CN104829605B - 1 substitution 5 trifluoromethyl 4 pyrazoles joins 1,3,4 oxadiazole thioethers or sulfone derivatives and its application - Google Patents
1 substitution 5 trifluoromethyl 4 pyrazoles joins 1,3,4 oxadiazole thioethers or sulfone derivatives and its application Download PDFInfo
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- 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
- A01N43/82—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 three ring hetero atoms
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Abstract
The invention discloses one kind 1 to substitute the pyrazoles of 5 trifluoromethyl 4 connection 1,3,4 oxadiazole thioethers or sulfone derivatives and its application, its structural formula such as A, shown in B, using trifluoroacetic ethyl acetoacetate as raw material, 1 substitution 5 trifluoromethyl 4 pyrazoles connection 1 has been synthesized through esterification, closed loop, hydrazinolysis, closed loop, substitution 5 steps reaction, 3,4 oxadiazole class compounds.Such compound has certain inhibitory action to vegetative bacteria or fungal diseases of plants, can make to prevent and treat the agricultural chemicals and pesticides additive agent of bacteriosis or plant mycosis.
Description
Technical field
The present invention relates to antiseptic field, discloses -5- trifluoromethyl-the 4- of substitution containing 1- pyrazoles and joins 1,3,4- oxadiazole sulphur
The application of ether or sulfone derivatives in terms of agricultural plant pathogen preventing and treating.
Background technology
For the great bacillary and fungal disease of current China agricultural, scientific and efficient discovery has potential market life
The green candidate's agricultural chemicals for ordering power is the vital task faced in China's New pesticides discovery basic research.In the development course of bactericide
In, synthesis chemical bactericide is in antibacterial, sterilization and ensures that farm-forestry crop stable yields etc. plays an important role.But due to
The shortcomings that synthesizing chemical bactericide itself and long-term irrational use, and gradually expose the problem of some are serious：As resisted
The generation of the property of medicine, the problems such as threat to human health.Therefore the initiative of green novel pesticide turns into emphasis in current agricultural industry
The problem in science of research of technique and real problem.
1,3,4- oxadiazole thioether or sulfone compound are containing the heteroatomic five member ring heterocyclic compound of S, O, N, its ring-type
Skeleton has obvious conjugacy and armaticity, thus has extensive bioactivity.1,3,4- oxadiazoles and its derivative
2,5 on substituent may participate in numerous chemical reactions, be often introduced into as active group in pesticide molecule, be
Modernize the hot subject of agronomy discipline research.
Pyrazole derivatives are a kind of compounds for having extensive bioactivity, are play in heterocyclic pesticide important
Role be widely used in sterilization, weeding, plant growth regulator, Insecticiding-miticiding etc..And the substitution of pyrazoles ring substituents
The change of type and the position of substitution can bring abundant structure diversity, have vast potential for future development.
In order to obtain the anti-pathogenic microbial inoculum of high-efficiency low-toxicity that structure is novel, mechanism of action is unique, to this seminar early stage
Synthesized 1- substitution -5- amino -4- pyrazoles joins 1,3,4- oxadiazole class compounds and carries out further structure of modification, in " 1-
On substituted pyrazolecarboxylic ring " architecture basics, pyrazole ring " 5- positions " introducing " trifluoromethyl ", design has synthesized a series of pyrazoles connection 1,3,4-
Oxadiazole thioether and sulfone derivatives.
The content of the invention
The purpose of the present invention is：
Join 1,3,4 oxadiazole class compounds to the 1- substitution -5- amino -4- pyrazoles synthesized by this seminar early stage to enter to advance
The structure of modification of one step, is prepared for a series of 1- substitutions -5- trifluoromethyl -4- pyrazoles 1,3,4- oxadiazole thioethers of connection or sulfone class is spread out
Biology, and crop plants are bacillary or fungal disease for preventing and treating；It is experimentally confirmed compound pair provided by the invention
Bacterial blight of rice, wheat scab, capsicum wilt, canker of apple fruit, sclerotinia sclerotiorum, the late blight of potato and rice line
Rot pathogen, show good inhibitory activity.
1- substitutions -5- trifluoromethyl -4- pyrazoles connection 1,3,4- oxadiazoles thioether or sulfone derivatives general structure of the present invention
As shown in A and B：
In formula：
R is selected from methyl, phenyl；
R1 is selected from alkyl, alkenyl, benzyl, substituted benzyl, substituted heterocycle methylene；
In formula A, B：
R1 is selected from C1-C3 alkyl, C1-C3 branched alkyl, C1-C3 alkenyl, benzyl, substituted benzyl, substituted heterocycle
Methylene；
In formula A, B：
Signified C1-C3 alkyl is methyl, ethyl, n-propyl in R1；Signified C1-C3 branched alkyl is isopropyl
Base；Signified C1-C3 alkenyl is pi-allyl；Signified substituted benzyl is methylbenzyl, halogen benzyl, methoxybenzyl, halogenated methyl
Benzyl；Signified substituted heterocycle methylene is haloperidid ring methylene, halo thiazole ring methylene；
Wherein halogen atom is F, Cl.
1- substitutions -5- trifluoromethyl -4- pyrazoles of the present invention joins 1,3,4- oxadiazole thioethers or sulfone derivatives, and it is to have closed
Into particular compound it is as follows：
Derivative provided by the invention can be as the agricultural chemicals and pesticides additive agent in preparation preventing and treating crop plants pathogen
In application；The crop plants pathogen be preferably rice leaf spot bacteria (X. oryzae), fusarium graminearum (G. zeae), capsicum wilt bacterium (F. oxysporum), Valsa mali (C. mandshurica), the late blight of potato
Bacterium（P.infestans）, Sclerotinia sclerotiorum（S.sclerotiorum）And Rhizoctonia solani Kuhn（T.cucumeris）.
The compounds of this invention A and B can be prepared using following method：
Intermediate 2 is obtained with various hydrazine reaction closed loops using 1, generation intermediate 3 is reacted by hydrazinolysis, exists with carbon disulfide
Solvent is removed after being reacted in appropriate solvent completely, alkali is added and reacts to obtain intermediate 4, is made with the reaction of various halogenated compounds
Target compound A, further oxidation obtain target compound B；Alkali can be selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, hydrogen
Change sodium, potassium carbonate, sodium carbonate, DMAP, triethylamine, pyridine, N,N-dimethylformamide etc.；Solvent can be selected from methanol, ethanol,
Propyl alcohol, isopropanol, butanol, DMF, acetonitrile, chloroform, dichloromethane, tetrahydrofuran, toluene, benzene, 1,4- dioxane, acetone etc..
In process of the present invention, used intermediate 1 can be prepared in the following ways：
Using trifluoromethyl ethyl acetoacetate 5 and triethyl orthoformate in acetic anhydride, 50 ~ 150oUnder conditions of C
Reaction 3 ~ 24 hours, obtains intermediate 1.Solvent can be selected from methanol, ethanol, propyl alcohol, isopropanol, butanol, DMF, acetonitrile, chlorine
Imitative, dichloromethane, tetrahydrofuran, toluene, benzene, 1,4- dioxane, acetone etc..
In process of the present invention, used intermediate 2 can be prepared in the following ways：
It is dissolved in using 1 with various hydrazines in appropriate solvent, 50 ~ 200oReact 5 ~ 24 hours, obtain under conditions of C
Intermediate 2.Solvent can be selected from methanol, ethanol, propyl alcohol, isopropanol, butanol, DMF, acetonitrile, chloroform, dichloromethane, tetrahydrochysene furan
Mutter, toluene, benzene, 1,4- dioxane, acetone etc..
In process of the present invention, used intermediate 3 can be prepared in the following ways：
It is dissolved in using 2 with hydrazine hydrate in appropriate solvent, 50 ~ 200oReact 5 ~ 48 hours, obtain middle under conditions of C
Body 3.Solvent can be selected from methanol, ethanol, propyl alcohol, isopropanol, butanol, DMF, acetonitrile, chloroform, dichloromethane, tetrahydrofuran, first
Benzene, benzene, 1,4- dioxane, acetone etc..
In process of the present invention, used intermediate 4 can be prepared in the following ways：
It is dissolved in the basic conditions in appropriate solvent with carbon disulfide using 3,20 ~ 120o2 are reacted under conditions of C
Solvent is removed after ~ 48 hours, alkali is added, 0 ~ 120oReacted 1 ~ 10 hour under conditions of C, intermediate 4 is made.Alkali can be selected from
Sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride, potassium carbonate, sodium carbonate, DMAP, triethylamine, pyridine, N, N- dimethyl methyls
Acid amides etc.；Solvent can be selected from methanol, ethanol, propyl alcohol, isopropanol, butanol, DMF, acetonitrile, chloroform, dichloromethane, tetrahydrochysene furan
Mutter, toluene, benzene, 1,4- dioxane, acetone etc..
Beneficial effect
Contain 1- substitution -5- trifluoromethyl -4- pyrazoles connection 1,3,4- oxadiazole class thioethers and sulfone class synthesized by the present invention
The biological activity test result of compound shows, compound to preventing and treating bacterial blight of rice, wheat scab, capsicum wilt,
Canker of apple fruit, sclerotinia sclerotiorum, the late blight of potato and rice sheath blight disease have good bioactivity.
Embodiment
Embodiment 1：1- phenyl -4- ((5- methyl mercaptos) -1,3,4- oxadiazolyls) -5- Trifluoromethyl-1 H- pyrazoles（A1）'s
Prepare
1）1- phenyl -5- Trifluoromethyl-1sHThe preparation of -4- pyrazoles hydrazides
With condenser pipe, thermometer 250 mL there-necked flasks in, sequentially add ethyoxyl methene trifluoroacetyl acetic acid second
Ester（66.05 mmol）, phenylhydrazine（69.35 mmol）, ethanol（50 mL）, it is heated to 80oC, react 24 h, TLC detection reactions
Terminate, be down to normal temperature, be evaporated under reduced pressure out solvent, remaining oily liquids is not purified to be directly dissolved in 80% hydrazine hydrate solution（100
mmol）In, it is heated to reflux 2 hours, TLC detection reactions terminate, and system is down into normal temperature, filtered, and solid is washed with water, after drying
Obtain product, white solid, yield 81.8%, fusing point 146-148oC; 1H-NMR (500 MHz, DMSO-D6): δ: 9.73
(s, 1H, NH), 8.05 (s, 1H, pyrazole H), 7.73-7.41 (m, 5H, benzene H), 4.50 (s,
2H, NH2); 13CNMR (125 MHz, DMSO-d 6 ) δ: 160.35, 139.94, 139.37, 130.51, 129.90,
126.50, 120.92, 120.35, 118.77; IR(KBr) ν: 3324, 3256, 3107, 3037, 1678,
1622, 1569, 1532, 1500, 1465, 1400, 1284, 1174, 1138, 973, 859, 768, 678 cm-1;
MS(ESI): m/z 271 [M+H] +。
2）The preparation of 5- (5- Trifluoromethyl-1s-phenyl -1H- pyrazoles -4- bases) -1,3,4- oxadiazole -2- mercaptan
With condenser pipe, thermometer 250 mL there-necked flasks in, be separately added into 1- phenyl -5- Trifluoromethyl-1sH- 4- pyrroles
Azoles hydrazides (13.1 mmol), potassium hydroxide（13.1mol）, carbon disulfide（26.1mmol）And ethanol（100 mL）, room temperature stirs
Mix 24 hours, TCL detection reactions terminate, and are not further purified, continuously add potassium hydroxide（13.1mol）, 70oC stirrings 24 are small
Shi Hou, TLC detection terminate reaction, and rotation removes solvent, dilute HCl（1 mol/L）Washing, filter, filter cake is washed with water, and is obtained in vain after drying
Color solid, yield 76.4%, fusing point 169-170oC; 1H-NMR (500 MHz, DMSO-D6) δ:9.43 (s, 1H,
SH), 8.43 (s, 1H, pyrazole H), 7.72 – 7.46 (m, 5H, Ar H); 13C NMR(125 MHz,
DMSO-d 6 ) δ: 177.96, 154.21, 141.15, 138.89, 130.96, 129.95, 126.65, 120.45,
118.30, 108.04; IR(KBr) ν: 3101, 2925, 2775, 1640, 1596, 1540, 1500, 1419,
1408, 1299, 1184, 1088, 980, 950, 767, 691 cm-1; MS(ESI): m/z 311 [M+H] +。
3）1- phenyl -4- ((5- methyl mercaptos) -1,3,4- oxadiazolyls) -5- Trifluoromethyl-1 H- pyrazoles（A1）Preparation
In 25 mL reaction bulb, 5- (5- Trifluoromethyl-1s-phenyl -1 are separately added intoH- pyrazoles -4- bases) -1,3,4-
Oxadiazole -2- mercaptan (1.6 mmol), iodomethane（3.2 mmol）With 50% potassium hydroxide aqueous solution（20 mL）, it is stirred at room temperature,
Reaction 12 hours, TLC detections terminate reaction, filtering, crude product are obtained, through column chromatography（Petrol ether/ethyl acetate=20:1）Purifying,
Obtain target compound A1, white solid, yield 98.0%, fusing point 88 ~ 89oC; 1H NMR (500 MHz, DMSO-d 6 )δ:
8.42 (s, 1H, pyrazole H), 7.99-7.24 (m, 5H, Ar H), 2.72 (s, 3H, CH3); 13C NMR
(125 MHz, DMSO-d 6 ) δ: 165.87, 158.47, 141.10, 138.97, 130.85, 129.90, 126.60,
120.56, 118.41, 108.46, 14.77; IR(KBr) ν: 3121, 3054, 2933, 1635, 1597, 1507,
1498, 1472, 1410, 1292, 1186, 1137, 979, 941, 767, 693 cm-1; MS(ESI): m/z 327
[M+H] +。
Embodiment 2：1- methyl -4- ((5- methyl mercaptos) -1,3,4- oxadiazolyls) -5- Trifluoromethyl-1 H- pyrazoles（A14）
Preparation
1）The preparation of 1- methyl -5- Trifluoromethyl-1 H- 4- pyrazoles hydrazides
With condenser pipe, thermometer 250 mL there-necked flasks in, sequentially add ethyoxyl methene trifluoroacetyl acetic acid second
Ester（66.05 mmol）, methyl hydrazine (40%)（69.35 mmol）, ethanol（50 mL）, it is heated to 80oC, react 24 h, TLC inspections
Survey reaction to terminate, be down to normal temperature, be evaporated under reduced pressure out solvent, remaining oily liquids is not purified to be directly dissolved in 80% hydrazine hydrate solution
（100 mmol）In, it is heated to reflux 2 hours, TLC detection reactions terminate, and system is down into normal temperature, filtered, solid is washed with water,
Product, white solid, yield 64.6%, fusing point 115-116 are obtained after dryingoC; 1H-NMR (500 MHz, DMSO-D6): δ:
9.42 (s, 1H, NH), 8.20 (s, 1H, pyrazole H), 4.37 (s, 2H, NH2), 3.89 (s, 3H,
CH3); 13CNMR (125 MHz, DMSO-d 6 ) δ: 160.51, 139.47, 133.82, 121.47, 115.42,
40.44; MS(ESI): m/z 209 [M+H] +。
2）The preparation of 5- (5- Trifluoromethyl-1s-methyl isophthalic acid H- pyrazoles -4- bases) -1,3,4- oxadiazole -2- mercaptan
With condenser pipe, thermometer 250 mL there-necked flasks in, be separately added into 1- methyl -5- Trifluoromethyl-1 H-4- pyrroles
Azoles hydrazides (13.1 mmol), potassium hydroxide（13.1mol）, carbon disulfide（26.1mmol）And ethanol（100 mL）, room temperature stirs
Mix 24 hours, TCL detection reactions terminate, and are not further purified, continuously add potassium hydroxide（13.1mol）, 70oC stirrings 24 are small
Shi Hou, TLC detection terminate reaction, and rotation removes solvent, dilute HCl（1 mol/L）Washing, filter, filter cake is washed with water, and is obtained in vain after drying
Color solid, yield 70.8%, fusing point 140-141oC; 1H-NMR (500 MHz, DMSO-D6) δ:14.81 (s, 1H,
SH), 8.16 (s, 1H, pyrazole H), 4.06 (s, 3H, CH3); 13C NMR(125 MHz, DMSO-d 6 ) δ:
177.78, 154.40, 139.74, 129.19, 119.75, 106.98, 40.46; MS(ESI): m/z 251 [M+H]+。
3）1- methyl -4- ((5- methyl mercaptos) -1,3,4- oxadiazolyls) -5- Trifluoromethyl-1 H- pyrazoles（A14）Preparation
In 25 mL reaction bulb, 5- (5- Trifluoromethyl-1s-methyl isophthalic acid H- pyrazoles -4- bases) -1,3,4- is separately added into
Oxadiazole -2- mercaptan (1.6 mmol), iodomethane（3.2 mmol）With 50% potassium hydroxide aqueous solution（20 mL）, it is stirred at room temperature,
Reaction 12 hours, TLC detections terminate reaction, filtering, crude product are obtained, through column chromatography（Petrol ether/ethyl acetate=20:1）Purifying,
Obtain target compound A14, white solid, yield 96.8%, fusing point 54 ~ 55oC; 1H NMR (500 MHz, DMSO-d 6 )δ:
8.17 (s, 1H, pyrazole H), 4.07 (s, 3H, N-CH3), 2.71 (s, 3H, S-CH3); 13C NMR
(125 MHz, DMSO-d 6 ) δ: 165.50, 158.64, 139.71, 129.09, 119.89, 107.42, 40.44,
14.81; MS(ESI): m/z 265 [M+H] +。
Embodiment 3：1- phenyl -4- ((5- ethylsulfonyls) -1,3,4- oxadiazolyls) -5- Trifluoromethyl-1sH- pyrazoles（B1）
Preparation
With condenser pipe, thermometer 25 mL there-necked flasks in, sequentially add 1- phenyl -4- ((5- ethylmercapto groups) -1,3,
4- oxadiazolyls) -5- Trifluoromethyl-1sH- pyrazoles（615.8μmol）, acetic acid（3 mL）And KMnO4（615.8μmol）, often
Temperature reaction 24 hours, TLC detections terminate reaction, regulation pH value to 7 ~ 8, filtered, crude product is through column chromatography（Dichloromethane：Acetic acid
Ethyl ester=10:1）Purifying, target compound B1.White solid, yield 64.6%, fusing point 72 ~ 73oC; 1H NMR(500
MHz, DMSO-d 6 ) δ: 8.58 (s, 1H, pyrazole H), 7.64-7.58 (m, 5H, benzene H), 3.78
(q, J = 7.3 Hz, 2H, S-CH2), 1.31 (t, J = 7.4 Hz, 3H, CH3);13C NMR(125 MHz,
DMSO-d 6 ) δ: 161.83, 159.90, 141.92, 138.81, 131.12, 130.02, 126.75, 120.40,
118.24, 107.54, 50.07, 7.15; IR (KBr): ν3089, 2981, 2936, 1627, 1595, 1506,
1489, 1457, 1418, 1354, 1186, 1155, 978, 944, 767, 730, 690, 621 cm-1; MS
(ESI): m/z 373 [M+H] +。
Using similar synthetic method, other compounds of the present invention, the proton nmr spectra of part of compounds have been synthesized
（1H NMR）Data, physico-chemical property and analytical data of mass spectrum are as shown in table 1：
Biological activity test example
Embodiment 4：Suppress in part of compounds room bacterial blight of rice pathogen (X. oryzae) biological activity test
By bacterial blight of rice pathogen in NA（Beef extract：3 g, peptone：5 g, yeast extract：1 g, glucose：
10 g, agar：15 g, secondary water：1 L；PH=7.0 or so are adjusted with 5 mol/L NaOH solution, 121o20 min of C sterilizings）Gu
Rule above body culture medium, 28 oCulture is until growing single bacterium colony under C.Rice bacterial leaf spot on picking NA solid mediums
Sick pathogen single bacterium drops down onto NB fluid nutrient mediums（Beef extract：3 g, peptone：5 g, yeast extract：1 g, glucose：10
G, secondary water：1 L；PH=7.0 or so are adjusted with 5 mol/L NaOH solution, 121o20 min of C sterilizings）In, 28 oC、180
Rpm constant-temperature tables shaken cultivation is standby to growth logarithmic phase.
Synthesized compound and comparison medicament are configured to concentration as 200,100 respectivelyμG/mL toxic NB liquid training
Base is supported, adds 40μThe NB fluid nutrient mediums containing bacterial blight of rice pathogen of the above-mentioned preparations of L, 28 oC, 180 rpm are permanent
The warm h of shaking table shaken cultivation 24 ~ 48, OD values are determined by the bacterium solution of each concentration on ELIASA（OD595）.And determine in addition dense
Spend for 200,100μThe NB fluid nutrient medium OD values of g/mL medicaments and comparison medicament, to medicament in itself caused by OD values carry out school
Just.The calculation formula for correcting OD values and inhibiting rate is as follows：
Correct the OD values=values of OD containing bacterium culture medium-aseptic culture medium OD values
Inhibiting rate=（Control medium bacterium solution OD values after correction-correct toxic culture medium OD values）Control medium after/correction
Bacterium solution OD value × 100%
Determined according to above method, the inhibitory activity of partial target compound is shown in Table 2.
From table 2 it can be seen that such thioether and sulfone compound are to rice leaf spot bacteria（X. oryzae）With certain
Inhibitory activity.100μgUnder/mL concentration, wherein compound A4, A6, B1, B2 is equal to the inhibiting rate of rice leaf spot bacteria
More than 60%, better than comparison medicament Yekuzuo（54.2%）；Target compound B1, B2 are 100μgIt is white to rice under/mL concentration
The inhibiting rate of leaf spoting bacteria nearly 100%；Compound A1, A8, A9, A11, B4 are to the inhibiting rate of rice leaf spot bacteria with compareing
Medicament Yekuzuo is suitable.Through analysis it can be found that compared with branched alkane when substituent is branched paraffin on thioether and sulfonyl in structure
Hydrocarbon activity will get well；To be got well compared with benzyl activity when substituent is alkane on sulfonyl in structure.
Embodiment 5：High-activity compound is to bacterial blight of rice pathogen virulence regression equation and EC50The measure of value
The compound of synthesis and commercial References medicament are each configured to the toxic NB fluid nutrient mediums of 5 respective concentrations,
5 mL are taken in test tube, toxic aseptic liquid nutrient medium OD values are determined with ELIASA（OD595）, add 40μL contains the white leaf of rice
The NB fluid nutrient mediums of rot pathogen, then 28 oC, the h of 180 rpm constant-temperature tables shaken cultivation 24, is determined with ELIASA
The OD values of each concentration bacterium solution（OD595）.And in addition determine the toxic sterile NB fluid nutrient mediums of comparison medicament OD values and
The OD values of each concentration bacterium solution after 24 h, to due to medicament in itself caused by OD values be corrected.By inhibiting rate data conversion into
NiqueMin（y）, drug concentration（μg/mL）It is converted into logarithm value（x）, regression analysis is carried out in Excel data processing softwares, is obtained
To virulence regression equation（y=ax+b）And coefficient correlation（R）, calculate concentration during medicament suppresses to pathogen（EC50）, and with corresponding
Commodity medicament as control.For bacterial blight of rice pathogen, choose high-activity compound B1, B2 in target compound and enter
Gone virulence regression equation and suppress in concentration（EC50）Measure, the results are shown in Table 3.
From table 3 it can be seen that the EC of target compound B1, B2 to rice leaf spot bacteria50Value is respectively 31.64 Hes
16.56 μG/mL, it is superior to commodity medicament Yekuzuo（92.61μg/mL）, show efficient bioactivity.
Embodiment 6：Part of compounds is to phytopathogen（Fusarium graminearum, capsicum wilt bacterium and canker of apple fruit
Bacterium）Biological activity test
Using isolated growth performance rate method（Tarum, K. C. et al.;J. Agric. Food Chem., 2006,
54, 2129-2133.）Determine the bacteriostatic activity of compound.Heat potato dextrose agar（PDA culture medium：Ma Ling
The g of potato 800, the g of agar 80, the g of glucose 80, the mL of distilled water 4000）To molten state, by 10 mL decoctions（10 times of final concentrations
Decoction）Import in 90 mL PDA culture mediums, fully shake up, uniformly pour into the cm of diameter 9 culture dish, it is horizontal positioned, treat cold
But solidify.The bacterium dish for taking a diameter of 4 mm is played in the edge card punch for the fresh pathogen bacterium colony for having cultivated 4 d, by bacterium dish
The center of PDA plate containing medicament is inverted in, is subsequently placed in 27 oCulture is inverted in C constant temperature and humidity incubators, treats that blank control bacterium colony is given birth to
Start to observe when length is to close at plate 2/3rds, crossing method measurement colony diameter, average.Blank control is not added with
Medicament, but solvent and 0.5% Tween 20 containing same concentration, each processing is in triplicate.
Inhibiting rate of the medicament to mycelial growth is calculated by below equation：
I(%)=(C-T)/（C-0.4）×100%
Wherein I is inhibiting rate, and C is blank control diameter（cm）, T is processing diameter（cm）
Part of compounds is 100μTo fusarium graminearum, capsicum wilt bacterium and Valsa mali under g/mL concentration
Inhibiting rate be shown in Table 4.
From table 4, it can be seen that it is 100 in concentrationμgDuring/mL, such thioether and sulfone compound are to fusarium graminearum
（G. zeae）, capsicum wilt bacterium（F. oxysporum）, Valsa mali（C. mandshurica）With certain suppression
System activity.When substituent is alkane or alkene, target compound is 100 in concentrationμgDuring/mL, to fusarium graminearum（G. zeae）Capsicum wilt bacterium（F. oxysporum）Valsa mali（C. mandshurica）There is good suppression to live
Property, wherein compound A1, A2, B1, B2 is to fusarium graminearum（G. zeae）Inhibiting rate more than 50%；A1, B1, B2 are to peppery
Green pepper wilt（F. oxysporum）Inhibiting rate more than 50%；A1, B1, B2 are to Valsa mali（C. mandshurica）Inhibiting rate more than 50%；Wherein compound B-11, B2 are to capsicum wilt bacterium（F. oxysporum）Suppression
Rate processed is superior to Dui Zhao Yao hymexazos（63.1%）；Target compound B1 is to Valsa mali（C. mandshurica）Suppression
Rate processed is better than Dui Zhao Yao hymexazos（66.1%）, target compound B2 is to Valsa mali（C. mandshurica）Suppression
Rate is suitable with Dui Zhao Yao hymexazos.Binding compounds structure, preliminary structure effect is carried out to measured compound antifungal activity and is closed
It is that analysis is found, in thioether and sulfone compound, when substituent is alkane, the antibacterial activity of compound is with the increasing of chain length
Grow and decline, when carbon atom number is identical, the compound of branched paraffin substitution is antibacterial compared with the compound that linear paraffin substitutes
Activity will height；When substituent is benzyl, compound is to fusarium graminearum（G. zeae）, capsicum wilt bacterium（F. oxysporum）, Valsa mali（C. mandshurica）3 kinds all do not show preferable inhibitory activity for examination fungi, take
The position of substitution for benzyl and its influenceed on electron attractivity on its bioactivity little, also its bioactivity has not been changed
Kind, when phenyl ring on benzyl is substituted with other heterocycles, its bioactivity still fails to increase.Compared with thio-ether type compounds,
The bioactivity of the sulfone compound of its alkane substitution increases, and to fusarium graminearum（G. zeae）, capsicum wilt
Bacterium（F. oxysporum）, Valsa mali（C. mandshurica）3 kinds are respectively provided with certain inhibitory activity for examination fungi,
Show certain broad spectrum activity.
Embodiment 7：Part of compounds is to phytopathogen（Sclerotinia sclerotiorum, phytophthora infestans and rice banded sclerotial blight
Germ）Biological activity test
Method of testing is same as Example 6, and part of compounds is to Sclerotinia sclerotiorum, phytophthora infestans and rice line
The inhibiting rate of rot bacterium is shown in Table 5.
As can be seen from Table 5, it is 100 in concentrationμgDuring/mL, such thioether and sulfone compound are to the late blight of potato
Bacterium（P. infestans）, Sclerotinia sclerotiorum（S. sclerotiorum）, Rhizoctonia solani Kuhn（T.cucumeris）Have
Certain inhibitory activity.When substituent is alkane or alkene, target compound is 100 in concentrationμgDuring/mL, to pony bell
Potato late disease bacteria（P. infestans）, Sclerotinia sclerotiorum（S. sclerotiorum）, Rhizoctonia solani Kuhn
（T.cucumeris）There are good inhibitory activity, wherein compound A1, A4, B1, B2 Phytophthora infestans（P. infestans）Inhibiting rate more than 50%；Target compound A1, A2, A4, A5, B1, B2 are to Sclerotinia sclerotiorum（S. sclerotiorum）Inhibiting rate more than 50%；Target compound A1, A2, A5, B1, B2 are to Rhizoctonia solani Kuhn
（T.cucumeris）Inhibiting rate more than 50%.Binding compounds structure, measured compound antifungal activity is carried out
Structure-activity Relationship analysis is found, in thioether and sulfone compound, when substituent is alkane, the antibacterial activity of compound with
The growth of chain length and decline, when carbon atom number is identical, the compound of branched paraffin substitution is compared with the change that linear paraffin substitutes
The bacteriostatic activity of compound will height；When substituent is benzyl, compound Phytophthora infestans（P. infestans）, rape
Hyphal cluster germ（S. sclerotiorum）, Rhizoctonia solani Kuhn（T.cucumeris）3 kinds all do not show preferably for examination fungi
Inhibitory activity, the position of substitution of substituted benzyl and its influenceed on electron attractivity on its bioactivity it is little, by benzene on benzyl
When ring is substituted with other heterocycles, its bioactivity fails to increase.Generally, compared with thio-ether type compounds, its alkane takes
The bioactivity of the sulfone compound in generation increases, and Phytophthora infestans（P. infestans）, sclerotinia sclerotiorum
Bacterium（S. sclerotiorum）, Rhizoctonia solani Kuhn（T.cucumeris）3 kinds are respectively provided with certain inhibitory activity for examination fungi,
Show certain broad spectrum activity.
Claims (3)
1.1- substitution -5- trifluoromethyl -4- pyrazoles joins 1,3,4- oxadiazole thioethers or sulfone derivatives, structure are as follows：
2. 1- substitutions -5- trifluoromethyl -4- pyrazoles connection 1,3,4- oxadiazoles thioether according to claim 1 or sulfone class derive
Application of the thing in the agricultural chemicals and pesticides additive agent of preventing and treating crop plants pathogen.
3. 1- substitutions -5- trifluoromethyl -4- pyrazoles connection 1,3,4- oxadiazoles thioether according to claim 2 or sulfone class derive
The application of thing, it is characterized in that preparing preventing and treating rice leaf spot bacteria, fusarium graminearum, capsicum wilt bacterium, apple decay
Germ, Sclerotinia sclerotiorum, phytophthora infestans and Rhizoctonia solani Kuhn agricultural chemicals and pesticides additive agent in application.
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| CN106167472B (en) * | 2016-03-30 | 2018-07-27 | 贵州大学 | A kind of 2,5- substituent groups -1,3,4- oxadiazole double thioethers analog derivative, preparation method and application |
| CN106336409B (en) * | 2016-07-28 | 2019-05-24 | 浙江工业大学 | A kind of thiadiazoles -2- thio-ether type compounds and its preparation method and application containing trifluoromethyl pyrazol |
| CN106234381B (en) * | 2016-07-28 | 2019-05-24 | 浙江工业大学 | A kind of application of the thiadiazoles -2- thio-ether type compounds as fungicide containing trifluoromethyl pyrazol |
| CN106243101B (en) * | 2016-07-28 | 2019-05-24 | 浙江工业大学 | A kind of 1,3,4- thiadiazoles sulfide derivative and its preparation method and application |
| CN107056773B (en) * | 2017-04-24 | 2020-07-14 | 贵州大学 | Pyrazole dioxa (thia) diazole compound containing pyridinium salt and preparation method and application thereof |
| CN108218848B (en) * | 2018-01-22 | 2020-12-18 | 贵州大学 | Trifluoromethyl pyridine bisoxadiazole (ether) derivative and application thereof |
| CN112239464B (en) * | 2019-07-19 | 2022-09-16 | 南京农业大学 | Quinazoline-4 (3H) -ketone derivative containing 1,3, 4-oxadiazole, preparation method and application |
| CN112898223A (en) * | 2021-02-01 | 2021-06-04 | 贵州大学 | 1,3, 4-oxadiazole compound containing sulfonate/carboxylate structure and preparation method and application thereof |
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| CN113563281B (en) * | 2021-07-06 | 2023-11-24 | 贵州大学 | Benzophenone compound containing 1,3, 4-thiadiazole thioether structure and application thereof |
| CN113880768A (en) * | 2021-09-07 | 2022-01-04 | 贵州大学 | Synthesis method of 1, 5-disubstituted-1H-pyrazole-4-ethyl formate |
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