CN101591307B - Di(1,2,3-thiadiazole-5-formic acid) and preparation method and application thereof - Google Patents

Abstract

The invention provides di(1,2,3-thiadiazole-5-formic acid) and a preparation method and application thereof, and relates to heterocyclic compounds containing 1,2-diazole, in particular to derivatives of 1,2,3-thiadiazole, which have chemical structural general formula shown as figure I. The invention discloses a chemical structure and a synthesis method of the di(1,2,3-thiadiazole-5-formic acid),application of the derivatives as pesticides, bactericides and plant virus resisting medicaments in inducing agricultural plants, economic plants, horticultural plants and forestry plants to resist pathogenic microorganisms and plant virus, and a process for preparing the pesticides, the bactericides, the plant virus resisting medicaments and plant activators by mixing the derivatives with agriculturally acceptable assistants or synergists. The invention also discloses application of the combined use of the compounds and the prior common commercial pesticides, bactericides, plant virus resisting medicaments and plant activators in preventing and controlling diseases and pests and virus diseases in agriculture, forestry and horticulture, and the preparation method.

Description

Connection 1,2,3-thiadiazoles-5-formic acid and its production and use

Technical field

Technical scheme of the present invention relates to the heterogeneous ring compound that contains 1,2-diazole, is specifically related to contain connection 1,2, the compound of 3-thiadiazoles group; Utilize immunological competence that these compounds and precursor compound thereof improve plant with resist Plant diseases infect and these compounds are improving the purposes that agricultural plants and gardening plant and forestry plant opposing virus disease and fungal disease and Micobial Disease infect.

Background technology

Plant diseases comprises that fungal disease, Micobial Disease and virus disease cause heavy losses to agriculture production every year, exploration utilizes plant self disease resistance to carry out disease control and has broad application prospects, the plant activator is exactly to give plant " immunity " with the method for chemistry, plant activator BTH worldwide is extensive use of (Bakulev V A, Dehaen W.The Chemistry of1,2,3-thiadiazole, 2004, John Wiley﹠amp; Sons, Inc.), TDL has good induced activity (Ni Changchun, world's agricultural chemicals, 2007,29 (1): 18-23), the both is 1,2, the derivative of 3-thiadiazoles, the contriver is from fundamental research, under the subsidy of state natural sciences fund (20872071 and 20672062 and 20911120069) and Tianjin natural science fund (07JCYBJC01200), synthetic and discovery N-(the 5-methyl isophthalic acid of design, the 3-thiazol-2-yl)-and the 4-methyl isophthalic acid, 2, (patent in past is called for short N-(5-methyl-1,3-thiazole-2-yl)-4-methyl-1,2,3-thiadiazole to 3-thiadiazoles-5-methane amide, the tentative Chinese common name that has now obtained the approval of national pesticide standard Technical Committee lures amine for the first thiophene) have a good biological activity (Fan Zhijin etc., ZL 200610013185.5); Consider that N and S are the important composition elements of especially wherein each kind of protein and amino acid and enzyme in the life system, and 1,2, the 3-thiadiazoles heterocyclic compounds has wide biological activity, as (Boschelli such as anti-inflammatory, expelling parasite, weeding, coordinate plant growth, et al., J.Med.Chem.1993,36:1802; Saad H., Indian J.Chem, 1996,35B:980; Bakulev, et al., The Chemistry of 1,2,3-thiadiazole, 2004, JohnWiley﹠amp; Sons, Inc.), novelty of the present invention with existing 4-methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate is a raw material, in molecule, introduce one 1 again, 2,3-thiadiazoles active group has synthesized connection 1,2,3-thiadiazoles-5-formic acid, and synthetic new compound and precursor compound thereof have been carried out the evaluated biological activity of system, the biological activity of the compound of a thiadiazoles ring of biological activity ratio of these compounds has obtained significant raising, and the present invention has also explored and utilized these compounds and precursor compound and commercial pesticide combination thereof to make to be used for improving the immunological competence of plant and prevent and treat the harm of plant pest and these compounds in the purposes that improves on agricultural plants and the gardening plant opposing disease and pest, and the present invention is efficient, synthetic and the exploitation of low toxicity and eco-friendly novel pesticide molecular designing provides the candidate compound.

Summary of the invention

Technical problem to be solved by this invention is: new connection 1 is provided, 2, the synthetic method of 3-thiadiazoles-5-formic acid and precursor compound thereof, provide this compounds to suppress agricultural, gardening and forestry pathogenic fungi, the biological activity of bacterium and plant virus and inducing plant produce the purposes of anti-disease activity and the working method of these medicaments, provide simultaneously these compounds and commercialization pesticide species be combined and used in agriculture field and gardening field and the field of forestry application and with agricultural on acceptable auxiliary agent or synergistic agent combined preparation sterilant, the technology and the method for sterilant and Antiphytoviral medicament and plant activator.

The present invention solves this technical problem the technical scheme that is adopted: have the connection 1 that agricultural, gardening and forestry fungicidal activity, anti-phytoviral activity and inducing plant produce anti-disease activity, 2, the chemical structure of general formula of 3-thiadiazoles-5-formic acid and precursor compound thereof is shown in figure I:

Wherein, R is cycloalkyl, phenyl, substituted-phenyl, pyridyl, pyrimidyl, thiazolyl, triazolyl, the pyrazolyl, 1 that is selected from C1-C8 such as straight chained alkyls such as methyl, ethyl, propyl group, butyl, cyclopropyl, cyclobutyl, cyclohexyl, 3, the group of 5-triazinyl, thiadiazolyl group, hydrogen, Na, K, Li or atom or element.

Of the present invention 1,2, the synthetic method of 3-thiadiazoles-5-formic acid F and precursor compound B, C, D, E is as follows:

Wherein: R is cycloalkyl, phenyl, substituted-phenyl, pyridyl, pyrimidyl, thiazolyl, triazolyl, the pyrazolyl, 1 that is selected from C1-C8 such as straight chained alkyls such as methyl, ethyl, propyl group, butyl, cyclopropyl, cyclobutyl, cyclohexyl, 3, the group of 5-triazinyl, thiadiazolyl group; M is the atom that is selected from Li, Na, K.

Specifically be divided into following steps:

A. the preparation of intermediate B:

With 3.44 gram (20 mmole) 4-methyl isophthalic acids, 2,3-thiadiazoles-5-ethyl formate and 2.64 gram (30 mmole) ethyl acetate join in 50 milliliters of single port flasks, the ice bath cooling down, add 0.96 gram (20 mmoles in batches, 50%) NaH, after the stirring at room 15 minutes, reaction soln becomes chocolate, reflux 3 hours, be cooled to room temperature, the glacial acetic acid neutralization, the anhydrous diethyl ether extraction, desolventizing obtains chocolate oily matter, (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 3: 1) obtains brown oil B, and productive rate is 42.1% to use 200～300 order silica gel column chromatographies at last; Ethyl acetate is replaced by corresponding other acetate compounds can prepares other intermediate B; The amount of compd B preparation enlarges by corresponding proportion or dwindles; The chemical structure of compd B sees Table 1.

B. the preparation of intermediate C:

2.14 gram (10 mmole) intermediate B are dissolved in 10 milliliters of dehydrated alcohols, 5 milliliters of ethanol solutions that in batches add 1.14 gram (11 mmole) carbazic acid ethyl esters, stirring at room 5 hours, desolventizing gets the brown thick liquid, leave standstill and obtained the brown solid in 3 days, washing, infrared lamp is dry down, (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 3: 1) obtains light brown solid C, and productive rate is 89.2% to use 200～300 order silica gel column chromatographies at last; The amount of Compound C preparation enlarges by corresponding proportion or dwindles; The chemical structure of Compound C sees Table 1.

C. the preparation of intermediate D:

With 1.67 gram (14 mmole) SOCl ₂Join in 50 milliliters of there-necked flasks, the ice bath cooling slowly drips the CH of 2.10 gram (7 mmole) intermediate C down ₂Cl ₂10 milliliters of solution dropwised in 20 minutes, and room temperature continues to stir 17 hours, and rotary evaporation is removed CH ₂Cl ₂And SOCl ₂, add NaHCO ₃CH is used in the saturated solution neutralization ₂Cl ₂Extraction, collected organic layer, anhydrous sodium sulfate drying, precipitation, (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 5: 1) obtains yellowish brown crystal D, and productive rate is 57.7% to use 200～300 order silica gel column chromatographies at last; The amount of Compound D preparation enlarges by corresponding proportion or dwindles; The chemical structure of Compound D sees Table 1.

D. the preparation of intermediate E:

0.512 gram (2 mmole) intermediate D is dissolved in 5 milliliters of anhydrous methanols, slow 0.08 gram (2 mmole) that drips) methanol solution of NaOH is 5 milliliters, dropwises in 10 minutes, continues under the room temperature to stir 0.5 hour, desolventizing obtains light brown solid E, and productive rate is 98.0%; Replace NaOH can prepare corresponding Li salt and K salt with LiOH or KOH, the amount of compd E preparation enlarges by corresponding proportion or dwindles; The chemical structure of compd E sees Table 1.

E. the preparation of product F:

The intermediate E of appropriate amount is dissolved in 20 ml waters, stirs down and drip the dilute hydrochloric acid acidifying, leave standstill, suction filtration, infrared lamp is dry down, obtains yellowish brown solid F, and productive rate is 95.0%; The amount of compound F 17-hydroxy-corticosterone preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound F 17-hydroxy-corticosterone sees Table 1.

G. of the present invention 1,2, the mensuration of 3-thiadiazoles-5-formic acid and precursor compound insecticidal activity thereof:

The screening method of insecticidal activity: the measuring method of black bean aphid adopts pickling process, the concrete operations step is to have cutting for the examination plant leaf of at least 60 healthy black bean aphids of the same size from basin, 5 seconds of dipping in 200 milliliters of each soups to be measured of 200 mcg/ml, taking-up is treated will try the death state that worm continues to raise placement inspection insect after 24 hours behind the soup natural air drying, standard is: to touch the examination worm gently, can creep or wherein one leg can strenuous exercise is worm alive, with the clear water is contrast, with the mean value calculation corrected mortality, each concentration of each medicament repeats respectively 3 times, and carrying out simultaneously with the clear water is the blank test of contrast; The mensuration of small cabbage moth or beet armyworm adopts the blade medicine embrane method, the solution that sample to be tested is mixed with 200 mcg/ml carries out, getting former medicine sample dissolves with small amount of acetone earlier, dilute with the 0.5 ‰ Triton-100 aqueous solution then, 0.5 the ‰ Triton-100 aqueous solution is contrast, each concentration repeats for 3 times, 10 examinations of each re-treatment worm; Get fresh free of contamination cabbage leaves, in soup, soaked for 10 seconds, after indoor drying (about 2 hours), put into the culture dish of 9 centimetres of diameters, insert small cabbage moth 3 instar larvaes of big or small basically identical respectively, tighten with bungee and be placed in the small cabbage moth constant temperature insectary check result after 96 hours, touch polypide with little writing brush or little sharp tweezers, can not coordinated movement as death.

H. join 1,2, the mensuration that 3-thiadiazoles-5-formic acid and precursor compound thereof influence the pathogenic fungi growth activity:

Of the present invention 1,2, the measuring method of 3-thiadiazoles-5-formic acid and precursor compound bacteriostatic activity thereof is as follows:

Adopt thalli growth rate assay method, detailed process is, get 5 milligrams of sample dissolution in an amount of dimethyl formamide, then with containing the medicament that a certain amount of polysorbas20 emulsifier aqueous solution is diluted to 500 mcg/ml, reagent agent is respectively drawn under aseptic condition in 1 milliliter of injection culture dish, add 9 milliliters of substratum more respectively, make 50 mcg/ml pastille flat boards after shaking up, do blank with the flat board that adds 1 milliliter of aqua sterilisa, punch tool with 4 millimeters of diameters cuts the bacterium dish along the mycelia outer rim, move on the pastille flat board, being equilateral triangle puts, every processing repeats 3 times, culture dish is placed in 24 ± 1 degree constant incubators cultivates, and colony diameter to be contrasted expands to 2～3 centimetres of " Invest, Then Investigate "s and respectively handles bacterium dish expansion diameter, average, relatively calculate relative bacteriostasis rate with blank, comprise frequently seen plants pathogenic bacteria on the various agricultural for the examination bacterial classification, its title and code name comprise AS: tomato early blight bacterium (Alternaria solani); BC: botrytis cinerea pers (Botrytis cinerea); CA: peanut Cercospora bacteria (Cercospora arachidicola); CB: sugar beet leaf spot bacteria (Cercospora beticola); CL: watermelon anthrax bacteria: (Colletotrichum lagenarium); FO: cucumber fusarium axysporum (Fusarium oxysporum); GZ: fusarium graminearum (Gibberella zeae); PG: rice blast fungus (Phyricularia grisea (Cooke) Sacc.); PI: phytophthora infestans (Phytophthora infestans (Mont.) de Bary); PP: ring rot of apple bacterium (Physalosporapiricola); PS: Rhizoctonia solani Kuhn (Pellicularia sasakii); RS: dry thread Pyrenomycetes (Rhizoctonia solani kuhn), these bacterial classifications have good representativeness, can represent the kind of most of pathogenic bacteria that the field takes place in the agriculture production.。

I. of the present invention 1,2, the mensuration of 3-thiadiazoles-5-formic acid and precursor compound inducing anti-disease activity thereof:

Of the present invention 1,2,3-thiadiazoles-5-formic acid and the active screening method of precursor compound evoking tobacco resisting tobacco mosaic virus (TMV) thereof are:

(1). the selection of standard plant inducing anti-disease activator: selecting tiadinil (TDL) (purity is greater than 99.5%) is the plant activator of standard;

(2). connection 1,2,3-thiadiazoles-5-formic acid and the active screening method of the anti-TMV of precursor compound evoking tobacco thereof: the mensuration of the direct antiviral activity that exsomatizes adopts half leaf method to carry out; It is common cigarette with the seedling age unanimity that live body is induced, 3 basins are one group, cigarette seedling respectively at inoculation pre-treatment in preceding 7 days, processing mode comprises: spray test compound solution 2 to 3 times, each 10 milliliters, or soil treatment, each 10 milliliters, the 7th day frictional inoculation TMV on the tobacco leaf that newly grows, the cigarette seedling is placed its growth optimal temperature and illumination, and cultivation is after 3 days down, and inspection incidence, comprehensive scab number are calculated as follows out the inducing anti-disease toxic effect fruit of test compound to TMV, 3 repetitions are established in each processing, and contrast divides blank and standard chemicals treatment to contrast 2 kinds:

$R=\frac{\mathrm{CK}-I}{\mathrm{CK}}\×100$

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 has prepared connection 1; 2; 3-thiadiazoles-5-formic acid and precursor compound thereof; and synthetic new compound and precursor compound thereof carried out the mensuration of bacteriostatic activity and inducing anti-disease activity and anti-phytoviral activity, this compounds can be used for the plant protection of agriculture field and field of forestry and gardening field disease and virus disease.This compounds can be used in combination the plant protection that is used for agriculture field and field of forestry and the insect pest of gardening field, disease and virus disease with common sterilant and sterilant and antiviral agent.

The present invention will more specifically describe connection 1 by specific preparation and biological activity determination embodiment, 2, synthetic and the biological activity and the application thereof of 3-thiadiazoles-5-formic acid and precursor compound thereof, but described embodiment only is used for specific description the present invention and unrestricted the present invention, especially its biological activity only illustrates, rather than the restriction this patent, embodiment is as follows:

Embodiment 1: the preparation of intermediate B:

With 3.44 gram (20 mmole) 4-methyl isophthalic acids, 2,3-thiadiazoles-5-ethyl formate and 2.64 gram (30 mmole) ethyl acetate join in 50 milliliters of single port flasks, the ice bath cooling adds 0.96 gram (20 mmoles down in batches, 50%) NaH, after the stirring at room 15 minutes, reaction soln becomes chocolate, reflux 3 hours is cooled to room temperature, the glacial acetic acid neutralization, the anhydrous diethyl ether extraction, desolventizing obtains chocolate oily matter, and (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 3: 1) obtains brown oil B, and productive rate is 42.1% to use 200-300 order silica gel column chromatography at last; The M-1 peak of negative ion appears in the ESI mass spectrum at 213.03 places; Ethyl acetate is replaced by corresponding other esters can prepares other intermediate B; The chemical structure of compd B sees Table 1.Adopting similar method can synthesize R is cycloalkyl, phenyl, substituted-phenyl, pyridyl, pyrimidyl, thiazolyl, triazolyl, the pyrazolyl, 1 that is selected from C1-C8 such as straight chained alkyls such as methyl, ethyl, propyl group, butyl, cyclopropyl, cyclobutyl, cyclohexyl, 3, the compound of the group of 5-triazinyl, thiadiazolyl group.

Embodiment 2: the preparation of intermediate C:

2.14 gram (10 mmole) intermediate B are dissolved in 10 milliliters of dehydrated alcohols, add 5 milliliters of the ethanol solutions of 1.14 gram (11 mmole) carbazic acid ethyl esters, stirring at room 5 hours in batches.Desolventizing gets the brown thick liquid, leave standstill and obtained the brown solid in 3 days, washing, infrared lamp is dry down, (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 3: 1) obtains light brown solid C, and productive rate is 89.2% to use 200-300 order silica gel column chromatography at last; The ESI mass spectrum goes out positive ion M+1 peak at 301.29 places; ¹H NMR (solvent: CDCl ₃, chemical shift): 1.300 (t, 3H, CH ₃), 1.360 (t, 3H, CH ₃), 2.931 (s, 3H, CH ₃), 3.740 (s, 2H, CH ₂), 4.245 (q, 2H, CH ₂), 4.343 (q, 2H, CH ₂), 9.325 (s, 1H, NH); This compound ¹The data presentation of H NMR is consistent with its chemical structure.Adopting similar method can synthesize R is cycloalkyl, phenyl, substituted-phenyl, pyridyl, pyrimidyl, thiazolyl, triazolyl, the pyrazolyl, 1 that is selected from C1-C8 such as straight chained alkyls such as methyl, ethyl, propyl group, butyl, cyclopropyl, cyclobutyl, cyclohexyl, 3, the compound of the group of 5-triazinyl, thiadiazolyl group.

Embodiment 3: the preparation of intermediate D:

With 1.67 gram (14 mmole) SOCl ₂Join in 50 milliliters of there-necked flasks, the ice bath cooling slowly drips the CH of 2.10 gram (7 mmole) intermediate C down ₂Cl ₂10 milliliters of solution dropwised in 20 minutes, and room temperature continues to stir 17 hours, and rotary evaporation is removed CH ₂Cl ₂And SOCl ₂, add NaHCO ₃CH is used in the saturated solution neutralization ₂Cl ₂Extraction, collected organic layer, anhydrous sodium sulfate drying, precipitation, (eluent is the sherwood oil of 60-90 degree: ethyl acetate) (volume ratio is 5: 1) obtains yellowish brown crystal D, and productive rate is 57.7% to use 200-300 order silica gel column chromatography at last; The ESI mass spectrum goes out positive ion M+1 peak at 257.25 places; ¹H NMR (solvent: CDCl ₃, chemical shift): 1.410 (t, 3H, CH ₃), 1.360 (t, 3H, CH ₃), 2.910 (s, 3H, CH ₃), 4.450 (q, 2H, CH ₂); ¹³C NMR (solvent: CDCl ₃, chemical shift): 13.955 (s), 14.532 (s), 63.627 (s), 137.027 (s), 142.297 (s), 151.592 (s), 158.386 (s), 160.209 (s), this compound ¹H NMR data presentation is consistent with its chemical structure.Adopting similar method can synthesize R is cycloalkyl, phenyl, substituted-phenyl, pyridyl, pyrimidyl, thiazolyl, triazolyl, the pyrazolyl, 1 that is selected from C1-C8 such as straight chained alkyls such as methyl, ethyl, propyl group, butyl, cyclopropyl, cyclobutyl, cyclohexyl, 3, the compound of the group of 5-triazinyl, thiadiazolyl group.

Embodiment 4: the preparation of intermediate E:

0.512 gram (2 mmole) intermediate D is dissolved in 5 milliliters of anhydrous methanols, slow 0.08 gram (2 mmole) that drips) methanol solution of LiOH, NaOH or KOH is 5 milliliters, dropwises in 10 minutes, continues under the room temperature to stir 0.5 hour, desolventizing obtains light brown solid E, and productive rate is 98.0%; The ESI mass spectrum goes out positive ion M at 250.34 places ⁺The peak; ¹H NMR (solvent: CDCl ₃, chemical shift): 2.730 (s, 3H, CH ₃); This compound ¹H NMR data presentation is consistent with its chemical structure.

Embodiment 5: the preparation of product F:

The intermediate E of appropriate amount is dissolved in 20 ml waters, stirs down and drip the dilute hydrochloric acid acidifying, leave standstill, suction filtration, infrared lamp is dry down, obtains yellowish brown solid F, and productive rate is 95.0%; The ESI mass spectrum goes out positive ion M-1 peak at 227.06 places; The chemical structure of compound F 17-hydroxy-corticosterone sees Table 1.

Embodiment 6: of the present invention 1,2, and the bacteriostatic activity of 3-thiadiazoles-5-formic acid and precursor compound thereof:

The title and the code name of the frequently seen plants pathogenic fungi of the present invention's test comprise AS: tomato is epidemic disease (Alternaria solani) early; BC: botrytis cinerea pers (Botrytis cinerea); RC: cereal rhizoctonia (Rhizoctonia cerealis); CR: peanut foxiness (Cercospora rachidicola); TC: Rhizoctonia solani Kuhn (Thanatephorus cucumeris (Frank) Domk); PI: phytophthora infestans (Phytophthora infestans (Mont.) de Bary); PG: rice blast fungus (Phyriculariagrisea); GZ: gibberella saubinetii (Gibberella zeae); SS: Sclerotinia sclerotiorum (Sclerotinia sclerotiorum); MK: apple wheel line (Macrophoma kuwatsukai), these bacterial classifications have good representativeness, can represent the kind of most of pathogenic bacteria that the field takes place in the agriculture production.Thalli growth rate method measurement result sees Table 2, table 2 shows, synthetic connection 1 of the present invention, 2,3-thiadiazoles-5-formic acid and precursor compound thereof have bacteriostatic action in various degree to the growth of the part pathogenic fungi measured: when 50 mcg/ml, compd B, C, D, F to the activity of BC greater than 50%; B, C, D to the activity of GZ greater than 50%; Compd B to the activity of PG and F to the activity of RC also greater than 50%; Compd B, D, E to the activity of SS greater than 50%; Compd B, D, F to the activity of TC greater than 50%; These connection 1,2, the activity of 3-thiadiazoles-5-formic acid and precursor compound thereof almost all is higher than the restraining effect of positive control medicament TDL.

Embodiment 7: of the present invention 1,2, and the effect of 3-thiadiazoles-5-formic acid and precursor compound evoking tobacco resisting tobacco mosaic virus thereof:

The result of the determination test of induced activity shows, the plant inducing anti-disease activator BTH of standard and tiadinil energy evoking tobacco produce the resistance to TMV, of the present invention 1,2,3-thiadiazoles-5-formic acid and precursor compound thereof have the activity of the anti-TMV of evoking tobacco preferably, its effect of inducing when 100 mcg/ml are irritated 10 milliliters of roots has reached 85%, all is higher than the induced activity 50% of the positive control medicament TDL under the same concentrations.

Embodiment 8: of the present invention 1,2,3-thiadiazoles-5-formic acid and precursor compound thereof and antiviral agent are combined in the application in control agricultural and forestry and the gardening plant virus disease:

The result of biological assay test shows, of the present invention 1,2,3-thiadiazoles-5-formic acid and precursor compound thereof and existing Antiphytoviral medicament BTH, TDL, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid (TDLA), DL-beta-aminobutyric acid (BABA), virazole, Ningnanmycin, antofine and tisocromide, the first thiophene lures amine and Whitfield's ointment, 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 dichloro-isonicotinic acid and the allyl isothiazole, also can be used to induce the anti-pepper virus disease of capsicum or directly prevent and treat other virus disease such as pepper virus disease, can also be used to induce the anti-tomato virus disease of tomato or directly prevent and treat tomato virus disease, all show summation action or synergism between these compositions, the effect that the effect of its antiviral activity is all used separately greater than any one compound, the result of all mensuration is all greater than 80%; Do not have to find to have the composition of antagonistic action, and the drug effect lasting period of composition 21 days have all been surpassed.

The staple crop that these compositions are suitable for comprises that cereal crop (comprise paddy, wheat, barley, oat, corn, millet, Chinese sorghum etc.), tuber crops (comprise sweet potato, potato, cassava etc.), legume crop (comprises 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, 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 crop such as tobacco (flue-cured tobaccos such as 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.), potato, wheat, corn, paddy rice, peanut, fruit tree, (apple, banana, citrus, peach, papaya), flowers (as orchid), potted landscape etc.; Virus disease comprises tobacco mosaic virus disease, various melon virus diseases, various solanberry viroid diseases, the beans virus disease, the Cruciferae virus disease, the grain and oil crop virus disease, cotton virus disease and various fruit tree virus diseases etc. wherein endanger serious mainly containing: tobacco virus, peppery pimento virus disease, tomato virus disease, Chinese cabbage virus disease, the paddy rice virus disease comprises rice dwarf virus disease, yellow dwart, stripe virus disease, the fern leaf of tomato viral disease, sick and the tobacco veinal necrosis virus disease of chilli pepper mosaic virus, the corn short mosaic disease, cauliflower mosaic virus, the oranges and tangerines virus disease, cymbidium mosaic virus, cybidium ring spot virus etc.

Embodiment 9: of the present invention 1,2, and the application in 3-thiadiazoles-5-formic acid and precursor compound thereof and sterilant combination control agricultural and forestry and the gardening plant disease:

The result of preliminary biological assay test shows, all connection 1 of the present invention, 2,3-thiadiazoles-5-formic acid and precursor compound thereof and existing sterilant such as white urea cyanogen, thiram, ziram, zinc manganese ethylenebisdithiocarbamate, phosethyl Al, thiophanate_methyl, m-tetrachlorophthalodinitrile, the enemy can be loose, derosal, procymidone, RP-26019, Vancide 89, the mould prestige of second, ester bacterium urea, fultolanil, F-1991, cyproconazole, methasulfocarb, fenpropidin, dislike acid amides, triazolone, thiophanate methyl, metaxanin, Metalaxyl-M, M 9834, hymexazol, dimethomorph, flumorph, tridemorph, fluzilazol, alkene azoles alcohol, tebuconazole, dislike mould spirit, Difenoconazole, mepanipyrim, Azoxystrobin, Wocosin 50TK, diazosulfide, Whitfield's ointment, tiadinil, tisocromide, the first thiophene lures other known any any one or two kinds that can be used as in the sterilant such as amine to be used in combination the control that can be used for agricultural plants disease and gardening plant disease, controlling object comprises the Achyla of Oomycete, Aphanomyces, pythium, phytophthora, Sclerospora, Plasmopara, false Peronospora, a disease that genus produces surplus the Peronospora etc. 20, as seedling blight of rice, the tomato root rot, the late blight of potato, black shank, the millet Powdery Mildew, downy mildew of garpe, downy mildew of lettuce, other diseases of plurality of cereals crops such as cucumber downy mildew and cash crop etc., the formulation of using can be a wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse dense dose, seed treatment emulsion, aqueous emulsion, big granula, granule, microemulsion, oil-suspending agent, finish, seed with coated pesticidal, suspension concentrates, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules or the like, of the present invention 1,2,3-thiadiazoles-5-formic acid and the ratio of precursor compound in composition thereof can be 1%-90%, the prevention effect of medicament is good, these compositions have certain synergism and summation action, do not find to have the composition of antagonistic action.

Utilize similar method can determine of the present invention 1,2, the combination between 3-thiadiazoles-5-formic acid and precursor compound thereof 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, potato, 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 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.

Embodiment 10: of the present invention 1,2, and the application in 3-thiadiazoles-5-formic acid and precursor compound thereof and sterilant combination control agricultural and forestry and the gardening plant insect pest:

All connection 1 of the present invention, 2,3-thiadiazoles-5-formic acid and precursor compound thereof and commercial other insecticide compositions can be to spray after directly converting water in both compare the scope that is listed in 1%: 99% to 99%: 1%, comprise agricultural in its preparation and go up acceptable solvent and emulsifying agent and solubility promoter, main formulation comprises wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse dense dose, seed treatment emulsion, aqueous emulsion, big granula, granule, microemulsion, oil-suspending agent, finish, seed with coated pesticidal, suspension concentrates, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules; The insect pest that can prevent and treat has bollworm, red spider, aleyrodid, aphid, leafhopper, thrips, nematode, armyworm, oriental tobacco budworm, bollworm, pink bollworm, heart-eating worm, cabbage caterpillar, small cabbage moth, snout moth's larva, plant hopper, stinkbug and sanitary insect pests such as plant hopper and mosquitos and flies, and controlling mode also comprises double controlling simultaneously; Of the present invention 1,2,3-thiadiazoles-5-formic acid and precursor compound thereof can with the sterilant of following group in one or more mix use: Chlorpyrifos 94, the inferior Nong in ground, acetamiprid, Affirm (Merck Co.), Avrmectin, Cypermethrin, effective cypermethrin, thiophene worm piperazine, fenvalerate, alkynes mite spy, the butyl ether urea, benfuracarb, azocyclotin, Buprofezin, ether chrysanthemum ester, ethoprophos, fluorine worm nitrile, flufenoxuron, the desinsection list, disosultap, Provado, flufenoxuron, UC 62644, Avrmectin, pleocidin and worm hydrazides and Rynaxypyr and Flubendiamide, the prevention effect of combination medicament is good, and drug effect is played stably.

Embodiment 98: of the present invention 1,2, and the complete processing and the stability of 3-thiadiazoles-5-formic acid and precursor compound thereof and commercialization compounded preparation of pesticide

Of the present invention 1,2, the mixed preparation complete processing of 3-thiadiazoles-5-formic acid and precursor compound and common agricultural chemicals sees Table 3, table 3 as seen, most medicament all can be processed according to the method for statement, the main component of liquid preparation is other a component of effective constituent and solubility promoter and tensio-active agent and synergistic agent and antifreezing agent etc., the composition of solid preparation mainly includes the effect composition, other agriculturals such as tensio-active agent and filler go up the acceptable adjuvant component, preparation to processing carries out cold storage test, liquid preparation is placed 1 week not have to precipitate at 0 ± 2 degree and is separated out, solid preparation placed for 2 weeks at 54 ± 2 degree, caking phenomenon does not appear in medicament, the medicament drug effect that all preparations store before and after placing does not have significant difference, and the rate of decomposition of mixing effective constituent illustrates the medicament qualified stability in 5%.

Table 1 synthetic connection 1,2 of the present invention, the chemical structure of 3-thiadiazoles-5-formic acid and precursor compound thereof

The fungicidal activity of the compound among table 2 the present invention (/ %)

Compound	AS	BC	CR	GZ	MK	PG	PI	RC	SS	TC
											B	21.43	60.00	12.50	85.29	0	55.56	20.00	41.67	57.14	78.95
C	28.57	52.00	37.50	82.35	0	27.78	20.00	36.11	35.71	26.32
											D	0	52.00	37.50	85.29	23.08	22.22	10.00	27.78	64.29	50.00
E	21.43	48.00	25.00	23.53	30.77	27.78	10.00	44.44	50.00	34.21
											F	28.57	64.00	25.00	23.53	23.08	5.56	15.00	61.11	42.86	60.53
TDL	36.36	25.00	37.50	9.09	39.13	14.29	20.00	18.75	56.25	23.08

Data are the measurement result of 50 mcg/ml in the table; ND: undetermined

Table 3 connection 1,2,3-thiadiazoles-5-formic acid and precursor compound thereof mix the working method of using preparation with conventional pesticide

Liquid preparation is formed	Active constituent content (%)	Solid preparation is formed	Active constituent content (%)	Explanation
					Compd B, C, D, other agricultural chemicals of E, F+	?1-90	Compd B, C, D, other agricultural chemicals of E, F+	1-90	The principle of combination is to examine synergy or consider doublely to control and lighten one's labor and save the dispenser cost
Solubility promoter	?2-8	Sodium lauryl sulphate	1-5
					Tensio-active agent	?2-10	Diatomite	5-30
Antifreezing agent	?2-5	Sodium lignosulfonate	2-8
					Synergistic agent	?2-8	Other agriculturals go up the acceptable auxiliary agent	1-5
Other agriculturals go up acceptable auxiliary agents as, stablizer, thickening material or permeate agent etc.	?1-5	Kaolin	Supply 100%
					Toluene, water	Supply 100%

Claims (3)

1. compound with formula I structure:

Wherein, R is ethyl, hydrogen, Na.

2. the synthetic method of compound F 17-hydroxy-corticosterone, its concrete synthetic route is as follows:

Specifically be divided into following steps:

(1). the preparation of intermediate B: with 3.44 gram 4-methyl isophthalic acids, 2,3-thiadiazoles-5-ethyl formate and 2.64 gram ethyl acetate join in 50 milliliters of single port flasks, the ice bath cooling down, add the NaH of 0.96 gram 50%, stirring at room is after 15 minutes in batches, and reaction soln becomes chocolate, reflux 3 hours, be cooled to room temperature, glacial acetic acid neutralization, anhydrous diethyl ether extraction, desolventizing obtains chocolate oily matter, obtain brown oil B with 200～300 order silica gel column chromatographies at last, eluent is the sherwood oil of 60-90 degree: ethyl acetate, volume ratio are 3: 1, drying obtains crude product, according to the pure product calculated yield of gained, measure fusing point, MS and ¹HNMR; The amount of compd B preparation enlarges by corresponding proportion or dwindles;

(2). the preparation of intermediate C: 2.14 gram intermediate B are dissolved in 10 milliliters of dehydrated alcohols, 5 milliliters of ethanol solutions that in batches add 1.14 gram carbazic acid ethyl esters, stirring at room 5 hours, desolventizing gets the brown thick liquid, leave standstill and obtained the brown solid in 3 days, washing, infrared lamp is dry down, obtain light brown solid C with 200～300 order silica gel column chromatographies at last, eluent is the sherwood oil of 60-90 degree: ethyl acetate, volume ratio is 3: 1, and drying obtains crude product, according to the pure product calculated yield of gained, measure fusing point, MS and ¹HNMR; The amount of Compound C preparation enlarges by corresponding proportion or dwindles;

(3). the preparation of intermediate D: with 1.67 gram SOCl ₂Add in 50 milliliters of there-necked flasks, the ice bath cooling slowly drips the CH of 2.10 gram intermediate C down ₂Cl ₂10 milliliters of solution dropwised in 20 minutes, and room temperature continues to stir 17 hours, and rotary evaporation is removed CH ₂Cl ₂And SOCl ₂, add NaHCO ₃CH is used in the saturated solution neutralization ₂Cl ₂Extraction, collected organic layer, anhydrous sodium sulfate drying, precipitation obtains yellowish brown crystal D with 200～300 order silica gel column chromatographies at last, and eluent is the sherwood oil of 60-90 degree: ethyl acetate, volume ratio is 5: 1, and drying obtains crude product, according to the pure product calculated yield of gained, measure fusing point, MS and ¹HNMR; The amount of Compound D preparation enlarges by corresponding proportion or dwindles;

(4). the preparation of intermediate E: 0.512 gram intermediate D is dissolved in 5 milliliters of anhydrous methanols, slowly the methanol solution of dropping 0.08 gram NaOH is 5 milliliters, dropwised in 10 minutes, continue under the room temperature to stir 0.5 hour, desolventizing obtains light brown solid E, drying obtains crude product, according to the pure product calculated yield of gained, measure fusing point, MS and ¹HNMR; The amount of compd E preparation enlarges by corresponding proportion or dwindles;

(5). the preparation of product F: the intermediate E of appropriate amount is dissolved in 20 ml waters, stirs and to drip the dilute hydrochloric acid acidifying down, leave standstill, suction filtration, infrared lamp are dry down, obtain yellowish brown solid F, and drying obtains crude product, according to the pure product calculated yield of gained, measure fusing point, MS and ¹HNMR; The amount of compound F 17-hydroxy-corticosterone preparation enlarges by corresponding proportion or dwindles.

3. the described formula I structural compounds of claim 1 is gone up the purposes of acceptable assistant in the preparation sterilant with agricultural.