[go: up one dir, main page]

CN109422704A - A kind of 4 substituted thiazole amide derivatives and its preparation method and application - Google Patents

A kind of 4 substituted thiazole amide derivatives and its preparation method and application Download PDF

Info

Publication number
CN109422704A
CN109422704A CN201811412725.6A CN201811412725A CN109422704A CN 109422704 A CN109422704 A CN 109422704A CN 201811412725 A CN201811412725 A CN 201811412725A CN 109422704 A CN109422704 A CN 109422704A
Authority
CN
China
Prior art keywords
base
amide derivatives
substituted
gxf05
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201811412725.6A
Other languages
Chinese (zh)
Inventor
范志金
郭晓凤
孙瀚翔
赵斌
孙学文
张乃楼
杨冬燕
吴启凡
于斌
周爽
孙耀正
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.)
Nankai University
Original Assignee
Nankai 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 Nankai University filed Critical Nankai University
Priority to CN201811412725.6A priority Critical patent/CN109422704A/en
Publication of CN109422704A publication Critical patent/CN109422704A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by 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, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

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

Abstract

The present invention provides a kind of 4 substituted thiazole amide derivatives and its preparation method and application, and the present invention relates to a kind of 4- hydroxyls or alkoxy thiazole amide derivative, general formula of the chemical structure to see formula IV:

Description

A kind of 4 substituted thiazole amide derivatives and its preparation method and application
Technical field
Technical solution of the present invention is related to the thiazole amide compound containing N containing S, and in particular to 4 substituted thiazole amides Derivative.
Background technique
Nitrogen-containing heterocycle is the most important active substructure of drug and pesticide molecule, and wherein thiazole ring contains sulphur nitrogen heteroatom, With unique Electron rich aromatic heterocycle structure, it is widely present in the natural products and drug molecule of many tool high bioactivities In, show bioactivity (Ayati A, the et al.Recent applications of 1,3-thiazole of multiplicity core structure in the identification of new lead compounds and drug Discovery.European Journal of Medicinal Chemistry, 2015,97,699-718), such as antibacterial, anti- The activity of cancer, antiviral, anti-inflammatory analgesic, hypoglycemic, treatment neurodegenerative disease etc., and the agricultures such as sterilization, desinsection, antiviral Medicine activity (Maienfisch P, et al.Thiazole and isothiazole ring-containing compounds In crop protection.Advances in heterocyclic chemistry, 2017,121:35-88).Commercialization Thiazoles pesticide mainly have insecticides thiamethoxam (Thiamethoxam), fungicide thifluzamide (Thifuzamide), kill line Worm agent fluorine thiophene worm sulfone (Fluensulfone) etc..
Succinate dehydrogenase (Succinate dehydrogenase, SDH) plays very important work in organism With being one of most important target of pesticide field.Succinate dehydrogenase inhibitors class fungicide because of its novel mechanism of action and The bactericidal activity of wide spectrum becomes hot spot (Sierotzki H, the et al.A review of current of Fungicides knowledge of resistance aspects for the next-generation succinate Dehydrogenase inhibitor fungicides.Phytopathology, 2013,103 (9), 880-887), at present There are multiple such fungicide variety development successes.Such fungicide largely contains amido bond, mainly includes oxygen thia hexamethylene two Acrylamide, benzamides, picolinamide class, pyrazol acid amide, thiazole amide, furans and thiophene-carboxamides class etc., it is close several Year research and development are in the majority with pyrazol acid amide, and wherein the substituent group of heterocycle acid moieties is essentially halogen, alkyl and halogenated alkyl.It is such to kill The important species of microbial inoculum mainly has: thifluzamide (Thifluzamide), Boscalid (Boscalid), fluorine azoles bacterium aniline (Penflufen), isopyrazam (Isopyrazam), fluorine azoles ring bacterium amine (Sedaxane) etc., since action site is single, SDHI class fungicide is classified as medium supreme resistance risk medicament by FRAC.
0371950 A2 of patent EP reports a kind of 5- thiazole amide derivatives and its bactericidal activity, and amine is substituted aniline, Fungicide thifluzamide including commercialization, 2006122933 A1 of patent WO report a kind of thiazole amide derivatives and its kill Bacterium activity, amine are the 2- benzidine replaced；But substituent group is essentially halogen, alkyl and halogenated alkyl on their thiazoles.
In order to find more efficient, wide spectrum, low resistance risk candidate compounds, the present invention utilizes pesticide molecule design Principle, design have synthesized 4 substituted thiazole amides compounds of a series of new, and carry out the bioactivity sieve of more system Choosing and evaluation.
Summary of the invention
The technical problems to be solved by the present invention are: the synthetic method of 4 novel substituted thiazole amide derivatives is provided, This kind of compound modulates agricultural, gardening and health and the bioactivity and its survey of forestry plant pest and the phytopathy original are provided Determine method, while providing these compounds in the middle application of agriculture field, horticultural field, field of forestry and health field.
The present invention solves technical solution used by the technical problem: have agriculture field, horticultural field, forestry and Health field insecticidal activity, bactericidal activity, anti-phytoviral activity, induction plant generate novel 4 substitutions thiophene of anti-disease activity The general formula of the chemical structure of azoles amide derivatives is shown in formula IV:
X is selected from oxygen or nitrogen；
R1Selected from H, C1-C6 alkyl, allyl, propargyl, cyclopropyl, 1,2- bis-fluoro ethyls；
R2Selected from E1Substituted C2-C4 alkyl, C3-C6 naphthenic base or by E2Substituted naphthenic base, phenyl or by E2Replace Phenyl, naphthalene or by E2Substituted naphthalene, tetralyl or by E2Substituted tetralyl, annelated heterocycles or by E2What is replaced is thick Close heterocycle, pyridyl group or by E2Substituted pyridyl group, pyrimidine radicals or by E2Substituted pyrimidine radicals, by E2What is replaced contains 1 or 2 N Five yuan of atom or six membered heteroaryl, containing 1 or 2 S atom by E2Five yuan or the six membered heteroaryl replaced contains 1 or 2 O atom by E2Five yuan or the six membered heteroaryl replaced, containing 1 N atom and 1 S atom by E2Five yuan or hexa-atomic miscellaneous replaced Aryl, containing 1 N atom and 1 O atom by E2Five yuan or the six membered heteroaryl replaced, containing 2 N atoms and 1 S atom By E2Five yuan or the six membered heteroaryl replaced, containing 2 N atoms and 1 O atom by E2Five yuan or the six membered heteroaryl replaced；On It states five yuan or six membered heteroaryl is selected from: substituted furyl, thienyl, pyrrole radicals, imidazole radicals, pyrazolyl, thiazolyl, different thiophene Oxazolyl, oxazolyl, isoxazolyl, oxadiazoles base, thiadiazolyl group, pyridyl group, pyridazinyl, pyrimidine radicals, pyrazinyl, triazine radical, four Piperazine base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazole base, benzothiazolyl, benzene And thiadiazolyl group, benzoxazolyl, the quinolyl of isomerization, the isoquinolyl of isomerization, phthalazinyl, quinoxalinyl, quinazoline The silicon substrate that base, cinnoline base or naphthyridines base, alkyl or alkenyl replace；
E1Selected from phenyl or heterocycle, (wherein phenyl and heterocycle can be by halogen, nitro, cyano, alkyl, halogenated alkyl, halogen Replace for alkoxy, alkoxy, alkylamino radical)；
E2Selected from halogen, nitro, cyano, C1-C6 alkyl, C1-C6 halogenated alkyl, C1-C6 halogenated alkoxy, C1-C6 alkane Oxygroup, C1-C6 alkylamino radical, C2-C6 alkenyl, C2-C6 halogenated alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, C2-C6 halo alkynyl, (wherein phenyl and heterocycle can be by halogens, nitro, cyano, alkyl, halogenated alkyl, halogenated for C3-C6 cycloalkynyl radical, phenyl or heterocycle One or more of alkoxy, alkoxy, alkylamino radical replace)；
R2And R3Ring can be formed together；
R3Selected from H, C1-C6 alkyl, C1-C6 alkoxy, allyl, propargyl, cyclopropyl；
Halogen is fluorine, chlorine, bromine or iodine in above-mentioned definition；
The alkyl, alkenyl or alkynyl are straight chain or branch alkyl；Alkyl itself or portion as other substituent groups It is selected from methyl, ethyl, propyl, butyl, amyl, hexyl and its isomers, isomers is selected from isopropyl, isobutyl group, Zhong Ding Base, tert-butyl, isopentyl or tertiary pentyl, but do not include 1,3- dimethylbutyl；
The halogenated alkyl group is selected from the group containing one or more identical or different halogen atoms, the alkyl halide Base is selected from CH2Cl、CHCl2、CCl3、CH2F、CHF2、CF3、CF3CH2、CH3CF2、CF3CF2Or CCl3CCl2；
Described naphthenic base itself or as other substituent groups part be selected from cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl；
Described alkenyl itself or as other substituent groups part be selected from vinyl, allyl, 1- acrylic, butene-2- Base, butylene -3- base, amylene -1- base, amylene -3- base, hexene -1- base or 4- methyl-3-pentenyl；
Described alkynyl itself or as other substituent groups part be selected from acetenyl, propine -1- base, propine -2- base, fourth Alkynes -1- base, crotonylene-base, 1- methyl -2- butynyl, hexin -1- base or 1- ethyl -2- butynyl.
The synthetic method of 4 substituted thiazole amide derivatives IV of the invention is as follows:
Wherein, R1It preferably is selected from H, methyl, allyl, propargyl, cyclopropyl, 1,2- bis-fluoro ethyls；R2Selected from 4- trifluoro methoxy The bromo- 4- fluorophenyl of base phenyl, 2-, 2- isopropyl phenyl, 2- tetralyl, 2- naphthalene, 2- hydroxy phenyl, 2- isopropoxy benzene Base, 2- (3 ', 4 '-difluorophenyl) phenyl, 2- (4 '-chlorphenyl) phenyl, 2- (3 ', 4 ', 5 '-trifluorophenyl) phenyl, 2- (3 ', 4 '-dichlorophenyls) -4- fluorophenyl, 2- (3 ', 4 ', 5 '-trifluorophenyl) -4- fluorophenyl, 1- (3- chloropyridine -2- base) methyl, 1- (3- fluorophenyl) methyl, 2- (2- chlorphenyl) ethyl；R3Selected from H, methyl, allyl, propargyl, cyclopropyl；R2And R3And ring selects From 6- fluoro- 1,2,3,4- tetrahydric quinoline groups, 5- fluoro indole quinoline base.
The synthesis of 4 substituted thiazole amide derivatives IV of target compound of the invention and biological activity determination it is specific Method is divided into following steps:
A. the preparation of intermediate II:
2.67 mMs of starting material I are added in 50 milliliters of single necked round bottom flask, 20 milliliters of acetone are added, to reactant 2.94 mMs of silver oxides and 5.34 mMs of R are added in system1I or R1Br, the condition of being protected from light are stirred overnight at room temperature, and after the reaction was completed, take out Filter, filtrate concentration, is removed under reduced pressure solvent, residue purifies to obtain intermediate II through 200~300 mesh silica gel column chromatographies, and eluant, eluent is Ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 25, with gained sterling calculated yield, yield 66%-75%.Intermediate The amount of II preparation and the volume of reaction vessel are expanded or shunk by corresponding proportion.The chemical structure and physical and chemical parameter of intermediate II are shown in Table 1.
B. the preparation of intermediate III:
1.88 mMs of intermediate IIs are placed in 50 milliliters of round-bottomed flasks, 4 milliliters 2 moles every liter of potassium hydroxide is added Methanol solution, be heated to reflux 2 hours, after the reaction was completed, be cooled to room temperature, reaction solution is concentrated, a small amount of water is added in residue, PH to 3~4 is adjusted with 2 moles every liter of hydrochloric acid solution, there is solid precipitation, is filtered, solid is dry, intermediate III is obtained, with gained Sterling calculated yield, yield 81-90%, the amount of intermediate III preparation and the volume of reaction vessel are expanded or are contracted by corresponding proportion It is small.The chemical structure and physical and chemical parameter of intermediate III are shown in Table 1.
C.4 the preparation of position substituted thiazole amide derivatives IV:
Work as R1For methyl, R3When for H, 4 substituted thiazole amide derivatives IV-1's the preparation method is as follows:
It takes 0.33 mM of intermediate III in reaction flask, 4 milliliters of methylene chloride dissolutions is added, add 0.66 mmoles 0.36 mM of 1H- benzotriazole -1- base oxygen tripyrrole is added in that n,N-diisopropylethylamine (DIPEA) under condition of ice bath 0.36 mM of R is added after stirring 15min in alkyl hexafluorophosphate (PyBOP)2NH2, it is stirred overnight at room temperature, after fully reacting, 10 milliliters of methylene chloride dilutions are added to reaction system, then successively wash one time with saturated sodium bicarbonate and saturated sodium-chloride, nothing Aqueous sodium persulfate is dry, filters, concentration, and solvent is removed under reduced pressure, and residue purifies to obtain 4 substitutions through 200~300 mesh silica gel column chromatographies Thiazole amide derivatives IV-1, eluant, eluent are ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 25~1: 15, with gained Sterling calculated yield, yield 60%-98%.The volume of amount and reaction vessel prepared by 4 substituted thiazole amide derivatives IV-1 It is expanded or shunk by corresponding proportion.The chemical structure and physical and chemical parameter of 4 substituted thiazole amide derivatives IV-1 is shown in Table 1.
Work as R1For H, R3When for H, 4 substituted thiazole amide derivatives IV-2's the preparation method is as follows:
It takes 0.27 mM of 4 substituted thiazole amide derivatives IV-1 in 50 milliliters of two mouthfuls of round-bottomed flasks, vacuumizes, nitrogen Gas shielded is added 3 milliliters of dry methylene chloride dissolutions, 3 milliliters 1 mole every liter of boron chloride is slowly added under condition of ice bath Dichloromethane solution, stir 2 hours, after fully reacting, be added 3 milliliters of saturated sodium bicarbonate solution quenching reactions, adjust anti- Answer liquid pH to neutrality, organic layer has solid precipitation, filters, and obtaining solid is 4 substituted thiazole amide derivatives IV-2, and ethyl alcohol is tied again It is brilliant to obtain sterling, yield 84-98%.The volume of amount and reaction vessel prepared by 4 substituted thiazole amide derivatives IV-2 is by corresponding Ratio is expanded or shunk.The chemical structure and physical and chemical parameter of 4 substituted thiazole amide derivatives IV-2 is shown in Table 1.
D. the bactericidal activity measurement of 4 substituted thiazole amide derivatives IV of the invention:
The sterilization of 4 substituted thiazole amide derivatives IV of the invention or bacteriostatic activity use thalli growth rate measuring method, Specific steps are as follows: take 1.8 milligrams of samples to be dissolved in appropriate dimethylformamide, then use and contain a certain amount of polysorbas20 emulsifier Aqueous solution is diluted to the medicament of 500 mcg/mls, and reagent agent is aseptically respectively drawn in 1 milliliter of injection culture dish, It is separately added into 9 milliliters of PDA culture mediums again, 50 mcg/ml drug containing tablets are made after shaking up, to add the flat of 1 milliliter of aqua sterilisa Plate does blank control, cuts bacterium disk along mycelia outer rim with 4 millimeters of diameter of punch, moves in drug containing tablet, is in equilateral triangle Shape is put, and every processing is repeated 3 times, and culture dish is placed on culture in 24 ± 1 degrees Celsius of constant incubators, colony diameter to be compareed expands Each processing bacterium disk extension diameter is investigated after opening up 2-3 centimetres, is averaged, and opposite bacteriostasis rate is calculated compared with blank control, is supplied Examination strain is the kind for most of typical plant pathogen that field actually occurs in China's agricultural production, and code name and title are such as Under: A.s: tomato early blight bacterium, latin name are as follows: Alternaria solani；B.c: botrytis cinerea pers, latin name are as follows: Botrytis cinerea；C.a: peanut Cercospora bacteria, latin name are as follows: Cercospora arachidicola；G.z: wheat Gibberellic hypha, latin name are as follows: Gibberella zeae；P.i: phytophthora infestans, latin name are as follows: Phytophthora infestans(Mont.)de Bary；P.p: Botryosphaeria berengeriana f. sp, latin name are as follows: Physalospora piricola；P.s: Rhizoctonia solani Kuhn, latin name are as follows: Pellicularia sasakii；R.c: Rhizoctonia cerealis is drawn Fourth name are as follows: Rhizoctonia cerealis；S.s: Sclerotinia sclerotiorum, latin name are as follows: Sclerotinia sclerotiorum。
The beneficial effects of the present invention are: having carried out guide's optimization to 4 substituted thiazole amide derivatives IV, and to synthesis Noval chemical compound has carried out the screening of bacteriostatic activity.
The present invention passes through specific preparation and 4 substituted thiazole amide derivatives of the more specific explanation of biological activity determination embodiment The synthesis of object IV and bioactivity and application, the embodiment, which is only used for illustrating the present invention, to be not intended to limit the present invention, especially It is that bioactivity is merely illustrative of, rather than limits this patent, specific embodiment is as follows:
Embodiment 1: the preparation of intermediate II -1:
2.67 mMs of intermediate compound Is are added in 50 milliliters of single necked round bottom flask, 20 milliliters of acetone are added, to reaction system 2.94 mMs of silver oxides and 5.34 mMs of iodomethane are added, the condition of being protected from light is stirred overnight at room temperature, after the reaction was completed, filters, Filtrate concentration, is removed under reduced pressure solvent, residue purifies to obtain intermediate II through 200~300 mesh silica gel column chromatographies, and eluant, eluent is acetic acid Ethyl ester: 60~90 degrees Celsius of fraction petroleum ether=1: 25, with gained sterling calculated yield, yield 75%.Nuclear magnetic data is as follows:1H NMR (400MHz, CDCl3) δ 4.21 (q, J=7.0Hz, 2H), 4.05 (s, 3H), 2.55 (s, 3H), 1.25 (t, J=7.0Hz, 3H)；13C NMR (101MHz, CDCl3) δ 167.66,165.43,161.38,99.93,60.64,58.12,20.08,14.38.
Embodiment 2: the preparation of intermediate III -1:
1.88 mMs of intermediate IIs -1 are placed in 50 milliliters of round-bottomed flasks, 4 milliliters 2 moles every liter of hydroxide is added The methanol solution of potassium is heated to reflux 2 hours, after the reaction was completed, is cooled to room temperature, reaction solution is concentrated, and residue is added a small amount of Water adjusts pH to 3~4 with 2 moles every liter of hydrochloric acid solution, there is solid precipitation, filters, and solid is dry, obtains intermediate III -1, With gained sterling calculated yield, yield 81%.Nuclear magnetic data is as follows:1H NMR (400MHz, DMSO) δ 3.97 (s, 3H), 2.59 (s, 3H)；13C NMR (101MHz, DMSO) δ 167.97,164.03,161.86,100.23,57.65,19.73.
Embodiment 3: work as R1For methyl, R3When for H, the preparation of compound Gxf05-51:
It takes 0.33 mM of intermediate III -1 in reaction flask, 4 milliliters of methylene chloride dissolutions is added, add 0.66 milli 0.36 mM of three pyrrole of 1H- benzotriazole -1- base oxygen is added in mole n,N-diisopropylethylamine (DIPEA) under condition of ice bath It coughs up alkyl hexafluorophosphate (PyBOP), 0.36 mM of 4- trifluoro-methoxyaniline is added after stirring 15min, was stirred at room temperature After fully reacting, 10 milliliters of methylene chloride dilutions are added to reaction system, then successively with saturated sodium bicarbonate and saturation chlorine in night Change sodium to wash one time, anhydrous sodium sulfate is dry, filters, and solvent is removed under reduced pressure, and residue is through 200~300 mesh silica gel column chromatographies in concentration Compound Gxf05-51 is purified to obtain, eluant, eluent is ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 25, with gained sterling Calculated yield, yield 74%.Nuclear magnetic data is as follows:1H NMR (400MHz, CDCl3) δ 8.82 (s, 1H), 7.62 (d, J= 9.0Hz, 2H), 7.19 (d, J=8.4Hz, 2H), 4.23 (s, 3H), 2.66 (s, 3H)；13C NMR (101MHz, CDCl3) δ 167.71,160.04,159.10,145.09,136.65,121.79,120.95,107.61,58.60,20.28.
Embodiment 4: work as R1For H, R3When for H, compound Gxf05-53's the preparation method is as follows:
It takes 0.27 mM of compound Gxf05-51 in 50 milliliters of two mouthfuls of round-bottomed flasks, vacuumizes, nitrogen protection, be added 3 milliliters of dry methylene chloride dissolve, and the methylene chloride of 3 milliliters 1 mole every liter of boron chloride is slowly added under condition of ice bath Solution stirs 2 hours, and after fully reacting, 3 milliliters of saturated sodium bicarbonate solution quenching reactions are added, and adjusts reaction solution pH into Property, organic layer has solid precipitation, filters, and obtaining solid is compound Gxf05-53, and ethyl alcohol recrystallization obtains sterling, yield 84%.Core Magnetic data is as follows:1H NMR (400MHz, DMSO) δ 9.73 (s, 1H), 7.73 (d, J=9.0Hz, 2H), 7.33 (d, J= 8.6Hz, 2H), 2.63 (s, 3H)；13C NMR (101MHz, DMSO) δ 167.86,162.31,160.44,144.06,138.12, 122.16,121.34,119.34,19.58.
Embodiment 5: 4 substituted thiazole amide derivatives IV Antifungal Activity in Vitro measurement results of the invention:
The code name and title for the frequently seen plants disease fungus that the present invention tests are as follows: A.s: tomato early blight bacterium, Latin Name are as follows: Alternaria solani；B.c: botrytis cinerea pers, latin name are as follows: Botrytis cinerea；C.a: peanut Brown patch germ, latin name are as follows: Cercospora arachidicola；G.z: fusarium graminearum, latin name are as follows: Gibberella zeae；P.i: phytophthora infestans, latin name are as follows: Phytophthora infestans (Mont.) de Bary；P.p: Botryosphaeria berengeriana f. sp, latin name are as follows: Physalospora piricola；P.s: Rhizoctonia solani Kuhn is drawn Fourth name are as follows: Pellicularia sasakii；R.c: Rhizoctonia cerealis, latin name are as follows: Rhizoctonia cerealis； S.s: Sclerotinia sclerotiorum, latin name are as follows: Sclerotinia sclerotiorum.These strains have to be represented well Property, the kind for most of pathogen that field occurs in agricultural production can be represented.Thalli growth rate measurement result is shown in Table 2, table 2 Show in 50 mcg/ml, most of 4 substituted thiazole amide derivatives IV that the present invention synthesizes have different degrees of Bactericidal activity.
For the late blight of potato, the inhibitory activity of compound Gxf05-63, Gxf05-84 and Gxf05-102 exist 35% or more, activity is higher by lead compound thifluzamide (inhibiting rate to the late blight of potato is 23%) and fluxapyroxad (inhibiting rate to the late blight of potato is 0%) is 10% or more.Compound is shown to the Activity Results of peanut Cercospora asparagagas For the inhibitory activity of Gxf05-59, Gxf05-82 and Gxf05-84 50% or more, activity is higher by lead compound thifluzamide (being 20% to the inhibiting rate of the cercospora brown spot of peanut) 10% or more, wherein compound Gxf05-59 to the activity of the cercospora brown spot of peanut most Height is 88%.Active testing to tomato early blight bacterium the result shows that, compound Gxf05-59, Gxf05-82 and Gxf05-84 Inhibitory activity 50% or more, activity is higher by lead compound fluxapyroxad, and (inhibiting rate to early blight of tomato is 38%) 10% or more, wherein the active highest of compound Gxf05-84, is 88%, with lead compound thifluzamide (to kind The inhibiting rate of eggplant early blight is 89%) close.To the active testing of Botryosphaeria berengeriana f. sp show compound Gxf05-69, For the bacteriostatic activity of Gxf05-70, Gxf05-73 and Gxf05-84 40% or more, it is (right that activity is higher by lead compound thifluzamide 28%) and fluxapyroxad the inhibiting rate of ring rot of apple is (inhibiting rate to ring rot of apple is 38%).To rape sclerotium The active testing of germ shows compound Gxf05-51, Gxf05-53, Gxf05-59, Gxf05-60, Gxf05-63, Gxf05- 66-1、Gxf05-69、Gxf05-70、Gxf05-80、Gxf05-86、Gxf05-87、Gxf05-93、Gxf05-96、Gxf05-97、 For the bacteriostatic activity of Gxf05-100, Gxf05-102 and Gxf05-104 80% or more, activity is higher by lead compound thifluzamide (being 79% to the inhibiting rate of sclerotinia sclerotiorum), wherein compound Gxf05-51, Gxf05-59, Gxf05-60, Gxf05-63, The suppression of Gxf05-69, Gxf05-80, Gxf05-86, Gxf05-87, Gxf05-93, Gxf05-96, Gxf05-97 and Gxf05-104 Bacterium activity is 90% or more.To the active testing of Rhizoctonia cerealis show compound Gxf05-59, Gxf05-60, Gxf05-69, 80% or more, activity is higher than the bacteriostatic activity of Gxf05-70, Gxf05-74, Gxf05-91, Gxf05-102 and Gxf05-104 Lead compound thifluzamide (inhibiting rate to Rhizoctonia cerealis is 77%) and the fluxapyroxad (inhibition to Rhizoctonia cerealis Rate is 33%) wherein compound Gxf05-60, Gxf05-69, Gxf05-74, Gxf05-91, Gxf05-102 and Gxf05-104 Bacteriostatic activity 90% or more.In summary, compound Gxf05-59 and Gxf05-84 has the bactericidal activity of wide spectrum, this hair The majority of compounds of bright synthesis has preferable inhibitory activity to Rhizoctonia cerealis, sclerotinia sclerotiorum and botrytis cinerea.
The present invention has further carried out accurate poison to dish sclerotiniose, Rhizoctonia cerealis and botrytis cinerea to reactive compound Power measurement result (EC50/ mcg/ml), as shown in table 3, for Rhizoctonia cerealis, compound Gxf05-53, Gxf05-59, Gxf05-60, Gxf05-69, Gxf05-70, Gxf05-88, Gxf05-91, Gxf05-102 and Gxf05-104 are to its EC50Value is equal In 20 mcg/mls hereinafter, activity is above control compound thifluzamide (EC50:22.12 mcg/ml), especially change Object Gxf05-59, Gxf05-69, Gxf05-102 and Gxf05-104 are closed, to the EC of Rhizoctonia cerealis50Value respectively 5.04, 6.16,4.72 and 1.23 mcg/ml, compound Gxf05-104 are the 1/25 of comparison medicament thifluzamide.To sclerotinia sclerotiorum For, compound Gxf05-51, Gxf05-59, Gxf05-69, Gxf05-70, Gxf05-86, Gxf05-96 and Gxf05-104 couple Its EC50Value is in 3 mcg/mls hereinafter, activity is above control compound thifluzamide (EC50: 4.35 mcg/mls), The EC of middle compound Gxf05-51 and Gxf05-6950Value is respectively 0.51 and 0.64 mcg/ml, is comparison medicament thifluzamide 1/80.For botrytis cinerea pers, compound Gxf05-60, Gxf05-73, Gxf05-74 and Gxf05-93 are to its EC50Value The mcg/ml of respectively 12.75,11.27,11.27 and 13.08 is comparison medicament thifluzamide (EC50: 10.42 micrograms/milli Rise) it is close.Therefore, the present invention designs difference of the new 4 substituted thiazole amide derivatives IV of synthesis due to introducing substituent group, mesh The bactericidal activity of compound is marked compared with lead compound, has obtained significant raising, this is that the invention is different from Has the place of invention.
Embodiment 6: 4 substituted thiazole amide derivatives IV of the invention and agriculturally acceptable auxiliary agent and following one kind Or a variety of commodity insecticide compositions are preparing the purposes in compounded pesticides:
The commodity insecticide is selected from: chlopyrifos, Asia Nong, Acetamiprid, emamectin benzoate, milbemectin, AVM hereinafter Rhzomorph, pleocidin, fenvalerate, esfenvalerate, cypermethrin, effective cypermethrin, Cyhalothrin, bromine cyanogen chrysanthemum Ester, Fenpropathrin, Beta- cyfloxylate, cyfloxylate, Lambda- Cyhalothrin, permethrin, benzyl chloride Pyrethroids, allethrin, cyhalothrin, Biphenthrin, Permethrin, ethofenprox, flumethrin, fluvalinate, pyrrole worm Quinoline, Nitenpyram, imidaclothiz, thiacloprid, Diacloden, clothianidin, dinotefuran, clothianadin, Da Tenan, diflubenzuron, goes out at Acetamiprid Young urea, Teflubenzuron, deinsectization be grand, flubenzuron, flufenoxuron, pyridine worm are grand, lufenuron, poisonous insect urea, penfluron, Noviflumuron are more Fluorine urea, CAS 121451-02-3, flucycloxuron, Novaluron, that is, Rimon, chlorfluazuron, Bay sir 6874 are { 1- [(chloro- 4) 4-nitrophenoxy phenyl 3-3- (2- the chlorobenzene)-urea of 3.5- bis- }, Bay SIR-8514 be [1- (4- trifluoromethoxy Phenyl) -3- (2- chlorobenzene)-urea], piperazine worm urea, Bistrifluron, that is, bistrifluron, furan tebufenozide, tebufenozide, chlorine worm acyl Hydrazine, methoxyfenozide, ring tebufenozide, Rogor, flolimat, DDVP, orthene, Hostathion, quinalphos, pyridazine sulphur Phosphorus, isazofos, isoprocarb, sevin, Aphox, MTMC, Mobucin, cartap, Bassa, leaf disperse, carbaryl, rosickyite Carbofuran, carbosulfan, cartap, fenisobromolate, Hexythiazox, fenpyroximate, pyridaben, clofentezine, propargite, diafenthiuron, third Carbosulfan, pymetrozine, Envidor, spiral shell worm ester, spiral shell worm ethyl ester, butene-fipronil, azacyclotin, Buprofezin, phonamiphos, fluorine worm Nitrile, Cupric sulfate, dimehypo, chlorantraniliprole, Flubendiamide, fluorine cyanogen insect amide, cyanogen insect amide, Tolfenpyrad, tebufenpyrad, bromine worm Nitrile, pyrazinones, etoxazole, tebufenpyrad, rattle away young ketone, Nylar, emaricin；4 substituted thiazole amide derivatives of the invention Total mass percentage of the IV in gained compounded pesticides is 1%-90%, 4 substituted thiazole amide derivatives of the invention The ratio of object IV and the commodity insecticide is mass percent 1%: 99% to 99%: 1%；What the compounded pesticides were applicable in Dosage form is selected from seed treatment emulsion, aqueous emulsion, big granula, microemulsion, suspoemulsion, water-soluble granule, soluble thick agent, water dispersion Property granula, poison grain, aerosol, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, micro-capsule suspension, Waterless Seed Dressing pulvis, cream Oil, electrostatic spray agent, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, smoke candle, smoke cartridge, smog stick, at seed Manage suspending agent, smog piece, smog ball, granular poison bait, foaming agent, drift pulvis, ointment, thermal fog, solid-liquid mixing dress agent, liquid/ Gu the agent of liquid mixing dress, harl agent, solid/mixing dress agent, medicine paint, fine granule, oil suspending agent, oil-dispersing property pulvis, sheet poison bait, dense glue Agent sprinkles and pours agent, seed coat agent, liniment, fritter poison bait, suspended emulsion, film forming finish, soluble powder, seed treatment water solubility Pulvis, ultra-low volume suspending agent, tracking pulvis, ultra low volume liquids, steam releasing agent, appointing in wet-mixing kind water-dispersible powder It anticipates one kind；The applicable plant of the compounded pesticides be selected from paddy, wheat, barley, oat, corn, sorghum, sweet potato, potato, It is cassava, soybean, garden pea, semen viciae fabae, pea, mung bean, red bean, cotton, silkworm and mulberry, peanut, rape, sesame, sunflower, beet, sweet Sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal hemp, tobacco, tomato, capsicum, radish, cucumber, Chinese cabbage, celery Dish, hot pickled mustard tuber, beet, rape, green onion, garlic, watermelon, muskmelon, "Hami" melon, pawpaw, apple, citrus, peach, tea, wild vegetables, bamboo Bamboo shoot, hops, pepper, banana, papaya, orchid, potted landscape；The insect pest of the compounded pesticides prevention and treatment is selected from Asiatic migrotory locust, cloud Spot vehicle locust, Chinese rice grasshopper, Patanga japonica (l.Bol.), single thorn mole cricket, Oriental burmeister, rice thrips, onion thrips, greenhouse thrips, haplothrips aculeatus, Mai Jian pipe thrips, Trialeurodes vaporariorum Westwood, Bemisia tabaci, rice green leafhopper, green leaf hopper, chlorita biguttula, spot clothing plant hopper, brown paddy plant hopper, white backward flight The flat angle plant hopper of lice, small brown rice planthopper, sugarcane, cotten aphid, green bugs, grain aphid, black peach aphid, kaoliang aphid, radish aphid, icerya purchasi, mulberry shield A red-spotted lizard, unaspis shield kuwana, san jose scale, wax insect, ceroplastes rubens, Didesmococcus koreanus Borchs, pear lace bug, banana lace bug, thin corner piece stinkbug, small flower Stinkbug, slender rice bug, paddy fly, niphe elongata, scotinophora lurida, green rice bug, green plant bug, alfalfa plant bug, black striped plant bug, chrysopa septempunctata, beautiful grass Sandfly, Chinese green lacewing, rain moth, casemaking clothes moth, oriental moth, brown slug moth, thosea siensis, gelechiid, pink bollworm, brachmia triannuella, diamondback moth, peach are small Heart-eating worm, eating-core bean worm, small heart-eating peach worm, apple Spilonota lechriaspis, brown belt length leaf roller, Adoxophyes cyrtosema, striped rice borer, Bean-pod borer, corn borer, yellow rice borer, Oeobia undalis, rice leaf roller, snout moth's larva, Notarchaderogata, dichocrocis punctiferalis, mythimna separata, prodenia litura, rice Corn earworm, anomis flava, beet armyworm, pink rice borer, bollworm, ancient cooking vessel point spark, black cutworm, big cutworm, yellow cutworm, robber Poison moth, gypsymoth, palaearctic sweet potato, greenish brown hawk moth, straight grain rice hesperiidae, pelopidas mathias, Papilio xuthus, Common Mormon, cabbage butterfly, ramie Numb red admiral, a ramie Huang a kind of butterfly harmful to crop plants, beans blister beetle, Venus ground beetle, wrinkle sheath ground beetle, wheat head ground beetle, pleonomus canaliculatus, Agriotes subrittatus Motschulsky, paddy The small buprestid beetle of spot khapra beetle, attagenus piceus, citrus, golden edge buprestid beetle, yellow meal worm, dark mealworm, red flour beetle, confused flour beetle, verdigris are different It is rutelian, H. parallela, holotrichia oblita, mulberry borer, longicorn beetle, nadezhdiella cantori, pink neck longicorn, big daikon leaf beetle, small Daikon leaf beetle, aulacophora femoralis, phyllotreta striolata, Callosobruchus chinensis, pea weevil, broad bean weevil, sitophilus zea-mais, rice weevil, dolerus tritici, pear fruit sawfly, Huang Band ichneumon wasp, mythimna separata white star ichneumon wasp, corn earworm hang cocoon ichneumon wasp, Campoletis chlorideae, snout moth's larva stain wart ichneumon wasp, mosquito, fly, horsefly, Mai Hong and inhale Starch worm, contarinia tritici, pachydiplosis oryzae, citrus fruit fly, melonfly, wheat leaf ash latent fly, Americal rice leaf miner, Soybean stem borer, wheat Stem maggot, Hylemyia Platura Meigen, onion fly, radish fly, full skirt Exorista civilis, corn borer are strict to post fly, mythimna separata.
Embodiment 7: 4 substituted thiazole amide derivatives IV of the invention and agriculturally acceptable auxiliary agent and following Any one or more combination in commodity fungicide is preparing the purposes in composite bactericide:
The commodity fungicide is selected from diazosulfide, tiadinil, first thiophene and lures amine, 4- methyl-1,2,3- thiadiazoles -5- Formic acid, 4- methyl-1,2,3- thiadiazoles -5- sodium formates, 4- methyl-1,2,3- thiadiazoles -5- Ethyl formates, bromomethyl -1 4-, 2,3- thiadiazoles -5- Ethyl formates, 4- iodomethyl -1,2,3- thiadiazoles -5- Ethyl formate, 4- bromomethyl -5- methyl-1,2,3- Thiadiazoles, 4- iodomethyl -5- methyl-1,2,3- thiadiazoles, 4,4- dibromo methyl-1,2,3- thiadiazoles -5- Ethyl formates, 3,4- Two chloroisothiazole -5- formic acid, 3,4-, bis- chloroisothiazole -5- sodium formate, 3,4-, bis- chloroisothiazole -5- Ethyl formate, DL- beta-amino Butyric acid, isotianil, virazole, antofine, Ningnanmycin, first thiophene lure amine, salicylic acid, cytosintetidemycin, dichloro-isonicotinic acid, allyl Isothiazole, cymoxanil, thiram, ziram, Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pine, procymidone, Fenpropidin, thiophanate methyl, thiophanate, Metalaxyl-M, salicylic acid, flumorph, dimethomorph, mefenoxam, efficient benzene frost Spirit, double chlorine zarilamid, flusulfamide, first flusulfamide, thiophene fluorine bacterium amine, flutolanil, tecloftalam, ring propionyl bacterium amine, cyflufenamid, ring acyl Bacterium amine, zarilamid, Silthiopham, furametpyr, pyrrole metsulfovax, mandipropamid, zoxamide, fenfuram, carboxin, second Bacterium benefit, iprodione, Fluoxastrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, SSF 126, orysastrobin, ZEN 90160, azoles bacterium amine Ester, trifloxystrobin, Enestroburin, alkene oxime amine, oxygen ring azoles, bromuconazole, Cyproconazole, difenoconazole, olefin conversion, efficient alkene azoles Alcohol, epoxiconazole, benzoxazole, Fluquinconazole, Flusilazole, Flutriafol, hexaconazole, glyoxalin, kind bacterium azoles, metconazole, nitrile bacterium azoles, penta bacterium Azoles, propiconazole, prothioconazoles, simeconazoles, Tebuconazole, tetraconazole, Triadimenol, triticonazole, bitertanol, probenazole, wheat Fringe is peaceful, imazalil, efficient imazalil, Prochloraz, fluorine bacterium azoles, cyazofamid, Fenamidone, dislike imidazoles, pefurazoate, Famoxate, Oxazole, hymexazol, Wakil, Guardian, Grandox fumigant, octhilinone, benthiozole, dodemorph, butadiene morpholine, ten Morpholine, fenpiclonil, fludioxonil, fluazinam, pyrifenox, ring pyridine bacterium amine, Boscalid, fluopicolide, pyridine bacterium amine, phonetic collarium Amine, fluorine mepanipyrim, ferimzone, mepanipyrim, pyrimethanil, Fenarimol, nuarimol, chinomethionat, dithianon, ethoxyquin Quinoline, oxyquinoline, the third oxygen quinoline, quinoxyfen, diethofencarb, iprovalicarb, benzene metsulfovax, Propamocarb, methasulfocarb, edifenphos, Different rice blast net, pyrazophos, tolelofos-methyl, blasticidin-S, kasugarnycin, polyoxin, Polyoxin, valida, well ridge are mould Element, streptomysin, metalaxyl, furalaxyl, M 9834, ofurace, mebenil, carbendazim, benomyl, thiophanate-methyl, triazolone, Bupirimate, dimethirimol, ethirimol, difoltan, captan, folpet, vinclozolin, fluoromide, sclerotium Only, Isoprothiolane, kitazine, Yekuzuo, pentachloronitrobenzene, Mancozeb, Propineb, phosethyl-Al, sulphur, Bordeaux mixture, Copper sulphate, copper oxychloride, cuprous oxide, Kocide SD, metrafenone, Pencycuron, diclomezin, Rabcide, pyroquilon, loop coil bacterium Amine, tricyclazole, triforine, more fruit pyridines, the pungent salt of biguanides, iminoctadine, botran, benzene flusulfamide, toluene flusulfamide, K-281, Fenaminosulf, oxolinic acide, probenazole, bronopol, iodomethane, metham-sodium, enemy line ester, dazomet, nemamort, lythidathion, Cadusafos, fensulfothion, thionazin, fenamiphos, phonamiphos, dichlofenthion, isazofos, fosthietan, oxamyl, Aldicarb, grams hundred Prestige, vikane, dichloropropylene, dichloro-isonicotinic acid, allyl isothiazole；4 substituted thiazole amide derivatives IV of the invention are in institute Total mass percentage in composite bactericide is 1%-90%, 4 substituted thiazole amide derivatives IV of the invention with The ratio of the commodity fungicide is mass percent 1%: 99% to 99%: 1%；The applicable dosage form choosing of the composite bactericide From any one in following dosage forms: wettable powder, micro-capsule suspension, dispersible body preparation, dispersible solid preparation, Seed treatment emulsion, aqueous emulsion, big granula, microemulsion, oil-suspending agent, seed, water-soluble granule, solubility with coated pesticidal Dense dose, water-dispersible granules, poison grain, aerosol, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, Waterless Seed Dressing pulvis, cream Oil, electrostatic spray agent, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, smoke candle, smoke cartridge, smog stick, at seed Manage suspending agent, smog piece, smog ball, granular poison bait, foaming agent, drift pulvis, ointment, thermal fog, solid-liquid mixing dress agent, liquid/ Gu the agent of liquid mixing dress, harl agent, solid/mixing dress agent, medicine paint, seed treatment liquor, fine granule, oil-dispersing property pulvis, sheet poison Bait, dense jelly sprinkle and pour agent, liniment, suspended emulsion, film forming finish, soluble powder, seed treatment water solube powder, ultralow Capacity suspending agent, tracking pulvis, ultra low volume liquids, steam releasing agent, wet-mixing kind water-dispersible powder；The composite bactericide Applicable plant is selected from paddy, wheat, barley, oat, corn, sorghum, sweet potato, potato, cassava, soybean, garden pea, silkworm Beans, pea, mung bean, red bean, cotton, silkworm and mulberry, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, shellfish Mother, rubber, coconut, oil palm, sisal hemp, tobacco, tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tuber, beet, rape, green onion, Garlic, watermelon, muskmelon, "Hami" melon, pawpaw, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, kind Pawpaw, orchid, potted landscape；The applicable controlling disease of the composite bactericide is selected from: wheat rust, wheat scab, wheat white powder Disease, wheat virus disease, wheat avenge mould leaf blight, the compacted spore leaf spot of wheat, flag smut of wheat, take-all, wheat sharp eyespot, Wheat downy mildew, the late blight of potato, wart of potatoes, potato scab, target, bacterial ring rot o potato, Potato bacterial wilt, blakleg of potato, Potyvirus and viroid disease, bacterial soft rot of potato, dry rot of potato, horse Bell potato verticillium wilt, black scurf of potato, potato bacterial wilt, bacterial ring rot o potato, blakleg of potato, bacterial soft rot of potato, Cotton wilt, cotton verticillium wilt, angular leaf spot of cotton, red leaf blight, cotton seedling blight, cotton samping off, cotton anthracnose, cotton Flower blight, cotton anthracnose, cotton spoting verticillium wilt, rice blast, rice sheath blight disease, water rice brown spot, rice Culm rot, bakanae disease of rice, downymildewofrice, rice green smut, rice leaf sheath rot disease, bacterial blight of rice, rice Bacterial stripe, Characters of Erwinia chrysanthemi pv. zeae, stripe disease, black streaked dwarf virus of rice, rice rice black sclerotium stalk Maize ear rot, the leaf blight of corn, corn southern leaf blight, Helminthosporium carbonum, maize brown spot, maize sheath blight, corn rust, maize head are black Fringe disease, Corn Stalk Rot, corn smut, corn dry rot, maize virus disease and corn stalk rot disease, sclerotinia sclerotiorum, rape Virosis, oilseed rape downy mildew, white rust of colza, root rot, soybean sclerotinia crown rot, grey speck of soybean, soybean Mosaic, It is soy bean cyst roundworm, root-knot nematode, soybean rust, soybean anthracnose, bacterial pustule of soybean, soybean spot blight, big Beans downy mildew, bacterial wilt of peanut, Diplodia gossypina, peanut root rot, the cercospora brown spot of peanut, Peanut Web Blotch Disease, activity of peanuts disease, flower Raw shot hole, tobacco bacterial wilt, wildfire, tobacco hollw stalk, Tobacco Angular Leaf Spot Disease, tobacco black shank, Alternaria alternate, cigarette Careless frog eye, anthracnose of tobacco, black root of tobacco, fusarium tabacinum root rot, Tobacco seedling diseases, tobacco damping-off, tobacco Tattered leaf spot, Powdery Mildew in Tobacco, tobacco southern blight, tobacco black spot, tobacco mosaic disease, cucumber mosaic virus, etch virus of tobacco, Chinese cabbage downy mildew, soft rot of cabbage, Chinese cabbage Tipburn Disease, Chinese cabbage virosis, Cabbage Leaf Spot, Seed detection, Chinese cabbage anthrax Disease, cabbage clubroot, bacterial spot of tomato, tomato late blight, tomato blossom-end rot, tomato powdery mildew, tomato samping off, kind Eggplant fish pelargonium mosaic disease, tomato bacterial speck, tomato yellow leaf curl virus, leaf muld of tomato, tomato virus disease, tomato evening Epidemic disease, tomato samping off and damping-off, tomato deformation fruit, tomato perforation fruit, tomato black ring virus disease, tomato rot stem nematodes Disease, tamato fruit buphthalmos disease, tomato stain root rot, tomato stain root rot, tomato branch spore fruit rot, tomato heartrot, kind Eggplant Rhizopus fruit rot, tomato low temperature obstacle, tomato bolter, tomato physiological leaf curl, tomato samping off, tomato fallen flowers are fallen Fruit disease, tomato bud blight, Tomato soft rot, tomato stem rot, tomato seedling damping-off, tomato sun burn, tomato shot hole, tomato red Powder disease, tomato virus disease, tomato cracked fruit, canker of tomato, tomato navel corruption fruit, tomato sesame pinta bacterium, tomato bacterial spot Select disease, tomato rot leaf viral disease, tomato yellow leaf curl virus disease, eggplant cotton disease, eggplant sclerotiniose, eggplant bacterial wilt, eggplant Phomopisis vexans, eggplant verticillium wilt, eggplant leaf spot, eggplant early blight, eggplant virosis, eggplant leaf spot disease, eggplant leaf mold, eggplant Powdery mildew, eggplant spot disease, eggplant coal spot disease, cercospora leaf spot of egg plant, helminthosporium leaf blight and fruit rot of egg plant, eggplant epidemic disease, eggplant anthracnose, eggplant It is sub- head mold soft rot, wilt of eggplant, grey mould of egg plant, eggplant base rot disease, capsicum green pepper virosis, capsicum early blight, peppery It is green pepper Leucoplakia, pepper white star disease, capsicum leaf spot, capsicum Scald, capsicum sooty mold, capsicum wilt, capsicum sclerotiniose, peppery Green pepper sunscald, pepper virus disease, capsicum malformed fruit, capsicum blossom-end rot, capsicum soft rot, bacterial spot of pepper, capsicum virosis It is spot, capsicum pythium rot, macrosporium leaf spot of red pepper, capsicum spot blight, capsicum black spot, capsicum verticillium wilt, pepper bacterial leaf spot, peppery It is green pepper brown rot, Fusarium solani, capsicum damping-off, pepper anthracnose, capsicum brown spot, capsicum downy mildew, Botrytis cinerea, peppery Green pepper leaf blight, pepper leaf mold, capsicum samping off, capsicum epidemic disease, downy mildew of garpe, uncinula necator, brown spot of grape, grape Leaf curl, Grapevine Fan Leaf Virus Disease, grape rust, grape ring spot, grape leaf spot, the small brown spot of grape, grape zonate spot, grape The golden yellow disease of graywall, grape young sprout wasting disease, grape mosaic disease, grape wasting disease, grape stripe disease, grape, grape infectivity Downright bad disease, grape Huang select disease, grape ear projection disease, grape vein necrosis disease, Grapevine fleck virus disease, the starlike mosaic disease of grape, Portugal Grape Pearls, fruit white rot of grape, bitter rot or anthracnose of grape, grape room blight, grape grey mould, grapevine anthracnose, black rot of grape, The big room blight of grape, grape coal select that disease, grape are brown to select disease, grape mould dirty disease, grape bitter rot, grape branch spore mildew, Portugal Grape penicilliosis, grape Alternaria rot, apple tree canker, dry rot of apple, ring rot of apple, apple branch canker, apple Fruit blister canker, Pink Disease of Apple, apple die back disease, apple branch-rot, apple anthracnose, Apple Mould Core, rust of apple (Gymnosporangium yamadai), Apple blossom rot, apple brown rot, black fruit rot of apple, apple phytophthora rot, Apple Sooty, sick apple marssonina leaf spot, apple spot Defoliation, Glomerella cingulata, apple graywall, apple mildew, scab of apple, silver leaf of apple, apple infectivity root-rot Disease, armillariella root rot of apple, apple Root―rot disease, apple southern blight, apple violet root rot, rosellinia trunk rot of apple, Apple crown gall, apple Decline disease, apple rough skin disease, apple mosaic, apple green wrinkle fruit disease, apple fruit-shrink disease, Apple little leaf, apple chlorosis, apple Fruit bitter pit, apple water core, apple superficial scald, carbuncle apple scab, Gold Delicious apple fruit russeting, green mold of apple, apple are soft The continuous disease of maize ear rot, Apples digested tankage, apple pulp brown stain disease, apple brown heart, pear scab, black rot of pear, Fungus of Pear Canker Disease, pears Southern blight, pear tree wood rot, pears die back disease, rust of pear, Pear black spot, pears graywall, pears brown spot, pears Socty Blotch And Greasy Blotch, pears top rot Disease, pears fruit-shrink disease, pears yellowtop, anthracnose of peach, peach reality maize ear rot, peach fruit rot, peach soft rot, peach canker, peach powdery mildew, The abnormal fruit disease of peach brown rot, peach scab, peach, peach sooty mould, peach leaf-curl, peach fungoid shothole disease, peach are bacillary Shothole disease, peach leaves pinta, peach leaf rust, peach mosaic disease, peach red-leaf disease, peach rot disease, peach gummosis, peach Wood rot, peach die back disease, Peach crown gall, peach root rot, peach root knot nematode disease, Citrus Huanglongbing pathogen, exocortis, The broken leaf disease of citrus, citrus decline, Satsuma dwarf virus, citrus bacterial canker disease, citrus scab, citrus anthracnose, citrus foot Maize ear rot, citrus resin disease, citrus bleeding disease, Citrus fuliginous, citrus powdery mildew, citrus rouge select maculopathy, citrus intends rouge point Huang The red clothing disease of pinta, citrus, citrus felt fungus, citrus seedling blight, citrus seedling epidemic disease, banana bunchy top disease, banana floral leaf centre rot Disease, research of fusarium wilt disesase of banana, Cercospora musae bacterium leaf spot, the banana secretly mould leaf spot of double spores, the mould leaf spot of the small Dou Shi of banana, perfume (or spice) Any of several broadleaf plants scab, Banana Leaf seasonal febrile diseases, banana anthracnose, banana crown rot, wild cabbage bacterial black rot, cottony rot of cabbage, wild cabbage are black The earlier bolting of maize ear rot, black spot of cabbage, wild cabbage brown spot, wild cabbage blastomere disease, wild cabbage virosis, wild cabbage soft rot, wild cabbage is sick, sweet Blue downy mildew, wild cabbage anthracnose, black leg of cabbage, sugarcane pineapple disease, smut of sugarcane, sugarcane ratoon stunting disease, the brown item of sugarcane Disease, sugarcane rust, jowar smut, jowar leaf spot, jowar anthracnose, jowar leaf blight, jowar virosis.
Embodiment 8: 4 substituted thiazole amide derivatives IV of the invention and agriculturally acceptable auxiliary agent and with it is as follows Any one or more combination in commodity activating plants agent is preparing the purposes in compound botanical activator:
The commodity activating plants agent is selected from: diazosulfide, tiadinil, first thiophene lure amine, 4- methyl-1,2,3- thiophenes two Azoles -5- formic acid, 4- methyl-1,2,3- thiadiazoles -5- sodium formates, 4- methyl-1,2,3- thiadiazoles -5- Ethyl formates, 4- bromine first Base -1,2,3- thiadiazoles -5- Ethyl formate, 4- iodomethyl -1,2,3- thiadiazoles -5- Ethyl formate, 4- bromomethyl -5- methyl - 1,2,3- thiadiazoles, 4- iodomethyl -5- methyl-1,2,3- thiadiazoles, 4,4- dibromo methyl-1,2,3- thiadiazoles -5- formic acid second Ester, 3,4-, bis- chloroisothiazole -5- formic acid, 3,4-, bis- chloroisothiazole -5- sodium formate, 3,4-, bis- chloroisothiazole -5- Ethyl formate, DL- beta-aminobutyric acid, virazole, antofine, Ningnanmycin, first thiophene lure amine, salicylic acid, cytosintetidemycin, dichloro-isonicotinic acid, allyl Isothiazole, well ridge azanol, jinggangmeisu；4 substituted thiazole amide derivatives IV of the invention are in gained compound botanical activator In total mass percentage be 1%-90%, 4 substituted thiazole amide derivatives IV of the invention and the commodity plant The ratio of activator is mass percent 1%: 99% to 99%: 1%；The dosage form of the compound botanical activator is selected from wettable It is pulvis, micro-capsule suspension, dispersible body preparation, dispersible solid preparation, seed treatment emulsion, aqueous emulsion, big granula, micro- Emulsion, oil-suspending agent, with the seed of coated pesticidal, water-soluble granule, soluble thick agent, water-dispersible granules, poison grain, aerosol Agent, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, Waterless Seed Dressing pulvis, missible oil, electrostatic spray agent, water-in-oil emulsion, Shui Bao Oil emu, smoke candle, granula subtilis, smoke candle, smoke cartridge, smog stick, seed treatment suspending agent, smog piece, smog ball, granular poison Gu the agent of bait, foaming agent, drift pulvis, ointment, thermal fog, solid-liquid mixing dress, the agent of liquid liquid mixing dress, harl agent, solid/mixing dress Agent, seed treatment liquor, fine granule, oil-dispersing property pulvis, sheet poison bait, dense jelly, sprinkles and pours agent, liniment, suspension cream medicine paint Agent, film forming finish, soluble powder, seed treatment water solube powder, ultra-low volume suspending agent, tracking pulvis, ultra-low volume liquid Agent, steam releasing agent, any one in wet-mixing kind water-dispersible powder；The applicable plant of the compound botanical activator is selected from It is paddy, wheat, barley, oat, corn, sorghum, sweet potato, potato, cassava, soybean, garden pea, semen viciae fabae, pea, mung bean, small Beans, cotton, silkworm and mulberry, peanut, rape, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil Palm fibre, sisal hemp, tobacco, tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tuber, beet, rape, green onion, garlic, watermelon, muskmelon, "Hami" melon, pawpaw, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, potted landscape； The applicable virus disease of the compound botanical activator is selected from rice dwarf virus disease, yellow dwarf, stripe virus disease, fern leaf of tomato poison Disease, tobacco veinal necrosis virus disease, maize dwarf mosaic, cauliflower mosaic virus, citrus virosis, is built at pepper mosaic virus disease viral disease Any one of clover mosaic virus, cybidium ring spot virus.
Embodiment 9: 4 substituted thiazole amide derivatives IV of the invention and agriculturally acceptable auxiliary agent and with it is as follows Any one or more combination in commodity acaricide is preparing Compositional acaricide and its purposes in prevention and treatment plant mites evil:
The commodity acaricide is selected from azacyclotin, plictran, fenbutatin oxide, three phosphor tins, chlorfenviphos, dimethylvinphos, bar poison Phosphorus, DDVP, heptenophos, Menite, Azodrin, 2-dichloroethylk dimethyl phosphate, chlopyrifos, Diothyl, imino-formyl chloride sulphur phosphorus, omethoate, enemy kill Phosphorus, Ethodan, malathion, methacrifos, Phosalone, phoxim, methylpyrimidine sulphur phosphorus, quinalphos, sulfotep, Hostathion, Kilval, isocarbophos, acephatemet, propetamphos, dialifos, phosmet, acrinathrin, Biphenthrin, chlorine fluorine cyanogen chrysanthemum Ester, smart gamma cyhalothrin, Fenpropathrin, flucythrinate, flumethrin, taufluvalinate, brofluthrinate, biphenyl hydrazine Ester, fenothiocarb, Aldicarb, butocarboxim, oxamyl, Talcord, thiofanox, benomyl, sok, carbofuran, fourth sulphur gram hundred Prestige, MTMC, promacyl, Carzol, single carbonamidine, medimeform, Amitraz, Spanon, Ergol, fenisobromolate, fourth fluorine mite Ester, acequinocyl, Nissol, flufenoxuron, macro tetrolide, piericidin, thuringiensin, tetranactin, macro tetrolide, avermectin, Doractin, eprinomectin, ivermectin, selamectin, moxidectin, pyrethrin, nicotine, matrine, nimbin, Rotenone, tebufenpyrad, pyridaben, fenpyroximate, clofentezine, propargite, Hexythiazox, Envidor, fluacrypyrim, chlorfenizon, propargite, Pyridaben；The total quality hundred of 4 substituted thiazole amide derivatives IV of the invention in gained Compositional acaricide in the composition Point content is 1%-90%, and 4 substituted thiazole amide derivatives IV of the invention and the acaricidal ratio of the commodity are quality Percentage 1%: 99% to 99%: 1%；The dosage form of the Compositional acaricide is selected from wettable powder, micro-capsule suspension, can divide Dispersion liquid body preparation, dispersible solid preparation, seed treatment emulsion, aqueous emulsion, big granula, microemulsion, oil-suspending agent, with pesticide packet Seed, water-soluble granule, soluble thick agent, water-dispersible granules, poison grain, aerosol, the blocky poison bait, sustained-release block, dense poison of clothing Bait, CG/Encapsulated granule, Waterless Seed Dressing pulvis, missible oil, electrostatic spray agent, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, cigarette Mist candle, smoke cartridge, smog stick, seed treatment suspending agent, smog piece, smog ball, granular poison bait, foaming agent, drift pulvis, oil Solid cream, thermal fog, solid-liquid mixing dress agent, the agent of liquid liquid mixing dress, harl agent, solid/mixing fill agent, medicine paint, seed treatment liquor, Fine granule, sheet poison bait, dense jelly, sprinkles and pours agent, liniment, suspended emulsion, film forming finish, soluble powder oil-dispersing property pulvis Agent, seed treatment water solube powder, ultra-low volume suspending agent, tracking pulvis, ultra low volume liquids, steam releasing agent, wet-mixing kind Any one in water-dispersible powder；The applicable plant of the Compositional acaricide is selected from paddy, wheat, barley, oat, jade Rice, jowar, sweet potato, potato, cassava, soybean, garden pea, semen viciae fabae, pea, mung bean, red bean, cotton, silkworm and mulberry, peanut, rape, Sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal hemp, tobacco, tomato, capsicum, Radish, cucumber, Chinese cabbage, celery, hot pickled mustard tuber, beet, rape, green onion, garlic, watermelon, muskmelon, "Hami" melon, pawpaw, apple, citrus, peach Tree, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, potted landscape；The applicable mite evil of the Compositional acaricide Selected from Tetranychidae, Tenuipalpidae, furan line mite, Eriophyidae, tetranychus telarius category, Eriophyidae harmful mite, these harmful mites are worldwide agriculturals Harmful mite, forestry harmful mites, gardening harmful mite and hygienic harmful mite.
Embodiment 10: the combination of 4 substituted thiazole amide derivatives IV and pesticide of the invention:
4 substituted thiazole amide derivatives IV and its intermediate are preparing the purposes in agricultural fungicidal agent.It is a kind of agricultural Bactericidal composition, it includes 4 substituted thiazole amide derivatives IV and intermediate can prepare agricultural bactericidal composition, the combination Object includes 4 substituted thiazole amide derivatives IV and its intermediate as active constituent, and the content of active constituent arrives for 0.1 99.9% weight, the surfactant of the solid or liquid adjuvants of 99.9 to 0.1% weight and optional 0 to 25% weight.
A kind of agricultural bactericidal complex composition, it includes 4 substituted thiazole amide derivatives IV and its intermediates and other The bactericide compounded ratio as active constituent, 4 substituted thiazole amide derivatives IV and its intermediate and other fungicide is Mass percent 1%: 99% to 99%: 1%, the content of active constituent are 1 to 99% weight, the solid of 99 to 1% weight or Liquid adjuvants.
A kind of activating plants agent complex composition, it includes 4 substituted thiazole amide derivatives IV and its intermediates and its He is used as active constituent, 4 substituted thiazole amide derivatives IV and its intermediate and other plant to activate at activating plants agent compounding The ratio of agent is mass percent 1%: 99% to 99%: 1%, and the content of active constituent is 1 to 99% weight, 99 to 1% weight The solid or liquid adjuvants of amount.
A kind of agricultural insecticidal, mite killing complex composition, 4 substituted thiazole amide derivatives IV of the invention and its intermediate Active constituent, 4 substituted thiazole amide derivatives IV and its intermediate and its homicide are used as with other Insecticidal and acaricidal agents compounding Worm, acaricidal ratio are mass percent 1%: 99% to 99%: 1%, and the content of active constituent is 1 to 99% weight, 99 To the solid or liquid adjuvants of 1% weight.
Antifungal Activity in Vitro (the suppression of 50 mcg/mls of the substituted thiazole amide derivatives IV of part 4 of the invention of table 2. Rate/% processed)
A.s: tomato early blight bacterium, latin name are as follows: Alternaria solani；B.c: botrytis cinerea pers, Latin Name are as follows: Botrytis cinerea；C.a: peanut Cercospora bacteria, latin name are as follows: Cercospora arachidicola； G.z: fusarium graminearum, latin name are as follows: Gibberella zeae；P.i: phytophthora infestans, latin name are as follows: Phytophthora infestans(Mont.)de Bary；P.p: Botryosphaeria berengeriana f. sp, latin name are as follows: Physalospora piricola；P.s: Rhizoctonia solani Kuhn, latin name are as follows: Pellicularia sasakii；R.c: Rhizoctonia cerealis is drawn Fourth name are as follows: Rhizoctonia cerealis；S.s: Sclerotinia sclerotiorum, latin name are as follows: Sclerotinia sclerotiorum.
The accurate toxicity test result (EC of the substituted thiazole amide derivatives IV of part 4 of the invention of table 3.50Microgram/milli It rises)
Serial number Compound number R.c S.s B.c Serial number Compound number R.c S.s B.c
1 Gxf05-51 > 80 0.51 68.15 18 Gxf05-84 43.51 18.10 43.07
2 Gxf05-53 11.32 6.82 63.42 19 Gxf05-86 30.00 1.05 24.33
3 Gxf05-59 5.04 2.61 59.08 20 Gxf05-87 40.31 4.80 42.36
4 Gxf05-60 7.94 8.33 12.75 21 Gxf05-88 9.83 13.00 128.25
5 Gxf05-63 55.49 14.10 77.46 22 Gxf05-91 16.38 12.28 21.70
6 Gxf05-66-1 68.26 13.95 64.51 23 Gxf05-92 25.80 34.42 > 80
7 Gxf05-68 108.50 19.96 26.71 24 Gxf05-93 30.88 10.99 13.08
8 Gxf05-69 6.16 0.64 42.26 25 Gxf05-96 > 80 1.88 > 80
9 Gxf05-70 13.21 1.30 39.97 26 Gxf05-97 59.40 16.99 35.97
10 Gxf05-72 60.05 > 80 > 80 27 Gxf05-100 29.75 14.69 81.92
11 Gxf05-73 > 80 23.44 11.27 28 Gxf05-101 > 80 > 80 > 80
12 Gxf05-74 27.10 29.01 11.27 29 Gxf05-102 4.72 9.76 33.65
13 Gxf05-76 > 80 16.19 70.09 30 Gxf05-103 81.05 10.56 79.36
14 Gxf05-80 143.54 7.96 39.71 31 Gxf05-104 1.23 2.32 33.65
15 Gxf05-81 49.60 34.97 > 80 32 Thifluzamide 22.12 4.35 10.42
16 Gxf05-82 21.67 33.72 > 80 33 Fluxapyroxad 6.26 Undetermined Undetermined
17 Gxf05-83 97.49 > 80 > 80 34

Claims (8)

1. a kind of 4 substituted thiazole amide derivatives, it is characterised in that: have the general structure as shown in formula IV:
Wherein:
X is selected from oxygen or nitrogen；
R1Selected from H, C1-C6 alkyl, allyl, propargyl, cyclopropyl, 1,2- bis-fluoro ethyls；
R2Selected from E1Substituted C2-C4 alkyl, C3-C6 naphthenic base or by E2Substituted naphthenic base, phenyl or by E2Substituted phenyl, Naphthalene or by E2Substituted naphthalene, tetralyl or by E2Substituted tetralyl, annelated heterocycles or by E2Condensing for replacing is miscellaneous Ring, pyridyl group or by E2Substituted pyridyl group, pyrimidine radicals or by E2Substituted pyrimidine radicals, by E2What is replaced contains 1 or 2 N atoms Five yuan or six membered heteroaryl, containing 1 or 2 S atom by E2Five yuan or the six membered heteroaryl replaced contains 1 or 2 O originals Son by E2Five yuan or the six membered heteroaryl replaced, containing 1 N atom and 1 S atom by E2Five yuan or the hexa-atomic heteroaryl replaced Base, containing 1 N atom and 1 O atom by E2Five yuan or the six membered heteroaryl replaced, containing 2 N atoms and 1 S atom by E2 Five yuan or the six membered heteroaryl replaced, containing 2 N atoms and 1 O atom by E2Five yuan or the six membered heteroaryl replaced；It is above-mentioned Five yuan or six membered heteroaryl are selected from: substituted furyl, thienyl, pyrrole radicals, imidazole radicals, pyrazolyl, thiazolyl, isothiazole Base, oxazolyl, isoxazolyl, oxadiazoles base, thiadiazolyl group, pyridyl group, pyridazinyl, pyrimidine radicals, pyrazinyl, triazine radical, tetrazine Base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazole base, benzothiazolyl, benzo Thiadiazolyl group, benzoxazolyl, the quinolyl of isomerization, the isoquinolyl of isomerization, phthalazinyl, quinoxalinyl, quinazolyl, The silicon substrate that cinnoline base or naphthyridines base, alkyl or alkenyl replace；
E1Selected from phenyl or heterocycle, (wherein phenyl and heterocycle can be by halogen, nitro, cyano, alkyl, halogenated alkyl, haloalkoxies Base, alkoxy, alkylamino radical replace)；
E2Selected from halogen, nitro, cyano, C1-C6 alkyl, C1-C6 halogenated alkyl, C1-C6 halogenated alkoxy, C1-C6 alkoxy, C1-C6 alkylamino radical, C2-C6 alkenyl, C2-C6 halogenated alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, C2-C6 halo alkynyl, C3-C6 (wherein phenyl and heterocycle can be by halogen, nitro, cyano, alkyl, halogenated alkyl, haloalkoxies for cycloalkynyl radical, phenyl or heterocycle One or more of base, alkoxy, alkylamino radical replace)；
R2And R3Ring can be formed together；
R3Selected from H, C1-C6 alkyl, C1-C6 alkoxy, allyl, propargyl, cyclopropyl；
Halogen is fluorine, chlorine, bromine or iodine in above-mentioned definition；
The alkyl, alkenyl or alkynyl are straight chain or branch alkyl；Alkyl itself or as other substituent groups part select From methyl, ethyl, propyl, butyl, amyl, hexyl and its isomers, isomers is selected from isopropyl, isobutyl group, sec-butyl, uncle Butyl, isopentyl or tertiary pentyl, but do not include 1,3- dimethylbutyl；
The halogenated alkyl group is selected from the group containing one or more identical or different halogen atoms, the halogenated alkyl choosing From CH2Cl、CHCl2、CCl3、CH2F、CHF2、CF3、CF3CH2、CH3CF2、CF3CF2Or CCl3CCl2；
Described naphthenic base itself or as other substituent groups part be selected from cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl；
Described alkenyl itself or as other substituent groups part be selected from vinyl, allyl, 1- acrylic, butene-2-base, fourth Alkene -3- base, amylene -1- base, amylene -3- base, hexene -1- base or 4- methyl-3-pentenyl；
Described alkynyl itself or as other substituent groups part be selected from acetenyl, propine -1- base, propine -2- base, butine -1- Base, crotonylene-base, 1- methyl -2- butynyl, hexin -1- base or 1- ethyl -2- butynyl.
2. 4 substituted thiazole amide derivatives IV, R according to claim 11It preferably is selected from H, methyl, allyl, propargyl, ring Propyl, 1,2- bis-fluoro ethyls；R2Selected from 4- Trifluoromethoxyphen-l, the bromo- 4- fluorophenyl of 2-, 2- isopropyl phenyl, 2- naphthane Base, 2- naphthalene, 2- hydroxy phenyl, 2- isopropyl phenyl, 2- (3 ', 4 '-difluorophenyl) phenyl, 2- (4 '-chlorphenyl) phenyl, 2- (3 ', 4 ', 5 '-trifluorophenyl) phenyl, 2- (3 ', 4 '-dichlorophenyl) -4- fluorophenyl, 2- (3 ', 4 ', 5 '-trifluorophenyl) - 4- fluorophenyl, 1- (3- chloropyridine -2- base) methyl, 1- (3- fluorophenyl) methyl, 2- (2- chlorphenyl) ethyl；R3Selected from H, first Base, allyl, propargyl, cyclopropyl；R2And R3And ring is selected from 6- fluoro- 1,2,3,4- tetrahydric quinoline groups, 5- fluoro indole quinoline base.
3. according to claim 1 with the specific route and synthetic method of 4 substituted thiazole amide derivatives IV described in claim 2 It is as follows:
The definition of the substituent group is as described in claim 1, and the definition of preferred substituents is as claimed in claim 2；Specific synthesis Method is divided into following steps:
A. the preparation of intermediate II:
Intermediate II is by starting material I and acetone and silver oxide and R1I or R1Br is stirred overnight at room temperature to react and make in the condition of being protected from light Standby, wherein the definition of the substituent group in starting material is as described in claim 1, the definition of preferred substituents such as claim 2 institute It states；
B. the preparation of intermediate III:
By intermediate II prepared by the heating reflux reaction in the methanol solution of potassium hydroxide for intermediate III, wherein each reaction raw materials As described in claim 1 with the definition of the substituent group in intermediate product, the definition of preferred substituents is as claimed in claim 2.
C.4 the preparation of position substituted thiazole derivative I V:
Work as R1For methyl, R3When for H, 4 substituted thiazole amide derivatives IV-1's the preparation method is as follows:
It takes intermediate III in reaction flask, methylene chloride and n,N-diisopropylethylamine is added, DIPEA is abbreviated as, in ice bath item 1H- benzotriazole -1- base oxygen tripyrrole alkyl hexafluorophosphate, i.e. PyBOP and R are added under part2NH2, reaction system is stirred at room temperature It is standby；
Work as R1For H, R3When for H, 4 substituted thiazole amide derivatives IV-2's the preparation method is as follows:
Take 4 substituted thiazole amide derivatives IV-1 that dry methylene chloride, ice bath are added in a round bottom flask, under nitrogen protection Under the conditions of be slowly added to the dichloromethane solution of boron chloride, be stirred to react and 4 substituted thiazole amide derivatives IV- be prepared 2；
The definition of each intermediate and reactant substituent group is as described in claim 1, the definition of preferred substituents such as claim 2 institute It states.
4. claim 1 and 4 substituted thiazole amide derivatives IV as claimed in claim 2 and its intermediate are preparing agricultural kill Purposes in epiphyte pharmaceutical.
5. a kind of agricultural bactericidal composition, it includes claims 1 and 4 substituted thiazole amide derivatives as claimed in claim 2 Object IV and intermediate can prepare agricultural bactericidal composition, and the composition includes claim 1 and 4 as claimed in claim 2 As active constituent, the content of active constituent is 0.1 to 99.9% weight for substituted thiazole amide derivatives IV and its intermediate, The surfactant of the solid or liquid adjuvants of 99.9 to 0.1% weight and optional 0 to 25% weight.
6. a kind of agricultural bactericidal complex composition, it includes claims 1 and 4 substituted thiazole amides as claimed in claim 2 Derivative I V and its intermediate and other it is bactericide compounded be used as active constituent, 4 substituted thiazole amide derivatives IV and wherein The ratio of mesosome and other fungicide is mass percent 1%: 99% to 99%: 1%, and the content of active constituent is 1 to 99% Weight, the solid or liquid adjuvants of 99 to 1% weight.
7. a kind of agricultural insecticidal, mite killing complex composition, it includes claims 1 and 4 substituted thiazoles as claimed in claim 2 Amide derivatives IV and its intermediate and other Insecticidal and acaricidal agents compounding are used as active constituent, 4 substituted thiazole amide derivatives The ratio of IV and its intermediate and other fungicide is mass percent 1%: 99% to 99%: 1%, and the content of active constituent is 1 to 99% weight, the solid or liquid adjuvants of 99 to 1% weight.
8. a kind of activating plants agent complex composition, it includes claim 1 claims 1 and 4 as claimed in claim 2 to take Active constituent, 4 substituted thiazole amides are used as thiazole amide derivatives IV and its intermediate and other plant activator compounding The ratio of derivative I V and its intermediate and other fungicide is mass percent 1%: 99% to 99%: 1%, active constituent Content is 1 to 99% weight, the solid or liquid adjuvants of 99 to 1% weight.
CN201811412725.6A 2018-11-26 2018-11-26 A kind of 4 substituted thiazole amide derivatives and its preparation method and application Pending CN109422704A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811412725.6A CN109422704A (en) 2018-11-26 2018-11-26 A kind of 4 substituted thiazole amide derivatives and its preparation method and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811412725.6A CN109422704A (en) 2018-11-26 2018-11-26 A kind of 4 substituted thiazole amide derivatives and its preparation method and application

Publications (1)

Publication Number Publication Date
CN109422704A true CN109422704A (en) 2019-03-05

Family

ID=65514799

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811412725.6A Pending CN109422704A (en) 2018-11-26 2018-11-26 A kind of 4 substituted thiazole amide derivatives and its preparation method and application

Country Status (1)

Country Link
CN (1) CN109422704A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109970650A (en) * 2019-05-17 2019-07-05 南开大学 A class of pyrazole phenyl carboxamide derivatives and its preparation method and use
CN110128346A (en) * 2019-05-17 2019-08-16 南开大学 A kind of biarylamide pyrazole derivatives and preparation method and use thereof
CN113788790A (en) * 2021-10-18 2021-12-14 华东理工大学 Aromatic heterocyclic amide derivative and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1646506A (en) * 2002-02-04 2005-07-27 拜尔农作物科学股份公司 Difluoromethyl thiazolyl carboxanilides
CN1871220A (en) * 2003-10-23 2006-11-29 拜尔农作物科学股份公司 1,3-dimethylbutyl carboxanilides for controlling undesirable micro-organisms
CN103159752A (en) * 2011-12-15 2013-06-19 天津都创科技有限公司 Preparation and bactericidal activity of N-pyridyl-substituted thiazole methanamide compounds
CN103450179A (en) * 2013-09-10 2013-12-18 湖南科技大学 N-(1, 3, 4-thiadiazolyl) thiazole carboxamide compounds and application thereof
CN108117529A (en) * 2016-11-30 2018-06-05 湖南化工研究院有限公司 N- phenyl thiazole amides compounds and preparation method and application

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1646506A (en) * 2002-02-04 2005-07-27 拜尔农作物科学股份公司 Difluoromethyl thiazolyl carboxanilides
CN1871220A (en) * 2003-10-23 2006-11-29 拜尔农作物科学股份公司 1,3-dimethylbutyl carboxanilides for controlling undesirable micro-organisms
CN103159752A (en) * 2011-12-15 2013-06-19 天津都创科技有限公司 Preparation and bactericidal activity of N-pyridyl-substituted thiazole methanamide compounds
CN103450179A (en) * 2013-09-10 2013-12-18 湖南科技大学 N-(1, 3, 4-thiadiazolyl) thiazole carboxamide compounds and application thereof
CN108117529A (en) * 2016-11-30 2018-06-05 湖南化工研究院有限公司 N- phenyl thiazole amides compounds and preparation method and application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS SERVICE: ""RN:329057-99-0"", 《DATABASE CA [ONLINE]》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109970650A (en) * 2019-05-17 2019-07-05 南开大学 A class of pyrazole phenyl carboxamide derivatives and its preparation method and use
CN110128346A (en) * 2019-05-17 2019-08-16 南开大学 A kind of biarylamide pyrazole derivatives and preparation method and use thereof
CN113788790A (en) * 2021-10-18 2021-12-14 华东理工大学 Aromatic heterocyclic amide derivative and application thereof

Similar Documents

Publication Publication Date Title
CN109485618A (en) A kind of 2 phenylsubstituted thiazoles derivatives and its preparation method and application
CN103172613A (en) O-formylamino benzamide derivative containing N-cyano sulfone(sulfur) imine and preparation method and use thereof
CN103467463A (en) Lignin derivatives as well as preparation method and use thereof
CN104650062B (en) A kind of nitrogenous heterocyclic thiazole and its production and use
CN104650061B (en) A kind of thiazole aldoxime ether compound and its production and use
CN109970650A (en) A class of pyrazole phenyl carboxamide derivatives and its preparation method and use
CN103172614A (en) O-formylamino benzamide derivative containing sulfone(sulfur) imine and preparation method and use thereof
CN109422704A (en) A kind of 4 substituted thiazole amide derivatives and its preparation method and application
CN102816134B (en) 1,2,3-thiadiazole-containing sulfilimine (sulfonimine) compounds and their preparation method and use
CN103483287A (en) 3,4-dichloroisothiazole containing bisamide compounds as well as preparation method and application thereof
CN105622597A (en) Chloroisothiazole neonicotine compound, as well as preparation method and application thereof
CN104649996A (en) Isothiazole oxime ether derivatives as well as preparation method and application thereof
CN101891710A (en) A class of 4-halomethyl-1,2,3-thiadiazole compounds and their preparation methods and uses
CN105732606A (en) Thiadiazole heterocycle-containing anabasine compound as well as preparation method and application thereof
CN109970653A (en) A class of difluoromethylpyrazole-containing methoxyacrylate derivatives and preparation method and use thereof
CN101891709A (en) A class of 5-halomethyl-1,2,3-thiadiazole compounds and their preparation methods and uses
CN104974150A (en) 3,4-dichloroisothiazolyl-5-formamidine derivatives, and preparation method and application thereof
CN103193769A (en) 4-methyl-1,2,3-thiadiazole-5-triazole compound as well as preparation method and use thereof
CN107226812A (en) One class piperidines thiazole oxime ether methoxy base acrylate derivative and its production and use
CN104650059B (en) A kind of thiazolone oxime ether derivative and its preparation method and application
CN106995417B (en) A kind of isothiazole oxime ether methoxy base acrylate derivative and its preparation method and application
CN113929696B (en) Acyl thiourea psoralen derivatives, and preparation method and application thereof
CN113929695B (en) Sulfimide psoralen derivatives, and preparation method and application thereof
CN103641795A (en) Acetophenone derivatives containing 1,2,3-thiadiazole and preparation method and use thereof
CN101921244A (en) Derivatives of 4-methyl-1,2,3-thiadiazole containing 4-(1,1,2,2-tetrafluoroethoxy)-3,5-dichloroanilino and their synthetic methods and use

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
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20190305