CN109485618A - A kind of 2 phenylsubstituted thiazoles derivatives and its preparation method and application - Google Patents
A kind of 2 phenylsubstituted thiazoles derivatives and its preparation method and application Download PDFInfo
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- CN109485618A CN109485618A CN201811414372.3A CN201811414372A CN109485618A CN 109485618 A CN109485618 A CN 109485618A CN 201811414372 A CN201811414372 A CN 201811414372A CN 109485618 A CN109485618 A CN 109485618A
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- 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
- C07D277/32—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 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
-
- 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
- A01N43/84—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 six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
-
- 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
Abstract
The present invention provides a kind of 2 phenyl thiazole analog derivatives and its preparation method and application, and the present invention relates to a new class of 2- phenyl thiazole analog derivative, general formula of the chemical structure is shown in Formulas I:
Description
Technical field
Technical solution of the present invention is related to a kind of thiazole compound containing N containing S, and in particular to 2 phenylsubstituted thiazoles
The preparation method of derivative and such compound and using these new compounds in agriculturally purposes.
Background technique
Nitrogen-containing heterocycle is one of most important structural constituent in drug and pesticide molecule, and wherein it is former to contain sulphur azepine for thiazole ring
Son has unique Electron rich aromatic heterocycle structure, it is widely present in the natural products and drug of many tool high bioactivities
In molecule, bioactivity (Ayati A, the et al.European Journal of Medicinal of multiplicity is shown
Chemistry, 2015,97,699-718), such as antibacterial, anticancer, antiviral, anti-inflammatory analgesic, hypoglycemic, treatment nervus retrogression
Disease etc., in pesticide activity (Maienfisch P, et al.Advances in Heterocyclic Chemistry,
, including sterilization, desinsection, antiviral etc. 2017,121,35-88).So far have multiple thiazoles pesticide commercializations, including desinsection
Agent Diacloden (Thiamethoxam), fungicide thifluzamide (Thifuzamide), nematicide fluorine thiophene worm sulfone
(Fluensulfone) etc..
Summary of the invention
The technical problems to be solved by the present invention are: the synthetic method of 2 novel phenylsubstituted thiazoles 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
2 phenyl that health field insecticidal activity, bactericidal activity, anti-phytoviral activity, induction plant generate anti-disease activity replace thiophene
The general formula of the chemical structure of Zole derivatives is shown in formula IV:
R1Selected from hydroxyl, C1-C6 alkoxy, the alkoxy that phenyl replaces, by E1The saturation of substituted amino, C3-C6 is nitrogenous
Heterocycle (can contain one or two N or O, but not include containing two O), wherein heterocycle can include: by one or more substitutions, substituent group
Halogen, halogenated alkyl, alkoxy；
R2Selected from nitro, amino or by E2Substituted acylamino-；
R3Selected from hydroxyl, C1-C6 alkoxy, amino or by alkylamino；
E1It is C1-C6 alkyl or halogenated alkyl, C3-C6 naphthenic base or halogenated cycloalkyl, C2-C6 alkenyl or halogenated alkenyl,
C3-C6 cycloalkenyl, C2-C6 alkynyl or halo alkynyl, C3-C6 cycloalkynyl radical, alkoxy-(C2-C4)-alkyl, heterocycle-(C2-
C4)-alkyl；
E2It is the phenyl or the alkyl-substituted phenyl of C1-C6 or C1-C6 alkyl halide that tert-butoxy, phenyl or halogen replace
Base replace phenyl or C3-C6 naphthenic base replace phenyl nitro replace phenyl or C2-C6 alkenyl replace phenyl or
The phenyl or C2-C6 of phenyl or C3-C6 the cycloalkenyl phenyl replaced that C2-C6 halogenated alkenyl replaces or C2-C6 alkynyl substituted
The pyridyl group or C1-C6 alkane that phenyl, pyridyl group or the halogen that the phenyl or C3-C6 cycloalkynyl radical that halo alkynyl replaces replace replace
The pyridyl group or nitro that the pyridyl group or C3-C6 naphthenic base that the pyridyl group or C1-C6 halogenated alkyl that base replaces replace replace take
The pyridyl group or C3-C6 cycloalkenyl that the pyridyl group or C2-C6 halogenated alkenyl that the pyridyl group or C2-C6 alkenyl in generation replace replace
The pyridyl group or C3-C6 cycloalkynyl radical that the pyridyl group or C2-C6 halo alkynyl of substituted pyridyl group or C2-C6 alkynyl substituted replace
The pyrimidine radicals or the alkyl-substituted pyrimidine radicals of C1-C6 or C1-C6 alkyl halide that substituted pyridyl group, pyrimidine radicals or halogen replaces
What the pyrimidine radicals or C2-C6 alkenyl that the pyrimidine radicals or nitro that the pyrimidine radicals or C3-C6 naphthenic base that base replaces replace replace replaced
The pyrimidine radicals or C2-C6 alkynyl substituted that the pyrimidine radicals or C3-C6 cycloalkenyl that pyrimidine radicals or C2-C6 halogenated alkenyl replace replace
Pyrimidine radicals or C2-C6 halo alkynyl replace pyrimidine radicals or C3-C6 cycloalkynyl radical replace pyrimidine radicals, pyrazolyl or halogen take
The pyrazolyl or C3-C6 naphthenic base that the alkyl-substituted pyrazolyl of pyrazolyl or C1-C6 or C1-C6 halogenated alkyl in generation replace
The pyrazolyl or C2-C6 halogenated alkenyl that the pyrazolyl or C2-C6 alkenyl that substituted pyrazolyl or nitro replace replace replace
Pyrazolyl or the pyrazolyl that replaces of C3-C6 cycloalkenyl or the pyrazolyl or C2-C6 halo alkynyl of C2-C6 alkynyl substituted take
The pyrazolyl or C1-C6 alkyl that pyrazolyl, pyrazolyl or the halogen that the pyrazolyl or C3-C6 cycloalkynyl radical in generation replace replace replace
Pyrazolyl or C1-C6 halogenated alkyl replace pyrazolyl C3-C6 naphthenic base replace pyrazolyl or nitro replace pyrrole
What the pyrazolyl or C3-C6 cycloalkenyl that the pyrazolyl or C2-C6 halogenated alkenyl that oxazolyl or C2-C6 alkenyl replace replace replaced
What the pyrazolyl or C3-C6 cycloalkynyl radical that pyrazolyl or the pyrazolyl or C2-C6 halo alkynyl of C2-C6 alkynyl substituted replace replaced
It is pyrazolyl, substituted five yuan for containing 1 or 2 N atom or six membered heteroaryl base, substituted containing 1 or 2 S atom
Five yuan or six membered heteroaryl base, substituted five yuan containing 1 or 2 O atom or six membered heteroaryl base contain 1 N atom and 1
Substituted five yuan of a S atom or six membered heteroaryl base, substituted five yuan or hexa-atomic containing 1 N atom and 1 O atom
Heteroaryl base, substituted five yuan containing 2 N atoms and 1 S atom or six membered heteroaryl base contain 2 N atoms and 1 O original
Substituted five yuan or six membered heteroaryl base of son；Above-mentioned five yuan or six membered heteroaryl are selected from: substituted furyl, thiophene
Base, imidazole radicals, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazoles base, thiadiazolyl group, pyridyl group, is rattled away at pyrrole radicals
Piperazine base, pyrimidine radicals, pyrazinyl, triazine radical, tetrazine base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazole
Base, benzotriazole base, benzothiazolyl, diazosulfide base, benzoxazolyl, the quinolyl of isomerization, isomerization isoquinoline
The silicon substrate that quinoline base, phthalazinyl, quinoxalinyl, quinazolyl, cinnoline base or naphthyridines base, alkyl or alkenyl replace.
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 2 phenylsubstituted thiazoles derivative I V of the invention is as follows:
Wherein, R1It preferably is selected from hydroxyl, methoxyl group, benzyloxy, morpholinyl, N methyl piperazine base, allylamino, the third ammonia of alkynes
Base, cyclopropylamino, N- methyl piperidine -4- amino, 2- morpholinyl ethylamino, morpholinyl ethylamino, 2,2- difluoro nafoxidine
Base；R preferably is selected from 4- trifluoromethyl, 4- fluorophenyl, 4- tert-butyl-phenyl, 1- methyl -3- difluoromethyl -4- pyrazolyl.
The synthesis of 2 phenylsubstituted thiazoles derivatives and the specific method of biological activity determination of the invention is divided into following
Step:
A. the preparation of intermediate II:
19.82 mMs of starting material I and 40 milliliters of ethyl alcohol and 59.46 mMs are added in 100 milliliters of round-bottomed flasks
Pyridine, stirring, is added dropwise 21.80 mMs of bromo diethyl malonates, is heated to reflux 2h, after fully reacting, is removed under reduced pressure molten
Agent adds EA to dissolve, and is successively washed one time with saturated ammonium chloride solution saturated sodium-chloride, and anhydrous sodium sulfate is dry, filters, is removed under reduced pressure
Solvent, solid obtain 5.42g sterling with ethyl alcohol recrystallization, with gained sterling calculated yield, yield 75-85%.Intermediate II preparation
Amount and the volume of reaction vessel 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:
13.72 mMs of intermediate IIs are placed in 100 milliliters of round-bottomed flasks, are vacuumized, nitrogen protection, are added 30 milliliters
Dry methylene chloride, stirring, is added 41.16 mMs of n,N-diisopropylethylamine (DIPEA), stirs 5min in ice salt bath,
27.44 mMs of trifluoromethyl sulfonic acid anhydride (Tf are added dropwise2O), 5h is stirred at room temperature after being added dropwise, after fully reacting, reaction solution
Add dichloro to dilute, pour into suitable quantity of water, separate organic layer, water layer is stripped twice with methylene chloride, merges organic layer, full with saturation
It is washed with sodium chloride, 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
Intermediate III is purified to obtain, eluant, eluent is ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 35~1: 20, it is pure with gained
Product calculated yield, yield 85-90%, the amount of intermediate III preparation and the volume of reaction vessel are expanded or shunk by corresponding proportion.
The chemical structure and physical and chemical parameter of intermediate III are shown in Table 1.
C.2 the preparation of position phenylsubstituted thiazoles derivative I V:
Work as R1For substituted-amino, R2When for tert-butoxycarbonylamino, compound IV-1's the preparation method is as follows:
It takes 0.33 mM of intermediate III in reaction flask, 4 milliliters of Isosorbide-5-Nitraes-dioxane dissolution and 0.66 mM is added
N, N- diisopropylethylamine (DIPEA) and 0.66 mM of amine, are heated to reflux 2-8h, after fully reacting, solvent are removed under reduced pressure,
Add EA to dissolve, successively washed one time with saturated ammonium chloride solution saturated sodium-chloride, anhydrous sodium sulfate is dry, filters, is removed under reduced pressure molten
Agent, residue purify to obtain compound IV-1 through 200~300 mesh silica gel column chromatographies, and eluant, eluent is ethyl acetate: 60~90 degrees Celsius
Fraction petroleum ether=1: 5~1: 1, with gained sterling calculated yield, yield 35%-98%.The amount of compound IV-1 preparation and anti-
Volume of a container is answered to expand or shrink by corresponding proportion.The chemical structure and physical and chemical parameter of compound IV-1 is shown in Table 1.
Work as R1For substituted-amino, R2When for amino, compound IV-2's the preparation method is as follows:
It takes 0.30 mM of compound IV-1 in 50 milliliters of two mouthfuls of round-bottomed flasks, vacuumizes, nitrogen protection, 5 millis are added
It rises dry methylene chloride dissolution and is stirred at room temperature 2 hours, fully reacting after being slowly added to 1 milliliter of trifluoroacetic acid under condition of ice bath
Afterwards, saturated sodium bicarbonate solution being added and adjusts reaction solution pH to 7-8, separate organic layer, organic layer is washed one time with saturated sodium-chloride,
Anhydrous sodium sulfate is dry, filters, solvent is removed under reduced pressure, and obtaining solid is compound IV-2, and recrystallize with dichloromethane obtains sterling, yield
85-98%.The amount of compound IV-2 preparation and the volume of reaction vessel are expanded or shunk by corresponding proportion.Compound IV-2's
Chemical structure and physical and chemical parameter are shown in Table 1.
Work as R1For substituted-amino, R2For replace acylamino- when, compound IV-3's the preparation method is as follows:
It takes 0.27 mM of compound IV-2 in reaction flask, 4 milliliters of dry methylene chloride dissolutions is added, add
0.41 mM of acyl chlorides is added under condition of ice bath, is stirred overnight at room temperature for 0.54 mM of triethylamine, after fully reacting, to anti-
It answers system that 10 milliliters of methylene chloride dilutions are added, is then successively washed one time with saturated sodium bicarbonate and saturated sodium-chloride, anhydrous sulphur
Sour sodium is dry, filters, and solvent is removed under reduced pressure in concentration, and residue purifies to obtain compound IV-3 through 200~300 mesh silica gel column chromatographies,
Eluant, eluent is ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 4~1: 1, with gained sterling calculated yield, yield
45%-95%.The amount of compound IV-3 preparation and the volume of reaction vessel are expanded or shunk by corresponding proportion.Compound IV-3's
Chemical structure and physical and chemical parameter are shown in Table 1.
D. the bactericidal activity measurement of 2 phenylsubstituted thiazoles derivative I V of the invention:
The sterilization of 2 phenylsubstituted thiazoles derivative I V 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 2 phenylsubstituted thiazoles derivative I V, and to synthesis
Noval chemical compound has carried out the screening of bacteriostatic activity.
The present invention is derivative by specific preparation and more specific 2 phenylsubstituted thiazoles of 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:
19.82 mMs of intermediate compound Is -1 are added in 100 milliliters of single necked round bottom flask, are added 40 milliliters of ethyl alcohol, 59.46
MM pyridine, stirring, is added dropwise 21.80 mMs of bromo diethyl malonates, is heated to reflux 2h, after fully reacting, decompression
Solvent is removed, adds EA to dissolve, is successively washed one time with saturated ammonium chloride solution saturated sodium-chloride, anhydrous sodium sulfate is dry, filters, subtracts
Pressure removes solvent, and solid obtains 5.42g sterling with ethyl alcohol recrystallization, with gained sterling calculated yield, yield 85%.Nuclear magnetic data is such as
Under: (400MHz, CDCl3) δ 9.94 (s, 1H), 8.03 (s, 1H), 7.66 (d, J=7.6Hz, 1H), 7.53 (s, 1H), 7.43-
7.34 (m, 1H), 6.58 (s, 1H), 4.39 (q, J=7.1Hz, 2H), 1.54 (s, 9H), 1.43 (t, J=7.1Hz, 3H)13C
NMR (101MHz, CDCl3) δ 169.89,169.56,165.97,152.64,139.32,133.14,129.71,121.57,
121.01,116.25,96.55,80.97,61.71,28.31,14.33.
Embodiment 2: the preparation of intermediate III -1:
13.72 mMs of intermediate IIs -1 are placed in 100 milliliters of round-bottomed flasks, are vacuumized, nitrogen protection, 30 millis are added
Dry methylene chloride is risen, 41.16 mMs of n,N-diisopropylethylamine (DIPEA) are added in stirring, stir in ice salt bath
27.44 mMs of trifluoromethyl sulfonic acid anhydride (Tf are added dropwise in 5min2O), 5h is stirred at room temperature after being added dropwise, after fully reacting, instead
It answers liquid that dichloro is added to dilute, pours into suitable quantity of water, separate organic layer, water layer is stripped twice with methylene chloride, merges organic layer, with full
It is washed with saturated sodium-chloride, anhydrous sodium sulfate is dry, filters, and solvent is removed under reduced pressure, and residue is through 200~300 mesh silicagel columns in concentration
Chromatographic purifying obtains intermediate III -1, and eluant, eluent is ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 35~1: 20, it uses
Gained sterling calculated yield, yield 90%, nuclear magnetic data is as follows: (400MHz, CDCl3) δ 7.99 (s, 1H), 7.59 (d, J=
7.6 Hz, 2H), 7.38 (t, J=7.9Hz, 1H), 6.82 (s, 1H), 4.43 (q, J=7.1Hz, 2H), 1.55 (s, 9H), 1.43
(t, J=7.1 Hz, 3H)13C NMR (101MHz, CDCl3) δ 168.66,159.01,152.62,151.14,139.57,
132.23,129.93,122.05,120.77,118.60 (d, J=320.9Hz), 115.94,81.17,62.53,28.27,
14.06。
Embodiment 3: work as R1For morpholinyl, R2When for tert-butoxycarbonylamino, the preparation of compound gxf02-107:
It takes 0.33 mM of intermediate III -1 in reaction flask, 4 milliliters of Isosorbide-5-Nitraes-dioxane dissolution is added, is added 0.66
MM n,N-diisopropylethylamine (DIPEA), adds 0.66 mM of morpholine, is heated to reflux 2h, after fully reacting, decompression
Solvent is removed, adds EA to dissolve, is successively washed one time with saturated ammonium chloride solution saturated sodium-chloride, anhydrous sodium sulfate is dry, filters, subtracts
Pressure removes solvent, and residue purifies to obtain compound gxf02-107 through 200~300 mesh silica gel column chromatographies, and eluant, eluent is ethyl acetate
: 60~90 degrees Celsius of fraction petroleum ether=1: 5, with gained sterling calculated yield, yield 53%.Nuclear magnetic data is as follows:
(400MHz, DMSO) δ 9.62 (s, 1H), 8.17 (s, 1H), 7.57 (d, J=7.6Hz, 2H), 7.39 (t, J=7.9Hz, 1H),
4.21 (q, J=7.1 Hz, 2H), 3.78-3.70 (m, 4H), 3.62-3.54 (m, 4H), 1.50 (s, 9H), 1.27 (t, J=
7.1Hz, 3H)13C NMR (101MHz, DMSO) δ 167.72,163.05,160.76,152.72,140.37,132.52,
129.64,120.97,119.86,115.35,98.26,79.44,66.08,60.42,49.96,28.06,14.27.
Embodiment 4: work as R1For morpholinyl, R2When for amino, the preparation of compound gxf02-112:
It takes 0.30 mM of compound gxf02-107 in 50 milliliters of two mouthfuls of round-bottomed flasks, vacuumizes, nitrogen protection adds
Enter 5 milliliters of dry methylene chloride dissolutions, after being slowly added to 1 milliliter of trifluoroacetic acid under condition of ice bath, is stirred at room temperature 2 hours, instead
After answering completely, saturated sodium bicarbonate solution is added and adjusts reaction solution pH to 7-8, separates organic layer, organic layer saturated sodium-chloride
It washes one time, anhydrous sodium sulfate is dry, filters, solvent is removed under reduced pressure, and obtaining solid is compound gxf02-112, and methylene chloride is tied again
It is brilliant to obtain sterling, yield 92%.Nuclear magnetic data is as follows: (400MHz, CDCl3) δ 7.29 (t, J=5.4Hz, 2H), 7.21 (t, J=
7.8Hz, 1H), 6.80-6.75 (m, 1H), 4.28 (q, J=7.1Hz, 2H), 3.90-3.85 (m, 4H), 3.81 (s, 2H),
3.70-3.64 (m, 4H), 1.35 (t, J=7.1Hz, 3H)13C NMR (101MHz, CDCl3) δ 168.88,163.97,
161.92,146.99,133.92,129.89,117.76,116.83,112.45,100.03,67.03,60.69,50.57,
14.50。
Embodiment 5: work as R1For morpholinyl, R2When for fluorobenzoylamino, the preparation of compound gxf02-116:
It takes 0.27 mM of compound IV-2 in reaction flask, 4 milliliters of dry methylene chloride dissolutions is added, add
0.54 mM of triethylamine is added 0.41 mM to fluorobenzoyl chloride under condition of ice bath, is stirred overnight at room temperature, has reacted
Quan Hou is added 10 milliliters of methylene chloride dilutions to reaction system, then successively washes one with saturated sodium bicarbonate and saturated sodium-chloride
Time, anhydrous sodium sulfate is dry, filters, concentration, and solvent is removed under reduced pressure, and residue purifies to change through 200~300 mesh silica gel column chromatographies
Object gxf02-116 is closed, eluant, eluent is ethyl acetate: 60~90 degrees Celsius of fraction petroleum ether=1: 4, it is calculated and is received with gained sterling
Rate, yield 71%.Nuclear magnetic data is as follows: (400MHz, CDCl3) δ 8.44 (s, 1H), 8.22 (s, 1H), 7.91 (dd, J=8.0,
5.4Hz, 2H), 7.81 (d, J=7.9Hz, 1H), 7.69 (d, J=7.6Hz, 1H), 7.40 (t, J=7.9Hz, 1H), 7.12
(t, J=8.1Hz, 2H), 4.28 (q, J=7.0Hz, 2H), 3.84 (s, 4H), 3.65 (d, J=3.9Hz, 4H), 1.35 (t, J
=7.1Hz, 3H)13C NMR (101MHz, CDCl3) δ 167.90,165.14,164.97 (d, J=253.2Hz), 163.95,
161.91,138.63,133.72,130.69,129.68,129.58,123.01,122.62,118.19,115.81 (d, J=
21.9Hz), 100.35,66.96,60.83,50.50,14.48.
Embodiment 6: 2 phenylsubstituted thiazoles derivative I V 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 2 phenylsubstituted thiazoles derivative I V that the present invention synthesizes are most of different
The bactericidal activity of degree.
For the late blight of potato, compound gxf02-86, gxf02-124, gxf02-138, gxf03-101,
For the inhibitory activity of gxf03-117-1 and gxf03-183-2 45% or more, activity is higher by positive control thifluzamide (to horse
The inhibiting rate of bell potato late blight is 23%) 10% or more.Compound gxf02- is shown to the Activity Results of peanut Cercospora asparagagas
86, the inhibitory activity of gxf02-124, gxf02-138, gxf02-202-1, gxf03-83, gxf03-189 and qzx02-2 exist
50% or more, activity is higher by positive control thifluzamide (inhibiting rate to the cercospora brown spot of peanut is 20%) 10% or more.To kind
The active testing of eggplant early epidemic germ the result shows that, the suppression of compound gxf02-86, gxf02-138, gxf03-83 and gxf03-189
System is active 50% or more, but more slightly lower than lead compound thifluzamide (inhibiting rate to early blight of tomato is 89%).It is right
The active testing of Botryosphaeria berengeriana f. sp shows compound gxf02-86, gxf02-138, gxf03-83, gxf03-101, gxf03-
For the bacteriostatic activity of 117-1, gxf03-195 and gxf03-196 50% or more, activity is higher by positive control thifluzamide (to apple
The inhibiting rate of fruit ring spot is 28%) 10% or more.To the active testing of Sclerotinia sclerotiorum show compound gxf02-82,
gxf02-86、gxf02-107、 gxf02-110、gxf02-116、gxf02-121、gxf02-124、gxf02-138、gxf02-
161, for the bacteriostatic activity of gxf02-202-2, qzx02-2 and xq01-03 80% or more, activity is higher by positive control thiophene furan acyl
Amine (being 79% to the inhibiting rate of sclerotinia sclerotiorum), wherein compound gxf02-82, gxf02-86, gxf02-107, gxf02-
110, the bacteriostatic activity of gxf02-124, gxf02-138, gxf02-202-2 and qzx02-2 are 90% or more.To cereal silk core
The active testing of bacterium show compound gxf02-86, gxf02-124, gxf02-138, gxf02-202-1, gxf03-83,
For the bacteriostatic activity of gxf03-101, gxf03-189 and gxf03-196 80% or more, activity is higher than positive control thifluzamide
(being 77% to the inhibiting rate of Rhizoctonia cerealis), wherein compound gxf02-86, gxf02-124, gxf02-138 and gxf03-83
Bacteriostatic activity 90% or more.In summary, compound gxf02-86, gxf02-138, gxf03-83, gxf03-117-1,
Gxf03-189 and qzx02-2 has the bactericidal activity of wide spectrum, most of 2 phenylsubstituted thiazoles derivatives that the present invention synthesizes
IV has preferable inhibitory activity to Rhizoctonia cerealis, sclerotinia sclerotiorum and botrytis cinerea.
The present invention further spreads out to 2 phenylsubstituted thiazoles that bacteriostatic activity is higher than 80% in 50 mcg/ml concentration
Biological IV has carried out accurate virulence (EC50/ mcg/ml) measurement, the results are shown in Table 3, for Rhizoctonia cerealis, change
Object gxf02-86, gxf02-124, gxf02-138, gxf03-117-1 and gxf03-189 are closed to its EC50Value 20 micrograms/
Milliliter is hereinafter, activity is above control compound thifluzamide (EC50: 22.12 mcg/mls), to Rhizoctonia cerealis
EC50Value is respectively 1.53,9.04,7.84,16.34 and 3.14 mcg/mls, and compound gxf02-86 is comparison medicament thiophene furan acyl
The 1/14 of amine.For sclerotinia sclerotiorum, compound gxf02-110, gxf02-116, gxf02-124, gxf02-138,
Gxf02-202-2, gxf03-81, gxf03-189 and qzx02-2 are to its EC50Value is in 10 mcg/mls hereinafter, especially change
Close the EC of object gxf02-110, gxf03-189 and qzx02-250Value is respectively 0.98,4.07 and 4.01 mcg/mls, and activity is high
In control compound thifluzamide (EC50: 4.35 mcg/mls), the wherein EC of compound gxf02-11050Value is comparison medicament
The 1/4 of thifluzamide.For botrytis cinerea pers, compound gxf02-86 and gxf02-138 is to its EC50Value is respectively 6.73
With 7.57 mcg/mls, activity is higher than comparison medicament thifluzamide (EC50: 10.42 mcg/mls).Therefore, the present invention designs
The noval chemical compound of synthesis has carried out structure optimization, the sterilization of the 2 phenylsubstituted thiazoles derivative I V in part around 4 substituted thiazoles
Activity has obtained significant raising compared with commodity fungicide thifluzamide, this is that the invention is different from and has invention
Place.
Embodiment 7: 2 phenylsubstituted thiazoles derivative I V living body Antibacterial Activity results of the invention:
The living body protection activity measurement result of 2 phenylsubstituted thiazoles derivative I V of the invention is shown in Table 4, the visible conjunction of table 4
At 2 phenylsubstituted thiazoles derivative I V in 200 mcg/ml to powdery mildew of cucumber and corn rust almost without sterilization
Activity.For cucumber downy mildew, compound gxf02-86, gxf02-105, gxf02-110, gxf02-112, gxf02-121,
For gxf02-202-1 and gxf02-202-2 to its activity 80% or more, activity is higher than control compound thifluzamide
(70%).Compound gxf02-82, gxf02-161, gxf03-37-2, gxf03-43-2, gxf03-183-2 and xq01-03 are aobvious
Medium bactericidal activity is shown, inhibiting rate is between 50-70%.
Embodiment 8: 2 phenylsubstituted thiazoles derivative I V 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；2 phenylsubstituted thiazoles derivatives of the invention
Total mass percentage of the IV in gained compounded pesticides is 1%-90%, and 2 phenylsubstituted thiazoles of the invention are derivative
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 9: 2 phenylsubstituted thiazoles derivative I V 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,
Bis- chloroisothiazole -5- formic acid of 4-, 3,4-, bis- chloroisothiazole -5- sodium formate, 3,4-, bis- chloroisothiazole -5- Ethyl formate, DL- β-ammonia
Base butyric acid, isotianil, virazole, antofine, Ningnanmycin, first thiophene lure amine, salicylic acid, cytosintetidemycin, dichloro-isonicotinic acid, alkene
Third isothiazole, cymoxanil, thiram, ziram, Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pines, rotten mould
Benefit, fenpropidin, thiophanate methyl, thiophanate, Metalaxyl-M, salicylic acid, flumorph, dimethomorph, mefenoxam, efficient benzene
White 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,
Chlozolinate, 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；2 phenylsubstituted thiazoles derivative I V of the invention are in institute
Total mass percentage in composite bactericide is 1%-90%, 2 phenylsubstituted thiazoles derivative I V 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 10: 2 phenylsubstituted thiazoles derivatives 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；2 phenylsubstituted thiazoles derivative I V of the invention compound anti-activating plants in gained
Total mass percentage in agent is 1%-90%, and 2 phenylsubstituted thiazoles derivative I V of the invention and the commodity are planted
The ratio of object activator is mass percent 1%: 99% to 99%: 1%；The dosage form of the compound botanical activator is selected from wettable
Property pulvis, micro-capsule suspension, dispersible body preparation, dispersible solid preparation, seed treatment emulsion, aqueous emulsion, big granula,
Microemulsion, 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 11: 2 phenylsubstituted thiazoles derivative I V of the invention and agriculturally acceptable auxiliary agent and with such as
Any one or more combination in lower 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 2 phenylsubstituted thiazoles derivative I V of the invention in gained Compositional acaricide in the composition
Point content is 1%-90%, and 2 phenylsubstituted thiazoles derivative I V 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 be selected from wettable powder, micro-capsule suspension, can
Dispersing liquid preparation, seed treatment emulsion, aqueous emulsion, big granula, microemulsion, oil-suspending agent, uses pesticide at dispersible solid preparation
It is the seed of coating, water-soluble granule, soluble thick agent, water-dispersible granules, poison grain, aerosol, 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, oil in water emulsion, smoke candle, granula subtilis,
Smoke 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, sorghum, 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 12: the combination of 2 phenylsubstituted thiazoles derivative I V and pesticide of the invention:
2 phenylsubstituted thiazoles derivative I V and its intermediate are preparing the purposes in agricultural fungicidal agent.It is a kind of agricultural
Bactericidal composition, it includes 2 phenylsubstituted thiazoles derivative I V and intermediate can prepare agricultural bactericidal composition, the combination
Object includes 2 phenylsubstituted thiazoles derivative I V 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 2 phenylsubstituted thiazoles derivative I V and its intermediates and other
The bactericide compounded ratio as active constituent, 2 phenylsubstituted thiazoles derivative I V 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 2 phenylsubstituted thiazoles derivative I V and its intermediates and its
He is used as active constituent, 2 phenylsubstituted thiazoles derivative I V 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, 2 phenylsubstituted thiazoles derivative I V of the invention and its intermediate
Active constituent, 2 phenylsubstituted thiazoles derivative I V 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 phenylsubstituted thiazoles derivative I V of part 2 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: standing grain
Phizoctonia cerealis, latin 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 2 phenylsubstituted thiazoles derivative I V of the invention of table 3.50/ mcg/ml)
: undetermined
Active (the inhibition of 200 mcg/mls of the 2- phenyl thiazole derivant IV greenhouse pot culture living body of the invention of table 4.
Rate/%)
| Serial number | Compound number | Cucumber downy mildew | Wheat powdery mildew | Corn rust |
| 1 | gxf02-82 | 75 | 0 | 0 |
| 2 | gxf02-86 | 90 | 0 | 0 |
| 3 | gxf02-99-3 | - | - | - |
| 4 | gxf02-105 | 80 | 0 | 0 |
| 5 | gxf02-107 | 30 | 0 | 0 |
| 6 | gxf02-110 | 80 | 0 | 0 |
| 7 | gxf02-112 | 80 | 0 | 0 |
| 8 | gxf02-116 | 45 | 0 | 0 |
| 9 | gxf02-121 | 82 | 0 | 0 |
| 10 | gxf02-124 | 40 | 0 | 0 |
| 11 | gxf02-125 | 0 | 0 | 0 |
| 12 | gxf02-138 | 0 | 0 | 0 |
| 13 | gxf02-161 | 60 | 0 | 0 |
| 14 | gxf02-163 | 0 | 0 | 0 |
| 15 | gxf02-164-2 | - | - | - |
| 16 | gxf02-165-xia | - | - | - |
| 17 | gxf02-202-1 | 80 | 0 | 0 |
| 18 | gxf02-202-2 | 80 | 0 | 0 |
| 19 | gxf03-33-1 | 0 | 0 | 0 |
| 20 | gxf03-37-2 | 50 | 0 | 0 |
| 21 | gxf03-43-2 | 70 | 0 | 0 |
| 22 | gxf03-49 | 0 | 0 | 0 |
| 23 | gxf03-56 | 0 | 0 | 0 |
| 24 | gxf03-81 | 40 | 0 | 0 |
| 25 | gxf03-83 | 0 | 0 | 0 |
| 26 | gxf03-90 | 0 | 0 | 0 |
| 27 | gxf03-101 | 0 | 0 | 0 |
| 28 | gxf03-117-1 | 0 | 0 | 0 |
| 29 | gxf03-151-2 | - | - | - |
| 30 | gxf03-170 | 0 | 0 | 0 |
| 31 | gxf03-180 | 0 | 0 | 0 |
| 32 | gxf03-183-2 | 65 | 0 | 0 |
| 33 | gxf03-188 | 0 | 0 | 20 |
| 34 | gxf03-189 | 0 | 0 | 0 |
| 35 | gxf03-194 | 0 | 0 | 0 |
| 36 | gxf03-195 | 0 | 0 | 0 |
| 37 | gxf03-196 | 0 | 0 | 0 |
| 38 | gxf03-197 | 0 | 0 | 0 |
| 39 | gxf05-21-1 | - | - | - |
| 40 | gxf05-21-2 | - | - | - |
| 41 | gxf05-31 | - | - | - |
| 42 | gxf05-33 | - | - | - |
| 43 | qzx01-31-2 | 0 | 0 | 0 |
| 44 | qzx02-2 | 40 | 0 | 0 |
| 45 | qzx02-4 | 25 | 0 | 0 |
| 46 | qzx02-5-3 | 0 | 0 | 0 |
| 47 | qzx02-6-2 | 30 | 0 | 0 |
| 48 | xq01-03 | 50 | 0 | 85 |
| 49 | gxf03-159 | 0 | 0 | 0 |
| 50 | gxf03-172 | 0 | 0 | 0 |
| 51 | gxf03-178 | - | - | - |
| 52 | Thifluzamide | 70 | 0 | 100 |
: for measurement.
Claims (8)
1. a kind of 2 phenylsubstituted thiazoles derivatives, it is characterised in that: have the general structure as shown in formula IV:
Wherein:
R1Selected from hydroxyl, C1-C6 alkoxy, phenyl replace alkoxy, by E1The saturation nitrogen-containing heterocycle of substituted amino, C3-C6
Base (can contain one or two N or O, but not include containing two O), wherein heterocycle can include: halogen by one or more substitutions, substituent group
Element, halogenated alkyl, alkoxy；
R2Selected from nitro, amino or by E2Substituted acylamino-；
R3Selected from hydroxyl, C1-C6 alkoxy, amino or by alkylamino；
E1It is C1-C6 alkyl or halogenated alkyl, C3-C6 naphthenic base or halogenated cycloalkyl, C2-C6 alkenyl or halogenated alkenyl, C3-C6
Cycloalkenyl, C2-C6 alkynyl or halo alkynyl, C3-C6 cycloalkynyl radical, alkoxy-(C2-C4)-alkyl, heterocycle-(C2-C4)-alkane
Base；
E2It is that tert-butoxy, the phenyl of phenyl or halogen substitution or the alkyl-substituted phenyl of C1-C6 or C1-C6 halogenated alkyl take
The phenyl or C2- that the phenyl or C2-C6 alkenyl that the phenyl or nitro that the phenyl or C3-C6 naphthenic base in generation replace replace replace
Phenyl or C3-C6 the cycloalkenyl phenyl replaced that C6 halogenated alkenyl replaces or the phenyl or C2-C6 of C2-C6 alkynyl substituted are halogenated
The pyridyl group or C1-C6 alkyl that phenyl, pyridyl group or the halogen that the phenyl or C3-C6 cycloalkynyl radical of alkynyl substituted replace replace take
What the pyridyl group or nitro that the pyridyl group or C3-C6 naphthenic base that the pyridyl group or C1-C6 halogenated alkyl in generation replace replace replaced
The pyridyl group or C3-C6 cycloalkenyl that the pyridyl group or C2-C6 halogenated alkenyl that pyridyl group or C2-C6 alkenyl replace replace replace
Pyridyl group or C2-C6 alkynyl substituted pyridyl group or C2-C6 halo alkynyl replace pyridyl group or C3-C6 cycloalkynyl radical replace
Pyridyl group, the pyrimidine radicals that replaces of pyrimidine radicals or halogen or the alkyl-substituted pyrimidine radicals of C1-C6 or C1-C6 halogenated alkyl take
The pyrimidine that the pyrimidine radicals or C2-C6 alkenyl that the pyrimidine radicals or nitro that the pyrimidine radicals or C3-C6 naphthenic base in generation replace replace replace
Pyrimidine radicals that the pyrimidine radicals or C3-C6 cycloalkenyl that base or C2-C6 halogenated alkenyl replace replace or C2-C6 alkynyl substituted it is phonetic
What pyrimidine radicals, pyrazolyl or the halogen that the pyrimidine radicals or C3-C6 cycloalkynyl radical that piperidinyl or C2-C6 halo alkynyl replace replace replaced
The pyrazolyl or C3-C6 naphthenic base that pyrazolyl or the alkyl-substituted pyrazolyl of C1-C6 or C1-C6 halogenated alkyl replace replace
Pyrazolyl or nitro replace pyrazolyl C2-C6 alkenyl replace pyrazolyl or C2-C6 halogenated alkenyl replace pyrazoles
The pyrazoles that base or the C3-C6 cycloalkenyl pyrazolyl replaced or the pyrazolyl or C2-C6 halo alkynyl of C2-C6 alkynyl substituted replace
The pyrazolyl or the alkyl-substituted pyrazoles of C1-C6 that pyrazolyl, pyrazolyl or the halogen that base or C3-C6 cycloalkynyl radical replace replace
The pyrazolyl of pyrazolyl or nitro substitution that the pyrazolyl or C3-C6 naphthenic base that base or C1-C6 halogenated alkyl replace replace,
Or the pyrazoles that the C2-C6 alkenyl pyrazolyl replaced or the pyrazolyl or C3-C6 cycloalkenyl of the substitution of C2-C6 halogenated alkenyl replace
The pyrazoles that the pyrazolyl or C3-C6 cycloalkynyl radical that base or the pyrazolyl or C2-C6 halo alkynyl of C2-C6 alkynyl substituted replace replace
Base, substituted five yuan for containing 1 or 2 N atom or six membered heteroaryl base, substituted five yuan containing 1 or 2 S atom
Or six membered heteroaryl base, substituted five yuan containing 1 or 2 O atom or six membered heteroaryl base, contain 1 N atom and 1 S original
Substituted five yuan or six membered heteroaryl base, substituted five yuan or six membered heteroaryl containing 1 N atom and 1 O atom of son
Base, substituted five yuan or six membered heteroaryl base, the quilt containing 2 N atoms and 1 O atom containing 2 N atoms and 1 S atom
Five yuan or the six membered heteroaryl base replaced；Above-mentioned five yuan or six membered heteroaryl are selected from: substituted furyl, thienyl, pyrroles
It is base, imidazole radicals, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazoles base, thiadiazolyl group, pyridyl group, pyridazinyl, phonetic
Piperidinyl, pyrazinyl, triazine radical, tetrazine base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzo
Triazolyl, benzothiazolyl, diazosulfide base, benzoxazolyl, the quinolyl of isomerization, the isoquinolyl of isomerization, phthalein
The silicon substrate that piperazine base, quinoxalinyl, quinazolyl, cinnoline base or naphthyridines base, alkyl or alkenyl replace；
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. 2 phenylsubstituted thiazoles derivative I V according to claim 1, wherein R1It preferably is selected from hydroxyl, methoxyl group, benzyloxy
Base, morpholinyl, N methyl piperazine base, allylamino, propargylamino, cyclopropylamino, N- methyl piperidine -4- amino, 2- morpholinyl
Ethylamino, morpholinyl ethylamino, 2,2- difluoro nafoxidine base；R preferably is selected from 4- trifluoromethyl, 4- fluorophenyl, uncle 4-
Butyl phenyl, 1- methyl -3- difluoromethyl -4- pyrazolyl.
3. according to claim 1 with the specific route and synthetic method of 2 phenylsubstituted thiazoles derivative I V 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 ethyl alcohol and pyridine, and stirring is lower to react preparation with bromo diethyl malonate, wherein originating
The definition of substituent group in raw material is as described in claim 1, and the definition of preferred substituents is as claimed in claim 2；
B. the preparation of intermediate III:
Intermediate III, under nitrogen protection with n,N-diisopropylethylamine, is abbreviated as DIPEA and trifluoromethyl sulphur by intermediate II
Acid anhydrides is abbreviated as Tf2O reacts preparation in methylene chloride, wherein the definition of the substituent group in each reaction raw materials and intermediate product
As described in claim 1, 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 substituted-amino, R2When for tert-butoxycarbonylamino, compound IV-1's the preparation method is as follows:
It takes intermediate III in reaction flask, Isosorbide-5-Nitrae-dioxane and n,N-diisopropylethylamine is added, is abbreviated as DIPEA and takes
For aminated compounds, compound IV-1 is prepared in heating reflux reaction；
Work as R1For substituted-amino, R2When for amino, compound IV-2's the preparation method is as follows:
Take compound IV-1 in a round bottom flask, after dry methylene chloride and trifluoroacetic acid are added under nitrogen protection, room temperature is stirred
It mixes reaction and is prepared into compound IV-2；
Work as R1For substituted-amino, R2For replace acylamino- when, compound IV-3's the preparation method is as follows:
It takes compound IV-2 in reaction flask, dry methylene chloride and triethylamine is added, acyl chlorides, room are added under condition of ice bath
Temperature, which is stirred to react, is prepared compound IV-3；
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 2 phenylsubstituted thiazoles derivative I V 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 claim 1 and 2 phenylsubstituted thiazoles as claimed in claim 2 are derivative
Object IV and intermediate can prepare agricultural bactericidal composition, and the composition includes claim 1 and 2 as claimed in claim 2
As active constituent, the content of active constituent is 0.1 to 99.9% weight for phenylsubstituted thiazoles derivative I V 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 2 phenylsubstituted thiazoles as claimed in claim 2
Derivative I V and its intermediate and other it is bactericide compounded be used as active constituent, 2 phenylsubstituted thiazoles derivative I V 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 2 phenyl as claimed in claim 2 to replace
Thiazole IV and its intermediate and other Insecticidal and acaricidal agents compounding are used as active constituent, 2 phenylsubstituted thiazoles 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 claims 1 and 2 phenyl as claimed in claim 2 to replace thiophene
Zole derivatives IV and its intermediate and other plant activator compounding are used as active constituent, 2 phenylsubstituted thiazoles derivative I V
And its ratio of intermediate and other fungicide is mass percent 1%: 99% to 99%: 1%, the content of active constituent is 1
To 99% weight, the solid or liquid adjuvants of 99 to 1% weight.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110870867A (en) * | 2019-12-02 | 2020-03-10 | 天津医科大学口腔医院 | Application of thiazole amide derivative in preparation of anti-cancer drugs |
| CN111196787A (en) * | 2020-01-19 | 2020-05-26 | 江西农业大学 | Citral thiazole hydrazone derivatives, and preparation method and application thereof |
| CN115477874A (en) * | 2022-10-14 | 2022-12-16 | 北京汇聚和新材料有限公司 | Water-based antirust primer and preparation method thereof |
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| CN110870867A (en) * | 2019-12-02 | 2020-03-10 | 天津医科大学口腔医院 | Application of thiazole amide derivative in preparation of anti-cancer drugs |
| CN111196787A (en) * | 2020-01-19 | 2020-05-26 | 江西农业大学 | Citral thiazole hydrazone derivatives, and preparation method and application thereof |
| CN115477874A (en) * | 2022-10-14 | 2022-12-16 | 北京汇聚和新材料有限公司 | Water-based antirust primer and preparation method thereof |
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