CN101845054B - Bis-triazolothiadiazole compounds containing 1,2,3-thiadiazole and preparation method and application thereof - Google Patents
Bis-triazolothiadiazole compounds containing 1,2,3-thiadiazole and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides bis-triazolothiadiazole derivatives containing 1,2,3-thiadiazole and a preparation method and application thereof. The invention relates to heterocyclic compounds containing 1,2-diazole, which have the following chemical structure general formula shown as the specification. The invention discloses a chemical structure and a synthesis method of the compounds with the general formula, a using method and application of the compounds for resisting TMV virus, and a using method and application of the compounds for inducing tobacco anti-TMV viruses. The invention further discloses a using method and application of the compounds with the general formula in inhibiting the growth of plant pathogenic fungi. The invention further discloses application of the compounds with the general formula in controlling agricultural, forest and garden plant diseases and plant virus diseases through the combination use with the traditional antivirus agents and bactericides.
Description
Technical field
Technical scheme of the present invention relates to the heterogeneous ring compound that contains 1,2-diazole, is specifically related to two triazolothiadiazole verivates.
Background technology
1,2, the 3-thiadiazoles derivative has wide biological activity; But commercial medical kind and pesticide species are all rare; Contriver's early-stage Study finds that this analog derivative has the activity of good inducing plant viral diseases and fungal disease, wherein; The first thiophene lures amine to belong to low toxicity compounds, just in the industrialization development process; Diazosulfide (BTH) and tiadinil (TDL) are the most successful plant activator of commercialized development, also are 1,2, the verivate of 3-thiadiazoles.1,2, the 4-triazole derivative also had suitable wide biological activity, and these two types of reactive groups are connected to the compound s-triazolo-thiadiazoles that forms in a part promptly had synthetic and bibliographical information (Shafiee, A. in 1977; Lalezari, I.; Mirrashed, M.; Nercesian, D.1,2,3-Selenadiazolyl-1,3,4-oxadiazole; 1,2,3-thiadiazolyl-1,3,4-oxadiazole and 5-(1,2; 3-thiadiazolyl)-and s-triazolo [3,4-b]-1,3,4-thiadiazole.J.Heterocyclic.Chem.1977,14,567-571); Thereafter, bibliographical information contain s-triazolo-thiadiazoles derivative and anti-microbial activity thereof (Zhang Ziyi, Chen Xin, the fused heterocyclic compound research-I.3-(4 '-pyridyl)-6-aryl-all-triazolo [3,4-b]-1 of pyridine group; 3, the synthetic and anti-microbial property of 4-thiadiazoles, chemical journal, 1991,49 (5): 513-520); The substituted s-triazolo-thiadiazoles derivative of part aryl has certain biological activity (Zhang Ziyi, Li Ming, Zhao Lan; Li Zhengming, Liao Renan, the research of fused heterocyclic compound (X)-3-aryl-6-benzamido-s-triazolo-[3; 4-b]-1,3, the synthetic and biological activity of 4-thiadiazole compound. SCI; 1994,15 (2): 220-223; Tensiometry, Zhang An incites somebody to action, Zhou Guangqiang, Zhang Ziyi .3-aryl-6-trichloromethyl-1,2,4-triazolo [3,4-b]-1,3, the synthetic and spectroscopic characterization of 4-thiadiazoles. organic chemistry, 2002,22 (9): 663-666); The s-triazolo-thiadiazoles derivative and the biological activity thereof that contain Glucopyranose (contain glucose substituting group s-triazolo-[3; 4-b]-1,3, the synthetic and bioactivity research of 4-thiadiazoles fused heterocyclic compound. Beijing Institute of Technology's journal; 2002,22 (6): 761-764).Contriver's research and design has in earlier stage been synthesized one type and has been contained 1,2, the triazolo thiadiazoles derivative (200810054334.1) of 3-thiadiazoles, and its chemical structure is following:
Bioactivity screening finds that this compounds has excellent bactericidal activity.In order to seek the more compound of high biological activity, the present invention designs and has synthesized one type and contain 1,2, and two s-triazolothiadiazole compounds of 3-thiadiazoles carry out bioactive screening and evaluation simultaneously, for the initiative research of novel pesticide provides the candidate compound.
Summary of the invention
Technical problem to be solved by this invention is: provide new and contain 1; 2; The compound method of two triazolo thiadiazoles derivatives of 3-thiadiazoles; Provide this compounds to suppress biological activity and the measuring method thereof of agricultural and gardening and forestry plant pathogen and plant virus, the middle application of these compounds in agriculture field and gardening field and field of forestry is provided simultaneously.
The present invention solves this technical problem the technical scheme that is adopted: have two [3-(4-methyl isophthalic acids that agricultural, gardening and forestry fungicidal activity or antiviral activity or inducing plant produce antiviral activity; 2,3-thiadiazoles-5-yl) s-triazolo-thiadiazoles] chemical structure of general formula of verivate is following:
Wherein: X is 0 or is selected from ethylene, trimethylene, tetramethylene, pentamethylene, 1; 6-hexylidene, 1, the inferior heptyl, 1 of 7-, 2-phenylene, 1,3-phenylene 1,4-phenylene, 2; 5-furylidene, 2, the inferior thienyl, 2 of 5-, 6-pyridylidene, suitable-vinylene, anti--vinylene, 2; 2 '-Ya biphenylyl, 1,1-cyclobutyl, 1,1-Dimethylenecyclohexacompound, 3, the group of the inferior imidazolyl of 5-.
The compound method of two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo-thiadiazoles] verivates of the present invention is following:
Wherein: X is 0 or is selected from ethylene, trimethylene, tetramethylene, pentamethylene, 1; 6-hexylidene, 1, the inferior heptyl, 1 of 7-, 2-phenylene, 1,3-phenylene 1,4-phenylene, 2; 5-furylidene, 2, the inferior thienyl, 2 of 5-, 6-pyridylidene, suitable-vinylene, anti--vinylene, 2; 2 '-Ya biphenylyl, 1,1-cyclobutyl, 1,1-Dimethylenecyclohexacompound, 3, the group of the inferior imidazolyl of 5-.
Embodiment
Enforcement of the present invention specifically is divided into following steps:
A.3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-4-amino-5-sulfydryl-1,2, the preparation of 4-triazole:
3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-4-amino-5-sulfydryl-1,2, the preparation of 4-triazole is carried out with reference to the method for Chinese patent 200810054334.1.
B. the preparation of two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo-thiadiazoles] verivates:
With 1-2.2 mmole 3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-4-amino-5-sulfydryl-1,2, the dicarboxylicacid of 4-triazole, 0.5-1.1 mmole and 0.25-0.5 mmole Tetrabutyl amonium bromide add 50 milliliters of round-bottomed flasks, add 15 milliliters of POCl again
3, under the induction stirring, oil bath is heated to 60 degrees centigrade, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, dry crude product, according to the pure article calculated yield of gained, measure fusing point and
1HNMR, the consumption of synthetic compound can or dwindle by corresponding proportion expansion; The chemical structure of compound is seen table 1;
C. contain 1,2, the mensuration that two triazolothiadiazole verivates of 3-thiadiazoles influence the pathogenic fungi growth activity:
Of the present inventionly contain 1,2, the two triazolo thiadiazoles derivative sterilization of 3-thiadiazoles or the measuring method of bacteriostatic activity are following:
Adopt thalli growth rate assay method, detailed process is to get 5 milligrams of sample dissolution in an amount of N; With containing the medicament that a certain amount of polysorbas20 emulsifier aqueous solution is diluted to 500 mcg/ml, will supply the reagent agent under aseptic condition, respectively to draw in 1 milliliter of injection petridish then, add 9 milliliters of substratum more respectively; It is dull and stereotyped to process 50 mcg/ml pastilles after shaking up, and does blank with the flat board that adds 1 milliliter of aqua sterilisa, cuts bacterium with the punch tool of 4 millimeters of diameters along the mycelia outer rim and coils; Move on the pastille flat board, be equilateral triangle and put, every processing repetition 3 times; Petridish is placed in 24 ± 1 degrees centigrade the constant incubator cultivates; Colony diameter to be contrasted expands to 2-3 centimetre of " Invest, Then Investigate " and respectively handles bacterium dish expansion diameter, averages, and relatively calculates relative bacteriostasis rate with blank; Supply the examination bacterial classification to comprise frequently seen plants pathogenic bacteria on 9 kinds of agriculturals, as: F: tomato early blight bacterium (Alternaria solani); D: peanut Cercospora bacteria (Cercospora arachidicola); I: ring rot of apple bacterium (Physalospora piricola); L: botrytis cinerea pers (Botrytis cinerea); T: Rhizoctonia solani Kuhn (Pellicularia sasakii); G: fusarium graminearum (Gibberella zeae); AK: phytophthora infestans (Phytophthorainfestans (Mont.) de Bary); N: Sclerotinia sclerotiorum (Sclerotinia sclerotiorum); RC: cereal rhizoctonia (Rhizoctonia cerealis);
D. of the present inventionly contain 1,2, the mensuration of the derivative induced anti-disease activity of two triazolothiadiazoles of 3-thiadiazoles:
Of the present inventionly contain 1,2, the active screening method of the derivative induced tobacco resisting tobacco mosaic virus of two triazolothiadiazoles of 3-thiadiazoles (TMV) is following: the mensuration of the direct antiviral activity that exsomatizes adopts half page of method to carry out; It is the common cigarette that seedling age is consistent that live body is induced, and 3 basins are one group, respectively at the cigarette seedling of inoculation pre-treatment in preceding 7 days; Processing mode comprises: spray test compound solution 2 to 3 times, and each 10 milliliters, or soil treating; Each 10 milliliters, the 7th day frictional inoculation TMV on the tobacco leaf that newly grows places its growth optimal temperature and the following cultivation of illumination after 3 days the cigarette seedling; The inspection incidence; Comprehensive scab number is calculated as follows out the inducing anti-disease toxic effect fruit of test compound to TMV, and 3 repetitions are established in each processing, and contrast divides blank and standard chemicals treatment to contrast 2 kinds; Selecting tiadinil (TDL) (purity is greater than 99.5%) is the plant inducing anti-disease activator of standard:
Wherein, R is the induce effect of new compound to the anti-TMV of tobacco, unit: %
CK is the average withered spot number of clear water contrast blade, unit: individual
I is for inducing the average withered spot number of handling rear blade, unit: individual through compound;
The invention has the beneficial effects as follows: the present invention is to containing 1; 2; Two triazolo thiadiazoles of 3-thiadiazoles have carried out the optimization of first guide structure; And the synthetic new compound carried out the screening of bacteriostatic activity, this compounds can be used for the plant protection that agriculture field and field of forestry and gardening field disease carry out.
The present invention will more specifically explain through specific preparation and biological activity determination embodiment and contain 1; 2; Synthetic and the biological activity and the application thereof of two triazolo thiadiazoles derivatives of 3-thiadiazoles, unrestricted the present invention, especially its biological activity only illustrate but said embodiment only is used to specify the present invention; And unrestricted this patent, embodiment is following:
Embodiment 1
Compound 3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-4-amino-5-sulfydryl-1,2, the preparation of 4-triazole and structure are identified
6.25 grams, 80% Hydrazine Hydrate 80 is joined in 50 milliliters of absolute ethyl alcohols, stir down, slowly drip 17.2 gram 4-methyl isophthalic acids, 2,3-thiadiazoles-5-ethyl formate; Drip complete vigorous stirring, about 15 minutes, moment was separated out a large amount of solids, and suction filtration is also washed with absolute ethyl alcohol, revolves and does filtrating; Obtain yellow solid, sherwood oil is washed, and combining solid, ir lamp are dry down; Obtain orange-yellow 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine 14.9 grams, productive rate 94.2%; With 11.6 gram 4-methyl isophthalic acids, 2,3-thiadiazoles-5-formyl hydrazine joins in 150 milliliters of ethanol solutions that are dissolved with 7.5 gram 82%KOH, stirs and makes it dissolving, drips CS again
28.36 gram has orange/yellow solid to separate out, stirring at room 4 hours gradually; Leave standstill, suction filtration obtains orange-yellow 4-methyl isophthalic acid, and 2,3-thiadiazoles-5-formohydrazide group dithio formic acid sylvite 19.57 grams, productive rate 98% directly is used for next step reaction; With 19 gram 4-methyl isophthalic acids, 2,3-thiadiazoles-5-formohydrazide group dithio formic acid sylvite joins in 120 milliliters of absolute ethyl alcohols, stirs to be yellow emulsion; Add 8.6 grams, 80% Hydrazine Hydrate 80 again, reflux 6 hours, cooling adds 100 ml waters, obtains yellow-green soln; Concentrated hydrochloric acid is acidified to pH=2-3, and a large amount of white solids are separated out, hold over night, and suction filtration and water are washed till neutrality; Dry 3-(4-methyl isophthalic acid, 2,3-the thiadiazolyl group)-4-amino-5-sulfydryl-1 that gets under the ir lamp; 2,4-triazole 10.4 grams, productive rate 70%;
1H NMR (δ, DMSO-d
6): 14.338 (s, H, NH), 6.805 (s, 2H, N-NH
2), 2.948 (s, 3H, thiadiazolyl-CH
3).
Embodiment 2
Compound WSX-8:1, the synthetic and structure of 6-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] hexane is identified
With 2.2 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 1 mmole suberic acid and 0.5 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 15 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 90% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 1.496-1.859 (m, 8H, 4CH
2), 3.137-3.173 (t, 4H, 2CH
2), 3.064 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 3
Compound WSX-11:1, the synthetic and structure of 1-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-methylene radical] hexanaphthene is identified
With 1.1 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.5 mmole 1,1-cyclohexanediacetic acid and 0.25 mmole Tetrabutyl amonium bromide join in 25 milliliters of round-bottomed flasks, add 8 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 76% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point: the 247-248 degree,
1HNMR (δ, DMSO-d
6) 1.605-1.710 (m, 10H, cyclohexyl-H), 3.115-3.139 (t, 4H, 2CH
2), 3.083 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 4
Compound WSX-12:1, the synthetic and structure of 1-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] tetramethylene is identified
With 1.1 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.5 mmole 1,1-cyclobutyl dioctyl phthalate and 0.25 mmole Tetrabutyl amonium bromide join in 25 milliliters of round-bottomed flasks, add 8 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 89% is used DMF-C
2H
5The OH recrystallization gets the yellowish brown crystal; Fusing point is greater than 250 degrees centigrade.
Embodiment 5
Compound WSX-16:2, the synthetic and structure of 6-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] pyridine is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole, 2,6 dinicotinic acids and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 90% is used DMF-C
2H
5The OH recrystallization gets pale yellow crystals; Fusing point is greater than 250 degrees centigrade.
Embodiment 6
Compound WSX-17:1, the synthetic and structure of 2-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] ethane is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole Succinic Acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 79% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 3.764 (s, 4H, 2CH
2), 3.023 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 7
Compound WSX-18: the synthetic and structure of di-[3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles] is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole oxalic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 55% is used DMF-C
2H
5The OH recrystallization gets the yellowish brown crystal; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 3.023 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 8
Compound WSX-19: suitable-1, the synthetic and structure of 2-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] ethene is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole maleic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3Behind the solution washing again water be washed till neutrality, dry crude product, productive rate 45% is used DMF-C
2H
5The OH recrystallization gets yellow crystals; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 8.180 (s, 2H, CH=CH), 3.102 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 9
Compound WSX-20: anti--1,2-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] ethene synthetic reaches the structure evaluation
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole FUMARIC ACID TECH GRADE and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 61% is used DMF-C
2H
5The OH recrystallization gets pale yellow crystals; Fusing point is greater than 250 degrees centigrade.
Embodiment 10
Compound WSX-22:1, the synthetic and structure of 3-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] benzene is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole m-phthalic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 88% is used DMF-C
2H
5The OH recrystallization gets white needle-like crystals; Fusing point is greater than 250 degrees centigrade.Results of elemental analyses: calculated value (%), C
18H
10N
12S
4: C, 41.37; H, 1.93; N, 32.16. measured value of experiment: C, 41.09; H, 1.96; N, 31.48.
Embodiment 11
Compound WSX-25:1, the synthetic and structure of 4-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] benzene is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole terephthalic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 91% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade.Results of elemental analyses: calculated value (%), C
18H
10N
12S
4: C, 41.37; H, 1.93; N, 32.16. measured value of experiment: C, 41.05; H, 1.96; N, 30.31.
Embodiment 12
Compound WSX-26:2, the synthetic and structure of 5-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] thiophene is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole 2,5-thiophene dioctyl phthalate and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3Behind the solution washing again water be washed till neutral crude product, productive rate 90% is used DMF-C
2H
5The OH recrystallization gets yellow crystals; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 7.953 (s, 2H, thienyl-H), 3.107 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 13
Compound WSX-28:2, the synthetic and structure of 5-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] furans is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole, 2,5 furans dioctyl phthalate and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3Behind the solution washing again water be washed till neutral crude product, productive rate 70% is used DMF-C
2H
5The OH recrystallization gets yellow crystals; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 8.011 (s, 2H, furyl-H), 3.116 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 14
Compound WSX-29:2, the synthetic and structure of 2 '-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] diphenyl is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole, 2,2 ' biphenyl dicarboxylic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 67% is used DMF-C
2H
5The OH recrystallization gets pale yellow crystals; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 7.714-7.947 (m, 8H, ArH), 2.906 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 15
Compound WSX-30:1, the synthetic and structure of 7-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] heptane is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole nonane diacid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 92% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 1.429-1.804 (m, 10H, 5CH
2), 3.127-3.163 (t, 4H, 2CH
2), 3.055 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 16
Compound WSX-32:1, the synthetic and structure of 3-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] propane is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole pentanedioic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 85% is used DMF-C
2H
5The OH recrystallization gets the grey needle-like crystal; Fusing point is greater than 250 degrees centigrade.Results of elemental analyses: calculated value (%), C
15H
12N
12S
4: C, 36.87; H, 2.48; N, 34.40. measured value of experiment: C, 36.51; H, 2.73; N, 33.17.
Embodiment 17
Compound WSX-33:1, the synthetic and structure of 5-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] pentane is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole pimelic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 78% is used DMF-C
2H
5The OH recrystallization gets pale yellow crystals; Fusing point: the 229-231 degree,
1HNMR (δ, DMSO-d
6): 1.550-1.910 (m, 6H, 3CH
2), 3.155-3.190 (t, 4H, 2CH
2), 3.060 (s, 6H, 2thiadiazolyl-CH
3).
Embodiment 18
Compound WSX-35:3, the synthetic and structure of 5-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] pyrazoles is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole 3,5-pyrazoles diacid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 78% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade,
1HNMR (δ, DMSO-d
6): 7.952 (s, 1H, pyrazolyl-NH), 3.110 (s, 1H, pyrazolyl-CH), 2.730 (s, 3H, thiadiazolyl-CH
3), 2.890 (s, 3H, thiadiazolyl-CH
3).
Embodiment 19
Compound WSX-39:1, the synthetic and structure of 2-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] benzene is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole phthalic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 45% is used DMF-C
2H
5The OH recrystallization gets the yellowish brown crystal; Fusing point is greater than 250 degrees centigrade.
Embodiment 20
Compound WSX-73:1, the synthetic and structure of 4-two [3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl) s-triazolo--[3,4-b]-1,3,4-thiadiazoles-6-yl] butane is identified
With 1.5 mmole 3-phenyl-4-amino-5-sulfydryl-1,2,4-triazole, 0.7 mmole hexanodioic acid and 0.35 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 10 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, the dry crude product that gets, productive rate 91% is used DMF-C
2H
5The OH recrystallization gets white crystal; Fusing point is greater than 250 degrees centigrade.
Embodiment 21
Of the present inventionly contain 1,2, the bacteriostatic activity of two triazolo thiadiazoles derivatives of 3-thiadiazoles:
The title and the code name of the frequently seen plants pathogenic fungi of the present invention's test comprise AS: tomato early blight bacterium (Alternariasolani); BC: botrytis cinerea pers (Botrytis cinerea); CA: peanut Cercospora bacteria (Cercospora arachidicola); GZ: fusarium graminearum (Gibberella zeae); PI: phytophthora infestans (Phytophthora infestans (Mont.) deBary); PP: ring rot of apple bacterium (Physalospora piricola); PS: Rhizoctonia solani Kuhn (Pellicularia sasakii); SS: Sclerotinia sclerotiorum (Sclerotinia sclerotiorum); RC: cereal rhizoctonia (Rhizoctonia cerealis), these bacterial classifications have good representativeness, can represent the kind of most of pathogenic bacteria that the field takes place in the agriculture prodn.Thalli growth rate method is measured the result and is seen table 2; Table 2 shows; Synthetic part of compounds of the present invention has bacteriostatic action in various degree to the growth of the part pathogenic fungi of mensuration: when 50 mcg/ml; Active best control compounds YZK-C-22 better active to most of pathogenic bacteria of test under equal conditions in the patent document 200810054334.1 that the contriver has applied for, but relatively poor to the restraining effect of GZ, BC, SS and four kinds of pathogenic fungies of RC of test; And WSX-26 is 35.29%% to the restraining effect of GZ, is higher than control compounds YZK-C-22 far away; WSX-12, WSX-16, WSX-33 and WSX-35 are respectively the restraining effect of BC: 34.38%, 43.75%, 68.75% and 43.75%, also be higher than control compounds YZK-C-22 far away; WSX-8, WSX-18, WSX-26, WSX-30 and WSX-35 and WSX-73 are respectively the inhibiting rate of SS: 41.67%, 33.33%, 69.44%, 88.89% and 61.11% and 38.89%, also be higher than control compounds YZK-C-22 far away; Other compounds are all not remarkable to the restraining effect of other pathogenic fungies.Above result shows, contains 1,2, and two triazolo thiadiazoles derivatives of 3-thiadiazoles have been because the introducing of close ester property spacer group has changed the close ester property of target molecule, thereby makes the biological activity of compound be significantly improved.
Embodiment 22
Of the present inventionly contain 1,2, the effect of the anti-tobacco resisting tobacco mosaic virus of two triazolo thiadiazoles derivatives of 3-thiadiazoles:
The active mensuration result of anti-TMV sees table 3; Table 3 shows; Commercial plant resisting tobacco mosaic virus medicament virazole has certain activity to TMV; The two triazolo thiadiazoles derivatives of major part of the present invention have the activity of direct anti-TMV preferably; WSX-8, WSX-18, WSX-20, WSX-25, WSX-26 and the WSX-32 part of compounds antiviral effect when 500 mcg/ml and 100 mcg/ml is all more than 40%, and these compounds all are higher than the mensuration result of similar medicament TDL far away in the activity of 500 mcg/ml, and measuring the result almost is the twice of TDL; The mensuration result who also is higher than the best Ningnanmycin of widely used conventional antiviral agent virazole and antiviral effect.And the antiviral effect of these medicaments also is significantly higher than three of mensuration contrast medicament TDL and virazole and Ningnanmycin when 100 mcg/ml.Therefore, above-claimed cpd can be prepared into antiviral agent with acceptable assistant on the agricultural, is used for the control of the viroses of plant.Select the good compound of antiviral activity to carry out the mensuration of induced activity; Found that; The induced activity of control compounds YZK-C-22 in the patent document 200810054334.1 that above-mentioned WSX-8, WSX-18, WSX-20, WSX-25, WSX-26 and the WSX-32 induced activity under same concentrations has all been applied for than the inventor is high; Also be higher than contrast medicament TDL and under same concentrations, induce effect, induced activity and the TDK of YZK-C-22 are suitable; Therefore, above-claimed cpd can be prepared into the plant activator with acceptable assistant on the agricultural, is used for the control of the viroses of plant.In process of the test, find that these compounds show poisoning in various degree to tobacco, therefore, this compounds possibly show certain weeding activity.The specific activity of compound WSX-8 of the present invention, WSX-18, WSX-20, WSX-25, WSX-26 and the anti-TMV of WSX-32 evoking tobacco has only a unitary chemical combination object height of triazolo thiadiazoles active structure; Maximum exceeds more than 20%; These compounds have the advantage of the comparison induced activity more outstanding than compound YZK-C-22; Its reason is to contain 1; 2, two triazolo thiadiazoles derivatives of 3-thiadiazoles have been because the introducing of close ester property spacer group has changed the close ester property of target molecule, thereby make the biological activity of compound be significantly improved.
Embodiment 23
Of the present inventionly contain 1,2, two triazolo thiadiazoles derivatives of 3-thiadiazoles and antiviral agent are combined in the application in control agricultural and forestry and the gardening plant virus disease:
The result of preliminary biological assay test shows; Of the present invention all contain 1,2, two triazolo thiadiazoles derivatives of 3-thiadiazoles and existing Antiphytoviral medicament diazosulfide (BTH), tiadinil (TDL), 4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formic acid (TDLA), 4-methyl isophthalic acid, 2,3-thiadiazoles-5-sodium formiate (TDLS), 4-methyl isophthalic acid; 2; 3-thiadiazoles-5-ethyl formate (ETDLA), DL-beta-aminobutyric acid (BABA), virazole, antofine, Ningnanmycin and tisocromide, first thiophene lure that any 1 or the combination of 2 compounds can be used for the anti-TMV of evoking tobacco or be used for directly preventing and treating TMV in amine and the Whitfield's ointment, all show summation action or synergism between these compsns, the effect that the effect of its antiviral activity is all used separately greater than any one compound; There is not antagonistic action.The reason that produces these effects is that the compound of compound of the present invention and its combination is complementary on mechanism of action, and the existing compound that directly acts on TMV also acts on plant itself, improves the compound of plant self-defense ability.
The staple crop that these compsns are suitable for comprise cereal crop (comprising paddy, wheat, barley, oat, corn, millet, Chinese sorghum etc.), tuber crops (comprising sweet potato, yam, cassava etc.), legume crop (comprising soybean, broad bean, pea, mung bean, red bean etc.) and fibre crops (cotton, crudefiber crop, silkworm and mulberry etc.), oil crops (peanut, rape, sesame, soybean, Sunflower Receptacle etc.), sugar crop (beet, sugarcane etc.), beverage crops (tealeaves, coffee, cocoa etc.), hobby crop (tobacco leaf etc.), medicinal crop (genseng, the bulb of fritillary etc.), tropical crops (rubber, coconut, oil palm, the sisal hemp etc.) food crop of etc.ing and fruit, flowers, oil plant, sugared expect and cash crop such as cotton, fiber crops, tea, tobacco, Chinese medicinal materials and plant melon, really, tea, silkworm and mulberry, vegetables (containing various wild vegetable etc.), bamboo shoots, flowers and garden crop such as tobacco (flue-cured tobaccos such as ornamental plant, hops, medicinal material, pepper, seedling and other garden crops; Air-curing of tobacco leaves, suncured tabacco), vegetables, (tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tube, beet, rape, green onion, garlic etc.), melon (watermelon, muskmelon, hami melon, pawpaw etc.), beans (soybean, broad bean, pea-pods etc.), yam, wheat, corn, paddy rice, peanut, fruit tree, (apple, banana, citrus, peach, papaya), flowers (like orchid), potted landscape etc.; Virus disease comprises tobacco mosaic virus disease, various melon virus disease, various solanberry viroid disease, beans virus disease, Cruciferae virus disease, grain and oil crop virus disease, cotton virus disease and various fruit tree virus diseases etc., wherein endangers serious mainly containing: tobacco virus, pepper virus disease, pimento virus disease, tomato virus disease, Chinese cabbage virus disease, paddy rice virus disease comprise rice dwarf virus disease, BYDV, stripe virus disease, fern leaf of tomato viral disease, chilli pepper mosaic virus disease and tobacco veinal necrosis virus disease, corn short mosaic disease, cauliflower mosaic virus, oranges and tangerines virus disease, cymbidium mosaic virus, cybidium ring spot virus etc.These medicaments are combined in the major reason why control of carrying out above-mentioned virus disease on the above-mentioned crop have a unusual effect, and compound of the present invention has good induced activity, and induced activity has wide spectrum and the characteristics of holding effect.
Embodiment 24
Of the present inventionly contain 1,2, the application in two triazolo thiadiazoles derivatives of 3-thiadiazoles and sterilant combination control agricultural and forestry and the gardening plant disease:
The result of preliminary biologicall test test shows; Of the present invention all contain 1; 2; Two triazol thiadiazoles derivatives of 3-thiadiazoles and existing bactericide such as white urea cyanogen, thiram, ziram, Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pines, carbendazim, procymidone, iprodione, captan, the mould prestige of second, ester bacterium urea, flutolanil, benomyl, cyproconazole, methasulfocarb, fenpropidin, evil acid amides, triazolone, thiophanate methyl, metalaxyl, Metalaxyl-M, M 9834, hydroxyisoxazole, dimethomorph, flumorph, tridemorph, Flusilazole, alkene azoles alcohol, Tebuconazole, the mould spirit of evil, Difenoconazole, mepanipyrim, Fluoxastrobin, propiconazole, diazosulfide, salicylic acid, tiadinil, tisocromide, first thiophene lure other known any any one or two kinds that can be used as in the bactericide such as amine to be used in combination the control that can be used for agricultural plant disease and gardening plant disease; Controlling object comprises surplus the Achyla, Aphanomyces, pythium, Phytophthora, Sclerospora, Plasmopara, false Peronospora, Peronospora of Oomycete etc. 20 and to belong to the disease that produces; Like other diseases of plurality of cereals crops such as seedling blight of rice, tomato root rot, the late blight of potato, black shank, millet powdery mildew, downy mildew of garpe, downy mildew of lettuce, cucumber downy mildew and industrial crops etc.; The formulation of using can be wettable powder, sustained release agent, pulvis, micro-capsule suspension, can disperse dense dose, seed treatment emulsion, aqueous emulsion, big granula, granule, microemulsion, finish, the seed with coated pesticidal, suspending agent, suspension emulsion, water-soluble granule, soluble thick agent, water-dispersible granules or the like; Of the present inventionly contain 1; 2; The ratio of two triazol thiadiazoles derivatives in composition of 3-thiadiazoles is between 1%-90%; The prevention effect of medicament is good; These compositions have synergistic effect and summation action, do not have antagonistic action.
Utilize similar method can confirm that combination between compound of the present invention and the above-mentioned commercial sterilant can be used to the disease of inducing anti-plant pathogenetic bacteria of agricultural crops and forestry plant and gardening plant and plant pathogenic fungi to cause.These crops comprise: cereal crop (comprise paddy; Wheat; Barley; Oat; Corn; Millet; Chinese sorghum etc.); Tuber crops (comprise sweet potato; Yam; Cassava etc.); Legume crop (comprises soybean; Broad bean; Pea; Mung bean; Red bean etc.) fibre crops (cotton; Crudefiber crop; Silkworm and mulberry etc.); Oil crops (peanut; Rape; Sesame; Soybean; Sunflower Receptacle etc.); Sugar crop (beet; Sugarcane etc.); Beverage crops (tealeaves; Coffee; Cocoa etc.); Hobby crop (tobacco leaf etc.); Medicinal crop (genseng; The bulb of fritillary; Safflower; Schizonepeta; Hindu Datura Flower Hairy Datura Flower; Monkshood and Root of Indigowoad etc.); Tropical crops (rubber; Coconut; Oil palm; Sisal hemp etc.) food crop and fruit such as; Flowers; Oil plant; Sugar material and cotton; Fiber crops; Tea; Tobacco; Cash crop and plantation melons such as Chinese medicinal materials; Really; Tea; Silkworm and mulberry; Vegetables (containing various wild vegetable etc.); Bamboo shoots; Flowers and ornamental plant; Hops; Medicinal material; Pepper; Garden crops such as seedling and other garden crops.
These medicaments are combined in the major reason why control of carrying out above-mentioned disease on the above-mentioned crop have a unusual effect, and compound of the present invention has good induced activity, and induced activity has wide spectrum and the characteristics of holding effect.
The chemical structure characteristic of the two triazolothiadiazole verivates of table 1 synthetic part of the present invention
The chemical structure characteristic (continuing) of the two triazolothiadiazole verivates of table 1 synthetic part of the present invention
The fungicidal activity of the compound among table 2 the present invention (/ %)
| Compound | AS | CA | GZ | PP | BC | SS | RC | PS | PI |
| WSX-8 | 11.11 | 21.43 | 5.88 | 22.58 | 25.00 | 41.67 | 3.85 | 7.14 | 22.73 |
| WSX-11 | 16.67 | 14.29 | 14.71 | 19.35 | 28.13 | 13.89 | 0 | 7.14 | 22.73 |
| WSX-12 | 5.56 | 14.29 | 0 | 22.58 | 34.38 | 22.22 | 3.85 | 14.29 | 13.64 |
| WSX-16 | 0 | 0 | 20.59 | 29.03 | 43.75 | 8.33 | 7.69 | 5.36 | 18.18 |
| WSX-17 | 27.78 | 28.57 | 2.94 | 22.58 | 28.13 | 16.67 | 0 | 75.00 | 18.18 |
| WSX-18 | 11.11 | 21.43 | 2.94 | 22.58 | 18.75 | 33.33 | 3.85 | 71.43 | 9.09 |
| WSX-19 | 33.33 | 28.57 | 26.47 | 25.81 | 25.00 | 11.11 | 7.69 | 5.36 | 18.18 |
| WSX-20 | 11.11 | 14.29 | 17.65 | 35.48 | 37.50 | 22.22 | 23.08 | 5.36 | 27.27 |
| WSX-22 | 0 | 21.43 | 14.71 | 19.35 | 34.38 | 22.22 | 11.54 | 44.64 | 36.36 |
| WSX-25 | 22.22 | 7.14 | 17.65 | 32.26 | 18.75 | 0 | 11.54 | 62.50 | 22.73 |
| WSX-26 | 16.67 | 0 | 35.29 | 74.19 | 25.00 | 69.44 | 11.54 | 80.36 | 18.18 |
| WSX-28 | 5.56 | 21.43 | 2.94 | 32.26 | 28.13 | 33.33 | 7.69 | 7.14 | 22.73 |
| WSX-29 | 11.11 | 28.57 | 11.76 | 35.48 | 28.13 | 19.44 | 7.69 | 7.14 | 9.09 |
| WSX-30 | 0 | 28.57 | 32.35 | 29.03 | 31.25 | 88.89 | 7.69 | 71.43 | 18.18 |
| WSX-32 | 11.11 | 21.43 | 14.71 | 35.48 | 37.50 | 27.78 | 15.38 | 7.14 | 22.73 |
| WSX-33 | 27.78 | 7.14 | 11.76 | 35.48 | 68.75 | 19.44 | 7.69 | 8.93 | 13.64 |
| WSX-35 | 11.11 | 14.29 | 17.65 | 45.16 | 43.75 | 61.11 | 7.69 | 17.86 | 36.36 |
| WSX-39 | 9.09 | 16.67 | 30.00 | 5.26 | 41.18 | 77.59 | 57.69 | 28.95 | 31.03 |
| WSX-73 | 16.67 | 0 | 8.82 | 38.71 | 25.00 | 38.89 | 15.38 | 14.29 | 22.73 |
| YZK-C-22 | 69.44 | 68.75 | 8.82 | 88.89 | 7.14 | 11.11 | 15.38 | 88.89 | 74.19 |
Data are the mensuration result of 50 mcg/ml in the table; ND: undetermined
The activity of the compound evoking tobacco resisting tobacco mosaic virus among table 3 the present invention
| Compound | Concentration (mcg/ml) | Average inhibiting rate ± SD (%) | Concentration (mcg/ml) | Average inhibiting rate ± SD (%) |
| WSX-8 | 500 | 56.40±3.53 | 100 | 45.13±2.87 |
| WSX-23 | 500 | 19.93±2.82 | 100 | 43.15±2.74 |
| WSX-11 | 500 | 43.22±15.90 | 100 | 22.99±4.67 |
| WSX-16 | 500 | 28.70±8.36 | 100 | 43.01±0.95 |
| WSX-17 | 500 | 33.53±7.55 | 100 | 35.95±4.53 |
| WSX-18 | 500 | 48.50±6.75 | 100 | 51.08±7.29 |
| WSX-19 | 500 | 19.29±8.78 | 100 | 21.77±1.59 |
| WSX-20 | 500 | 48.50±6.75 | 100 | 41.90±23.81 |
| WSX-22 | 500 | 30.44±13.05 | 100 | 60.54±4.49 |
| WSX-25 | 500 | 57.09±2.56 | 100 | 43.31±10.73 |
| WSX-26 | 500 | 60.78±4.11 | 100 | 42.90±13.52 |
| WSX-28 | 500 | 37.43±1.89 | 100 | 36.21±2.62 |
| WSX-29 | 500 | 38.21±0.95 | 100 | 32.46±5.43 |
| WSX-30 | 500 | 39.35±4.98 | 100 | 29.98±5.81 |
| WSX-32 | 500 | 53.82±5.95 | 100 | 40.85±4.65 |
| WSX-33 | 500 | 37.29±3.09 | 100 | 32.65±2.75 |
| WSX-35 | 500 | 27.55±4.62 | 100 | 21.77±1.59 |
| WSX-39 | 500 | 25.03±2.91 | 100 | 18.07±3.73 |
| WSX-73 | 500 | 21.08±6.12 | 100 | 33.74±11.98 |
| YZK-C-22 | 500 | 33.05±5.37 | 100 | 38.99±3.52 |
| TDL | 500 | 32.09±2.97 | 100 | 37.00±2.08 |
| Ningnanmycin | 500 | 48.07±4.22 | 100 | 38.99±5.74 |
| Virazole | 500 | 39.15±4.17 | 100 | 35.51±1.90 |
Claims (9)
1. one kind contains 2, and two triazolo thiadiazoles derivatives of 3-thiadiazoles is characterized in that having following chemical structure of general formula:
Wherein: X is not for or be selected from ethylene, trimethylene, tetramethylene, pentamethylene, 1; 6-hexylidene, 1, the inferior heptyl, 1 of 7-, 2-phenylene, 1,3-phenylene, 1,4-phenylene, 2; 5-furylidene, 2, the inferior thienyl, 2 of 5-, 6-pyridylidene, suitable-vinylene, anti--vinylene, 2; 2 '-Ya biphenylyl, 1,1-cyclobutyl, 1,1-Dimethylenecyclohexacompound, 3, the group of the inferior imidazolyl of 5-.
2. claim 1 is described contains 1,2, and the compound method of two triazolo thiadiazoles derivatives of 3-thiadiazoles is specially:
With 2.2 mmole 3-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-4-amino-5-sulfydryl-1,2,4-triazole, 1.1 mmole dicarboxylicacid and 0.5 mmole Tetrabutyl amonium bromide join in 50 milliliters of round-bottomed flasks, add 15 milliliters of POCl again
3, under the induction stirring, the oil bath heating keeps 60 degrees centigrade of temperature, is incubated 4 hours, is warming up to 120 degrees centigrade of refluxed then 10 hours, and reaction is finished, and the ice-water bath cooling slowly drips frozen water down, separates out a large amount of solids, hold over night, suction filtration is used saturated NaHCO
3The solution washing product, water is washed till neutrality again, dry crude product, according to the pure article calculated yield of gained, measure fusing point and
1H NMR, the consumption of synthetic compound enlarges by corresponding proportion or dwindles.
3. claim 1 is described contains 1,2, and two triazolo thiadiazoles derivatives of 3-thiadiazoles are gone up the purposes of acceptable assistant in the agent of preparation resisting tobacco mosaic virus with agricultural.
4. claim 1 is described contains 1,2, and two triazolo thiadiazoles derivatives of 3-thiadiazoles are gone up the purposes of acceptable assistant at the medicament of preparation evoking tobacco resisting tobacco mosaic virus with agricultural.
5. the described X of claim 1 is not 2,6-pyridylidene, 1,3-phenylene, 1, the inferior heptyl of 7-contain 1,2, two triazolo thiadiazoles derivatives of 3-thiadiazoles are gone up the purposes of acceptable assistant in preparing anti-mycotic agent with agricultural; Said fungi is selected from tomato early blight bacterium, botrytis cinerea pers, peanut Cercospora bacteria, fusarium graminearum, phytophthora infestans, ring rot of apple bacterium, Rhizoctonia solani Kuhn, Sclerotinia sclerotiorum, cereal rhizoctonia.
6. the compsn of an Antiphytoviral; It is characterized in that: claim 1 is described to contain 1,2, two triazolo thiadiazoles derivatives of 3-thiadiazoles and agricultural go up acceptable assistant and be selected from diazosulfide, tiadinil, 4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formic acid, 4-methyl isophthalic acid, 2,3-thiadiazoles-5-sodium formiate, 4-methyl isophthalic acid; 2,3-thiadiazoles-5-ethyl formate, DL-beta-aminobutyric acid, virazole, antofine, Ningnanmycin, first thiophene lure any one or the two kinds of combined preparation in amine or the Whitfield's ointment to become anti-plant virus agent; Claim 1 is described to contain 1; 2; The ratio of two triazolo thiadiazoles derivatives in compsn of 3-thiadiazoles is 1%-90%, the processing formulation be selected from sustained release dosage, pulvis, micro-capsule suspension, can disperse dense dose, seed treatment emulsion, aqueous emulsion, in the big granula, microemulsion, oil-suspending agent, finish, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules any one.
7. the compsn of the said Antiphytoviral of claim 6 is in the purposes of control in the viral diseases of plants, and said viral diseases of plants is selected from tobacco mosaic virus disease and chilli pepper mosaic virus disease.
8. bactericidal composition; It is characterized in that: claim 1 is described to contain 1; 2, two triazol thiadiazoles derivatives of 3-thiadiazoles and agricultural go up acceptable assistant and be selected from white urea cyanogen, thiram, ziram, Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pine, carbendazim, procymidone, iprodione, captan, the mould prestige of second, ester bacterium urea, flutolanil, benomyl, cyproconazole, methasulfocarb, fenpropidin, evil acid amides, triazolone, thiophanate methyl, metalaxyl, Metalaxyl-M, M 9834, hydroxyisoxazole, dimethomorph, flumorph, tridemorph, Flusilazole, alkene azoles alcohol, Tebuconazole, the mould spirit of evil, Difenoconazole, mepanipyrim, Fluoxastrobin, propiconazole, diazosulfide, salicylic acid, tiadinil, first thiophene lure any one or two kinds of bactericide in the amine to make up to be used to prepare bactericide; Claim 1 is described to contain 1; 2; The ratio of two triazol thiadiazoles derivatives in composition of 3-thiadiazoles is 1%-90%, and the formulation of wherein said bactericide is selected from sustained release agent, pulvis, micro-capsule suspension, can disperse in dense dose, seed treatment emulsion, aqueous emulsion, big granula, microemulsion, oil-suspending agent, finish, suspension emulsion, water-soluble granule, soluble thick agent, water-dispersible granules any one.
9. the purposes of the said fungicidal compsn of claim 8 in controlling plant diseases, said disease are selected from the Plant diseases that tomato early blight bacterium, botrytis cinerea pers, peanut Cercospora bacteria, fusarium graminearum, phytophthora infestans, ring rot of apple bacterium, Rhizoctonia solani Kuhn, Sclerotinia sclerotiorum, cereal rhizoctonia cause.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101348496A (en) * | 2008-08-28 | 2009-01-21 | 南开大学 | S-triazolothiadiazole compound, and preparation and use thereof |
| CN101591307A (en) * | 2009-06-26 | 2009-12-02 | 南开大学 | Connection 1,2,3-thiadiazoles-5-formic acid and its production and use |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101348496A (en) * | 2008-08-28 | 2009-01-21 | 南开大学 | S-triazolothiadiazole compound, and preparation and use thereof |
| CN101591307A (en) * | 2009-06-26 | 2009-12-02 | 南开大学 | Connection 1,2,3-thiadiazoles-5-formic acid and its production and use |
Non-Patent Citations (1)
| Title |
|---|
| B. Shivarama Holla et al..Studies on some N-bridged heterocycles derived from bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl] alkanes.《Il Farmaco》.1998,第53卷(第8-9期),第574-578页. * |
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