CN102850342B - Oxdiazole compound containing thiadiazole, preparation method and applications thereof - Google Patents

Oxdiazole compound containing thiadiazole, preparation method and applications thereof Download PDF

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CN102850342B
CN102850342B CN201210324830.0A CN201210324830A CN102850342B CN 102850342 B CN102850342 B CN 102850342B CN 201210324830 A CN201210324830 A CN 201210324830A CN 102850342 B CN102850342 B CN 102850342B
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cucumber
phenyl
fluorophenyl
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CN102850342A (en
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武宏科
童建颖
孙娜波
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Zhejiang University of Technology ZJUT
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Abstract

The present invention relates to an oxdiazole compound containing thiadiazole, and a preparation method thereof. The compound of the present invention has a structure represented by a formula (I), wherein R is a substituted phenyl, the benzene ring on the substituted phenyl is monosubstituted or polysubstituted, the substituted group is independently selected from one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy and halogen. The compound of the present invention has characteristics of simple preparation and excellent bactericidal activity, and can be used as a bactericidal agent for prevention and control of cucumber tan disease, cucumber bacterial angular leaf spot disease, cucumber gummy stem blight, cucumber downy mildew, and cucumber sclerotium disease. The present invention further relates to a bactericidal agent containing the compound.

Description

A kind of containing thiadiazoles oxadiazole compounds and preparation and application thereof
technical field
The present invention relates to a kind of containing thiadiazoles oxadiazole compounds and 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(replacement benzylthio-)-1,3,4-oxadiazole derivatives and preparation and application thereof.
background technology
Heterogeneous ring compound has been the main flow of novel pesticide development, and in heterogeneous ring compound, again based on nitrogen heterocyclic ring.1,3,4-oxadiazole compounds also has very important biological activity, comprises anti-inflammatory, anticancer, antiviral, bacteriostasis and herbicides isoreactivity.As 2-substituted pyrazolecarboxylic-5-methylthio group-1,3, the 4-oxadiazole of synthesis, when 100 mg/L, good inhibit activities is shown to Rhizoctonia solani Kuhn; 2-methyl-5-replaces benzylthio--1,3,4-oxadiazole and have good inhibition to rape under 100ppm.1,2,3 thiadiazole compounds are development in recent years classes more rapidly, and many commercial desinsections, sterilization, weedicide, plant induced resistance agent belongs to such.Such as, the sterilant tiadinil (thiadinal) with interior absorption of Japanese agricultural chemicals company exploitation is mainly used in the control of rice blast, to other diseases as brown spot, bacterial leaf-blight, banded sclerotial blight and sesame leaf rot etc. also have good prevention effect.And the induced resistance of plant activiator Bion(BTH of Novartis Co., Ltd's exploitation).
But, there is not yet relevant 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(replacement benzylthio-) synthesis of-1,3,4-oxadiazole derivatives and the bibliographical information of bioactivity research thereof.
summary of the invention
The object of the invention is to provide a kind of 2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(replacement benzylthio-)-1,3,4-oxadiazole derivatives with fungicidal activity and preparation method thereof and application.
The object of the present invention is achieved like this:
Shown in formula (I) containing thiadiazoles oxadiazole compounds:
（I）
In formula (I): R is substituted-phenyl, described replacement is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxyl group and halogen.
Formula of the present invention (I) compound can obtain by the following method: formula (II) compound and formula (III) compound are mixed with organic solvent, under the existence of alkaline matter, 0 ~ 25 DEG C of (preferably 25 DEG C) stirring reaction, TLC follows the tracks of reaction (with the sherwood oil of volume ratio 1:1 ~ 5 and ethyl acetate mixture for developping agent, follow the tracks of raw material point to disappear for reacting completely), after reacting completely, reaction solution is placed in frozen water, separate out solid, filter, it (take volume ratio as sherwood oil and the ethyl acetate mixture of 5:1 is eluent that filtrate carries out silica gel column chromatography, collect the elutriant containing target components, dry) or carry out recrystallization with recrystallization solvent, shown in acquisition formula (I) containing thiadiazoles oxadiazole compounds,
Recrystallization solvent is one or more in sherwood oil, ethyl acetate, normal hexane or ethanol, the mixing solutions of preferred sherwood oil and ethyl acetate;
Organic solvent is one or more in DMF, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane or acetone, is preferably DMF (DMF);
Alkaline matter is one or more in salt of wormwood, sodium bicarbonate, sodium hydroxide, potassium hydroxide or sodium hydride, is preferably salt of wormwood;
The ratio of the amount of substance of formula (II) compound, formula (III) compound and alkaline matter is 1:1.0 ~ 1.5:1.0 ~ 1.5, is preferably 1:1.0:1.2; Organic solvent volume consumption with the gauge of formula (II) combinations of materials for 2-10ml/mmol, preferred 4ml/mmol.
In formula (I) and formula (III): as previously mentioned, X is halogen or tosic acid ester group in the definition of R.
The present invention also provides the thiadiazoles oxadiazole compound that contains shown in formula (I) preventing and treating the application in Cucumber Target Leaf Spot, cucumber bacterial angular leaf spot, cucumber blight dis-ease, cucumber downy mildew, cucumber timberrot.
The present invention also provides containing the sterilant containing thiadiazoles oxadiazole compound shown in formula (I), and it also comprises acceptable auxiliary agent at least one agricultural chemicals.
Compared with prior art, beneficial effect of the present invention is mainly reflected in: the invention provides a kind of its preparation method and the application that contain thiadiazoles oxadiazole compounds and intermediate, this compound is the new compound with fungicidal activity, for the research and development of novel pesticide provide the foundation.
embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Oxadiazole compounds (I) containing thiadiazoles of the present invention can synthesize in the following manner:
The K of 2 mmol Compound II per, 2 mmol replacement benzyl chlorides, 8mL DMF and 2.4mmol is added in 25 mL round-bottomed flasks 2cO 3, stirring at room temperature, TLC detection reaction progress.After completion of the reaction, in reaction solution impouring 30mL frozen water, separate out solid, filter, precipitation, silica gel column chromatography, obtains solid product.
Embodiment 1
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(2,4-benzyl dichloride sulfenyl)-1,3,4-oxadiazoles (Ia): white crystal, productive rate 84%, fusing point 85-86 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.06 (s, 3H, Het-Me), 4.60 (s, 2H, SCH 2), 7.22 (d, j=8.49Hz, 1H, ArH), 7.44 (s, 1H, ArH), 7.61 (d, j=8.27Hz, 1H, ArH). MS (ESI), m/z:360 (M+1). Elemental anal. (%), calculated:C, 40.12; H, 2.24; N, 15.60; Found:C, 39.88; H, 2.55; N, 15.79.
Embodiment 2
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(3-benzyl chloride sulfenyl)-1,3,4-oxadiazoles (Ib): white crystal, productive rate 88%, fusing point 88-89 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.06 (s, 3H, Het-Me), 4.51 (s, 2H, SCH 2), 7.30 (s, 2H; ArH); (7.34-7.39 m, 1H, ArH); 7.47 (s; 1H, ArH). MS (ESI), m/z:326 (M+1). Elemental anal. (%); calculated:C, 44.37; H, 2.79; N, 17.25; Found:C, 44.67; H, 2.85; N, 17.43.
Embodiment 3
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(3-fluorine benzylthio-)-1,3,4-oxadiazoles (Ic): white crystal, productive rate 79%, fusing point 63-64 ?c; 1h NMR (CDCl 3, 400 MHz), δ: 3.06 (s, 3H, Het-Me), 4.53 (s, 2H, SCH 2), 7.04 (t, j=7.46Hz, 1H, ArH), 7.19 (d, j=9.27Hz, 1H, ArH), 7.29-7.35 (m, 2H, ArH). and MS (ESI), m/z:309 (M+1). Elemental anal. (%), calculated:C, 46.74; H, 2.94; N, 18.17; Found:C, 46.45; H, 3.12; N, 18.44.
Embodiment 4
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(2-benzyl chloride sulfenyl)-1,3,4-oxadiazoles (Id): white crystal, productive rate 81%, fusing point 98-99 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.06 (s, 3H, Het-Me), 4.65 (s, 2H, SCH 2), 7.26-7.30 (m, 2H, ArH), 7.41 (d, j=7.45Hz, 1H, ArH), 7.63 (d, j=7.14Hz, 1H, ArH). MS (ESI), m/z:326 (M+1). Elemental anal. (%), calculated:C, 44.37; H, 2.79; N, 17.25; Found:C, 44.64; H, 2.99; N, 17.01.
Embodiment 5
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(2-fluorine benzylthio-)-1,3,4-oxadiazoles (Ie): white crystal, productive rate 85%, fusing point 78-79 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.06 (s, 3H, Het-Me), 4.58 (s, 2H, SCH 2), 7.07-7.14 (m, 2H, ArH), 7.29-7.33 (m, 1H, ArH), 7.55 (t, j=8.20Hz, 1H, ArH). MS (ESI), m/z:309 (M+1). Elemental anal. (%), calculated:C, 46.74; H, 2.94; N, 18.17; Found:C, 46.88; H, 3.12; N, 18.43.
Embodiment 6
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(2-methyl benzylthio-)-1,3,4-oxadiazoles (If): white crystal, productive rate 83%, fusing point 79-80 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 2.45 (s, 3H, Ar-Me), 3.06 (s, 3H, Het-Me), 4.59 (s, 2H, SCH 2), 7.8-7.23 (m, 2H, ArH), 7.29-7.34 (m, 1H, ArH), 7.42 (d, j=6.11Hz, 1H, ArH). MS (ESI), m/z:305 (M+1). Elemental anal. (%), calculated:C, 51.30; H, 3.97; N, 18.41; Found:C, 51.55; H, 3.87; N, 18.49.
Embodiment 7
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(4-fluorine benzylthio-)-1,3,4-oxadiazoles (Ig): white crystal, productive rate 77%, fusing point 84-85 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 2.45 (s, 3H, Ar-Me), 3.06 (s, 3H, Het-Me), 4.52 (s, 2H, SCH 2), 7.06 (t, j=8.55Hz, 2H, ArH), 7.46 (d, j=5.76Hz, 2H, ArH). MS (ESI), m/z:305 (M+1). Elemental anal. (%), calculated:C, 46.74; H, 2.94; N, 18.17; Found:C, 46.88; H, 3.06; N, 17.99.
Embodiment 8
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(benzylthio-)-1,3,4-oxadiazole (Ih): white crystal, productive rate 88%, fusing point 72-73 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.05 (s, 3H, Het-Me), 4.55 (s, 2H, SCH 2), 7.30-7.37 (m, 3H, ArH), 7.46 (d, j=7.21Hz, 2H, ArH). MS (ESI), m/z:291 (M+1). Elemental anal. (%), calculated:C, 49.64; H, 3.47; N, 19.30; Found:C, 50.01; H, 3.78; N, 19.12.
Embodiment 9
2-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-base)-5-(4-methoxybenzyl sulfenyl)-1,3,4-oxadiazoles (Ii): white crystal, productive rate 79%, fusing point 56-57 DEG C; 1h NMR (CDCl 3, 400 MHz), δ: 3.05 (s, 3H, Het-Me), 3.80 (s, 3H, OMe), 4.52 (s, 2H, SCH 2), 6.87 (d, j=8.41Hz, 2H, ArH), 7.41 (d, j=8.46Hz, 2H, ArH). MS (ESI), m/z:321 (M+1). Elemental anal. (%), calculated:C, 48.73; H, 3.78; N, 17.49; Found:C, 48.78; H, 3.99; N, 17.54.
Fungicidal activity is tested
For studying thing: cucumber (Cucumis sativusl .), kind is: the close thorn in Xintai City.
Envrionment conditions: cucumber seedling 2 cotyledon periods.
Test medicine and treatment dosage: each sample all establishes an experimental concentration 500mg/L.
Strains tested: cucumber aphid, cucumber bacterial angular leaf spot bacterium, cucumber didymella bryoniae, bacterium of downy mildew of cucumber, cucumber sclerotiorum, above-mentioned bacterial strains is all from vegetable or flower institute of the Chinese Academy of Agricultural Sciences.
3 repetitions are established in all process respectively, and each repetition 10 young plants, adopt random alignment in greenhouse.
Dispenser, vaccination ways: reagent agent and contrast medicament are prepared by experimental concentration respectively, reagent agent and contrast medicament are evenly sprayed in cucumber cotyledons the morning in fine day, inoculate pathogenic bacteria after 2 hours, moisturizing is cultivated.
Wait contrast abundant morbidity " Invest, Then Investigate " disease index and calculate prevention effect, the results are shown in Table 1.
table 1the live body fungicidal activity of target compound
Numbering Cucumber Target Leaf Spot Cucumber bacterial angular leaf spot Cucumber blight dis-ease Cucumber downy mildew Cucumber timberrot
Ia 77.66 68.08 -2.73 41.78 36.93
Ib 53.68 38.02 19.13 35.97 12.98
Ic 84.55 53.30 59.52 68.43 21.16
Id 92.77 58.22 48.17 53.13 -10.26
Ie 94.64 47.98 56.81 53.13 -21.48
If 88.12 53.27 26.02 45.39 3.05
Ig 72.35 14.78 31.99 46.24 16.48
Ih 72.72 65.59 23.72 42.75 32.51
Ii 64.26 32.62 -11.66 59.56 0.81

Claims (2)

1. the oxadiazole compounds containing thiadiazoles shown in formula (I),
R is Chloro-O-Phenyl, adjacent fluorophenyl, a fluorophenyl, to fluorophenyl, and o-methyl-phenyl-, phenyl, 2,4 dichloro benzene base.
2. the application of oxadiazole compound in the following disease of control containing thiadiazoles as claimed in claim 1, wherein prevent and treat Cucumber Target Leaf Spot, wherein R is Chloro-O-Phenyl, adjacent fluorophenyl, between fluorophenyl, to fluorophenyl, o-methyl-phenyl-, phenyl, 2,4 dichloro benzene base; Cucumber bacterial angular leaf spot, wherein R is Chloro-O-Phenyl, 2,4 dichloro benzene base; Cucumber blight dis-ease, R is adjacent fluorophenyl, a fluorophenyl, to fluorophenyl, o-methyl-phenyl-, phenyl; Cucumber timberrot, R be between fluorophenyl, to fluorophenyl, o-methyl-phenyl-, phenyl, 2,4 dichloro benzene base.
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CN102838593B (en) * 2012-10-08 2015-01-07 贵州大学 2-(4-methyl-1,2,3-thiadiazole)-5-(substituent)-1,3,4-oxa(thia)diazole derivative and application thereof
CN103896934A (en) * 2014-02-28 2014-07-02 盐城工学院 Thiadiazole-containing oxadiazole compound as well as preparation method and application thereof
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
CN114989155B (en) * 2021-03-01 2024-04-02 河北农业大学 1,3, 4-oxadiazole thioether derivative, and preparation method and application thereof

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CN102276596A (en) * 2011-06-23 2011-12-14 浙江工业大学 Thiadiazole compound as well as preparation and application thereof

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WO2004089367A1 (en) * 2003-04-11 2004-10-21 Novo Nordisk A/S Pharmaceutical use of substituted 1,2,4-triazoles
CN102276596A (en) * 2011-06-23 2011-12-14 浙江工业大学 Thiadiazole compound as well as preparation and application thereof

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