进行描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案做出的各种变形和改进，均应落入本发明权利要求书确定的保护范围内。

Claims (9)

1.一种含异丙醇胺结构的三氯生类化合物，其特征在于，具有如通式(I)所示的结构：
其中，R1和R2各自独立的选自氢、C1-6烷基、C2-6炔基、C1-6烷氧基、C5-10芳基或C5-10杂芳基；或R1和R2相连构成5-10元环或含杂原子的环，所述杂原子为N或O。
2.一种含异丙醇胺结构的三氯生类化合物，其特征在于，具有如通式(I)所示的结构：
其中，R1和R2各自独立的选自氢、甲基、乙基、丙基、丁基、丙炔基、苯基、甲氧基苯基、三氟苯基、氯苯基、 当R1和R2相连成环时为下述基团：/>
3.一种含异丙醇胺结构的三氯生类化合物，其特征在于，选自下述化合物：
4.权利要求1-3任一项所述含异丙醇胺结构的三氯生类化合物的制备方法，其特征在于，合成路线如下：
其中，R1和R2各自独立的选自氢、C1-6烷基、C2-6炔基、C1-6烷氧基、C5-10芳基或C5-10杂芳基；或R1和R2相连构成5-10元环或含杂原子的环，所述杂原子为N或O。
5.权利要求1-3任一项所述含异丙醇胺结构的三氯生类化合物的制备方法，其特征在于，合成路线如下：
其中，R1和R2各自独立的选自氢、甲基、乙基、丙基、丁基、丙炔基、苯基、甲氧基苯基、三氟苯基、氯苯基、 当R1和R2相连成环时为下述基团：/>
6.一种组合物，其特征在于，含有权利要求1-3任一所述含异丙醇胺结构的三氯生类化合物，以及农业上可用的助剂或杀菌剂、杀虫剂或除草剂。
7.权利要求1-3任一项所述含异丙醇胺结构的三氯生类化合物或权利要求6所述组合物在防治农业病害方面的用途，所述农业病害致病病源为细菌或真菌。
8.一种防治农业病害的方法，其特征在于，使权利要求1-3任一项所述含异丙醇胺结构的三氯生类化合物或权利要求6所述组合物作用于有害物或其生活环境，所述农业病害致病病源为细菌或真菌。
9.用于保护植物免受农业病害侵害的方法，其特征在于，使权利要求1-3任一项所述含异丙醇胺结构的三氯生类化合物或权利要求6所述组合物作用于植物或其生活环境，所述农业病害致病病源为细菌或真菌。
CN202211404321.9A 2022-11-10 2022-11-10 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用 Active CN115536543B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211404321.9A CN115536543B (zh) 2022-11-10 2022-11-10 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211404321.9A CN115536543B (zh) 2022-11-10 2022-11-10 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用

Publications (2)

Publication Number Publication Date
CN115536543A CN115536543A (zh) 2022-12-30
CN115536543B true CN115536543B (zh) 2023-11-03

Family

ID=84719829

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211404321.9A Active CN115536543B (zh) 2022-11-10 2022-11-10 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用

Country Status (1)

Country Link
CN (1) CN115536543B (zh)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999031036A2 (en) * 1997-12-12 1999-06-24 Ciba Specialty Chemicals Holding Inc. O-derivatives of halogenated diphenyl ether compounds
WO1999038830A1 (en) * 1998-01-30 1999-08-05 Ciba Specialty Chemicals Holding Inc. Oligomeric halogenated diphenyl ether compounds
CN1887847A (zh) * 2005-06-28 2007-01-03 沈阳化工研究院 取代的对三氟甲基苯醚类化合物及其制备与应用
CN105985246A (zh) * 2015-03-05 2016-10-05 湖南化工研究院有限公司 具除草、杀虫或杀菌活性的二苯醚类化合物
CN112624931A (zh) * 2020-11-24 2021-04-09 贵州大学 一类含异丙醇芳香醚类结构的紫檀芪胺类化合物及其制备方法和应用
CN113683509A (zh) * 2021-10-27 2021-11-23 南京农业大学 一种二苯醚酯类化合物及其应用和农药杀菌剂

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110171279A1 (en) * 2009-11-02 2011-07-14 Ndsu Research Foundation Polyethylenimine biocides

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999031036A2 (en) * 1997-12-12 1999-06-24 Ciba Specialty Chemicals Holding Inc. O-derivatives of halogenated diphenyl ether compounds
WO1999038830A1 (en) * 1998-01-30 1999-08-05 Ciba Specialty Chemicals Holding Inc. Oligomeric halogenated diphenyl ether compounds
CN1887847A (zh) * 2005-06-28 2007-01-03 沈阳化工研究院 取代的对三氟甲基苯醚类化合物及其制备与应用
CN105985246A (zh) * 2015-03-05 2016-10-05 湖南化工研究院有限公司 具除草、杀虫或杀菌活性的二苯醚类化合物
CN112624931A (zh) * 2020-11-24 2021-04-09 贵州大学 一类含异丙醇芳香醚类结构的紫檀芪胺类化合物及其制备方法和应用
CN113683509A (zh) * 2021-10-27 2021-11-23 南京农业大学 一种二苯醚酯类化合物及其应用和农药杀菌剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Synthesis and characterization of novel antimicrobial polymers containing pendent triclosan moieties;Alex J. Kugel等;Reactive & Functional Polymers;第72卷;69–76 *

Also Published As

Publication number Publication date
CN115536543A (zh) 2022-12-30

Similar Documents

Publication Publication Date Title
CN109627206B (zh) 一类具有手性中心的咔唑基异丙醇胺衍生物的制备方法和应用
CN109651350B (zh) 一类杂环取代的1,3,4-噁(噻)二唑类化合物及其制备方法和用途
CN111454260B (zh) 一类含异丙醇胺亚结构的1，2，3，4-四氢-β-咔啉类化合物及其制备方法和应用
CN110713512B (zh) 一类含异丙醇胺亚结构的甘草次酸哌嗪类化合物及其制备方法和应用
CN112592335A (zh) 一类含1，2，3-三氮唑的咔唑异丙醇二胺类化合物及其制备方法和应用
CN112608307A (zh) 一类杂环取代1,3,4-噁二唑酰肼类化合物及其制备方法和应用
CN113636984B (zh) 一类含吗啉基团的1,3,4-噁二唑类化合物及其制备方法和用途
CN111285814B (zh) 一种含腙结构单元的喹唑啉酮化合物或其立体异构体、或其盐或其溶剂化物
CN110776548B (zh) 一类含异丙醇胺亚结构的乙酰氧基熊果酸哌嗪类化合物及其制备方法和应用
CN112624931A (zh) 一类含异丙醇芳香醚类结构的紫檀芪胺类化合物及其制备方法和应用
JP3874434B2 (ja) ケトンオキシムエーテル誘導体、その製造方法及び農園芸用殺菌剤
CN115260046B (zh) 一种松香酸酯类化合物及其制备方法和应用
CN115536543B (zh) 一种含异丙醇胺结构的三氯生类化合物及其制备方法和应用
CN114751885B (zh) 一种含异丙醇胺结构的香豆素类化合物及其制备方法和应用
CN113461634B (zh) 一类噻唑酰肼类化合物及其制备方法和应用
CN112592321B (zh) 一类1，2，3-三氮唑酰肼或酰胺类化合物及其制备方法和应用
JPS6345277A (ja) イソオキサゾリルエタノ−ル誘導体、抗真菌剤および農業用殺菌剤
CN112745312B (zh) 哒嗪酮异恶唑甲醚类化合物及其应用
CN115521306B (zh) 一种1,2,3,4-四氢-β-咔啉衍生物及其制备方法和应用
CN112624962B (zh) 一类具有双手性中心的咔唑基异丙醇胺衍生物及其制备方法和应用
CN116730852A (zh) 一类含取代苯基异丙醇胺类化合物及其制备方法和应用
CN116730954A (zh) 一类含查尔酮结构的异丙醇胺类化合物及其制备方法和应用
CN117486770A (zh) 一类2-氰基丙烯酸类化合物及其制备方法和应用
CN116217471A (zh) 一种紫檀芪吡啶盐类化合物、中间体化合物、组合物、药物、制备方法和应用
CN117024333A (zh) 一类含苯乙烯基的肟醚类化合物及其制备方法和应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant