阅读说明：本技术 高效低毒无公害杀菌农用新化合物及其组合物 (High-efficiency low-toxicity pollution-free bactericidal agricultural new compound and composition thereof ) 是由 刘力 于 2018-08-27 设计创作，主要内容包括：本发明的高效低毒无公害农用新化合物为噻唑锌ν型化合物,制备中的能耗更低,更易于制备,更绿色环保,且具有更低的吸湿性、更好的存储稳定性或防治效果等,适用于制备含有该化合物的组合物及防治农作物上各种细菌性和真菌性病害和或促进作物健康或生长发育的农药或用于保护工业材料不受病菌侵害等领域的药剂中的应用。(The high-efficiency low-toxicity pollution-free agricultural new compound is a thiazole zinc v-type compound, has lower energy consumption in preparation, is easier to prepare, is more green and environment-friendly, has lower hygroscopicity and better storage stability or prevention and treatment effect, and the like, and is suitable for preparing a composition containing the compound and application in the fields of preventing and treating various bacterial and fungal diseases on crops and/or promoting the health or growth and development of the crops or medicaments for protecting industrial materials from being damaged by the diseases and the like.)

1. Novel zinc thiazole compounds, characterized in that: the new zinc thiazole compound is zinc thiazole crystal hydrate with the molecular formula of C₄H₄N₆S₄Zn·0.25H₂O。

2. Novel zinc thiazole compounds according to claim 1 characterized in that: measured by powder X-ray diffraction method, the diffraction angle 2 theta, in the measurement range of 3-60 degrees, has corresponding characteristic values at the following 2 theta values: 8.56, 11.22, 13.30, 15.48, 17.77, 19.15, 20.76, 22.90, 24.31, 24.98, 26.20, 26.87, 28.05, 28.76, 30.81, 31.29, 32.28, 33.38, 33.96, 35.74, 37.44, 39.87, 43.97, 46.14, 46.87, 47.59, 49.31, 51.09, 52.71, 53.57, 55.19.

3. Novel zinc thiazole compounds according to claim 1 characterized in that: measured by powder X-ray diffraction method, the diffraction angle 2 theta, in the measurement range of 3-60 degrees, has corresponding characteristic values at the following 2 theta values: 10.22, 11.14, 13.30, 15.46, 16.31, 17.75, 19.16, 20.74, 22.88, 23.94, 24.24, 24.95, 25.25, 26.26, 28.16, 30.78, 31.33, 32.38, 32.94, 33.44, 33.96, 35.91, 38.00, 39.81, 43.74, 47.48, 49.19, 51.05.

4. A process for the preparation of novel zinc thiazole compounds according to any of claims 1 to 3, characterized in that: the preparation method comprises the following steps:

adding 2-amino-5-mercapto-1, 3, 4-thiadiazole into a reaction vessel, adding water, stirring, adding one or more of sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium bicarbonate and potassium hydroxide or water solution thereof, stirring, adding one or more of zinc sulfate, zinc heptahydrate, zinc chloride, zinc acetate and zinc nitrate or water solution thereof, stirring until solid is fully separated out, filtering, adding water and an organic solvent C₁-C₆Low molecular alcohol of (2), C₂-C₈Low molecular ether of (2), C₃-C₈Low molecular ketone of (2), C₂-C₆Low molecular nitrile of (2), C₁-C₆Low molecular halogenated hydrocarbon of C₂-C₈Washing one or more of the low molecular weight ester(s) once to several times, filtering, and drying the obtained solid to obtain a novel thiazole zinc compound, namely thiazole zinc crystalline hydrate;

wherein the equivalent ratio of 2-amino-5-mercapto-1, 3, 4-thiadiazole to base used in the reaction is about 1: 1 to 1.1; the weight volume ratio of the 2-amino-5-mercapto-1, 3, 4-thiadiazole used in the first step to water, or C1-C6 low molecular alcohol, C2-C8 lower ether, or C2-C6 low molecular nitrile organic solvent is generally as follows: 1 (g): 3.5 to 60(ml), preferably in the ratio: 1 (g): 5 to 40 (ml); the equivalent weight ratio of one or more of 2-amino-5-mercapto-1, 3, 4-thiadiazole and zinc salt is preferably from about 1: 0.98 to 1.0;

wherein, the organic solvent C₁-C₆The low molecular alcohol of (1) is selected from but not limited to methanol, ethanol, isopropanol and butanol; c₂-C₆The low molecular nitrile of (a) is selected from, but not limited to, acetonitrile; c₂-C₈The low molecular ether or low molecular ether of (2) is selected from but not limited to diethyl ether, isopropyl ether, tetrahydrofuran, methyl tetrahydrofuran; c₁-C₆The lower halogenated hydrocarbon is selected from but not limited to dichloromethane and chloroform; c₂-C₈The low molecular ester is selected from but not limited to butyl acetate, ethyl acetate and ethyl formate; c₃-C₈The low molecular ketone is selected from but not limited to acetone, butanone and isohexanone.

5. Novel zinc thiazole compounds according to any of claims 1 to 4 characterized in that: preparing a novel pharmaceutical composition from an effective dose of an active ingredient A, namely a novel thiazole zinc compound, and an effective dose of an active ingredient B; wherein the weight ratio of active ingredient A to active ingredient B is preferably 1: 100-100: 1, and the active ingredient B is selected from but not limited to any one or more compounds selected from B.1) -B.13) and pharmaceutically acceptable salts thereof;

b.1) a strobilurin fungicide selected from one of, but not limited to, azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, enestroburin, picoxystrobin, kresoxim-methyl, enestroburin or metominostrobin, phenamacril, Picarbtrazox, orysastrobin, pyraclostrobin, coumoxystrobin, closterin, benzothiostrobin, UBF307, KZ165, probenazole, diclosamide;

b.2) triazole fungicide, which is selected from but not limited to one of difenoconazole, diniconazole, epoxiconazole, fenbuconazole, flusilazole, flutriafol, tebuconazole, hexaconazole, myclobutanil, penconazole, propiconazole, tetraconazole, triadimenol, triadimefon, metconazole, ipconazole, prothioconazole, imibenconazole, triticonazole, cyproconazole, mefentrifluconazole, ipfentrifluconazole;

b.3) an amide fungicide selected from one of but not limited to metalaxyl, flutolanil, mandipropamid, boscalid, fluopyram, carboxin, bixafen, penflufen, epoxiconazole, fluxapyroxad, penthiopyrad, thifluzamide, fluopicolide and isopyrazam, flufen-amide, fluofen-amide, cyclamate and thifluzamide;

b.4) one of imidazole bactericides which is selected from one of but not limited to cyazofamid, triflumizole, imazalil, fenamidone, oxpoconazole, and prothioconazole;

b.5) dicarboximide bactericides selected from one of but not limited to procymidone, iprodione, vinclozolin, captan and dimethachlon;

b.6) carbamate bactericide which is selected from one of but not limited to propamocarb hydrochloride, diethofencarb, benomyl, carbendazim, thiophanate-methyl, iprovalicarb and benthiavalicarb;

b.7) antibiotic bactericide selected from one of validamycin, streptomycin sulfate, kasugamycin, tetramycin, shenqinmycin, polyoxin, ningnanmycin, streptomycin sulfate, zhongshengmycin, nong antibiotic 120, aureonucleomycin, Changchuan mould, and tetramycin;

b.8) an oxazole based fungicide selected from but not limited to one of oxadixyl, hymexazol, famoxadone, pyrisoxazole, oxadixyl fluorothiazole, benfurazolesulfone, oxazazole dichloride and methylsulfonyl;

b.9) morpholine bactericide which is selected from but not limited to one of tridemorph, dimethomorph and flumorph;

b.10) a pyrimidine bactericide which is selected from but not limited to one of cyprodinil, pyrimethanil, ethirimol, mepanipyrim, fluopyram, dimoxystrobin, SYP-3773 and SYP-3810;

b.11) quinoline bactericide which is selected from but not limited to one of dithianon, propoxymoline, phenoxyquinoline and quinoflulin;

b.12) dithiocarbamate bactericide which is selected from but not limited to one of metiram, thiram, zineb, mancozeb and propineb;

b.13) other bactericides selected from but not limited to one of diphenoxylate, fosetyl-aluminum, chlorothalonil, isoprothiolane, fludioxonil or copper hydroxide, copper rosinate, copper dehydroabietate, fenpiclonil, fludioxonil, isolong vinyl ketoxime lactam, osthole, Dufulin, phenol cycloheximide, mehtothiazine, polyhexamethylene biguanide hydrochloride, bromothalonil, indazole flusulfamide, copper oxychloride, copper quinolate, moroxydine hydrochloride, copper succinate, Xinjunan acetate, amino-oligosaccharide, lentinan, benziothiazolinone, ethylicin, probenazole, diclosamide, physcion, chrysophanol, fluzole activated ester, S-abscisin, amino-oligosaccharide, zinc sulfate, berberine and pharmaceutically acceptable salts thereof, eugenol, sulfur, copper sulfate pentahydrate, and isolong vinyl ketoxime lactam; or the plant growth regulator is selected from one of but not limited to diethyl aminoethyl hexanoate, forchlorfenuron, compound sodium nitrophenolate, brassin, gibberellin, 6-benzylaminopurine, triacontanol, naphthylacetic acid or its medicinal salt, paclobutrazol and ethephon.

6. The composition of novel zinc thiazole compounds according to claim 5 wherein: the bactericide contains an active ingredient A and any one active ingredient B selected from but not limited to azoxystrobin, kresoxim-methyl, pyraclostrobin, enestroburin, trifloxystrobin, pyraclostrobin, fluoxastrobin, kresoxim-methyl, enestroburin or metominostrobin, cyazoxystrobin, Picarbitrazox, orysastrobin, pyraclostrobin, coumoxystrobin, clotrimoxystrobin, UBF307, KZ165, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, flusilazole, flutriafol, triadimenol, triadimefon, metconazole, prothioconazole, imibenconazole, triticonazole, cyproconazole, metalaxyl, flutolanil, mandipropamid, boscalid, fluopyram, cyazofamid, triflumizole, imazalil, fenpyr, iprazole, fenpyr, iprodione, fenpyr, iprazole, fenugreek, captan, dimetachlone, propamocarb hydrochloride, benomyl, carbendazim, thiophanate-methyl, iprovalicarb, benthiavalicarb, validamycin, streptomycin sulfate, kasugamycin, shenqimycin, oxadixyl, hymexazol, famoxadone, pyrisoxazole, tridemorph, dimethomorph, flumorph, cyprodinil, pyrimethanil, ethametrafil, flufenamid, dithianon, proquinazine, phenoxyquinoline, metiram, thiram, zineb, mancozeb, propineb, edifenphos, fosetyl, chlorothalonil, isoprothiolane, fludioxonil or copper hydroxide, copper rosinate, copper dehydroabietate, fenpiclonil, fludioxonil, prochloraz, manganese prochloraz, a complex of prochloraz, osthol, diphenhydrabamine, okadamycin sulfate, kasugamycin, validamycin, tetramycin, streptomycin sulfate, streptomycin, Zhongshengmycin, pesticide 120, aureonucleomycin, Chanchuan mycin, Dufulin, phenol cycloheximide, albendazole, mefentrifluconazole, ipfentrifluconazole, fluorothiazole pyriethanone, probenazole, diclorocyanid, physcion methyl ether, chrysophanol, fluzole activated ester, oxazole dichloride and methylsulfonyl oxazole, S-elicitor, amino-oligosaccharin, zinc pyridine sulfate, berberine hydrochloride, berberine sulfate or plant growth regulator, wherein the weight ratio of the active component A to the active component B is preferably 1: 60-60: 1.

7. Novel zinc thiazole compounds according to any of claims 1 to 6 characterized in that: the novel compound or the composition thereof and a pharmaceutically acceptable carrier are prepared into a pharmaceutically acceptable preparation which is selected from but not limited to wettable powder, water dispersible granules, suspending agents, suspoemulsions, emulsion in water, granules, dry powder for seed treatment, dispersible powder for seed treatment, microcapsule suspending agents, suspending agents for seed treatment microcapsules or suspended seed coating agents.

8. The composition of claim 7, wherein: the pharmaceutically acceptable carrier is selected from, but not limited to, wetting agents, binders, dispersants, thickeners, antifreezes, preservatives, disintegrants, stabilizers, film formers, antifoaming agents, colorants, lubricants or glidants, emulsifiers, fillers, and/or water.

9. The use of the novel zinc thiazole compounds or pharmaceutical compositions thereof according to any of claims 1 to 8, characterized in that: the application of the compound in preparing medicines for preventing and treating diseases on crops and/or promoting the health or growth and development of the crops or medicines in the field of protecting industrial materials from being invaded by germs.

10. The use of novel zinc thiazole compounds or pharmaceutical compositions thereof according to any of claims 1 to 9, crops of crops preferably or selected from but not limited to the following species: cereal wheat, barley, rice, corn, sorghum, sweet potato; fruit trees such as apple, pear, peach, hickory, orange, grape, lychee, banana, longan, mango and loquat; vegetables such as cucumber, watermelon, snake gourd, towel gourd, melon, spinach, celery, tomato, pepper, eggplant, ginger, shallot, garlic, leek, cabbage, Chinese cabbage, strawberry, asparagus lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam, taro, lotus root, water chestnut and water bamboo; sugar plants such as beet and sugarcane; oil crops such as soybean, peanut, rape, sesame and sunflower; or such as tobacco, tea; the diseases are selected from but not limited to: one or more of canker, stripe disease, rust disease, glume blight, net blotch, powdery mildew, downy mildew, epidemic disease, leaf spot, take-all disease, snow mold, smut, leaf blight, brown spot or rice blast.

Technical Field

The invention relates to the technical field of pesticides, and particularly provides a novel compound with high efficiency, low toxicity and no public nuisance, a bactericidal medicine zinc thiazole with better stability, a pesticide composition thereof, a preparation method and application thereof.

Background

Zinc thiazole, chemical name bis (2-amino-5-mercapto-1, 3, 4-thiadiazole) zinc, CAS: 1202750-31-9, molecular formula C₄H₄N₆S₄Zn with molecular weight of 329.77 can be used in the fields of fine chemical engineering including sensitization or materials science, and is also an organic zinc broad-spectrum bactericide developed by Xin nong chemical industries of Zhejiang. The pesticide has multiple functions of systemic absorption, conduction, prevention, protection, treatment and the like, has the treatment effect greater than the protection effect, is a new generation of high-efficiency, low-toxicity and broad-spectrum bactericide for preventing and treating crop bacterial diseases, and has better prevention and treatment effects on various bacterial and fungal diseases. 20% zinc thiazole suspending agent (trade name: Bisheng) is recognized as 'new product of national firefly promotion' by the four departments of science and technology, etc. Has six characteristics: firstly, the bactericidal spectrum is wide. Has special effect on bacterial diseases and high efficiency on fungal diseases, and is a bactericide with complete functions. Secondly, the effect is prominent. Strong protection and rapid systemic treatment, has the lasting period of half a month, low toxicity and no public nuisance. Thirdly, the preparation is environment-friendly. The superfine preparation is like milk after being mixed with water, has no pollution to fruit and is the first choice for producing nuisanceless agricultural products. And fourthly, the fertilizer is suitable for almost all crops, has no phytotoxicity and is safe to flowers and young fruits of the crops. The product is suitable for target and is superior to copper preparation in preventing and treating period. Fifthly, the zinc is supplemented efficiently. Can promote flower bud differentiation, pollen tube elongation, pollination, promote flower and fruit retention, and eliminate zinc deficiency of fruit tree such as lobular disease, lotus leaf and drumstick. Sixthly, the bactericide composition is good in synergistic effect when being mixed, can be mixed with strong acid and strong alkali pesticides, can be scientifically mixed with commercially popularized fungistatic bactericides (such as dimethomorph, triazoles with good safety, thiophanate-methyl, carbendazim, metalaxyl and the like) under recommended dosage, has far higher comprehensive control effect than that of a fungistatic medicament when being singly used, simultaneously delays resistance, ensures safety and no phytotoxicity, and is good in safety, and does not stimulate mites,The breeding of the ticks has high popularity of farmers, and the ticks become an excellent mainstream bactericide for promoting the health cultivation of pollution-free agricultural products.

The zinc thiazole has bactericidal property, has outstanding control effect on bacterial diseases of plants and also has good effect on partial fungal diseases, and the zinc thiazole with proper concentration has the functions of promoting the growth of roots and leaves of partial plants and improving stress resistance and disease resistance. The zinc thiazole has good safety to crops and strong miscibility with other bactericides, and is a good product conforming to modern health-care cultivation.

For example, zinc thiazoles are used to control non-bacterial infestation in Chinese cabbage: soft rot bacterial diseases, black spot, anthracnose, rust disease, powdery mildew, zinc deficiency and aged leaves; peanut: peanut bacterial wilt, root rot disease and peanut leaf spot; rice: stiff seedlings, yellow seedling rot, bacterial streak, bacterial leaf blight, sheath blight, rice blast and zinc deficiency fire burning seedlings; cucumber: bacterial angular leaf spot, canker, downy mildew, target disease, yellow spot disease, zinc deficiency and yellowing of leaves; the virus can be inactivated; tomato: bacterial canker, late blight, brown spot, anthracnose, zinc deficiency, inactivating virus; at the early stage of the disease, the liquid with the volume of 500-. The dilution factor is increased (decreased) seriously. The prevention and treatment are carried out continuously for 2-3 times at intervals of about 7 days. Note the secondary dilution spray.

According to the rice yield test in Hubei proctor/Guangxi Yulin/Sichuan tribute and other places, the zinc thiazole is applied for more than 2 times under the same fertility condition, and the average yield is increased by 15-20 percent compared with that without application; the yield increasing effect is more obvious in the cold waterlogged paddy field affected by the disaster weather; the flower and fruit promoting effect is good for fruit vegetables such as hot pepper, tomato, beans, watermelon and the like, and the average yield increasing amplitude reaches more than 10% by applying zinc thiazole for more than 2 times; the yield increasing effect on tuber crops such as potatoes, ginger, konjak and the like is obvious, the yield increasing effect is more than three times all year around, and the conventional yield increasing amplitude reaches more than 15%.

The action mechanism of zinc thiazole is as follows: the zinc thiazole structure consists of two groups for sterilization. One is thiazole group, which has no inhibition to bacteria in vitro but is a highly effective therapeutic agent in vivo, and the agent is in the perforated vessel of the plant, the bacteria are seriously damaged, the cell wall is thinned and then is disintegrated, and the bacteria die. And zinc ions have the functions of killing fungi and bacteria. Zinc ions in the medicament are exchanged with cations (H +, K + and the like) on the surfaces of the cell membranes of pathogenic bacteria, so that proteins on the cell membranes of the pathogenic bacteria are coagulated to kill the pathogenic bacteria; part of zinc ions permeate into pathogenic bacteria cells, are combined with certain enzymes, influence the activity of the pathogenic bacteria, cause dysfunction, and cause the pathogenic bacteria to die. Under the combined action of the two groups, the bactericide is more thorough in sterilization, better in prevention and treatment effect and wider in prevention and treatment objects. And the disease is not easy to generate drug resistance to zinc thiazole.

The zinc thiazole can improve the coloring of the fruits and improve the smoothness of the fruits, thereby improving the commodity of the fruits; the coloring can be improved and the yield can be improved by using the tomato vegetable; the use of the compound in fruits such as watermelon, grape and the like shows that the compound has certain effect of improving the fruit endoplasm, particularly certain effect of sweetening.

The zinc thiazole can be widely used for controlling more than 20 crops and more than 60 bacterial and fungal diseases, wherein the main control objects comprise: bacterial leaf spot of rice, bacterial leaf blight of rice, basal rot of rice, citrus canker, sleeve canker, angular leaf spot of cucumber, angular leaf spot of cotton, leaf blight of garlic, angular leaf spot of melon, soft rot of cabbage, scab of citrus, scab of sleeve, leaf spot of banana, fusarium wilt of watermelon, leaf spot of longan, leaf spot of peanut, anthracnose of grape, ring rot of fruit tree, anthracnose, etc.; in addition, the fertilizer can also supplement trace element copper, promote the growth and development of plants, maintain photosynthesis and improve the cold and drought resistance of crops. Particularly, the prevention effect on bacterial leaf streak of rice, bacterial leaf blight, basal rot, soft rot of Chinese cabbage and angular leaf spot of cucumber reaches 71 to 86 percent, the prevention effect on citrus canker and scab reaches over 86 percent, and the control effect on other fungal diseases such as sigatoka and watermelon fusarium wilt is also excellent. The prevention and control effect of zinc thiazole is remarkable through the prevention and control test demonstration of 6000 to ten thousand mu of bacterial leaf streak and bacterial leaf blight of rice and two major diseases, canker and scab of oranges and tangerines all over the country [ reference: ye Lin, Liang Xiao Yu, Xu dao, etc., zinc thiazole to rice yellow single cell bacillus biological activity preliminary study [ J ]. agricultural and pharmaceutical science report, 2014,16 (02): 125- > 131; fanglin, schsandwort, precious gold, etc., creating the field efficacy of the pesticide thiazole zinc on citrus canker [ J ] pesticide, 2008 (02): 90-91+ 96; ginger is suitable for flying, Zhaoyonghui, Li guo ping, research on a thiazole zinc original drug high performance liquid chromatography analysis method [ J ] pesticide science and management, 2009, 30 (08): 44-46.; wenxiang, san Dan Qian, Lijun, et al, high performance liquid chromatography analysis of 20% thiazole zinc suspension [ J ]. modern pesticides, 2014,13 (05): 23-24+ 27.; wangwanglong, Liuzongquan, Wangxiang, etc., 20% thiazole zinc suspending agent for preventing and treating garlic leaf blight effect research [ J ] modern agricultural science 2014 (23): 155-; chekia, liu source, swiftlet, wang kezhen, liu yong.20% thiazole zinc suspension agent prevention and cure cabbage bacterial black spot test [ J ] Jilin vegetable, 2010 (04): 91.; wu national peak, in feng cui, liu yu, bi sheng 20% thiazole zinc suspension for preventing and treating lotus root rot disease initial exploration [ J ] modern horticulture, 2013 (06): 5, cutting the blank into a required shape; cryopeng, novel creative fungicide zinc thiazole [ J ] pesticide market information, 2010 (14): 42.; chenopodium, cloc, shengling, sun phoenix.20% thiazole zinc suspension agent apple disease control test bulletin [ J ]. northwest horticulture (fruit tree special), 2010 (01): 42-43; 20% thiazole zinc SC prevention and treatment test briefing on peach tree disease [ J ] southern agriculture, 2010,4 (01): 53-54.; cyrophor, fuhuiyao, fangyongqiang, etc., and the test for zinc thiazole to prevent and treat bacterial leaf spot of tomato [ J ]. zhejiang agricultural science, 2011 (05): 1125. 1126; verdant, wanhuifu, emblic leafflower bud, kasugamycin and zinc thiazole 40% suspending agent for preventing and treating rice blast test initial report [ J ] pesticide science and management, 2013, 34 (07): 47-49.; cold peng, the application effect of the fungicide zinc thiazole [ J ] Zhejiang agricultural science, 2010 (06): 1355, applying; weifang forest, precious, schsandaran, etc., creating the field effect of the pesticide thiazole zinc on rice bacterial diseases [ J ] pesticide, 2007 (12): 810-; mozu root, shendongping, dongdao, 40% wuezole-thiazole zinc suspension concentrate effect research on prevention and treatment of rice sheath blight [ J ] modern agricultural science, 2012 (05): 182+ 184; weifang lin, daijingui, julian minds, zhuhbin, create a fungicide, zinc thiazole [ J ], a world pesticide, 2008 (02): 47-48.; the coldpeng fungicide zinc thiazole has wide application prospect in vegetable fitness cultivation [ J ] Zhejiang agricultural science 2010 (02): 381; zhongchang' an, zinc thiazole is really an absolute [ J ] for preventing and controlling celery soft rot, beijing agriculture, 2012 (07): 15.; synergistic effect of piceid, vermifuil, pistil, chenjie, zinc thiazole and azoxystrobin on cucumber downy mildew [ J ] pesticide, 2012,51 (01): 73-74.].

At present, zinc thiazole (C) has been reported in the patent publications and the like₄H₄N₆S₄Zn·0.5H₂O, molecular weight: 338.78, [ reference 1, thiadiazole metal complex, and preparation method and application thereof CN 1152869; document 2, a preparation method of zinc thiazole raw drug CN106045939 a; document 3(CN107047573 a); literature 4, Wang Yifeng, Cheng Ruxiang, Su Dan Qian creating a ball milling synthesis process of pesticide thiazole zinc [ J]Pesticide, 2015,54 (04): 251 and 253; document 5, zinc thiazole suspending agent and preparation method thereof WO/2008/151513, publication No.: 101194611, respectively; document 6, zinc thiazole water dispersible granules and a preparation method thereof, CN 103704222;]。

in the current agricultural field, due to single administration and other unscientific administration modes, part of bacterial and fungal diseases generate drug resistance to a plurality of medicaments, and the method becomes a great problem in the agricultural sterilization process. Due to the generation of resistance of pathogenic bacteria, the pesticide is applied in an indiscriminate way in agriculture, frequently applied, mixed with pesticides randomly, even extremely toxic and highly toxic pesticides are used, so that the application cost is increased, the environmental pollution is aggravated, the residual risk is increased, and the food safety is seriously challenged. Even highly effective novel pesticides, if used alone for a long time, are also at risk of developing resistance to drugs. The development of new pesticides has high investment risk, and the requirements on environmental protection and food safety are increased, so that the restriction is increased, and the development period is longer. The scientific and reasonable pesticide compounding can improve the control effect, increase the quick-acting property, prolong the lasting period, expand the control spectrum, reduce the dosage, reduce the cost, or improve the multifunction of one-time pesticide application, and the like, can overcome or delay the generation or development of the resistance of pests, prolong the service life of the pesticide, reduce the environmental pollution, protect natural enemies, maintain the biological diversity, keep the ecological balance or be convenient to use, reduce the working hours, and the like. The method has important value in the aspects of protecting the high yield and high quality of crops in the research and application of the efficient, safe, low-drug-resistance and convenient-to-use pesticide composition. Because of the limited sterilization capability of zinc thiazole, the sterilizing agents Biye compounded by zinc thiazole and azoxystrobin, Bisui compounded by zinc thiazole and tebuconazole, Birui compounded by zinc thiazole and tebuconazole and the like are on the market at present, and meanwhile, the published Chinese patent documents report the compounding or combined administration of zinc thiazole, such as [ a sterilization composition containing zinc thiazole, CN 101953346; a compound high-efficiency bactericidal composition containing zinc thiazole, CN: 107018980, respectively; a pesticide composition containing zinc thiazole and application thereof, and the publication number is CN 106962367; a method of reducing the resistance of gram-negative phytopathogenic bacteria to zinc thiazole, CN 106962389; a flower and fruit retention agent and application thereof, CN 106879604; a composition containing zinc thiazole and xinjunan acetate, a preparation and an application thereof, CN 106508919; a sterilization composition containing zinc thiazole and phosphite, and a preparation and an application thereof, CN 106172497; a bactericidal composition containing oxolinic acid and zinc thiazole, CN 105994312; a bactericidal composition containing copper rosinate and zinc thiazole, CN 105284828; a bactericidal composition containing tetramycin and zinc thiazole, CN 105076165; a bactericidal composition containing amisulbrom and zinc thiazole, CN 104904727; an agricultural composition containing zinc thiazole and phenamacril, and a preparation and an application thereof, CN 104585220; a compound composition and a preparation containing methylsulfonylconazole and zinc thiazole, CN 104488899; a bactericidal composition containing fluxapyroxad and zinc thiazole, CN 104957148; a compound high-efficiency sterilization composition containing zinc thiazole, CN 104642351; a sterilization composition containing zinc thiazole, CN 104642341; a compound sterilization composition containing zinc thiazole, CN 104642350; a sterilization composition containing zinc thiazole and triazole, CN 104642343; a high-efficiency sterilization composition containing zinc thiazole, CN 104642346; a high-efficiency sterilization composition containing zinc thiazole, CN 104642339; a bactericidal composition containing zinc thiazole and benziothiazolinone, CN 104542630; a sterilization composition containing zinc thiazole and a preparation and application thereof, CN 104396970; a high-efficiency sterilization yield-increasing composition containing zinc thiazole, CN 104336081; a pesticide composition containing zinc thiazole and bismerthiazol, CN 104222107; a sterilization composition and preparation and application thereof, CN 102835403; ].

The stability of the original drug is the basis for ensuring the stability and good preparation performance of the pharmaceutical preparation, and is the basis for maintaining the effectiveness of the drug, the most stable form of the raw drug is continuously pursued in pharmacology, the pharmacology is an experimental science, the molecular form with good stability is unpredictable in advance, a plurality of cases are provided in the development history of the European and American drugs to clarify the value of searching the molecular form of the drug with good stability, and the continuous development and progress of the pharmacology are objectively promoted. It is not known to many professionals that some bulk drugs produced industrially for years have different product stabilities when being put into the same batch of starting materials in the same plant and the same equipment under the same process flow, some bulk drugs can only keep the stability for about 3 months even under the specified conditions, and some quality control indexes have different obvious changes, which causes the problem of confusion or trouble. From the actual situation at present, although zinc thiazole has been on the market for many years, the stability of zinc thiazole anhydride still has some problems, such as large hygroscopicity, reduced storage period content or excessive increase of related substances, and the like, and the problems are not solved for many years, which makes us seek to solve the stability problem of the compound. Although valuable results are expected to be obtained by changing the crystal form on the basis of unchanged compound molecular formula, no significant improvement is obtained, and various problems still remain.

The situation is not an individual phenomenon, and according to the media disclosure, the quality problem of the pesticide product in China is relatively serious, and the quality difference of the raw pesticide is large due to various factors (documents: the quality difference of the raw pesticide is large due to various factors-the quality current situation and the main problem of the pesticide product in China are analyzed, China quality news network, 2008-03-26,http://www.can.com.cn/news/cpkkxbg/199443.htm 1). This focus is reflected in:

1. quality difference between products of the same variety and the same enterprise

There may also be differences in quality, even large, between products of the same variety produced by the same enterprise. The following two cases are mainly included: firstly, the product quality is unstable due to the immature production process, and the product quality of different production batches is different, which mainly exists in some small and medium-sized enterprises and some new products which are developed shortly; and secondly, part of production enterprises produce high-content products meeting export requirements through a traditional refining and purifying process, and as a result, low-content products containing a large amount of impurities are produced, and the products are partially self-digested and processed into preparation products by the production enterprises and partially pushed to domestic markets in a way of being mixed with fish eyes, so that the phenomenon is not lost even in some large and medium-sized enterprises.

2. Most raw medicine products have no control or not strict control on impurity content

At present, most of raw medicine products lack control indexes for the content of toxic and harmful impurities, and the impurity content of part of raw medicine products is obviously higher. Although it is required to provide an analysis report of the product at the time of product registration, the impurity content does not appear in the quality control index of the corresponding product (crude drug and its preparation) for most products. High impurity content of the original drug product may cause various adverse effects, some impurities have high toxicity, some impurities bring difficulty to preparation processing, and some impurities reduce the stability of active ingredients. With the use of preparation products, the impurities may also affect the environmental and ecological safety and even cause large-area crop phytotoxicity.

So far, no published literature reports the novel thiazole zinc compound with better stability at home and abroad, such as a thiazole zinc v-type crystal compound, namely a novel thiazole zinc crystal hydrate with different molecular formulas or different crystal forms, and a preparation method and application thereof.

The polymorphism of the chemical drug plays an important role in drug research, not only constructs a drug compound library and the like, but also is suitable for better pharmaceutical requirements. Thermal analysis methods have important value and status in material science, chemistry or pharmaceutical analysis, etc., and can be used alone to detect polymorphic forms of a compound or changes in the crystalline form during the process (lee, thermal analysis, university of qinghua press, first edition 8 months 1987). Differential Thermal Analysis (DTA) is a relatively common analytical method used for both qualitative and quantitative identification of substances, and is used by Barta et al to identify unknown compounds as early as the second international conference on thermal analysis in 1968. The pharmacopoeia of many foreign countries has already collected the differential thermal analysis method, and over a decade ago, the differential thermal analysis method has been widely applied to chemical and pharmaceutical systems.

Disclosure of Invention

It is well recognized in the chemical arts that the presence or absence of a specific solvent compound for a compound is unpredictable, cannot be defined in advance by the Markush formula, and that some solvent compounds are highly toxic, some are highly hygroscopic, some are easily weathered, and some are poorly stable. The invention relates to a new compound with better stability of a high-efficiency, low-toxicity and pollution-free bactericidal medicine zinc thiazole, a pesticide composition thereof, a preparation method and application thereof. The new compound with better stability of zinc thiazole is 0.25 hydrate of bis (2-amino-5-mercapto-1, 3, 4-thiadiazole) zinc, and the molecular formula is C₄H₄N₆S₄Zn·0.25H₂O, namely thiazole zinc v type new compound and a composition, a preparation method and application thereof.

In the process of completing the invention, unexpectedly, it is found that although the current literature reports that thiazole zinc anhydride is used as pesticide, the research also finds that the stability of thiazole zinc is not the best choice in pharmacology or pesticide, the thermal stability is not good enough, the content of the raw material drug is reduced or unqualified or the content of the pesticide preparation in subpackaging is not accurate, or the thiazole zinc is easy to replace or can not be used by more pesticide preparations due to high impurity content or the impurity content is higher, the environmental and ecological safety is influenced, even large-area crop phytotoxicity is caused, various adverse effects are caused, or the disadvantage is caused when the field such as sensitive sensitivity to purity or high-grade materials is further applied. Furthermore, the present study found that zinc thiazole 0.25 hydrate, which has better stability, has better accessibility than zinc thiazole anhydride, which has been ignored by the industry for a long time.

Moreover, the invention also finds the advantages of the novel compound in the production and manufacturing process or the environment-friendly disposal process, the temperature for preparing the thiazole zinc anhydride in the prior art in the document 1(CN1152869) is required to be as high as 70-80 ℃, and the drying temperature of the embodiment is required to be i00 ℃, so that more energy is consumed, the energy-saving production is not facilitated to be constructed, the total impurities are increased, and the storage stability of the raw materials is not facilitated; in the document 2(CN106045939A), the temperature required for preparing zinc thiazole anhydride is 50-80 ℃, and the drying temperature of the example is 90-110 ℃, which is also not beneficial to constructing energy-saving production, increasing total impurities and not beneficial to the storage stability of raw materials; document 3(CN107047573A) in example 1, the intermediate needs to be prepared under reflux, which not only increases energy consumption, but also causes color change, actually, degradation of 2-amino-5-mercapto-1, 3, 4-thiadiazole is increased, and the total impurities are obviously increased by more than 8% compared with those before feeding, and the number of impurities is also increased by HPLC; an increase in the number of impurities is also evident by thin layer chromatography, which is detrimental to both synthesis and the final product and does not facilitate more stable storage of the product. In document 4 (ball milling synthesis process [ J ] for preparing pesticide thiazole zinc [ pesticide, 2015,54 (04): 251-. The above problems have been overlooked for a long time, but no professional has done what seems simple and easy to improve.

The stability of the zinc thiazole 0.25 hydrate can meet the requirement of pharmacy. This reflects that zinc thiazole 0.25 hydrate with different degrees of better stability has better availability in the production process and lower energy consumption advantage, and also shows that the material of the invention has more production convenience and better industrialization value. This also reflects from another perspective that the availability of zinc thiazole anhydride production is somewhat poor, which has been overlooked for a long time.

The thiazole zinc compound entity with the novel molecular structure obtained by the invention has the advantages that the hygroscopicity of the thiazole zinc compound containing the crystal water is far lower than that of the thiazole zinc compound without the crystal water, the deliquescence of an anhydrate ensures that air is isolated to prevent adhesion and the like during treatment, the hydrate of the invention has good sliding property, so the operability of a pesticide preparation is improved, the substance of the invention containing the crystal water can exist more stably than the thiazole zinc compound without the crystal water, the storage and the transportation are convenient, the manufacturing cost and the cost are reduced, and the preparation of the pesticide preparation is also facilitated. In addition, the stability of the existing anhydrous zinc thiazole in the storage process is lower. The zinc thiazole crystal hydrates with different novel molecular formulas and novel molecular structures have different advantages in the aspects of stability and the like. Furthermore, the invention finds that the zinc thiazole 0.25 hydrate has better industrial value or pesticide value than zinc thiazole anhydride.

Surprisingly, the hydrate of the invention has a characteristic thermogram which shows thiazole zinc compound with novel structure, thiazole zinc v type crystal compound-thiazole zinc 0.25 hydrate (C-DSC or TG-DTA) and has a corresponding endothermic peak under a weight loss platform (under a weight loss curve before about 160 ℃) of the thermogram₄H₄N₆S₄Zn·0.25H₂O). Even if different crystal forms of the same compound are prepared or obtained, the actual or potential or future significance or value can be realized in pharmacology, and the fact that different structural forms of the same drug are obtained can be needless to say that the actual or potential or future significance or value can be realized in pharmacology.

The preparation of the novel zinc thiazole compound comprises the following methods:

adding 2-amino-5-mercapto-1, 3, 4-thiadiazole into a reaction vessel, adding water and/or an organic solvent C₁-C₆Is selected from low molecular alcohol (such as methanol, ethanol, isopropanol, n-butanol, etc.), C₂-C₈Low molecular ether (selected from but not limited to diethyl ether, tetrahydrofuran, isopropyl ether, etc.), C₂-C₆Stirring for dissolving one or more of low molecular nitrile, adding one or more of sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium bicarbonate and potassium hydroxide or their water solution, stirring, and adding water soluble zinc salt selected fromBut not limited to one or more of zinc sulfate, zinc sulfate heptahydrate, zinc chloride, zinc acetate, zinc nitrate or their water solution, stirring, precipitating solid sufficiently, filtering, adding water and C₁-C₆Low molecular alcohol of (2), C₂-C₈Low molecular weight ethers, C₃-C₈Low molecular ketone, C₂-C₆Low molecular weight nitrile, C₁-C₆Low molecular weight halogenated hydrocarbon, C₂-C₈Washing one or more of the low molecular weight ester for several times, filtering and drying to obtain a novel thiazole zinc compound;

wherein, the 2-amino-5-mercapto-1, 3, 4-thiadiazole used in the reaction: one of alkali (one of sodium carbonate, sodium hydroxide, potassium hydroxide and the like, but not limited to) is in an equivalent ratio of about 1: 1-1.2; the weight volume ratio of one or more of the 2-amino-5-mercapto-1, 3, 4-thiadiazole (weight g) used in the first step reaction to water, or C1-C6 low molecular alcohol, or C2-C8 lower ether (selected from but not limited to diethyl ether, tetrahydrofuran, isopropyl ether, etc.), or C2-C6 lower nitrile (selected from but not limited to acetonitrile, propionitrile, etc.) is generally: 1(g) to 3.5-60 (ml), preferably in the following ratio: 1(g) to 5-40 (ml); the equivalent ratio of one or more of 2-amino-5-mercapto-1, 3, 4-thiadiazole and zinc salt is preferably about 1: 0.98-1.0.

The solvent used in the synthesis process of the new thiazole zinc compound is selected from one or more of water, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, ethyl acetate, butyl acetate, ethyl formate, diethyl ether, tetrahydrofuran, isopropyl ether, dichloromethane, chloroform, DMF (N, N-dimethylformamide), DMSO (dimethyl sulfoxide) and the like; more preferably one or more of water, methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, isopropyl ether, dichloromethane, chloroform, DMF, and DMSO.

The carbon number of the organic solvent lower alcohol or low molecular alcohol in the present invention is defined as C1-C6 (i.e., alcohol of 1-6 carbon atoms), such as methanol, ethanol, isopropanol, etc.; the carbon atom number of the lower ether or low molecular ether is defined as C2-C8, such as diethyl ether, dibutyl ether, tetrahydrofuran, etc.; the lower halogenated hydrocarbon has carbon number defined as C1-C6, and includes dichloromethane, dichloroethane, chloroform, etc.; the lower ester has carbon number of C2-C8, and comprises butyl acetate, ethyl formate, etc.; the C3-C8 low molecular ketone is defined as ketone with 3-8 carbon atoms, including acetone, butanone, isohexanone, etc.; the labeling method for the number of carbon atoms of any of the compounds described as "lower or low molecular" appears once in the text, and the number of carbon atoms of any of the other unlabeled compounds of the same class described as "lower or low molecular" is consistent with the number already indicated herein.

The product of the present invention may be dried at various temperatures (e.g., between 20-60 c), for drying times (e.g., 0.5 hours to several days), or under ambient conditions with other drying agents (including silica gel, phosphorus pentoxide, anhydrous calcium chloride, anhydrous sodium sulfate, soda lime, etc.), or using atmospheric or reduced pressure. The drying temperature is preferably 40 to 60 ℃.

The anhydrate can be prepared by different drying methods, and can be prepared by drying the final product at different temperatures (e.g., 25-120 deg.C), drying time (up to several days), or with other drying agents (including silica gel, molecular sieve, phosphorus pentoxide, sodium hydroxide, soda lime, anhydrous sodium carbonate, anhydrous calcium chloride, anhydrous sodium sulfate, anhydrous magnesium sulfate, etc.), or by drying under normal or reduced pressure, or by mixing anhydrous benzene and standing for several days or distilling to remove water, and drying by combining other drying methods.

Methods under the literature reference methods (literature 7, ginger yifei, zuo qiao, li guo ping, research on the high performance liquid chromatography analysis method of thiazole zinc technical material [ J ]. pesticide science and management, 2009, 30 (08): 44-46; literature 8, weixialin, xudanqian, li junjun, etc., high performance liquid chromatography analysis of 20% thiazole zinc suspending agent [ J ]. modern pesticide, 2014,13 (05): 23-24+ 27.). The moisture determination in the invention refers to a first method A of an appendix VIII M of Chinese pharmacopoeia of 2010 edition, adopts a Karl Fischer method, and determines the moisture of related compounds by using a specific Karl Fischer moisture determinator.

Powder X-ray diffraction can generally be used to characterize and/or identify polymorphic forms, for which the modifier "about" is used before the peak is reported when characterizing and/or identifying. This is common practice in the field of solid state chemistry in view of the inherent variation of the peak. Typical accuracy of the 2 theta X-axis values of the peaks of the powder pattern spectrum is on the order of + -0.2 deg. 2 theta, therefore, a powder X-ray diffraction peak occurring at "about 8.0 deg. 20 means that the peak may be between 7.8 deg. 2 theta and 8.2 deg. 2 theta when measured on most X-ray diffractometers. The change in peak intensity is a result of how the individual crystals are oriented in the sample container relative to the external X-ray source, the orientation effect not providing structural information about the crystals.

In one aspect, the present invention provides different specific crystalline hydrates or polymorphs of zinc thiazole.

In another aspect of the invention, different crystalline hydrates are provided, as well as methods for their preparation.

In another aspect, the invention provides a pharmaceutical composition comprising any one or more of the zinc thiazoles prepared by the process of the invention, and one or more pharmaceutically acceptable excipients.

The invention further provides a process for preparing a pharmaceutical formulation comprising combining any one or more of the zinc thiazole formulations prepared by the process of the invention or with at least one or pharmaceutically acceptable excipients.

The invention further provides crystal hydrates of zinc thiazole with different crystal forms, and the crystal hydrates are applied to preparation of pesticide compositions for preventing and treating crop diseases and the like.

Compared with zinc thiazole, the zinc thiazole 0.25 hydrate provided by the invention is beneficial to reducing energy consumption and reducing the operation cost of the medicament, and has positive significance.

The cost of the zinc thiazole crystal hydrate of the invention is not obviously increased compared with that of zinc thiazole.

The zinc thiazole 0.25 hydrate provided by the invention is basically a loose crystal, the material is relatively loose in the whole crystallization process, the filtration and the drying are convenient, and the preparation time is relatively short.

In addition, the zinc thiazole 0.25 hydrate is easier to prepare than zinc thiazole anhydride, and the situation that the degradation of zinc thiazole is accelerated in the storage period is easy to occur in the preparation of the zinc thiazole anhydride, so that the original target product is unqualified.

In addition, the preparation process of the zinc thiazole anhydride is long, and the zinc thiazole anhydride is easy to decompose by heating and drying.

The hygroscopicity of the drug is an important content for examining the stability of the drug, and is a work which must be carried out in the research process of the drug, and the work is often neglected. The crystal hydrate of zinc thiazole and the anhydride of the invention are compared and researched by a hygroscopicity test to find the advantages.

1. Wicking test

The zinc thiazole hydrate and the anhydrous sample were subjected to a hygroscopicity test: taking zinc thiazole anhydride (prepared by the method of example of document 1, after vacuum drying at 90-100 ℃ for 3 hours, then placing in a drying oven containing solid sodium hydroxide and soda lime, vacuum drying at room temperature for one day, and measuring the moisture content by the Karl Fischer method to be about 0.2%), placing about 5g of zinc thiazole anhydride and the new compound of the invention in a dry constant weight petri dish, precisely weighing, placing in an experimental box at about 25 +/-2 ℃ and relative humidity of about 55 +/-5%, sampling at 0h and 8h respectively, and calculating the percentage of moisture-induced weight increase.

The results show that the hygroscopicity of the anhydride is significantly different from that of the zinc thiazole crystal hydrate, the novel compound is not weathered in the experimental process, the novel compound can be better and stably stored, and the zinc thiazole crystal hydrate can better and stably respond to the change of drying temperature or humidity and the like, so that the stable storage is more favorable. The dosage is more accurate in the preparation process, the yield of the raw material medicine or the pesticide preparation is improved, and the accuracy and the effectiveness of the application and the administration are facilitated. The pharmacology always tends to select a drug form with better stability from the bulk drug, namely, the pharmaceutically active compound with better stability always tends to be selected as the bulk drug. The results are shown in Table 1.

TABLE 1 moisture wicking test results

The results of the moisture absorption test show that the moisture absorption of the zinc thiazole anhydride is about 8 times or more that of the novel zinc thiazole compound, and the two are obviously different.

The novel zinc thiazole compound has no efflorescence phenomenon but good sliding property, is different from the deliquescence of an anhydride, so that air is isolated to prevent adhesion and the like during treatment, the operability of a preparation in a subpackaging process is improved, and the novel zinc thiazole compound can better and stably respond to the change of drying temperature, humidity and the like and is more beneficial to stable storage. The dosage is more accurate in the preparation process, the yield of the production of the raw material medicines or the pesticide preparations is improved, the phenomenon that the dosage is insufficient due to the difference of the loading amount caused by moisture absorption is avoided, the product is unqualified, the scrapping loss is caused in the production process, and the like is avoided, and the accuracy and the effectiveness of application and administration are facilitated. The pharmaceutical science always tends to select a drug form with better stability from the bulk drugs, namely a compound with better stability is always selected as the bulk drug.

2. Stability test

Samples of zinc thiazole crystal hydrate (prepared by the methods of example 1 and example 2, respectively) and zinc thiazole anhydride (prepared by the method of reference 1) of the present invention were sealed in a vial under conditions of RH65 ± 5% and 30 ± 2 ℃ and protected from light for a stability test for 12 months, and changes in appearance color were observed, and related substances before and after the test were measured. The relevant substances were determined by HPLC using a Waters ODS (4.6 mm. times.250 mm, 4.6 μm) column, a column temperature of 25 ℃ and a detection wavelength of 330nm, mobile phase: acetonitrile-0.1% aqueous trifluoroacetic acid (25: 70); flow rate: 1mL/min, sample size: 20 μ L. Reference methods [ references 7, 8] the total impurity content of zinc thiazole in the test samples was determined and the results are shown in table 2.

TABLE 2 stability test results

The experimental results show that although the change of the appearance color is not obvious, the related substances of the thiazole zinc anhydrous sample are greatly increased more than the samples of each group of the examples. The results show that the zinc thiazole crystal hydrate has good storage stability at room temperature, is more beneficial to preventing the reduction of the sterilization effect of the medicament or the unexpected reduction of the sterilization effect to cause the yield reduction of crops or the toxic action of impurities to the crops or is not beneficial to being used for producing other high-performance materials in fine chemical industry or being not beneficial to being purchased and used due to the increase of the quantity of the impurities.

The invention not only prepares a more stable new zinc thiazole compound, but also provides a composition of the new compound, wherein the composition of the new compound contains the new zinc thiazole compound (A) and any one of other known bactericidal active compounds (B), and the new compound is applied to controlling diseases caused by plant fungi and bacteria. The bactericidal active compound composition has synergistic bactericidal activity and improves the compatibility with plants, thereby meeting the requirements of agricultural production.

The novel zinc thiazole compound is used for preparing a pharmaceutical composition or a pesticide composition which comprises the novel zinc thiazole compound and an effective dose of bactericidal drugs or antibacterial drugs andor plant growth regulators, and other pharmaceutically acceptable auxiliary materials for preparing pharmaceutically acceptable pesticide preparations; namely, preparing a novel pharmaceutical composition or a pesticide composition from an effective dose of an active ingredient A, namely a novel thiazole zinc compound, and an effective dose of an active ingredient B; wherein the weight ratio of active ingredient A to active ingredient B is 180: 1-1: 100 (calculated by weight of anhydrous or hydrous substance); wherein the weight ratio of the active component A to the active component B is preferably 100: 1 to 1: 100 (the weight can be calculated by the anhydrous substance or the hydrous substance); wherein the weight ratio of the active component A to the active component B is preferably from 80: 1 to 1: 80 (calculated as the weight of the anhydrous or hydrous product); the active ingredient B is selected from any one or more of B.1) -B.13) and pharmaceutically acceptable salts thereof (reference: liu Chang Ling, Chaibaoshan Master eds, "creation and Synthesis of New pesticides," chemical industry Press, 2013, Beijing; document 2: grandfather, qijunshan, a modern pesticide application technology series: volume of fungicides, chemical industry publishers, 2017, beijing);

b.1) a strobilurin fungicide selected from one of, but not limited to, azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, enestroburin, picoxystrobin, kresoxim-methyl, enestroburin or metominostrobin, phenamacril, Picarbtrazox, orysastrobin, pyraclostrobin, coumoxystrobin, closterin, benzothiostrobin, UBF307, KZ165, probenazole, diclosamide and the like;

b.2) a triazole fungicide selected from but not limited to difenoconazole, diniconazole, epoxiconazole, fenbuconazole, flusilazole, flutriafol, tebuconazole, hexaconazole, myclobutanil, penconazole, propiconazole, tetraconazole, triadimenol, triadimefon, metconazole, ipconazole, prothioconazole, imibenconazole, triticonazole, cyproconazole, mefentriflumizole, iprazole, ipfenflurrifluconazole and the like;

b.3) an amide bactericide selected from but not limited to metalaxyl, flutolanil, mandipropamid, boscalid, fluopyram, carboxin, bixafen, penflufen, epoxiconazole, fluxapyroxad, penthiopyrad, thifluzamide, fluopicolide and isopyrazam, flufen-ethyl, thifluzamide and the like;

b.4) one of imidazole bactericides which is selected from one of cyazofamid, triflumizole, imazalil, fenamidone, oxpoconazole, albendazole and the like but not limited to;

b.5) dicarboximide bactericides selected from but not limited to one of procymidone, iprodione, vinclozolin, captan, dimethachlon and the like;

b.6) carbamate bactericide which is selected from but not limited to one of propamocarb hydrochloride, diethofencarb, benomyl, carbendazim, thiophanate-methyl, iprovalicarb, benthiavalicarb and the like;

b.7) antibiotic bactericide selected from one of validamycin, streptomycin sulfate, kasugamycin, tetramycin, shenqinmycin, polyoxin, ningnanmycin, streptomycin sulfate, zhongshengmycin, nong antibiotic 120, aureonucleomycin, Changchuan, tetramycin, etc.;

b.8) oxazole based fungicide selected from but not limited to oxadixyl, hymexazol, famoxadone, pyrisoxazole, fluorothiazolepyrietone, benfurazolesulfone, dichloroazole and methanesulfonylazole;

b.9) morpholine bactericide, which is selected from but not limited to one of tridemorph, dimethomorph, flumorph and the like;

b.10) a pyrimidine fungicide selected from but not limited to one of cyprodinil, pyrimethanil, ethirimol, mepanipyrim, fluopyram, dimoxystrobin, SYP-3773, SYP-3810 and the like;

b.11) quinoline bactericide, selected from but not limited to dithianon, propoxymoline, phenoxyquinoline, quinoliflumein (quinoflulin), and the like;

b.12) dithiocarbamate bactericide which is selected from but not limited to one of metiram, thiram, zineb, mancozeb, propineb and the like;

b.13) other fungicides selected from, but not limited to, diphenoxylate, fosetyl-aluminium, chlorothalonil, isoprothiolane, fludioxonil or copper hydroxide, copper rosinate, copper dehydroabietate, fenpiclonil, fludioxonil, isovinonoxim lactam, osthole, Dufulin, phenoxathiin, methylhexamethylene biguanide hydrochloride, bromothalonil, indazole flusulfamide, copper oxychloride, cuppric, copper quinolate, moroxydine hydrochloride, copper succinate, Xinjunan acetate, amino-oligosaccharins, lentinan, benziothiazolinone, ethylicin, probenazole, diclosamide, physcion, chrysophanol, fludioxonil, S-abscisin, amino-oligosaccharins, zinc pyridinesulfate, berberine and pharmaceutically acceptable salts (such as berberine hydrochloride, berberine hydrogen sulfate, berberine, etc.), eugenol, sulphur, copper sulfate, berberine, copper sulfate, berberiberi, One of copper sulfate pentahydrate, iso-long vinyl ketoxime lactam and the like; or the plant growth regulator is selected from one of but not limited to diethyl aminoethyl hexanoate, forchlorfenuron, compound sodium nitrophenolate, brassin, gibberellin, 6-benzylaminopurine, triacontanol, naphthylacetic acid or its medicinal salt, paclobutrazol, ethephon, etc.

The composition of the novel thiazole zinc compound contains an effective dose of an active ingredient A and an effective dose of any one active ingredient B, which is selected from but not limited to azoxystrobin, kresoxim-methyl, pyraclostrobin, enestroburin, trifloxystrobin, pyraclostrobin, fluoxastrobin, kresoxim-methyl, alkene oxime amine or metominostrobin, cyazoxystrobin, Picarbuzrazox, orysastrobin, coumoxystrobin, clotrimtrobin, UBF307, KZ165, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, flusilazole, flutriafol-methyl, tebuconazole, myclobutanil, cyproconazole, penconazole, propiconazole, tetraconazole, triadimenol, bitertanol, triadimenol, metconazole, ipconazole, prothioconazole, triticonazole, cyproconazole, metalaxyl, flutolanilide, mandipropamid, fluoxafen-methyl, fluometipristal, fluoxafen-ethyl, fluoxastrobin, fluoxafen-methyl, fluoxapyroxafen, pyrad, trifloxystrobin, imazalil, fenamidone, oxpoconazole, oryzanol, procymidone, iprodione, vinclozolin, captan, dimeticone, propamocarb hydrochloride, benomyl, carbendazim, thiophanate-methyl, valcarb, benthiavalicarb, jinggangmycin, streptomycin sulfate, kasugamycin, shenqimycin, oxadixyl, hymexazol, famoxadone, pyrisoxazole, tridemorph, dimethomorph, flumorph, cyprodinil, pyrimethanil, ethirimol, mepanipyrim, flufenamid, dithianon, propoxymine, phenoxyquinoline, metiram, thiram, mancozeb, propineb, distemper, fosetyl, chlorothalonil, fludioxonil or copper hydroxide, copper rosinate, copper dehydroabietate, fenpiclonil, fludioxonil, prochloraz complex, fenaminostrobilurin, fenamate, fenamiphos, fenamate, prochloraz, fenaminostrobilurin, streptomycin sulfate, kasugamycin, tetramycin, shenqimycin, polyoxin, ningnanmycin, streptomycin sulfate, zhongshenmycin, nong-antibiotic 120, aureon, chancromycin, Dufulin, phenazon, prothioconazole, Chlorofloxacin (mefenfluconazole, mefentrifluconazole), iprifluconazole (ipfenfluconazole), Fluthiazole pyriethanone, probenazole, diclocyanide chloride, physcion, chrysophanol, fluthiazopyrazole, allylbenzothiazole, diclocyanide chloride, physcion, chrysophanol, fluconazole-activated ester, dichloroazole and methanesulfonylazole, S-abscisic acid, amino-oligosaccharin, zinc pyrithione, berberine hydrochloride, berberine sulfate, plant growth regulator, or the like, the weight ratio of the active component A to the active component B is preferably 1: 80-80: 1, and the more preferred weight ratio is 1: 60-60: 1.

The novel thiazole zinc compound is used for preparing a pharmaceutical composition containing the novel thiazole zinc compound, the novel compound or the composition and a pharmaceutically acceptable carrier are prepared into a pharmaceutically acceptable preparation, and the pharmaceutically acceptable preparation is selected from but not limited to dry suspending agent, wettable powder, granules, dispersible granules, tablets, effervescent tablets, microcapsules, water dispersible granules, suspending agent, suspoemulsion, emulsion in water, microemulsion, missible oil, controlled-release or sustained-release preparation, microcapsule preparation, oil suspending agent, dispersible liquid (DC), seed treatment dry powder, seed treatment dispersible powder, granules, dispersible granules, microcapsule suspending agent, seed treatment microcapsule suspending agent or suspension seed coating agent and the like.

In the composition preparation, the pharmaceutically acceptable carrier is selected from one or more of wetting agent, adhesive, dispersing agent, thickening agent, antifreezing agent, preservative, disintegrating agent, stabilizing agent, film forming agent, defoaming agent, coloring agent, lubricant or glidant, filler and/or water.

The new thiazole zinc compound or the application of the pharmaceutical composition thereof is the application in preparing the medicines for preventing and treating diseases on crops or non-crops and promoting the growth and development of the crops.

The diseases are selected from but not limited to: one or more of canker, stripe disease, rust disease, glume blight, net blotch, powdery mildew, downy mildew, epidemic disease, leaf spot, take-all disease, snow mold, smut, leaf blight, brown spot or rice blast. Chinese cabbage: soft rot bacterial diseases, black spot, anthracnose, rust disease, powdery mildew, zinc deficiency and aged leaves; peanut: peanut bacterial wilt, root rot disease and peanut leaf spot; rice: stiff seedlings, yellow seedling rot, bacterial streak, bacterial leaf blight, sheath blight, rice blast and zinc deficiency fire burning seedlings; cucumber: bacterial angular leaf spot, canker, downy mildew, target disease, yellow spot disease, zinc deficiency and yellowing of leaves; the virus can be inactivated; tomato: bacterial canker, late blight, brown spot, anthracnose, zinc deficiency, inactivating virus; at the early stage of the disease, the 100-fold and 800-fold liquid is diluted and sprayed on plants or crops. The dilution factor can be reduced (increased) to spray plants or crops according to the serious disease. Continuously preventing and treating for 2-3 times at an interval of 5-12 days. Note the secondary dilution spray.

The bactericidal composition has remarkable synergistic effect. According to the fact that the bactericidal action of the novel thiazole zinc compound, namely the component A and the component B is greater than the sum of the bactericidal action of the novel thiazole zinc compound, namely the component A and the component B, the synergistic effect of the bactericidal composition is obvious.

When the component B is an acrylic ester bactericide of a formula B.1), the mass ratio of I to B is selected from but not limited to 5: 50-80: 1, and the preferred mass ratio is 20: 30-40: 5.

When the component B is the triazole bactericide of the formula B.2), the mass ratio of A to B is selected from but not limited to 5: 50-80: 1, and the preferred mass ratio is 20: 20-40: 5.

When the component B is the formula B.3) amide bactericide, the mass ratio of A to B is selected from but not limited to 5: 40-80: 1, and the preferred mass ratio is 20: 20-40: 5.

When the component B is the imidazole bactericide of the formula B.4), the mass ratio of A to B is selected from but not limited to 5: 60-80: 1, and the preferred mass ratio is 20: 30-40: 10.

When the component B is a dicarboximide bactericide of a formula B.5), the mass ratio of A to B is selected from but not limited to 5: 60-80: 1, and the preferred mass ratio is 20: 50-40: 20.

When the component B is a carbamate bactericide of a formula B.6), the mass ratio of A to B is selected from but not limited to 5: 80-80: 5, and the preferred mass ratio is 20: 60-40: 10.

When the component B is B.7) antibiotic bactericide, the mass ratio of A to B is selected from but not limited to 5: 80-80: 1, and the preferred mass ratio is 20: 70-40: 2.

When the component B is B.8) oxazole bactericide, the mass ratio of A to B is selected from but not limited to 5: 60-80: 5, and the preferred mass ratio is 20: 50-40: 10.

When the component B is a morpholine bactericide of a formula B.9), the mass ratio of A to B is selected from but not limited to 5: 80-80: 5, and the preferred mass ratio is 20: 50-40: 20.

When the component B is a pyrimidine bactericide of a formula B.10), the mass ratio of A to B is selected from but not limited to 5: 60-80: 10, and the preferred mass ratio is 20: 50-40: 20.

When the component B is a quinazol (azol) one bactericide of formula B.11, the mass ratio of A to B is selected from but not limited to 5: 60-80: 10, and the preferred mass ratio is 20: 50-40: 20.

When the component B is a dithiocarbamate bactericide of a formula B.12), the mass ratio of A to B is selected from but not limited to 5: 80-80: 10, and the preferred mass ratio is 20: 50-40: 20.

When the component B is represented by the formula B.13) and other bactericides, the mass ratio of A to B is selected from but not limited to 5: 80-100: 1, and the preferred mass ratio is 20: 50-40: 10.

The novel compounds or the bactericidal compositions thereof have good bactericidal activity and are effective against pathogenic bacteria and fungi, such as but not limited to those selected from the following: xanthomonas (Xanthomonas), Pseudomonas (Pseudomonas), Erwinia (Erwinia) among pathogenic bacteria;

ascomycetes in pathogenic fungi (Ascomycetes): venturia (Venturia), Erysiphe (Erysiphe), Sclerotinia (Sclerotinia);

basidiomycetes (Basidiomycetes) in pathogenic fungi: smut (Ustilago), Gibberella (Gibberella);

oomycetes (Oomycota) in pathogenic fungi: phytophthora (Phytophthora), Plasmopara (Plasmopara);

fungi imperfecti (Deuteromyces) in pathogenic fungi: rhizoctonia (Rhizoctonia), Botrytis (Botrytis), Pyricularia (Pyricularia), Cercospora (Cercospora), helminthosporium (Bipolaris), anthrax (Colletotrichum).

The novel compound or the bactericidal composition thereof has good compatibility with plants, reduces the stress tolerance of the plants, and particularly reduces the seedling, young tip, flower and young fruit parts which are particularly sensitive to the plants.

Within the scope of the present invention, the plants or crops referred to in this disclosure are preferably or selected from, but not limited to, the following species: cereal wheat, barley, rice, corn, sorghum, sweet potato; fruit trees such as apple, pear, peach, hickory, orange, grape, lychee, banana, longan, mango and loquat; vegetables such as cucumber, watermelon, snake gourd, towel gourd, melon, spinach, celery, tomato, pepper, eggplant, ginger, shallot, garlic, leek, cabbage, Chinese cabbage, strawberry, asparagus lettuce, kidney bean, cowpea, broad bean, radish, carrot, potato, yam, taro, lotus root, water chestnut and water bamboo; sugar plants such as beet and sugarcane; oil crops such as soybean, peanut, rape, sesame and sunflower; or such as tobacco, tea. This list is not meant to be limiting in any way.

The novel compounds of the present invention or compositions thereof are also useful as pharmaceuticals in the field of protecting industrial materials from pathogens, including or selected from, but not limited to, wood, paper, leather, buildings, etc., and the compositions of the present invention can prevent undesirable effects such as rot, discoloration, or mold.

The novel compounds of the present invention or compositions thereof are effective against the following plant diseases selected from, but not limited to:

cucumber bacterial angular leaf spot, tobacco wildfire, solanaceous bacterial wilt and the like caused by Pseudomonas (Pseudomonas) strains;

cucumber bacterial leaf blight, cabbage black rot, citrus canker and the like caused by Xanthomonas (Xanthomonas) strains;

chinese cabbage soft rot and pear fire blight caused by Erwinia (Erwinia) strains;

blight of potato and tomato caused by phytophthora (Pyhtophthora) strains;

grape downy mildew caused by Plasmopara species, and the like;

powdery mildew caused by Erysiphe (Erysiphe) strains such as tobacco, sesame, sunflower and melon and the like;

gibberellic disease and bakanae disease of rice of various graminaceous plants such as barley, wheat and corn caused by gibberellic (Gibberella) strains;

apple scab caused by Venturia (Venturia) strains, and the like;

various plant Sclerotinia caused by Sclerotinia (sclerotiotinia) strains, and the like;

wheat powdery mildew caused by Ustil-ago strain;

gray mold of various plants caused by Botrytis (Botrytis) strains, and the like;

rice blast caused by Pyricularia (Pyricularia) species;

cercospora (Cercospora) species cause brown spot in sugar beets and brown spot in peanuts;

corn small leaf spot and rice flax leaf spot caused by Helminthosporium (Bipolaris) strains;

cotton blight and rice sheath blight caused by rhizoctonia (Rhi-zoctonia) species;

anthracnose of various fruit trees and vegetables such as apples, pears, cotton, grapes, white gourds, cucumbers, hot peppers, eggplants and the like caused by anthracnose bacteria (Colletotrichum).

More significantly, the application of the compounds according to the invention or their compositions in the case of plants or seeds which are exposed to unfavorable growth conditions or are damaged, results in a very marked improvement in the ability of the plants or seeds to withstand stress, for example restoration of growth, greenish leaf, promotion of root growth, etc., the fact that the plants have good tolerance to the active compound compositions at the concentrations required for controlling plant diseases, allowing the flowers and fruits and seeds of the aerial parts of the plants to be treated. The term "adverse conditions" includes improper humidity, hail, drought, low temperature, heavy rain, etc.

The fungicidal compositions of the present invention are used in a method which comprises applying to the plants to be treated or their locus of growth, or seeds, or materials, in admixture, a total effective fungicidal amount of an active compound of formula a and an active compound of formula B. The application may be before or after the fungal infestation of the material, plant or seed.

The formula A is the novel thiazole zinc compound, and the formula B is a bactericidal active compound selected from any one or more of the B.1) -B.13).

The term "growing locus" as used herein includes a field where plants are grown or where seeds of cultivated plants are sown or where seeds are buried in soil. The term "seed" includes plant propagation material such as cuttings, seedlings, seeds, germinated or soaked seeds.

The novel compound or the composition thereof of the present invention can be prepared into solid or liquid preparations acceptable for agriculture or agricultural chemicals. The novel compounds or compositions can be prepared in a known manner by mixing the active ingredients A and B with pharmaceutically or agriculturally acceptable adjuvants or adjuvants. The preparation is selected from but not limited to dry suspending agent, wettable powder, granule, dispersible granule, tablet, effervescent tablet, microcapsule, water dispersible granule, suspending agent, suspoemulsion, aqueous emulsion, controlled release or slow release preparation, microcapsule preparation, oil suspending agent, dispersible liquid (DC), seed treatment dry powder, seed treatment dispersible powder, granule, dispersible granule, microcapsule suspending agent, seed treatment microcapsule suspending agent or suspended seed coating agent, etc.

The novel compounds or compositions thereof of the present invention are selected from, but not limited to, wetting agents, binders, dispersants, thickeners, antifreezes, preservatives, disintegrants, stabilizers, film-forming agents, antifoaming agents, colorants, lubricants or glidants, emulsifiers, pH regulators, fillers and/or water, and other known substances useful for stabilizing or activating active ingredients in formulations, and are various ingredients commonly used in preparation or agriculturally pharmaceutically acceptable, and the specific ingredients and amounts thereof are determined by experiments according to need.

The wetting agent is selected from one or more of EO/PO block polyether, fatty alcohol-polyoxyethylene ether, fatty alcohol ethoxy compound, tallow ethoxy ammonium salt, alkyl naphthalene sulfonate, alkyl naphthalene sodium sulfonate, alkyl naphthalene calcium sulfonate, fatty alcohol-polyoxyethylene ether sulfate, acyl glutamate and the like which are acceptable in pharmacy.

The dispersing agent is selected from one or more of sodium naphthalene sulfonate condensate, sodium phenol sulfonate condensate, sodium methyl naphthalene sulfonate formaldehyde condensate, sodium lignin sulfonate, sodium methylene dinaphthalene sulfonate, sodium acrylic acid homopolymer, polycarboxylate dispersing agent, dioctyl sodium sulfosuccinate, EO/PO block polyether, maleic acid-acrylic acid copolymer sodium salt, Darun D06, Darun DCM-82 and the like which are acceptable in pharmacy;

wherein the polycarboxylate dispersant is selected from, but not limited to: products of foreign companies: 1) geropon T/36 and Geropon T/72 (polycarboxylates) from Solvay (Solvay) (Protoya); 2) tersperse2700 (polyacrylic acid graft copolymer), Tersperse2735 (polyacrylic acid graft copolymer, liquid) and Tersperse2100 from Huntsman corporation; 3) Yus-WG5 (polycarboxylate), CH7000 (white liquid), Yus-WG5 and Yus-WP1, respectively, from Takemoto (bamboo fat and oil Co., Ltd., Japan). 4) Atlox4913 (copolymer of methacrylic acid/methyl methacrylate and polyoxyethylene) and Atlox Metaperse 550S (modified acrylic-styrene copolymer) from Croda (Heda). 5) Sokalan PA15/20 (acrylic acid homopolymer sodium salt), Sokalan CP 5 (acrylic acid-maleic acid copolymer sodium salt), Sokalan HP 25 (modified polycarboxylate), and Sokalan PA80S (polyacrylic acid) from BASF (BASF) corporation. 6) Dispersogen PSL 100 (polyacrylate graft copolymer) from Clariant (Craine). 7) Agrilan700 (modified polyacrylate copolymer) from akzo nobel (akksonobel). 8) Emulsona AG TP1 (polycarboxylate, white emulsion), and Emulson AG TRN 14105 (polycarboxylate comb structure) from Lamberti (Ningbo di). 9) Tanatex chemical company D1001 (polycarboxylate). 10) DURAMAXM D-205 (liquid), D-305 (liquid), D-518 (polycarboxylate) from Dow corporation. Products of domestic companies: 1) beijing Guangyuan company: GY-D (D03-D08) series products (polycarboxylates of styrene sulfonate polymers). 2) Mokk chemical technology company, beijing han: d1001, D1002, D1003 (polycarboxylate). 3) LG-3 (polycarboxylate), Beijing university of Physician. 4) Shanghai is a large polymer materials ltd: SD-816, SD-817, SD-818, SD-819 (polycarboxylate). 5) Jiangsu Optic chemical science and technology: SP-2728, SP-2750, SP-2836 (polycarboxylate). 6) Beijing Grignard (Green-times) auxiliaries: one or more of greensperse BD55, BD58, BE13 (liquid) (polycarboxylate) and the like which are pharmaceutically acceptable.

The emulsifier is selected from one or more of sodium dodecyl benzene sulfonate, calcium dodecyl benzene sulfonate, fatty alcohol potassium phosphate ester, alkylphenol polyoxyethylene phosphate, fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene, polyoxyethylene sorbitan fatty acid ester, propylene glycol polyoxyethylene polyoxypropylene ether block copolymer, span or span series (such as span-40, span-60, span-80 and the like), tween series (such as tween-40, tween-60, tween-80 and the like), agricultural milk 700#, agricultural milk 2201#, TX-10, agricultural milk 1601 (common name: phenethylphenol polyoxyethylene polyoxypropylene ether), agricultural milk 600#, agricultural milk 400# and the like which are acceptable in pharmacy;

the thickener is selected from, but not limited to, pectin, acacia, tragacanth, xanthan gum, sodium alginate, magnesium aluminum silicate, sodium carboxymethylcellulose, calcium carboxymethylcellulose, sodium starch phosphate, sodium starch octenylsuccinate, polyvinyl alcohol, cross-linked carboxymethylcellulose, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, polyethylene glycol 800-, PEG-8 dioleate, PEG-200 glyceryl stearate, PEG-n (n ═ 28, 200) glyceryl tallowate, PEG-7 hydrogenated castor oil, PEG-40 jojoba oil, PEG-2 laurate, PEG-120 methyl glucose dioleate, PEG-150 pentaerythrityl tetrastearate, PEG-55 propylene glycol oleate, PEG-160 sorbitan triisostearate, PEG-n (n ═ 8, 75, 100) stearate, PEG-150/decyl/SMDI copolymer (polyethylene glycol-150/decyl/methacrylate copolymer), PEG-150/stearyl/SMDI copolymer, PEG-90. Isostearate, PEG-8PPG-3 dilaurate, cetyl myristate, cetyl palmitate, ethylene glycol C18-36, pentaerythrityl stearate, pentaerythrityl behenate, propylene glycol stearate, behenyl ester, cetyl ester, glyceryl tribehenate, glyceryl trihydroxystearate, etc.

The solvent is selected from one or more of toluene, xylene, trimethylbenzene, cyclohexanone, N-methyl pyrrolidone, solvent oil (trade marks of S-150, S-180 and S-200), biodiesel, methyl esterified vegetable oil, methyl oleate, fatty acid methyl ester, soybean oil, turpentine-based vegetable oil, methanol, ethanol, isopropanol, N-butanol, sec-butyl acetate, ethylene glycol monoethyl ether, water and the like; the water is deionized water, distilled water, pure water, etc.

The antifreezing agent is one or more of pharmaceutically acceptable materials such as ethylene glycol, propylene glycol, glycerol, polyethylene glycol 100-2000, isopropanol, urea, inorganic salts such as sodium chloride and the like.

The film forming agent is selected from one or more of pharmaceutically acceptable polymers with adhesive and film forming properties, such as polyvinyl alcohol, polyvinyl acetate, polyethylene glycol, polyethylene glycol methacrylate, carboxymethyl cellulose, gum arabic, xanthan gum, starch, polyethylene glycol 2000-20000 and the like.

The disintegrating agent is selected from one or more of urea, sucrose, glucose, sodium chloride, ammonium sulfate, sodium sulfate, soluble starch, modified starch, microcrystalline cellulose, cross-linked carboxymethyl cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, surfactant (sodium dodecyl sulfate, etc.) and the like which are acceptable in pharmacy.

The preservative is selected from one or more of formaldehyde, phenyl salicylate, butyl p-hydroxybenzoate, methyl paraben, ethyl paraben, propyl paraben, potassium sorbate, benzoic acid, sodium benzoate and the like which are acceptable in pharmacy.

The stabilizer is selected from one or more of glycerol, epoxidized soybean oil, epichlorohydrin, triphenyl phosphite, glycidyl ether or pentaerythritol, xylitol, 2, 6-di-tert-butyl-4-methylphenol, polyethylene glycol 400-20000, disodium EDTA 2 hydrate, calcium sodium EDTA 4 hydrate, sorbitol, sodium carboxymethyl cellulose, ionic surfactant or nonionic surfactant, hydroxyethyl or propyl cellulose, polyvinyl alcohol, span series, Tween series, alginate series and the like which are acceptable in pharmacy.

The defoaming agent is selected from one or more of silicone defoaming agents (including but not limited to AFE-316, tanafoamSLX, Tanaform S, Tanaform AF and the like), polyether defoaming agents, polyether modified silicone defoaming agents (including but not limited to DF-825, DF-281, DT-650, DM-115M, DM-193, DM198, DM-M1040, DM-1090, DM-DA1952, LM-110, JH-935 and the like), N-type defoaming agents, sucrose fatty acid ester defoaming agents, fatty alcohol defoaming agents, composite defoaming agents and the like which are acceptable in pharmacy.

The pharmaceutically acceptable pH regulator may be a pharmaceutically acceptable inorganic acid or organic acid, an inorganic base or an organic base, or may be a generalized lewis acid or base, and may contain one or more selected from, but not limited to, hydrochloric acid, phosphoric acid, propionic acid, acetic acid and acetate, lactic acid and its pharmaceutically acceptable salts, citric acid pharmaceutically acceptable salts, sodium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, phosphate, tartaric acid and its pharmaceutically acceptable salts, borax, boric acid, polyhydroxy carboxylic acid and its pharmaceutically acceptable salts, such as one or more of glucuronic acid, gluconic acid, lactobionic acid, malic acid, threonic acid, glucoheptonic acid, ammonia, triethanolamine, triethylamine, diethylenetriamine, and the like.

The colorant is selected from one or more of iron oxide, titanium oxide, azo dye and the like which are acceptable in pharmacy.

The filler is selected from one or more of sodium sulfate, ammonium sulfate, urea, sucrose, glucose, diatomite, talcum powder, bentonite, attapulgite, kaolin, light calcium carbonate, white carbon black, starch, modified starch, microcrystalline cellulose, cyclodextrin, sorbitol, mannitol, calcium phosphate and the like which are acceptable in pharmacy;

the pharmaceutically acceptable wetting agent and the binding agent are selected from one or more of starch, gelatinized starch, methyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, low-substituted hydroxypropyl cellulose, polyvinylpyrrolidone, PVP K-30, tragacanth, alginic acid and salts thereof and the like;

the pharmaceutically acceptable lubricant and glidant are selected from one or more of stearic acid, magnesium stearate, polyethylene glycol 4000-20000, talcum powder, superfine silica powder, lauryl magnesium sulfate and the like which are pharmaceutically acceptable;

for wettable powders, the adjuvants which may be used are selected from, but not limited to: dispersing agent, wetting agent and filler are one or more of the same pharmaceutically acceptable materials as described in the invention.

For the water dispersible granule, the water dispersible granule is selected from but not limited to one or more of dispersing agents, wetting agents, disintegrating agents, binding agents, stabilizing agents, fillers and the like which are selected from but not limited to those described before in the invention.

For the suspending agent, the auxiliaries which can be used are selected from, but not limited to: dispersing agents, emulsifiers, wetting agents, thickeners, preservatives, defoamers, stabilizers, antifreeze agents and the like are one or more of those previously described herein.

For suspended seed coatings, adjuvants that may be used are selected from, but not limited to: binders such as one or more selected from the group consisting of polysaccharide high molecular compounds (soluble starch, polypropylene graft copolymer, xanthan gum, microbial mucilage), cellulose derivatives (hydroxypropyl methylcellulose, sodium carboxymethylcellulose, ethyl cellulose), marine algae such as sodium alginate, agar, rosin, paraffin, gelatin, pectin, polyvinyl alcohol, polyethylene glycol, polyvinyl acetate, polyacrylamide, polyvinyl pyrrolidone and water-soluble synthetic products of polyol polymers, inorganic binders (magnesium aluminum silicate, clay, water glass, gypsum); dispersing agents, emulsifiers, wetting agents, thickeners, preservatives, defoamers, stabilizers, antifreeze agents and the like are as described previously herein.

The preparations or medicaments of the active compound combinations described in the present invention can be prepared by customary methods.

The preparation for preventing and treating plant diseases of the composition generally comprises 1-90 mass percent of active compounds, preferably 10-80 mass percent.

The fungicidal composition of the present invention may be used in the form of its own concentrate or in the form of a generally conventional formulation, using a method of pouring, spraying, misting, dressing, broadcasting or brushing depending on the nature of the target disease, and the total effective active fungicidal amount applied varies depending on weather conditions, crop conditions or application methods.

The fungicidal active compound combinations according to the invention have very outstanding advantages:

1. the bactericidal composition has obvious synergistic effect, and can fully exert the characteristics of high efficiency of the new zinc thiazole compound on bacterial diseases, universal effectiveness on fungal diseases and good protective performance of the new zinc thiazole compound;

2. the bactericidal composition consists of active ingredients with different action mechanisms, can effectively slow down the resistance generation of diseases, and reduces the resistance risk caused by the independent use of a new zinc thiazole compound or any other known active compounds;

3. the bactericidal composition improves the antibacterial or bacteriostatic effect, enlarges the disease prevention spectrum, can simultaneously play a good role in preventing or treating bacterial diseases and partial fungal diseases of crops, reduces the times of medication and relieves the environmental pressure, thereby playing the role of prevention and comprehensive control;

4. the sterilization composition reduces the using amount of the medicament by compounding, lightens the pressure of the pesticide on the environment and simultaneously reduces the cost;

5. the bactericidal composition can obviously improve the tolerance of crops, so that the safety of the pesticide to the crops is higher;

6. the bactericidal composition can supplement trace elements, promote the growth of plants and improve the stress resistance and disease resistance.

Drawings

FIG. 1 is a thermogram spectrum of zinc thiazole 0.25 hydrate (example 1)

FIG. 2 is a powder X-ray diffraction pattern of zinc thiazole 0.25 hydrate (example 1)

FIG. 3 is a thermogram spectrum of zinc thiazole 0.25 hydrate (example 2)

FIG. 4 is a powder X-ray diffraction pattern of zinc thiazole 0.25 hydrate (example 2).

Detailed Description

Other than in the examples, and where otherwise indicated, all numbers expressing quantities of ingredients used in the specification and claims are to be understood as being modified in all instances by the term "about", and thus, unless otherwise indicated, the numerical parameters set forth in this specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure, and at the very least, and are not intended to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations. The numerical values set forth in the specific examples are reported as precisely as possible, and any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing.

It is noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents and, therefore, for example, unless the context clearly dictates otherwise. If reference is made to a composition containing "a compound" including mixtures of two or more compounds, it is further noted that the term "or" generally includes "and/or" unless the context clearly dictates otherwise.

As used herein, the term "obtained" or "obtaining" refers to isolating a compound of value at a level of content or purity, including but not limited to, greater than 90%, 95%, 96%, 97%, 98%, and 99%. The content or purity level can be determined by a high performance liquid chromatography method specified in the 2010 version of chinese pharmacopoeia standards for zinc thiazole. The infrared spectrum data of the sample is measured by a Fourier transform infrared spectrometer, and the used instruments comprise a Nexus intelligent Fourier transform infrared spectrometer (Thermo Nicolet) and the like.

The present "solvate" is meant herein to also include crystalline forms of molecules, atoms and/or ions of solvent molecules that penetrate into the crystal structure, which may be in a regular and/or disordered arrangement, and which are solvates of the present invention.

Polymorphism herein refers to crystals having the same chemical composition but differing in the spatial arrangement of the molecules, atoms and/or ions that form the crystal.

Pharmaceutical or agrochemical compositions: as used herein, "pharmaceutical or pesticidal composition" refers to a composition of a medicament or a composition of a pesticide, which may contain at least one pesticidally pharmaceutically acceptable carrier.

As used herein, "pharmaceutically acceptable excipient or carrier" refers to a pharmaceutically acceptable carrier or vehicle suitable for administration of the compounds provided herein, including any such carriers known to those skilled in the art to be suitable for the particular mode of administration.

In the present invention, the "which" in the pharmaceutically acceptable salt or solvate thereof or the clathrate thereof represents one of them or either of them unless otherwise specified.

In the present invention, unless otherwise specified, "suitable amount" means a preferred or optimum amount or the minimum required amount or mass or weight or volume or the like required for carrying out the present invention.

In the present invention, unless otherwise specified, "such a combination or a combination thereof" means a multi-component mixture of the respective elements described, for example, two, three, four and up to the maximum possible multi-component mixture.

In the present invention, all "parts" and percentages (%) may refer to parts by weight or percent by weight volume, unless otherwise indicated.

For a further understanding of the invention, reference will now be made to the preferred embodiments of the present invention by way of example, and it is to be understood that the description is intended to further illustrate features and advantages of the present invention, and not to limit the scope of the claims.

And (3) moisture determination: the moisture was measured using V310S-KHF lithium battery material and a Karl moisture tester (Sichuan cereal science and technology Co., Ltd.) dedicated to electrode membranes. The method comprises the following steps: connecting a gas source to a heating furnace, filling a dry sample bottle into a heating tank, setting the temperature to be 168 ℃, and increasing the temperature: 30 ℃/min, adjusting the flow of dry nitrogen to 50ml/min, purging the sample bottle and the pipeline to possibly have water, and waiting for re-balancing. Taking a dried sample bottle and filling about 0.15-0.4g of sample; delay of titration: 180S; and (3) deduction of drift: automatic; blank deduction: deducting; the rest were operated according to the instrument instructions and related protocols.

Infrared spectrum: potassium bromide pellets were pressed and the IR spectral data of the samples were measured using instruments including the US thermo electric company NICOLET 5700 FTIR Spectrometer, Nexus intelligent Fourier transform Infrared Spectrometer (ThermoNicolet) and the like. Name of infrared spectrometer instrument company: the united states thermoelectric company NICOLET 5700 FTIR Spectrometer, uses the functions: the mid-infrared light is 4000-400cm-1, and the resolution is 4 cm-1. The maximum can reach 0.09cm < -1 >. Thermal analysis method

And (3) testing conditions are as follows: setsys 16, Setaram corporation, sample size about 3-10mg, rate of temperature rise: 10K/min, N2 flow rate: 50ml/min, temperature: generally, the temperature is about room temperature to 400 ℃.

Surprisingly, characteristically, the hydrates of the present invention have a corresponding endothermic peak at the weight loss plateau of the thermogram (TG-DTA or TG-DSC) showing the crystalline hydrate of zinc thiazole, such as its 0.25 hydrate.

Powder X-ray diffraction method

Using a D/MX-IIIA X-ray diffractometer, voltage: about 30-60kv, current: about 30-100mA, scanning speed: 10 °/min, copper target, wavelength (a): 1.54, diffraction angle 2 theta, scanning range 3-60 degrees, and measuring powder X-ray diffraction pattern of zinc thiazole crystal hydrate, wherein all peak positions are within +/-0.2 degrees 20; or by using D8 advanced X-ray diffractometer from Bruker, Germany, wavelength

: 1.54, diffraction angle 2 theta, scan range 3-60 deg., and other indices (voltage, current, etc.) approximately as before, the samples were measured. The drawings and data in this specification are mutually attested. In the embodiment 1 (fig. 2), the zinc thiazole hydrate of the invention can have corresponding characteristic values at positions including the following 2 θ ± 0.2 values in the measurement range of the diffraction angle 2 θ (3-60 °), as measured by powder X-ray diffractometry:

in the embodiment 2 (FIG. 4), the zinc thiazole hydrate of the invention may have corresponding characteristic values at positions including the following 2 θ. + -. 0.2 values in the measurement range of diffraction angles 2 θ (3 to 60 °), as measured by powder X-ray diffractometry: