Abstract:
A pharmaceutical composition of fungicide including at least a compound represented by Formula (I). 
     
       
                 
         
             
             
         
       
     
     The pharmaceutical composition of fungicide can further include an emulsifier, a cosolvent, a stabilizer, and a solvent. The fungicide can prevent and treat powdery mildew, downy mildew, gray mold, brown spot, scab of vegetables and fruits, southern leaf blight of corn, rice false smut, citrus stem-end rot, and rape sclerotinia rot, with high efficiency, low toxicity, and relative environmental friendliness. A method of preparing the fungicide and a method of using thereof are also provided.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of International Patent Application No. PCT/CN2009/071301 with an international filing date of Apr. 16, 2009, designating the United States, now pending, and further claims priority benefits to Chinese Patent Application No. 200810047642.1 filed May 8, 2008. The contents of all of the aforementioned applications, including any intervening amendments thereto, are incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    1. Field of the Invention 
         [0003]    The invention relates to a methoxyacrylate, the preparation, fungicides containing same, and the use as a fungicide 
         [0004]    2. Description of the Related Art 
         [0005]    The methoxyacrylate fungicides were firstly developed by Zeneca Co., Ltd. (Syngenta) in 1980s and exhibit advantages such as high efficiency, broad-spectrum, and relative environmental friendliness. The structure unit of β-methoxyacrylate is the pharmacophore of this kind of fungicide. However, with the increase of fungus having drug resistance, a more powerful fungicide is desired. 
       SUMMARY OF THE INVENTION 
       [0006]    In view of the above-described problems, it is one objective of the invention to provide a pharmaceutical composition of fungicide. 
         [0007]    It is another objective of the invention to provide a method for preparing a pharmaceutical composition of fungicide. 
         [0008]    It is still another objective of the invention to provide a method for preventing and treating a plant disease. 
         [0009]    To achieve the above objectives, in accordance with one embodiment of the invention, there is provided a pharmaceutical composition of fungicide comprising a compound represented by Formula (I): (E)-methyl 3-methoxy-2-(2-((5-methoxy-benzothiazol-2-ylthio)methyl)phenyl)acrylate. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0010]    In a class of this embodiment, the compound is mixed with an emulsifier, a cosolvent, a stabilizer, and a solvent to yield an emulsifiable concentrate. The emulsifiable concentrate can be used to prevent and treat powdery mildew, downy mildew, gray mold, brown spot, scab of vegetables and fruits, southern leaf blight of corn, rice false smut, citrus stem-end rot, and rape sclerotinia rot. The emulsifiable concentrate has effect even on resistant strains, with high efficiency, low toxicity, and environmentally friendliness. 
         [0011]    In a class of this embodiment, the pharmaceutical composition of fungicide comprises between 5 and 10 wt % of the compound represented by Formula (I), between 0 and 15 wt % of the emulsifier, between 0 and 30 wt % of the cosolvent, between 0 and 2 wt % of the stabilizer, and between 0 and 65.5 wt % of the solvent. 
         [0012]    In a class of this embodiment, the pharmaceutical composition of fungicide comprises between 5 and 10% wt of the compound represented by Formula (I), 10% wt of the emulsifier, between 20 and 30 wt % of the cosolvent, 2% wt of the stabilizer, and between 48 and 65.5% wt of the solvent. 
         [0013]    In a class of this embodiment, the emulsifier is pesticide emulsifier No. 500, pesticide emulsifier No. 33, pesticide emulsifier No. 700, pesticide emulsifier No. 601, sodium C 8-20 alkyl sulfate, Tween 80, Tween 60, ammonium styryl polyethenoxy ether sulfate, pesticide emulsifier No. 300, pesticide emulsifier No. 600 having a polymerization degree of 15-30, styrenephenol polyethenoxy polyoxypropylene ether, nonylphenol polyethenoxy ether, alkylphenol formal polyethenoxy ether, diphenol polyethenoxy ether, or a mixture thereof. 
         [0014]    In a class of this embodiment, the solvent is toluene, xylene, methanol, ethanol, isopropanol, or a mixture thereof. 
         [0015]    In a class of this embodiment, the cosolvent is dichloromethane, N, N-dimethylformamide (DMF), dimethylacetamide (DMAC), dimethyl sulfoxide (DMSO), acetone, pyrrolidone, or a mixture thereof. 
         [0016]    In a class of this embodiment, the stabilizer is epoxidized soybean oil, epoxy chloropropane, 3-chloro-1,2-propylene oxide, butyl glycidyl ether, phenyl glycidyl ether, cresyl glycidyl ether, polyethylene glycol diglycidyl ether, sodium sorbitol, 0.1 wt. % citric acid aqueous solution, 0.1 wt. % benzoic acid aqueous solution, or 0.1 wt. % sodium dihydrogen phosphate buffer. 
         [0017]    In accordance with another embodiment of the invention, there provided is a method for preparing a pharmaceutical composition of fungicide comprising mixing the compound of Formula (I), an emulsifier, a cosolvent, a stabilizer, and a solvent and stiffing uniformly. 
         [0018]    In a class of this embodiment, upon mixing and stirring, the compound of Formula (I) is between 5 and 10 weight parts, the emulsifier is between 0 and 15 weight parts, the cosolvent is between 0 and 30 weight parts, the stabilizer is between 0 and 2 weight parts, and the solvent is between 0 and 65.5 weight parts. The resultant emulsifiable concentrate comprises between 5 and 10 wt. % of the compound of Formula (I), between 0 and 15 wt. % of the emulsifier, between 0 and 30 wt. % of the cosolvent, between 0 and 2 wt. % of the stabilizer, and between 0 and 65.5 wt. % of the solvent. 
         [0019]    In a class of this embodiment, upon mixing and stiffing, the compound of Formula (I) is between 5 and 10 weight parts, the emulsifier is 10 weight parts, the cosolvent is between 20 and 30 weight parts, the stabilizer is 2 weight parts, and the solvent is between 48 and 65.5 weight parts. The resultant emulsifiable concentrate comprises between 5 and 10 wt. % of the compound of Formula (I), 10 wt. % of the emulsifier, between 20 and 30 wt. % of the cosolvent, 2 wt. % of the stabilizer, and between 48 and 65.5 wt. % of the solvent. 
         [0020]    The emulsifier, cosolvent, stabilizer, and solvent are the same as defined above. 
         [0021]    In a class of this embodiment, the compound of Formula (I) is prepared as follows. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0022]    The intermediate (II) reacts with the intermediate (III) in the presence of a base. The base is sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate. A reaction solvent is water, methanol, ethanol, N,N-dimethyl formamide, or a mixture thereof, particularly a mixed solvent of water and N, N-dimethyl formamide with a volume ratio of 5:1. A reaction temperature is from room temperature to the boiling point of the solvent. A reaction time is between 4 and 6 hrs. A molar ratio of the intermediate (II) to the intermediate (III) to sodium hydroxide is 1:1:1.2. 
         [0023]    In a class of this embodiment, the intermediate (II) is prepared as follows. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0024]    1-chloro-4-methoxy-2-nitrobenzene, carbon disulfide, and sodium polysulfide are mixed and refluxed for between 4 and 6 hrs to yield the intermediate (II). 
         [0025]    In a class of this embodiment, the intermediate (III) is prepared following the method disclosed in Pestic. Sci., 1991, 31, 499-519, the steps are: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0026]    Advantages of the invention are summarized below:
       1. The pharmaceutical composition of fungicide is broad-spectrum and highly efficient in killing pathogens and can be used to prevent and treat powdery mildew, downy mildew, gray mold, brown spot, scab of vegetables and fruits, and so on, and its efficacy is higher than that of azoxystrobin and kresoxim-methyl;   2. The pharmaceutical composition of fungicide is particularly effective on powdery mildew of melons; results of field trial show that 3.75 g/acre of active ingredients can effectively control powdery mildew of melons; and   3. The pharmaceutical composition of fungicide has effect even on resistant strains and no cross resistance occurs.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0030]    The invention is described hereinbelow with reference to accompanying drawings, in which the sole FIGURE is a schematic diagram of crystal structure of the compound of Formula (I) according to one embodiment of the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0031]    For further illustrating the invention, experiments detailing a pharmaceutical composition of fungicide, a preparation method and use thereof are described below. It should be noted that the following examples are intended to describe and not to limit the invention. 
       Example 1 
     Preparation of Compound of Formula (I) 
     (E)-methyl 3-methoxy-2-(2-((5-methoxy-benzothiazol-2-ylthio)methyl)phenyl)acrylate 
     Preparation of Intermediate (II) 
       [0032]    244 g of sodium polysulfide solution was mixed with 30 g of 1-chloro-4-methoxy-2-nitrobenzene, and then 20 mL of carbon disulfide was added with stiffing. The mixture was heated and refluxed for about 5 hrs and a yellow solid precipitated. The mixture was filtered and the filtrate was diluted with water to 1000 mL. An orange yellow solution was obtained. The solution was neutralized with hydrochloric acid (6M) to yield a light yellow solid. The solid was filtered, washed with water, and dried. 29.4 g of products was obtained with a yield of 93.1%. 
       Preparation of Intermediate (2): methyl 2-o-tolylacetate 
       [0033]    To a flask (1000 mL), 120 g of 2-methylphenylacetic acid and 400 mL of anhydrous methanol were added, and then 24 mL of concentrated sulfuric acid was further added with stiffing. The mixture was heated with an oil bath and refluxed. The reaction was monitored with thin layer chromatography (TLC) until the reactants were basically consumed. Subsequently, the solvent was removed by vacuum distillation. The residue was dumped into 400 mL of water and extracted with 400 mL of ethyl acetate. The organic layer was washed with water (2×200 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. A light yellow oily product was obtained. The light yellow oily product was further distilled under vacuum condition to yield 117.3 g of a colorless oily product (135-140° C., 16 mmHg) with a yield of 92%. 
       Preparation of Intermediate (3): methyl 3-hydroxy-2-o-tolylacrylate 
       [0034]    To a three neck flask (1000 mL), 50 g of methyl 2-o-tolylacetate and 600 mg of toluene were added, and then 54.3 g of sodium methoxide was further added with stiffing. The mixture was cooled with an ice-water bath to less than 10° C., and then a mixture of methyl formate (65 mL) and toluene (50 mL) was dripped. After that, the ice-water bath was removed and the temperature was raised slowly to room temperature. The solution was allowed to react with stirring for 12 hrs, and then dumped into 1000 mL of water, shaken, standed for demix. The organic layer was extracted with 500 mL of water twice. The water layer was combined, acidized with 6M hydrochloric acid to pH value of 4-5, extracted with ethyl acetate, dried with anhydrous magnesium sulfate, and distilled under vacuum condition to yield 55.9 g of light red oily product with a yield of 95%. 
       Preparation of Intermediate (4): methyl 3-methoxy-2-o-tolylacrylate 
       [0035]    To a flask (1000 mL), 48 g of methyl 3-hydroxy-2-o-tolylacrylate, 54.4 g of potassium carbonate, and 500 mL of ethylene glycol dimethyl ether were added. The mixture was stirred at room temperature for an hour, and then 36 mL of dimethyl sulfate was added. The mixture was allowed to react for between 6 and 8 hrs with stiffing at room temperature. The reaction was monitored with thin layer chromatography (TLC) until the reactants were basically consumed. Subsequently, the mixture was filtered, the solvent was removed by vacuum distillation, the residue was washed with water (1000 mL), extracted with ethyl acetate (2×300 mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure to yield a light yellow oily product with a yield of 97%. 
       Preparation of Intermediate (III) 
       [0036]    39.14 g of methyl 3-methoxy-2-o-tolylacrylate, 41.3 g of N-bromosuccinimide (NBS), and 1.44 g of azobisisobutyronitrile (AIBN) were mixed with 200 mL of carbon tetrachloride. The mixture was lighted with an incandescent lamp for 6 hrs, cooled, and filtered. The filtrated was concentrated under reduced pressure to yield a yellow viscous material which could be used directly for further reaction. 
       Preparation of the Compound of Formula (I) 
       [0037]    To 350 mL of an aqueous solution having 8.0 g of sodium hydroxide, 31.8 g of Intermediate (II) was added and stirred for 20 min. Subsequently, 70 mL of N, N-dimethylformamide (DMF) solution having 54 g of Intermediate (III) was added. The mixture was stirred at room temperature for 6 hrs and water added until the total volume was 1000 mL. The solution was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the product purified by chromatography over silica gel eluted with ethyl acetate/hexane, 52.1 g of a yellow solid was obtained with a total yield was 80.5%. m.p. 85-87° C.  1 H NMR (400 MHz, CDCl 3 ) δ: 3.72 (s, 3H, COOCH 3 ), 3.82 (s, 3H, ═CH—OCH 3 ), 3.84 (s, 3H, OCH 3 ), 4.52 (s, 1H, CH 2 ), 6.94 (dd, J=2.4 Hz, J=8.8 Hz, 1H, ArH), 7.16 (t, J=4.6 Hz, 1H, ArH), 7.29-7.31 (m, 2H, ArH), 7.40 (d, J=2.8 Hz, 1H, ArH), 7.54-7.61 (m, 3H, ═CH—OCH 3 , ArH). EI MS: m/z (%) 401 (M+, 4), 369(19), 205 (11), 167 (24), 144 (100), 101 (37). Anal. Calcd for C 20 H 19 NO 4 S 2 : C, 59.83; H, 4.77; N, 3.49. Found: C, 59.89; H, 5.01; N, 3.27. 
         [0038]      FIG. 1  shows the crystal structure of the compound of Formula (I). 
       Example 2 
     Evaluation on Indoor Bioactivity of Compound of Formula (I) 
       [0039]    To verify the bioactivity of the compound of Formula (I), experiments evaluating indoor bioactivity comprising fungicidal activity test on potted plants at room temperature, fungicidal spectrum assay (in vitro), and in vivo micro-screening assay are carried out. 
         [0040]    1. Fungicidal Activity Assay on Potted Plants at Room Temperature 
         [0041]    Take cucumber downy mildew and powdery mildew as examples, the assay were carried out as follows: 
         [0042]    1)  Pseudoperonospora cubensis : Pathogen of Cucumber Downy Mildew 
         [0043]    Two cucumber seedlings (the growing point had been removed) having the same growth status and in the true leaf stage were collected, sprayed with the compound of Formula (I), and dried naturally for 24 hrs for inoculation. Fresh cucumber leaves infected by downy mildew were collected, and sporangium on the back was rinsed with distilled water (about 10° C.) dipped with a brush. The obtained sporangium was prepared into a suspension (2-3×10 5  cells/mL). The suspension was sprayed uniformly with an inoculation sprayer (0.1 MPa) to the naturally-dried cucumber seedlings. Subsequently, the seedlings were cultured in an artificial climate chamber. The relative humidity was maintained at 100%, with temperature of between 15 and 20° C. 24 hrs later, the relative humidity was maintained at 90%, with temperature of between 15 and 24° C. 5 days later, compared with the control, the disease of the cucumber seedlings was graded. Based on the resultant disease index, the efficacy was calculated. 
         [0044]    2)  Sphaerotheca uliginea : Pathogen of Cucumber Powdery Mildew 
         [0045]    A cucumber seedling having uniform growth status and in the true leaf stage was collected, sprayed with the compound of Formula (I), and dried in the shade for 24 hrs. Fresh spore was collected from cucumber leaves infected by  Sphaerotheca uliginea , filtered with a double-layer gauze, and prepared into a suspension (1.0×10 5  cells/mL). The suspension was sprayed to the dried cucumber seedling. Subsequently, the inoculated seedling was dried naturally and cultured under light in a thermostatic chamber (21-23° C.). 7-8 days later, compared with the blank control, the disease of the cucumber seedlings was graded. Based on the resultant disease index, the efficacy was calculated. 
         [0046]    3) Calculation Method 
         [0047]    The grading standard follows “Guidelines on efficacy evaluation of pesticides”, and the efficacy is calculated on the basis of the disease index. 
         [0000]      Disease index=Σ(total amount of diseased leaves of a grade×value of the grade)×100/(total amount of leaves×9); 
         [0000]      Efficacy(%)=(disease index of blank control−disease index of experiment group)×100/disease index of blank control 
         [0048]    The results are listed in Table 1 and Table 2. 
         [0000]    
       
         
               
             
               
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Efficacy of the compound of Formula (I) on potted cucumber 
               
               
                 infected by downy mildew and powdery mildew 
               
             
          
           
               
                 Concentration 
                 Efficacy (%) 
               
             
          
           
               
                 (mg/L) 
                 Cucumber downy mildew 
                 Cucumber powdery mildew 
               
               
                   
               
             
          
           
               
                 200 
                 100 
                 100 
               
               
                 100 
                 100 
                 100 
               
               
                 50 
                 100 
                 100 
               
               
                 25 
                 94.16 
                 100 
               
               
                 12.5 
                 87.34 
                 97.22 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Results of secondary screening of the compound of Formula (I) on 
               
               
                 potted cucumber infected by downy mildew and powdery mildew 
               
             
          
           
               
                   
                 Cucumber downy 
                 Cucumber powdery 
               
               
                 Concentration 
                 mildew 
                 mildew 
               
             
          
           
               
                 (mg/L) 
                 Efficacy (%) 
                 EC 50 /EC 90   
                 Efficacy (%) 
                 EC 50 /EC 90   
               
               
                   
               
             
          
           
               
                 50 
                 100 
                 1.52/9.76 
                 100 
                 0.96/3.87 
               
               
                 25 
                 98.15 
                   
                 100 
               
               
                 12.5 
                 91.50 
                   
                 98.50 
               
               
                 6.25 
                 82.89 
                   
                 97.22 
               
               
                 3.125 
                 69.92 
                   
                 85.24 
               
               
                   
               
             
          
         
       
     
         [0049]    2. Fungicidal Spectrum Assay (In Vitro) 
         [0050]    To broaden the fungicidal spectrum of the compound of Formula (I), as targets the following 20 pathogens were assayed in vitro. The results showed the compound of Formula (I) had a wide fungicidal spectrum, particularly effective on  Helminthosporum maydis, Ustilaginoidea virens , and  Diaporthe medusa  in vitro. The 20 pathogens and resultant plant diseases were:
       Rice sheath blight ( Rhizoctonia solani ),   Cucumber gray mold ( Botrytis cinerea ),   Rape sclerotinia rot ( Sclerotinia sclerotirum ),   Wheat scab ( Gibberella zea ),   Rice blast ( Pyricularia oryzae ),   Cucumber anthracnose ( Colletotrichum lagenarium ),   Potato late blight ( Phytophthora infestans ),   Pepper phytophthora blight ( Phytophthora capsici ),   Southern leaf blight of corn ( Helminthosporum maydis ),   Tomato early blight ( Alternaria solani ),   Apple ring rot ( Botryosphaeria berengeriana ),   Tobacco brown spot ( Alternaria alternata ),   Banana leaf spot ( Helminthosporium torulosum ),   Wheat sheath blight ( Rhizoctonia solani ),   Wheat root rot ( Bipolaris sorokiniana ),   Cotton wilt ( Fusarium oxysporum ),   Citrus stem-end rot ( Diaporthe medusae ),   Cotton boll rot ( Fusarium moniliforme ),   Rice false smut ( Ustilaginoidea virens ), and   Peanut brown spot ( Cercospora arachidicola ).       
 
         [0071]    Measurement of In Vitro Inhibitory Rate 
         [0072]    5 wt % formulation of the active compound of Formula (I) was prepared into a solution (300 mg/L). To a sterilized Erlenmeyer flask, 2 mL of the solution and 18 mL of PDA culture medium (50° C.) were added. The mixture was shaken uniformly and dumped into two dishes whose diameter was 9 cm to yield two toxic PDA culture mediums having a concentration of 30 mg/L. Various cultured pathogens were punched at the edge of colony by a puncher having a diameter of 5 mm respectively, and the obtained pieces were transferred to the center of the toxic PDA culture medium by an inoculating needle and cultured in an incubator at 25° C. Repeat the above steps. According to the growth status of CK colony, the colony diameter of pathogens was measured by crossing method with a caliper and thereby a corrected inhibition percentage was calculated. 
         [0073]    Calculation of Efficacy 
         [0074]    For each colony, diameter was measured twice by crossing method and the average was practicable. The colony growth inhibition rate was calculated as follows: 
         [0000]      Colony growth inhibition rate %=(diameter of CK colony−diameter of target colony)×100/diameter of CK colony 
         [0075]    The results are listed in Table 3. 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Fungicidal activity (in vitro) of compound of formula (I) 
               
               
                 on 20 pathogens 
               
             
          
           
               
                   
                 Inhibition rate (%) 
               
             
          
           
               
                   
                 Concentration 
                 Concentration 
                 Concentration 
               
               
                   
                 (mg/L) 
                 (mg/L) 
                 (mg/L) 
               
               
                 Pathogen 
                 30 
                 3 
                 0.3 
               
               
                   
               
             
          
           
               
                 
                   Rhizoctonia solani 
                 
                 68.93 
                 62.14 
                 42.72 
               
               
                 
                   Botrytis cinerea 
                 
                 54.85 
                 42.73 
                 42.31 
               
               
                 
                   Sclerotinia sclerotirum 
                 
                 80.00 
                 61.03 
                 50.77 
               
               
                 
                   Gibberella zea 
                 
                 54.59 
                 45.87 
                 34.86 
               
               
                 
                   Pyricularia oryzae 
                 
                 82.61 
                 56.52 
                 23.60 
               
               
                 
                   Colletotrichum 
                 
                 50.72 
                 44.20 
                 42.03 
               
               
                 
                   lagenarium 
                 
               
               
                 
                   Phytophthora infestans 
                 
                 38.00 
                 33.74 
                 15.34 
               
               
                 
                   Phytophthora capsici 
                 
                 28.85 
                 23.07 
                 0 
               
               
                 
                   Helminthosporum 
                 
                 100 
                 100 
                 86.11 
               
               
                 
                   maydis 
                 
               
               
                 
                   Alternaria solani 
                 
                 43.92 
                 39.19 
                 32.43 
               
               
                 
                   Botryosphaeria 
                 
                 63.64 
                 49.65 
                 44.06 
               
               
                 
                   berengeriana 
                 
               
               
                 
                   Alternaria alternata 
                 
                 43.14 
                 41.83 
                 37.25 
               
               
                 
                   Helminthosporium 
                 
                 21.43 
                 18.45 
                 11.31 
               
               
                 
                   torulosum 
                 
               
               
                 
                   Rhizoctonia solani 
                 
                 68.52 
                 44.44 
                 22.22 
               
               
                 
                   Bipolaris sorokiniana 
                 
                 43.75 
                 40.63 
                 18.75 
               
               
                 
                   Fusarium oxysporum 
                 
                 43.70 
                 36.13 
                 29.41 
               
               
                 
                   Fusarium moniliforme 
                 
                 43.58 
                 30.77 
                 9.60 
               
               
                 
                   Diaporthe medusae 
                 
                 87.23 
                 80.14 
                 55.32 
               
               
                 
                   Ustilaginoidea virens 
                 
                 100 
                 100 
                 74.77 
               
               
                 
                   Cercospora 
                 
                 40.48 
                 35.71 
                 30.95 
               
               
                 
                   arachidicola 
                 
               
               
                   
               
             
          
         
       
     
         [0076]    Following the above method, as targets 17 pathogens originated from tropical plants were tested. The pathogens were  Rhizopus  sp.,  Aspergillus, Colletotrichum gloeosporioides  Penz, Banana Fusarium wilt,  Colletouichum coccodes .Hughas,  B. heveas , Cucumber mosaic virusstrain banana, Banana Sigatoka Leaf Spot Disease,  Colletotrichum gloeosporioides, Colletotrichum musae  (Berk &amp; Curt)Arx,  Botryodiplodia theobromae, Cladosporium cucumerinum  Ellis et Arthur,  Periconia hevenae, Colletotrichum gloeosporioides, B. cinerea, Diplodia natalensis , and  Curvularia.    
         [0077]    The results are listed in Table 4. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Fungicidal activity (in vitro) of compound of formula (I) 
               
               
                 on 17 pathogens originated from tropical plants 
               
             
          
           
               
                   
                 Concentration 
                   
                   
               
               
                 Pathogen 
                 (mg/L) 
                 Inhibition rate (%) 
                 EC 50   
               
               
                   
               
             
          
           
               
                   Rhizopus  sp. 
                 20 
                 88.5 
                 4.1774 
               
               
                   
                 15 
                 83.6 
               
               
                   
                 10 
                 69.3 
               
               
                   
                 5 
                 53.1 
               
               
                   
                 1 
                 18.4 
               
               
                 
                   Aspergillus 
                 
                 50 
                 86.12 
                 5.0287 
               
               
                   
                 25 
                 71.43 
               
               
                   
                 10 
                 58.37 
               
               
                   
                 5 
                 47.76 
               
               
                   
                 1 
                 27.35 
               
               
                   
                 0.1 
                 10.61 
               
               
                 
                   Colletotrichum 
                 
                 50 
                 80.93 
                 4.6266 
               
               
                   gloeosporioides  Penz 
                 25 
                 69.26 
               
               
                   
                 10 
                 54.86 
               
               
                   
                 5 
                 50.19 
               
               
                   
                 1 
                 31.13 
               
               
                   
                 0.1 
                 16.73 
               
               
                 Banana  Fusarium  wilt 
                 50 
                 80.43 
                 9.2172 
               
               
                   
                 25 
                 67.62 
               
               
                   
                 10 
                 60.50 
               
               
                   
                 5 
                 30.25 
               
               
                   
                 1 
                 13.52 
               
               
                 
                   Colletouichum 
                 
                 25 
                 83.54 
                 7.1258 
               
               
                   coccodes.  Hughas 
                 15 
                 61.28 
               
               
                   
                 5 
                 42.07 
               
               
                   
                 2 
                 22.26 
               
               
                   
                 0.1 
                 10.06 
               
               
                 
                   B. heveas 
                 
                 15 
                 81.44 
                 1.9902 
               
               
                   
                 10 
                 70.45 
               
               
                   
                 5 
                 61.36 
               
               
                   
                 1 
                 43.94 
               
               
                   
                 0.1 
                 9.09 
               
               
                 Cucumber mosaic 
                 15 
                 84.84 
                 1.9212 
               
               
                 virusstrain banana 
                 10 
                 76.64 
               
               
                   
                 5 
                 62.30 
               
               
                   
                 1 
                 40.16 
               
               
                   
                 0.1 
                 9.84 
               
               
                 Banana Sigatoka Leaf 
                 20 
                 85.77 
                 1.4987 
               
               
                 Spot Disease 
                 10 
                 77.90 
               
               
                   
                 5 
                 63.67 
               
               
                   
                 1 
                 43.45 
               
               
                   
                 0.1 
                 17.23 
               
               
                 
                   Colletotrichum 
                 
                 20 
                 83.16 
                 1.9699 
               
               
                 
                   gloeosporioides 
                 
                 10 
                 69.36 
               
               
                   
                 5 
                 55.89 
               
               
                   
                 1 
                 42.42 
               
               
                   
                 0.1 
                 18.18 
               
               
                 
                   Colletotrichum musae 
                 
                 20 
                 85.82 
                 1.6555 
               
               
                 (Berk &amp; Curt) Arx 
                 10 
                 78.72 
               
               
                   
                 5 
                 64.54 
               
               
                   
                 1 
                 37.23 
               
               
                   
                 0.1 
                 19.15 
               
               
                 
                   Botryodiplodia 
                 
                 20 
                 83.97 
                 3.6962 
               
               
                 
                   theobromae 
                 
                 10 
                 65.85 
               
               
                   
                 5 
                 51.57 
               
               
                   
                 1 
                 31.71 
               
               
                   
                 0.5 
                 14.63 
               
               
                 
                   Cladosporium 
                 
                 20 
                 84.86 
                 4.844 
               
               
                   cucumerinum  Ellis et 
                 10 
                 72.11 
               
               
                 Arthur 
                 5 
                 54.98 
               
               
                   
                 2.5 
                 28.29 
               
               
                   
                 1 
                 6.77 
               
               
                 
                   Periconia hevenae 
                 
                 15 
                 81.72 
                 0.3775 
               
               
                   
                 10 
                 77.61 
               
               
                   
                 5 
                 74.25 
               
               
                   
                 1 
                 66.42 
               
               
                   
                 0.1 
                 33.21 
               
               
                 
                   Colletotrichum 
                 
                 20 
                 87.24 
                 6.9152 
               
               
                 
                   gloeosporioides 
                 
                 10 
                 55.19 
               
               
                   
                 5 
                 33.83 
               
               
                   
                 1 
                 19.29 
               
               
                   
                 0.1 
                 7.12 
               
               
                 
                   B. cinerea 
                 
                 10 
                 88.09 
                 1.0016 
               
               
                   
                 5 
                 73.35 
               
               
                   
                 1 
                 54.55 
               
               
                   
                 0.5 
                 35.11 
               
               
                   
                 0.1 
                 12.85 
               
               
                 
                   Diplodia natalensis 
                 
                 20 
                 82.35 
                 1.7048 
               
               
                   
                 10 
                 73.68 
               
               
                   
                 5 
                 60.68 
               
               
                   
                 1 
                 40.25 
               
               
                   
                 0.1 
                 20.74 
               
               
                 
                   Curvularia 
                 
                 15 
                 80.60 
                 0.5051 
               
               
                   
                 10 
                 76.59 
               
               
                   
                 5 
                 75.92 
               
               
                   
                 1 
                 63.55 
               
               
                   
                 0.1 
                 28.76 
               
               
                   
               
             
          
         
       
     
         [0078]    3. In Vivo Micro-Screening Assay 
         [0079]    To further study the fungicidal spectrum of the compound of Formula (I), indoor in vivo micro-screening assay were carried out on cucumber gray mold, cucumber scab, cucumber sclerotinia rot, cucumber brown spot, pepper phytophthora blight, and rice sheath blight. The results showed that the compound of Formula (I) had good prevention and treatment effect on cucumber gray mold, cucumber scab, cucumber brown spot, and rice sheath blight. 
         [0080]    1) Target Strains 
         [0081]    Cucumber scab strain: HX; cucumber brown spot strain: SDHGHB060509; cucumber sclerotinia rot strain: HGJH; pepper phytophthora blight strain: NSGP; and rice sheath blight strain: WK-1. 
         [0082]    Cucumber gray mold strain had three different resistant strains: F109 (anti-benzimidazole and its derivatives, sensitive to N-phenylcarbamate, dicarboximide, and pyrimidine amine); Q503001 (sensitive to benzimidazole and its derivatives, N-phenylcarbamate, dicarboximide, and pyrimidine amine); and SC504002 (sensitive to benzimidazole and its derivatives as well as dicarboximide, anti-N-phenylcarbamate and anti-pyrimidine amine). 
         [0083]    2) Medication and Inoculation 
         [0084]    Medicament to be tested and medicament of control groups were prepared as needed in a sunny morning. Cucumber gray mold, cucumber scab, cucumber brown spot, cucumber sclerotinia rot, and rice sheath blight were medicated by spray, and after air dry, pathogens of cucumber scab and of cucumber brown spot were inoculated through spraying spore suspension respectively, pathogens of cucumber gray mold, of cucumber sclerotinia rot, and of rice sheath blight were inoculated through lawn foliage. Pepper phytophthora blight was medicated and inoculated by root-irrigation. Subsequently, all seedlings were cultured in wet environment. 
         [0085]    3) Investigation 
         [0086]    After the disease of control groups were serious, spot area, disease index, and the diseased seedling rate were investigated to calculate the efficacy. Cucumber scab, cucumber brown spot, and pepper phytophthora blight were investigated by grading method. The spot extension area of cucumber gray mold and of rice sheath blight was investigated. The diseased seedling rate of cucumber sclerotinia rot was investigated. 
         [0000]      Disease index=Σ(amount of infected diseased leaves in a grade×relative value of the grade)×100/(total amount of leaves×9); 
         [0000]      Diseased seedling rate(%)=(total amount of seedlings−amount of diseased seedlings)/total amount of seedlings×100% 
         [0000]      Prevention and treatment effect(%)=(disease of control group−disease of experiment group)/disease of control group×100% 
         [0087]    The results are listed in Table 5. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Results of in vivo micro-screening test of Compound of Formula (I) 
               
             
          
           
               
                   
                   
                 Concentration 
                 Spot area (mm 2 ) 
                 Efficacy 
               
               
                 Target 
                 Medicament 
                 (mg/L) 
                 or disease index 
                 (%) 
               
               
                   
               
             
          
           
               
                 Cucumber gray mold 
                 Compound of 
                 500 
                 3.67 
                 96.43 
               
               
                 (F-109) 
                 Formula (I) 
                 100 
                 8.03 
                 92.19 
               
               
                   
                 25% Amistar SC 
                 125 
                 8.65 
                 89.82 
               
               
                   
                 CK 
                 Clear water 
                 102.81 
                 — 
               
               
                 Cucumber gray mold 
                 Compound of 
                 500 
                 5.64 
                 90.67 
               
               
                 (SC504002) 
                 Formula (I) 
                 100 
                 6.82 
                 88.71 
               
               
                   
                 25% Amistar SC 
                 125 
                 6.14 
                 89.82 
               
               
                   
                 CK 
                 Clear water 
                 60.46 
                 — 
               
               
                 Cucumber gray mold 
                 Compound of 
                 500 
                 2.82 
                 97.71 
               
               
                 (Q503001) 
                 Formula (I) 
                 100 
                 7.78 
                 93.69 
               
               
                   
                 25% Amistar SC 
                 125 
                 8.53 
                 93.09 
               
               
                   
                 CK 
                 Clear water 
                 123.39 
                 — 
               
               
                 Cucumber sclerotinia rot 
                 Compound of 
                 500 
                 34.65 
                 58.88 
               
               
                   
                 Formula (I) 
                 100 
                 70.08 
                 16.84 
               
               
                   
                 25% Amistar SC 
                 125 
                 24.45 
                 70.99 
               
               
                   
                 CK 
                 Clear water 
                 84.27 
                 — 
               
               
                 Cucumber scab 
                 Compound of 
                 500 
                 0 
                 100.00  
               
               
                   
                 Formula (I) 
                 100 
                 0 
                 100.00  
               
               
                   
                 25% Amistar SC 
                 125 
                 4.44 
                 91.31 
               
               
                   
                 CK 
                 Clear water 
                 51.11 
                 — 
               
               
                 Cucumber brown spot 
                 Compound of 
                 500 
                 4.44 
                 89.10 
               
               
                   
                 Formula (I) 
                 100 
                 6.11 
                 85.00 
               
               
                   
                 25% Amistar SC 
                 125 
                 3.33 
                 91.82 
               
               
                   
                 CK 
                 Clear water 
                 40.74 
                 — 
               
               
                 Pepper  phytophthora   
                 Compound of 
                 500 
                 24 
                 30.09 
               
               
                 blight 
                 Formula (I) 
                 100 
                 25.33 
                 26.22 
               
               
                   
                 25% Amistar SC 
                 125 
                 10 
                 70.87 
               
               
                   
                 CK 
                 Clear water 
                 34.33 
                 — 
               
               
                 Rice sheath blight 
                 Compound of 
                 500 
                 46.87 
                 70.04 
               
               
                   
                 Formula (I) 
                 100 
                 59.96 
                 61.67 
               
               
                   
                 25% Amistar SC 
                 125 
                 86.43 
                 44.74 
               
               
                   
                 CK 
                 Clear water 
                 156.42 
               
               
                   
               
               
                 *F-109, SC504001, Q503001, cucumber sclerotinia rot, and pepper  phytophthora  blight referred to spot area (mm 2 ), cucumber scab, cucumber brown spot, rice sheath blight referred to disease index. 
               
             
          
         
       
     
       Example 3 
     Acute Toxicity and Ames Test 
       [0088]    Bioassay results showed that the compound of Formula (I) had good preventive effect on downy mildew and powdery mildew. The toxicological indexes of the compound were tested following the standard GB15670-1995 “Toxicological test methods of pesticides for registration” by Tongji Medical College, Huazhong University of Science and Technology. The results showed that the compound had low toxicity. 
         [0089]    The results are listed in Table 6. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Results of Acute Toxicity and Ames test of compound (I) 
               
             
          
           
               
                 No. 
                 Items 
                 Toxicity 
               
               
                   
               
               
                 1 
                 Acute oral test 
                 Male rat: LD 50  &gt; 5000 mg/kg 
               
               
                   
                   
                 Female rat: LD 50  &gt; 5000 mg/kg 
               
               
                   
                   
                 Low toxicity 
               
               
                 2 
                 Acute skin test 
                 Male rat: LD 50  &gt; 2000 mg/kg 
               
               
                   
                   
                 Female rat: LD 50  &gt; 2000 mg/kg 
               
               
                   
                   
                 Low toxicity 
               
               
                 3 
                 Eye stimulation test 
                 Mild stimulation on rabbit&#39;s eye 
               
               
                 4 
                 Skin stimulation test 
                 No stimulation on rabbit&#39;s skin 
               
               
                 5 
                 Skin sensitization test 
                 Weak allergen (grade I) on guinea 
               
               
                   
                   
                 pig skin 
               
               
                 6 
                 Ames test 
                 Negative 
               
               
                 7 
                 Micronucleus Test of Mice 
                 Negative 
               
               
                   
                 Polychromatic Erythrocytes 
               
               
                 8 
                 Chromosome aberration test 
                 Negative 
               
               
                   
                 of mice spermatogonial 
               
               
                   
               
             
          
         
       
     
       Example 4 
     Environmental Assessment Test 
       [0090]    After acute toxicity and Ames test had been finished, environmental toxicity test was conducted following “Guideline for Environmental Safety Evaluation of Chemical Pesticides” of Agriculture Ministry of China by Shenyang Chemical Research Institute/Supervision and Test Center for Pesticide Safety Evaluation and Quality Control. The results showed that the compound was environmentally friendly. 
         [0091]    The results are listed in Table 7. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Results of environmental toxicity test 
               
             
          
           
               
                 No. 
                 Items 
                 Toxicity 
               
               
                   
               
               
                 1 
                 Acute toxicity test on zebra fish 
                 LC 50  (24 hrs): 0.069 mg.a.i/L 
               
               
                   
                   
                 LC 50  (48 hrs): 0.060 mg.a.i/L 
               
               
                   
                   
                 LC 50  (72 hrs): 0.047 mg.a.i/L 
               
               
                   
                   
                 LC 50  (96 hrs): 0.043 mg.a.i/L 
               
               
                 2 
                 Acute oral toxicity test on quail 
                 LC 50  &gt; 1100 mg/kg.bw 
               
               
                 3 
                 Acute contact toxicity test on bee 
                 LC 50  (48 hrs) &gt; 100 μg a.i./per bee 
               
               
                 4 
                 Toxicity test on silkworm after 
                 LC 50  (24 hrs) &gt; 300.0 mg/kg mulberry leaves 
               
               
                   
                 96 hrs&#39; administration 
                 LC 50  (48 hrs) &gt; 300.0 mg/kg mulberry leaves 
               
               
                   
                   
                 LC 50 (96 hrs) &gt; 132.1 mg/kg mulberry leaves 
               
               
                   
               
             
          
         
       
     
       Example 5 
     Enzyme Activity Test 
       [0092]    Take NADH oxidase (NOX), succinate-cytochrome C oxidase (SCO), and Complex III as target enzymes, the inhibitory activity of the compound of Formula (I) was tested. The results showed that, the compound had much higher inhibitory activity on NOX, SCO, and Complex III than azoxystrobin which functioned as a control agent, particularly on Complex III. 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Results of enzyme activity test of the compound of Formula (I) 
               
             
          
           
               
                   
                 IC 50  (nM) 
               
             
          
           
               
                   
                 Medicament 
                 NOX a   
                 SCO a   
                 Complex III b   
               
               
                   
                   
               
             
          
           
               
                   
                 Compound of Formula (I) 
                 5.3 
                 3.4 
                 4 
               
               
                   
                 Azoxystrobin 
                 27 
                 13 
                 200 
               
               
                   
                   
               
             
          
         
       
     
         [0093]      a  NOX is generally used to detect an inhibitor of Complex I and Complex III; SCO is generally used to detect an inhibitor of Complex II and Complex III. Thus, an inhibitor of Complex III should have inhibitory activity on the two enzymes. 
         [0094]      b  The test target is cytochrome bc1 complex of pig heart. 
       Example 6 
     Preparation of Emulsifier Concentrate 
       [0095]    Materials: 
         [0096]    1) (E)-methyl 3-methoxy-2-(2-((5-methoxy-benzothiazol-2-ylthio)methyl)phenyl)acrylate. (prepared following Example 1) having 98% active ingredient. 
         [0097]    2) Emulsifier: pesticide emulsifier No. 500 and Tween 80 (both from market) 
         [0098]    3) Cosolvent: DMF, DMSO, and acetone (all from market) 
         [0099]    4) Stabilizer: epoxidized soybean oil (from market) 
         [0100]    5) Solvent: toluene and xylene (both from market) 
         [0101]    Emulsifier Concentrate 1 
         [0102]    To a beaker (1000 mL), 50 g (100% basis) of the compound of Formula (I), 150 g of DMF, and 50 g of acetone were added and stirred for dissolution. To the solution, 25 g of pesticide emulsifier No. 500 and 50 g of Tween 80, 20 g of epoxidized soybean oil, and 655 g of toluene were added. Thus, the emulsifier concentrate 1 having 5 wt. % of the compound of Formula (I) was obtained and further packed. 
         [0103]    Emulsifier Concentrate 2 
         [0104]    To a beaker (1000 mL), 75 g (100% basis) of the compound of Formula (I), 150 g of DMF, and 50 g of acetone were added and stirred for dissolution. To the solution, 50 g of pesticide emulsifier No. 500 and 50 g of Tween 80, 20 g of epoxidized soybean oil, and 605 g of toluene were added. Thus, the emulsifier concentrate 2 having 7.5 wt. % of the compound of Formula (I) was obtained and further packed. 
         [0105]    Emulsifier Concentrate 3 
         [0106]    To a beaker (1000 mL), 100 g (100% basis) of the compound of Formula (I), 150 g of DMF, and 150 g of acetone were added and stirred for dissolution. To the solution, 50 g of pesticide emulsifier No. 500 and 50 g of Tween 80, 20 g of epoxidized soybean oil, and 480 g of toluene were added. Thus, the emulsifier concentrate 3 having 10 wt. % of the compound of Formula (I) was obtained and further packed. 
       Example 7 
     Field Efficacy Trial 
       [0107]    On the basis of indoor activity evaluation, field efficacy trials of the compound of Formula (I) on cucumber downy mildew, cucumber powdery mildew, and melon powdery mildew were conducted. The results are listed in Tables 9-11. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
               
                   
               
               
                 Efficacy of emulsifier concentrate 1 (comprising 5 wt. % of the 
               
               
                 compound of Formula (I)) on cucumber powdery mildew 
               
               
                 (After three times&#39; administration) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Active 
                   
                 Disease index 
                 At 7 th  day 
               
             
          
           
               
                   
                 ingredient 
                   
                 (%) prior to 
                 Disease 
                 Efficacy 
               
               
                 Medicament 
                 (mg/L) 
                 No. 
                 administration 
                 index (%) 
                 (%) 
               
               
                   
               
               
                 Compound 
                 100 
                 1 
                 9.2 
                 1.7 
                 91.17 
               
               
                 of Formula 
                   
                 2 
                 7.6 
                 1.2 
                 92.74 
               
               
                 (I) 
                   
                 3 
                 8.4 
                 1.9 
                 90.16 
               
               
                   
                   
                 4 
                 7.6 
                 1.2 
                 92.41 
               
               
                   
                   
                 Average 
                 8.2 
                 1.5 
                 91.67 
               
               
                   
                 50 
                 1 
                 7.2 
                 2.1 
                 85.88 
               
               
                   
                   
                 2 
                 7.2 
                 2.4 
                 84.49 
               
               
                   
                   
                 3 
                 8.0 
                 2.8 
                 86.18 
               
               
                   
                   
                 4 
                 7.2 
                 2.2 
                 85.31 
               
               
                   
                   
                 Average 
                 7.6 
                 2.4 
                 85.63 
               
               
                   
                 25 
                 1 
                 8.1 
                 3.6 
                 78.48 
               
               
                   
                   
                 2 
                 8.4 
                 4.2 
                 76.74 
               
               
                   
                   
                 3 
                 8.1 
                 4.6 
                 77.57 
               
               
                   
                   
                 4 
                 7.0 
                 3.3 
                 77.35 
               
               
                   
                   
                 Average 
                 7.9 
                 3.9 
                 77.54 
               
               
                   
                 12.5 
                 1 
                 9.2 
                 5.5 
                 71.05 
               
               
                   
                   
                 2 
                 8.7 
                 5.5 
                 70.59 
               
               
                   
                   
                 3 
                 9.3 
                 6.7 
                 71.54 
               
               
                   
                   
                 4 
                 9.2 
                 5.8 
                 69.71 
               
               
                   
                   
                 Average 
                 9.1 
                 5.9 
                 70.50 
               
               
                 25% Amistar 
                 167 
                 1 
                 7.4 
                 2.7 
                 82.33 
               
               
                 SC 
                   
                 2 
                 8.2 
                 2.8 
                 84.11 
               
               
                   
                   
                 3 
                 7.7 
                 3.2 
                 83.58 
               
               
                   
                   
                 4 
                 7.1 
                 2.3 
                 84.44 
               
               
                   
                   
                 Average 
                 7.6 
                 2.8 
                 83.24 
               
             
          
           
               
                 CK 
                 1 
                 9.2 
                 19.0 
                   
               
               
                   
                 2 
                 8.7 
                 18.7 
               
               
                   
                 3 
                 7.9 
                 20.0 
               
               
                   
                 4 
                 8.6 
                 17.9 
               
               
                   
                 Average 
                 8.6 
                 18.9 
               
               
                   
               
             
          
           
               
                   
                 At 14 th  day 
                 At 21 st  day 
               
             
          
           
               
                   
                 Active 
                   
                 Disease 
                   
                 Disease 
                   
               
               
                   
                 ingredient 
                   
                 index 
                 Efficacy 
                 index 
                 Efficacy 
               
               
                 Medicament 
                 (mg/L) 
                 No. 
                 (%) 
                 (%) 
                 (%) 
                 (%) 
               
               
                   
               
               
                 Compound 
                 100 
                 1 
                 0.9 
                 96.46 
                 3.3 
                 91.58 
               
               
                 of Formula 
                   
                 2 
                 1.3 
                 94.43 
                 2.6 
                 92.15 
               
               
                 (I) 
                   
                 3 
                 1.4 
                 95.18 
                 2.8 
                 93.17 
               
               
                   
                   
                 4 
                 1.0 
                 95.68 
                 3.0 
                 91.23 
               
               
                   
                   
                 Average 
                 1.2 
                 95.23 
                 2.9 
                 91.52 
               
               
                   
                 50 
                 1 
                 2.1 
                 89.44 
                 3.2 
                 89.57 
               
               
                   
                   
                 2 
                 1.8 
                 91.85 
                 3.0 
                 90.44 
               
               
                   
                   
                 3 
                 2.7 
                 90.23 
                 4.4 
                 88.74 
               
               
                   
                   
                 4 
                 1.9 
                 91.34 
                 3.7 
                 88.58 
               
               
                   
                   
                 Average 
                 2.1 
                 90.99 
                 3.6 
                 89.45 
               
               
                   
                 25 
                 1 
                 3.5 
                 84.35 
                 6.8 
                 8030 
               
               
                   
                   
                 2 
                 4.2 
                 83.71 
                 6.8 
                 81.42 
               
               
                   
                   
                 3 
                 4.8 
                 82.85 
                 8.0 
                 79.79 
               
               
                   
                   
                 4 
                 3.5 
                 83.59 
                 6.2 
                 80.32 
               
               
                   
                   
                 Average 
                 4.0 
                 83.51 
                 7.0 
                 77.78 
               
               
                   
                 12.5 
                 1 
                 6.4 
                 74.80 
                 12.6 
                 67.88 
               
               
                   
                   
                 2 
                 6.3 
                 76.40 
                 12.0 
                 68.34 
               
               
                   
                   
                 3 
                 7.8 
                 75.73 
                 13.9 
                 69.40 
               
               
                   
                   
                 4 
                 6.6 
                 76.45 
                 12.3 
                 70.29 
               
               
                   
                   
                 Average 
                 6.8 
                 75.66 
                 12.7 
                 68.91 
               
               
                 25% Amistar 
                 167 
                 1 
                 2.7 
                 86.78 
                 4.9 
                 84.46 
               
               
                 SC 
                   
                 2 
                 3.2 
                 87.28 
                 5.3 
                 85.16 
               
               
                   
                   
                 3 
                 3.2 
                 87.97 
                 5.2 
                 86.18 
               
               
                   
                   
                 4 
                 2.5 
                 88.44 
                 4.7 
                 85.29 
               
               
                   
                   
                 Average 
                 2.9 
                 87.57 
                 5.0 
                 85.34 
               
             
          
           
               
                 CK 
                 1 
                 25.4 
                   
                 39.2 
                   
               
               
                   
                 2 
                 26.7 
                   
                 37.9 
               
               
                   
                 3 
                 27.3 
                   
                 38.6 
               
               
                   
                 4 
                 26.2 
                   
                 38.7 
               
               
                   
                 Average 
                 26.4 
                   
                 38.6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 10 
               
               
                   
               
               
                 Efficacy of emulsifier concentrate 1 (comprising 5 wt. % of the 
               
               
                 compound of Formula (I)) on cucumber downy mildew 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                   
                   
                 At 12 th  day after 
               
               
                   
                 Active 
                   
                 second administration 
               
             
          
           
               
                   
                   
                 ingredient 
                   
                 Total 
                 Disease 
                 Efficacy 
               
               
                   
                 Medicament 
                 (mg/L) 
                 No. 
                 leaves 
                 index 
                 (%) 
               
               
                   
                   
               
               
                   
                 Compound of 
                 100 
                 1 
                 34.0 
                 0.98 
                 83.71 
               
               
                   
                 Formula (I) 
                   
                 2 
                 32.0 
                 1.39 
                 76.93 
               
               
                   
                   
                   
                 3 
                 32.0 
                 0.69 
                 88.46 
               
               
                   
                   
                   
                 Average 
                 32.7 
                 1.02 
                 83.04 
               
               
                   
                   
                 50 
                 1 
                 32.0 
                 1.04 
                 82.70 
               
               
                   
                   
                   
                 2 
                 32.0 
                 1.74 
                 71.16 
               
               
                   
                   
                   
                 3 
                 32.0 
                 1.39 
                 76.93 
               
               
                   
                   
                   
                 Average 
                 32.0 
                 1.39 
                 76.93 
               
               
                   
                   
                 25 
                 1 
                 32.0 
                 1.74 
                 71.16 
               
               
                   
                   
                   
                 2 
                 32.0 
                 2.08 
                 65.39 
               
               
                   
                   
                   
                 3 
                 32.0 
                 1.74 
                 71.16 
               
               
                   
                   
                   
                 Average 
                 32.0 
                 1.85 
                 69.24 
               
               
                   
                 25% Amistar 
                 125 
                 1 
                 32.0 
                 1.39 
                 76.93 
               
               
                   
                   
                   
                 2 
                 32.0 
                 0.69 
                 88.46 
               
               
                   
                   
                   
                 3 
                 32.0 
                 1.39 
                 76.93 
               
               
                   
                   
                   
                 Average 
                 32.0 
                 1.16 
                 80.77 
               
             
          
           
               
                   
                 CK 
                   
                 1 
                 32.0 
                 1.16 
                   
               
               
                   
                   
                   
                 2 
                 32.0 
                 6.25 
               
               
                   
                   
                   
                 3 
                 32.0 
                 5.90 
               
               
                   
                   
                   
                 Average 
                 32.0 
                 6.02 
               
               
                   
                   
               
             
          
           
               
                   
                   
                   
                 At 5 th  day after third 
                 At 9 th  day after third 
               
               
                   
                 Active 
                   
                 administration 
                 administration 
               
             
          
           
               
                   
                 ingredient 
                   
                 Total 
                 Disease 
                 Efficacy 
                 Total 
                 Disease 
                 Efficacy 
               
               
                 Medicament 
                 (mg/L) 
                 No. 
                 leaves 
                 index 
                 (%) 
                 leaves 
                 index 
                 (%) 
               
               
                   
               
               
                 Compound 
                 100 
                 1 
                 32.0 
                 2.08 
                 81.99 
                 48.0 
                 8.10 
                 78.08 
               
               
                 of Formula 
                   
                 2 
                 32.0 
                 2.43 
                 78.99 
                 48.0 
                 7.18 
                 80.58 
               
               
                 (I) 
                   
                 3 
                 32.0 
                 3.13 
                 72.99 
                 48.0 
                 6.02 
                 83.72 
               
               
                   
                   
                 Average 
                 32.0 
                 2.55 
                 77.99 
                 48.0 
                 7.10 
                 80.79 
               
               
                   
                 50 
                 1 
                 32.0 
                 3.47 
                 69.99 
                 48.0 
                 10.65 
                 71.19 
               
               
                   
                   
                 2 
                 32.0 
                 4.51 
                 60.99 
                 48.0 
                 7.18 
                 80.58 
               
               
                   
                   
                 3 
                 32.0 
                 3.82 
                 66.99 
                 48.0 
                 8.33 
                 77.45 
               
               
                   
                   
                 Average 
                 32.0 
                 3.94 
                 65.99 
                 48.0 
                 8.72 
                 76.41 
               
               
                   
                 25 
                 1 
                 32.0 
                 4.86 
                 57.99 
                 48.0 
                 12.04 
                 67.43 
               
               
                   
                   
                 2 
                 32.0 
                 4.51 
                 60.99 
                 48.0 
                 10.42 
                 71.82 
               
               
                   
                   
                 3 
                 32.0 
                 4.86 
                 57.99 
                 48.0 
                 12.04 
                 67.43 
               
               
                   
                   
                 Average 
                 32.0 
                 4.75 
                 58.99 
                 48.0 
                 11.50 
                 68.89 
               
               
                 25% Amistar 
                 125 
                 1 
                 32.0 
                 3.47 
                 69.99 
                 48.0 
                 8.80 
                 76.20 
               
               
                   
                   
                 2 
                 32.0 
                 3.13 
                 72.99 
                 48.0 
                 5.79 
                 84.34 
               
               
                   
                   
                 3 
                 32.0 
                 2.43 
                 78.99 
                 48.0 
                 9.95 
                 73.07 
               
               
                   
                   
                 Average 
                 32.0 
                 3.01 
                 73.99 
                 48.0 
                 8.18 
                 77.87 
               
             
          
           
               
                 CK 
                 1 
                 32.0 
                 12.85 
                   
                 48.0 
                 36.34 
                   
               
               
                   
                 2 
                 32.0 
                 10.42 
                   
                 48.0 
                 34.72 
               
               
                   
                 3 
                 32.0 
                 11.46 
                   
                 48.0 
                 39.81 
               
               
                   
                 Average 
                 32.0 
                 11.57 
                   
                 48.0 
                 36.96 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
               
                   
               
               
                 Efficacy of emulsifier concentrate 1 (comprising 5 wt. % of the 
               
               
                 compound of Formula (I)) on melon powdery mildew 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                   
                 Prior to 
                 At 7 th  day after first 
               
               
                   
                 Active 
                 administration 
                 administration 
               
             
          
           
               
                   
                 ingredient 
                 Total 
                 Disease 
                 Total 
                 Disease 
                 Efficacy 
               
               
                 Medicament 
                 (mg/L) 
                 leaves 
                 index 
                 leaves 
                 index 
                 (%) 
               
               
                   
               
               
                 Compound of 
                 100 
                 1394 
                 6.29 
                 1490 
                 6.29 
                 39.15 
               
               
                 Formula (I) 
                 50 
                 1374 
                 7.20 
                 1452 
                 7.92 
                 35.77 
               
               
                   
                 25 
                 1412 
                 6.97 
                 1435 
                 7.11 
                 34.38 
               
               
                   
                 12.5 
                 1169 
                 6.90 
                 1416 
                 8.80 
                 27.16 
               
               
                 25% Amistar SC 
                 125 
                 1387 
                 7.37 
                 1499 
                 7.54 
                 37.81 
               
               
                 CK 
                   
                 1326 
                 10.30 
                 1306 
                 17.42 
               
               
                   
               
             
          
           
               
                   
                   
                 At 7 th  day after 
                 At 14 th  day 
               
               
                   
                   
                 second 
                 after second 
               
               
                   
                 Active 
                 administration 
                 administration 
               
             
          
           
               
                   
                 ingredient 
                 Total 
                 Disease 
                 Efficacy 
                 Total 
                 Disease 
                 Efficacy 
               
               
                 Medicament 
                 (mg/L) 
                 leaves 
                 index 
                 (%) 
                 leaves 
                 index 
                 (%) 
               
               
                   
               
               
                 Compound of 
                 100 
                 1478 
                 4.52 
                 86.22 
                 1339 
                 19.45 
                 63.47 
               
               
                 Formula (I) 
                 50 
                 1483 
                 10.88 
                 75.54 
                 1559 
                 30.42 
                 54.57 
               
               
                   
                 25 
                 1473 
                 13.63 
                 67.15 
                 1523 
                 31.50 
                 47.00 
               
               
                   
                 12.5 
                 1545 
                 13.44 
                 61.65 
                 1587 
                 40.33 
                 29.55 
               
               
                 25% Amistar SC 
                 125 
                 1497 
                 10.31 
                 74.87 
                 1541 
                 30.95 
                 53.41 
               
               
                 CK 
                   
                 1283 
                 48.66 
                   
                 1505 
                 75.36 
               
               
                   
               
             
          
         
       
     
         [0108]    While particular embodiments of the invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and therefore, the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention.