BENZAMIDOXIME DERIVATIVE, PROCESS FOR PRODUCTION THEREOF, AND AGROHORTICULTURAL BACTERICIDE

Abstract: The present invention relates to benzamidoxime derivatives represented by the formula [I]; wherein R 1 is unsubstituted or substituted C 1 - C 4 alkyl, unsubstituted or substituted C 2 - C 4 alkenyl or unsubstituted or substituted C 2 - C 4 alkynyl, R 2 is phenyl optionally having substituents or heterocycle optionally having substituents, X 1 , X 2 , X 3 and X 4 are each independently hydrogen, halogen, C 1 - C 4 alkyl, C 1 - C 4 haloalkyl, C 1 - C 4 alkoxy, C 1 - C 4 haloalkoxy, C 1 - C 4 alkylthio or the like, and r 1 and r 2 are each independently hydrogen, C 1 - C 4 alkyl or the like, having excellent fungicidal activity and being useful as a fungicide for agricultural and horticultural use, and methods for preparation thereof.

Description: Technical Field: The present invention relates to novel benzamidoxime derivatives. methods for preparation thereof and fungicides for agricultural and horticultural uses. Background Art: In farming of agricultural and horticultural crops in the past, various fungicides have been used for the control of plant diseases on the crops, however, many of them are not enough useful because of their insufficient effectiveness in plant disease control, the limitation in their use due to the appearance of resistant strain of plant disease pathogens to the fungicides, the development of phytotoxicity and contamination to the crops, and/or their strong toxicity to humans. domestic animals and wildlife. For this reason, there is still intensive requirement to develop safe fungicides for agricultural and horticultural uses, which do not have the disadvantages as described above. Some benzamidoxime derivatives, which are close to the compounds of the present invention, and their use as fungicides have been disclosed in Japanese Patent Laid-opened No. Hei 2-6453 Gazette. However, it is obvious that the biological activity of those benzamide oxime derivatives are not enough in the practical plant disease control. Therefore. it is an object of the present invention to provide novel compounds which can be a fungicide for agricultural and horticultural use capable of advantageously manufacturing the compound in an industrial scale, controlling plant diseases steadily and using it safely. Disclosure of the Invention: The present invention is directed to benzamidoxime derivatives represented by a general formula [I]; wherein R 1 is unsubstituted or substituted C 1 - C 4 alkyl, unsubstituted or substituted C 2 - C 4 alkenyl or unsubstituted or substituted C 2 - C 4 alkynyl, R 2 is phenyl optionally having substituents or heterocycle optionally having substituents, X 1 is-CF 3 X 2 , X 3 , X 4 and X 5 are each independently hydrogen, halogen, C 1 - C 4 alkyl, C 1 - C 4 haloalkyl, C 1 - C 4 alkoxy, C 1 - C 4 haloalkoxy, C 1 - C 4 alkylthio, C 1 - C 4 alkylsulfinyl, C 1 - C 4 alkylsulfonyl, nitro, amino or C 1 - C 4 alkylcarbonylamino, and r 1 and r 2 are each independently hydrogen, halogen, C 1 - C 4 alkyl, C 1 - C 4 haloalkyl, C 1 - C 4 alkoxy, C 1 - C 4 alkylthio or amino, or r 1 and r 2 together may form a carbonyl. The present invention is also directed to methods for preparation thereof and fungicides for agricultural and horticultural use comprising the said derivatives. In the present invention, for the examples of C 1 - C 4 alkyl of the unsubstituted or substituted C 1 - C 4 alkyl represented by R 1 , methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl can be given. For the examples of C 2 - C 4 alkenyl of the unsubstituted or substituted C 2 - C 4 alkenyl represented by R 1 , vinyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl and 3-butenyl can be given. For the examples of C 2 - C 4 alkynyl of the unsubstituted or substituted C 2 - C 4 alkynyl represented by R 1 , ethynyl, propargyl, 2-butynyl and 3-butynyl can be given. Further, according to formula I' R 1 may be a group represented by general formula R 3 -CH 2 wherein R 3 is a group selected from; C 3 - C 8 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl; C 3 - C 8 halocycloalkyl, such as 1-fluorocyclopropyl, 2-fluorocyclopropyl, 1-chlorocyclopropyl, 2-chlorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-dichlorocyclopropyl, 2-fluorocyclopentyl, 3-fluorocyclopentyl, 2-chlorocyclopentyl, 3-chlorocyclopentyl, 3.4-difluorocyclohexyl, 3,4-dichlorocyclohexyl and 3,4-dibromosilocyclohexy 1; C 3 - C 8 cycloalkenyl, such as 2-cyclohexenyl and 3-cyclohexenyl; halogens, such as fluorine, chlorine, bromine and iodine; C 1 - C 4 alkoxy, such as methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy and t-butyloxy; unsubstituted, mono-substituted or di-substituted amino by C 1 - C 4 alkyl, such as amino, methylamino and dimethylamino; unsubstituted, mono-substituted or di-substituted carbamoyl by C 1 - C 4 alkyl, such as carbamoyl, methylcarbamoyl and dimethylcarbamoyl; C 1 - C 4 alkylthio, such as methylthio, ethylthio, propylthio and isopropylthio; C 1 - C 4 alkylsulfinyl, such as methylsulfinyl and ethylsulfinyl; C 1 - C 4 alkylsulfonyl, such as methylsulfonyl and ethylsulfonyl; C 1 - C 4 alkoxycarbonyl, such as methoxycarbonyl and ethoxycarbonyl; carboxy and cyano, can be given for the examples of the substituents for any of C 1 - C 4 alkyl, C 2 - C 4 alkenyl and C 2 - C 4 alkynyl. However, straight chain or branched C 1 - C 4 alkyl being unsubstituted or substituted is more preferable for the examples of the substituent represented by R 1 . More particularly, straight chain or branched C 1 - C 4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, s-butyl and t-butyl; a group represented by a general formula, R 3 CH 2 , wherein R 3 is C 3 - C 8 cycloalkyl, C 1 - C 3 haloalkyl, C 1 - C 3 alkoxy, C 1 - C 3 alkylthio, C 1 - C 3 alkylsulfinyl, C 1 - C 3 alkylsulfonyl, C 1 - C 3 alkoxycarbonyl, cyano, amino, C 1 - C 3 monoalkylamino, C 1 - C 3 dialkylamino or acylamino, such as C 1 - C 8 cycloalkylmethyl including cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl, C 1 - C 8 cyclohaloalkylmethyl including 2-fluorocyclopropylmethyl, 1-fluorocyclopropylmethyl, 1,2-difluorocyclopropylmethyl and 3,4-dibromocyclohexyl, C 1 - C 4 haloalkyl including 2-chloroethyl, 2-fluoroethyl, 2,2-dichloroethyl, 2,2-difluoroethyl and 2,2,2-trifluoroethyl, C 1 - C 4 alkoxymethyl including methoxymethyl, ethoxymethyl and propoxymethyl, C 2 - C 4 alkynyl including propargyl, C 2 - C 4 alkenyl including allyl, 2-butenyl, cyanomethyl, alkoxycarbonylmethyl including methoxycarbonylmethyl and ethoxycarbonylmethyl, alkylthiomethyl including methylthiomethyl and ethylthiomethyl, alkylsulfinylmethyl including methylsulfinylmethyl and ethylsulfinylmethyl, alkylsulfonylmethyl including methylsulfonylmethyl and ethylsulfonylmethyl, aminomethyl, substituted aminomethyl including N-methylaminomethyl, N,N-dimethylaminomethyl, N-acetylaminomethyl and N-benzoylaminomethyl, can be given for the examples of the straight chain or branched C 1 - C 4 alkyl being unsubstituted or unsubstituted described above. For the examples of heterocycle of the unsubstituted or substituted heterocycle group represented by R 2 , 5- or 6-membered aromatic heterocycle containing 1 - 4 heteroatoms, such as N. 0 and S, such as pyridine ring, fran ring, thiophene ring. pyrazole ring, imidazole ring, triazole ring, pyrrole ring, pyrazine ring. pyrimidine ring, pyridazine ring, oxazole ring, isoxazole ring and thiazole ring, can be given. The substituents for phenyl and heterocycle represented by R 2 may substitute one or more optional positions of the benzene ring or the heterocycle thereof and may be different with each other if 2 or more positions are substituted thereby. For the preferable examples of the substituents described hereinabove, halogens, such as fluorine, chlorine and bromine, C 1 - C 4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl and t-butyl, C 1 - C 4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy and t-butoxy, C 2 - C 4 alkenyloxy, such as allyoxy and crotyloxy, C 2 - C 4 alkynyloxy, such as propargyloxy, C 1 - C 4 haloalkyl, such as chloromethyl, fluoromethyl, bromomethyl, dichloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, tribromomethyl, trifluoroethoxy and pentafluoroethoxy, and C 1 - C 4 haloalkoxy, such as chloromethoxy, fluoromethoxy, bromomethoxy, dichloromethoxy, difluoromethoxy, trichloromethoxy, trifluoromethoxy, tribromomethoxy and trifluoroethoxy, can be given. For the examples of halogen atoms represented by X 2 , X 3 , X 4 and X 5 , fluorine, chlorine, bromine and iodine can be given, and for the examples of the C 1 - C 4 alkyl represented by X 2 , X 3 , X 4 and X 5 , methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl can be given, and further for the examples of the C 1 - C 4 haloalkyl represented by X 2 , X 3 , X 4 and X 5 , straight chain or branched C 1 - C 4 haloalkyl, such as chloromethyl, dichloromethyl, trichloromethyl, difluoromethyl, trifluoromethyl. bromomethyl, dibromomethyl, chloroethyl, fluoroethyl, dichloroethyl, difluoroethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, chloropropyl, fluoropropyl, perfluoropropyl, chloroisopropyl, fluoroisopropyl, perfluoroisopropyl, chlorobutyl, fluorobutyl, perfluorobutyl, chloroisobutyl, fluoroisobutyl, perfluoroisobutyl, chloro-s-butyl, fluoro-s-butyl, perfluoro-s-butyl, chloro-t-butyl, fluoro-t-butyl and perfluoro-t-butyl, can be given, and still for the examples of the C 1 - C 4 alkoxy represented by X 2 , X 3 , X 4 and X 5 , methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy and t-butyloxy can be given. In addition, for the examples of the C 1 - C 4 alkylthio represented by X 2 , X 3 , X 4 and X 5 , methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio and t-butylthio can be given, and for the examples of the C 1 - C 4 haloalkoxy represented by X 2 , X 3 , X 4 and X 5 , trifluoromethoxy, difluoromethoxy, trichloromethoxy, trifluoroethoxy and tetrafluoroethoxy can be given. Furthermore, for the examples of the groups represented by r 1 and r 2 , which may be the same or different groups with each other, hydrogen, halogen atoms, such as fluorine, chlorine, bromine and iodine, C 1 - C 4 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl and t-butyl, C 1 - C 4 alkoxy, such as methoxy, ethoxy, propoxy, isopropoxy. butoxy and t-butoxy, C 1 - C 4 alkylthio, such as methylthio, ethylthio, propylthio, ispropylthio, butylthio and t-butylthio, C 1 - C 4 haloalkyl, such as trifluoromethyl, trichloromethyl, tribromomethyl, trifluoroethyl, chloromethyl, fluoromethyl and pentafluoroethyl, and amino can be given. Moreover, r 1 and r 2 may in together form a carbonyl group. (Manufacturing of the Compounds) The compounds of the present invention can be manufactured according to the following reaction formula; wherein Hal represents halogen, and R 1 , R 2 , X 2 , X 3 , X 4 , X 5 , r 1 and r 2 are as described above. The reaction described above is carried out by reacting the compound represented by the general formula [II] and the compound represented by the general formula [III] in an organic solvent for from 10 min. to several dozens of hours at a temperature range of from 0°C to the boiling point of the solvent used and in the presence of a base, if appropriate. For the examples of the solvent usable in the reaction described above, aromatic hydrocarbons, such as benzene and toluene, ethers, such as THF and diethyl ether, halogenated hydrocarbons. such as chloroform and dichloro methane, amides, such as DMF, DMSO, acetonitrile and the mixture of the solvent exemplified above, can be given. As the base usable in the reaction, pyridine, triethyl amine, DBU, sodium hydroxide, sodium carbonate, potassium carbonate or the like can be exemplified. After completed the reaction, the objective compounds can be obtained by taking an ordinary post-treatment procedure and allowing the products to the purification by using silica gel column chromatography or the else. Whereas, the raw material compound of the present invention, represented by the general formula [II] can be synthesized according to the following reaction formula; wherein L is an eliminating group, such as paratoluenesulfonyloxy, methylsulfonyloxy and halogen atoms, and R 1 , X 2 , X 3 , X 4 and X 5 are as described above. The first step reaction in the reaction formula shown above is to obtain a benzamide oxime compound represented by the general formula [V], wherein a nitrile compound represented by the general formula [IV] and hydroxyl amine hydrochloride are allowed to a reaction for 10 min. to several dozens of hours in an inactive solvent and in the presence of a base at a temperature range of from 0 °C to the boiling point of the solvent used. For the examples of the solvent usable in the reaction described above, alcohols, such as methanol, ethanol and propanol, ethers, such as THF and diethyl ether, amides, such as DMF, DMSO, water and the mixture of the solvent exemplified hereinabove, can be given. Further, for the examples of the base usable in the reaction described above, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, sodium hydroxide, potassium hydroxide triethyl amine, pyridine and the like can be given. The second step reaction in the reaction formula shown above is to obtain the raw material compound represented by the general formula [II]. wherein the compound represented by the general formula [V] and a compound represented by a general formula, R 1 -L, are allowed to a reaction for 10 min. to several dozens of hours in a solvent and in the presence of a base at a temperature range of from -15 °C to the boiling point of the solvent used. For the examples of the base usable in the second step reaction, metal alkoxide, such as sodium methoxide and sodium ethoxide. inorganic bases, such as sodium hydride, sodium hydroxide, potassium hydroxide and potassium carbonate. and organic bases, such as triethyl amine and pyridine, can be given. Furthermore, if appropriate, catalysts may be used in the second step reaction, though it depends on the type of the solvent and the base to be used. For the examples of the catalysts usable in the reaction, crown ethers, such as 18-crown-6 and dicyclohexyl-18-crown-6, tetrabutyl ammonium bromide and other chlorides, quaternary ammonium salts, such as methyltrioctyl ammonium chloride and benzyltriethyl ammonium chloride, and phosphonium salts, such as tetraphenyl phosphonium bromide and hexadecyltributyl phosphonium iodide, can be given. The chemical structures of the compounds of the present invention were determined by using NMR, IR, MS and the other analytical apparatuses. Best Mode for Carrying Out the Invention : Now, the present invention is further described in detail with referring to the examples described hereinbelow. Example 1 Preparation of N'-cyclopropylmethyloxy-N-(4-methoxyphenyl)acetyl-2-fluoro-6-trifluoromethylbenzamidine(Compound No. 56) In 200ml of benzene was dissolved 20.0g of N'-cyclopropylmethyloxy-2-fluoro-6-trifluoromethylbenzamidine, and to the solution was added 16. 0g of 4-methoxyphenylacetylchloride. The solution was heated under refluxing for 10 hours. After cooling, ethyl acetate was added to the solution, followed by washing with water and drying over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 23.6g of the objective compound.m.p. 75-76°C Example 2 Preparation N'-cyclopropylmethyloxy-N-(4-methoxyphenyl)acetyl-2-trifluoromethyl benzamidine (Compound No. 12) In 80ml of benzene was dissolved 10.4g of N'-cyclopropylmethyloxy-2-fluoro-6-trifluoromethylbenzamidine. and to the solution was added 8.9g of 4-methoxyphenylacetylchloride. The solution was heated under refluxing for 3 hours. After cooling, ethyl acetate was added to the solution, followed by washing with water and drying over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure and the residue obtained in crystal was washed with a mixed solvent hexane and ether to thereby obtain 13.7g of crude crystal. The crystal was then re-crystallized in hexane. thereby affording 11.5g of the objective compound.m.p. 88-90 °C Now, the examples for preparing the raw material compounds described above to be used for the preparing of the compounds of the present invention are described hereinbelow. Reference Example 1 Preparation of 2-fluoro-6-trifluoromethylbenzamidoxime In 540ml of methanol was dissolved 58.8g of hydroxylamine hydrochloride and to the solution was added 160ml of aqueous solution of sodium carbonate containing 49.4g thereof. 40g of 2-fluoro-6-trifluoromethylbenzonitrile was added thereto at room temperature with stirring, and then further stirred 3 hours at 60°C. After removing the solvent methanol by distillation from the solution, the solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and it was concentrated under reduced pressure, thereby obtaining crude crystals. The crystals were then added with 200ml of 3N aqueous solution of hydrochloric acid and thoroughly stirred, then the insoluble substance resulted in the solution was removed by filtration. The filtrate was then neutralized with 10% aqueous solution of sodium hydroxide under cooling and then extracted again with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solution was concentrated under reduced pressure to obtain 26.6g of the objective compound. m.p. 155-157°C The examples of benzamide oxime derivatives represented by the general formula [V], which can be manufactured according to the methods as described above, are given in Table 1 hereinbelow. Reference Example 2 Preparation of N'-cyclopropylmethyloxy-2-fluoro-6-trifluoromethylbenzami dine In 100ml of DMF was dissolved 26.6g of 2-fluoro-6-trifluoromethyl-benzamidoxime and 17.8g of cyclopropylmethylbromide, and to the solution was added 4.8g of sodium hydride (60% in oil) at 10 °C over 30 min. The solution was then stirred for 3 hours, and the solution reacted was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 24.8g of the objective compound. m.p. 63-64°C Reference Examples 3 Preparation of N'-cyclopropylmethyloxy-3,6-bistrifluoromethyl-2-chloro-benzamidine Preparation of N'-cyclopropylmethyloxy-3,6-bistrifluoromethyl-2-chloro benzamidine In 10ml of chloroform was dissolved 0.60g of 3,6-bistriftuoromethyl-2-chlorobenzamidoxime and 0.50g of cyclopropylmethylbromide, and to the solution was added 0.1g of tetrabutylammonium bromide at room temperature with stirring, and then 1.2ml of 10% aqueous solution of sodiumhydroxide, then stirred for 3 hours at 30-40°C. The solution was washed with water, washed with saturated saline solution and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.40g of the objective compound.m.p. 75-80°C The examples of benzamidoxime derivatives represented by the general formula [II], which can be prepared according to the methods similar to the methods as described above, are given in Table 2 hereinbelow. Now, the representative examples for the compounds of the present invention, which can be manufactured according to the praparation methods similar to the ones described in Examples 1 and 2, are given in Tables 3 and 4. However, it should be noted that X 1 , X 2 , X 3 , X 4 , X 5 , R 1 , R 2 , r 1 and r 2 given in the Tables 3 and 4 correspond to X 1 , X 2 , X 3 , X 4 , X 5 , R 1 , R 2 , r 1 and r 2 given for the compounds represented by the general formula [I], respectively. (r 1 , r 2 =H) No. X 1 X 2 X 3 X 4 X 5 R 1 R 2 Physical const. mp (°C) refractive index 1 CF 3 H H H H Et Ph-4-OMe 72-73 2 CF 3 H H H H Me Ph-4-OMe 3 CF 3 H H H H CH 2 cPr 2-thienyl 93-95 4 CF 3 H H H H CH 2 cPr 3-thienyl 92-93 5 CF 3 H H H H CH 2 cPr Ph-2,4-F 2 100-101 6 CF 3 H H H H CH 2 cPr Ph-2-F 84-85 7 CF 3 H H H H CH 2 cPr Ph-2-F,4-OMe 84-85 8 CF 3 H H H H CH 2 cPr Ph-3-Me 81-82 9 CF 3 H H H H CH 2 cPr Ph-3-Me-4-OMe 77-79 10 CF 3 H H H H CH 2 cPr Ph-4-F 113-114 11 CF 3 H H H H CH 2 cPr Ph-4-Me 80-81 12 CF 3 H H H H CH 2 cPr Ph-4-OMe 88-90 13 CF 3 H H H H CH 2 cPr Ph 100-102 14 CF 3 H H H H nBu Ph-4-OMe 15 CF 3 H H H H tBu Ph-4-OMe 16 CF 3 H H H F CH 2 CH=CH 2 Ph-4-OMe n 27.0 / D 1.5290 17 CF 3 H H H F CH 2 CH=CH 2 Ph n 26.5 / D 1.5132 18 CF 3 H H H F CH(CH 3 )CH=CH 2 Ph-4-OMe 76-78 19 CF 3 H H H F CH 2 CH=CHCl Ph-4-OMe n 25.4 / D 1.5333 20 CF 3 H H H F CH 2 CH=CCl 2 Ph-4-OMe n 25.7 / D 1.5362 21 CF 3 H H H F CH 2 CH=CH-CH 3 Ph-4-OMe n 23.2 / D 1. 5148 22 CF 3 H H H F Et Ph-4-OMe 70-73 23 CF 3 H H H F Et Ph 59-61 24 CF 3 H H H F CH 2 CH 2 Cl Ph-4-OMe n 24.0 / D 1.5330 25 CF 3 H H H F CH 2 CHF 2 Ph-4-OMe 78-80 26 CF 3 H H H F Me Ph-4-OMe 27 CF 3 H H H F CH 2 C(Cl)=CH 2 Ph-4-OMe n 25.5 / D 1.5242 28 CF 3 H H H F CH 2 C(CH 3 )=CH 2 Ph-4-OMe n 25.0 / D 1.5162 29 CF 3 H H H F CH 2 CN Ph-4-OMe n 23.5 / D 1.5113 30 CF 3 H H H F CH 2 CN Ph n 23.5 / D 1. 5226 31 CF 3 H H H F CH 2 OCH 3 Ph-4-OMe n 24.0 / D 1.5288 32 CF 3 H H H F CH 2 OCH 3 Ph n 24.5 / D 1.5279 33 CF 3 H H H F CH 2 cPr 3-methyl--pyrazol-1-yl n 21.8 / D 1.5133 34 CF 3 H H H F CH 2 cPr 4-methyl--pyrazol-1-yl n 23.6 / D 1.5121 35 CF 3 H H H F CH 2 cPr pyrazol-1-yl n 22.9 / D 1.5126 36 CF 3 H H H F CH 2 cPr 3-methyl-- 2-thienyl n 23.2 / D 1.5310 37 CF 3 H H H F CH 2 cPr 4-methyl--2-thienyl n 23.2 / D 1.5313 38 CF 3 H H H F CH 2 cPr 5-methyl--2-thienyl n 23.9 / D 1.5353 39 CF 3 H H H F CH 2 cPr 2-thienyl n 22.2 / D 1.5346 40 CF 3 H H H F CH 2 cPr 4-methyl--3-thienyl n 26.5 / D 1.5302 41 CF 3 H H H F CH 2 cPr 5-methyl-- 3-thienyl 57-58 42 CF 3 H H H F CH 2 cPr 3-thienyl 70-72 43 CF 3 H H H F CH 2 cPr Ph-2,4- F 2 n 26.0 / D 1.5083 44 CF 3 H H H F CH 2 cPr Ph-2-F n 26.0 / D 1. 5191 45 CF 3 H H H F CH 2 cPr Ph-2-F-3-Me n 23.4 / D 1.5197 46 CF 3 H H H F CH 2 cPr Ph-2-F-4-OMe n 27.5 / D 1.5193 47 CF 3 H H H F CH 2 cPr Ph-2-F-4-OMe--5-Me n 27.0 / D 1.6190 48 CF 3 H H H F CH 2 cPr Ph-2-F-5-Me n 26.7 / D 1.5143 49 CF 3 H H H F CH 2 cPr Ph-3,5-Me 2 88-89 50 CF 3 H H H F CH 2 cPr Ph-3-Et 63-64 51 CF 3 H H H F CH 2 cPr Ph-3-Me 52-53 52 CF 3 H H H F CH 2 cPr Ph-3-Me-4-F 73-74 53 CF 3 H H H F CH 2 cPr Ph-3-Me-4-OMe n 26.0 / D 1. 5307 54 CF 3 H H H F CH 2 cPr Ph-4-F 58-59 55 CF 3 H H H F CH 2 cPr Ph-4-Me n 26.0 / D 1.5248 56 CF 3 H H H F CH 2 cPr Ph-4-OMe 75-76 57 CF 3 H H H F CH 2 cPr Ph 72-74 58 CF 3 H H H F CH 2 C≡CH 2-thienyl 54-56 59 CF 3 H H H F CH 2 C≡CH 3-thienyl 56-58 60 CF 3 H H H F CH 2 C≡CH Ph-2-F 57-58 61 CF 3 H H H F CH 2 C≡CH Ph-2-F-4-OMe n 22.5 / D 1.5257 62 CF 3 H H H F CH 2 C≡CH Ph-2-F-5-Me n 26.0 / D 1.5192 63 CF 3 H H H F CH 2 C≡CH Ph-3,5-Me 2 98-100 64 CF 3 H H H F CH 2 C≡CH Ph-4-Me 95-96 65 CF 3 H H H F CH 2 C≡CH Ph-4-OMe n 27.5 / D 1.5370 66 CF 3 H H H F CH 2 C≡CH Ph 58-60 67 CF 3 H H H F CH 2 C≡CI Ph-4-OMe n 22.5 / D 1. 5557 68 CF 3 H H H F iPr Ph-4-OMe 85-86 69 CF 3 H H H F iPr Ph 84-85 70 CF 3 H H H F nBu Ph 71 CF 3 H H H F nPr Ph-2-F-4-OMe n 18.5 / D 1.5121 72 CF 3 H H H F nPr Ph-2-F-5-Me n 18.0 / D 1. 5129 73 CF 3 H H H F nPr Ph-4-Me 59-60 74 CF 3 H H H F nPr Ph-4-OMe 54-55 75 CF 3 H H H F nPr Ph n 26.5 / D 1. 5106 76 CF 3 H H H F tBu Ph 77 CF 3 H H H Cl CH 2 CH=CH 2 Ph-4-OMe 78 CF 3 H H H Cl CH(CH 3 )CH=CH 2 Ph-4-OMe 79 CF 3 H H H Cl CH 2 CH=CHCl Ph-4-OMe 80 CF 3 H H H Cl CH 2 CH=CCl 2 Ph-4-OMe 81 CF 3 H H H Cl CH 2 CH=CHCH 3 Ph-4-OMe 82 CF 3 H H H Cl Et Ph-4-OMe 68-70 83 CF 3 H H H Cl CH 2 CH 2 Cl Ph-4-OMe 84 CF 3 H H H Cl CH 2 CHF 2 Ph-4-OMe 85 CF 3 H H H Cl Me Ph-4-OMe 86 CF 3 H H H Cl CH 2 C(Cl)=CH 2 Ph-4-OMe 87 CF 3 H H H Cl CH 2 C(CH 3 )=CH 2 Ph-4-OMe 88 CF 3 H H H Cl CH 2 CN Ph-4-OMe 89 CF 3 H H H Cl CH 2 OMe Pb-4-OMe 90 CF 3 H H H Cl CH 2 cPr 3-methyl-- pyrazol-1-yl 91 CF 3 H H H Cl CH 2 cPr 4-methyl--pyrazol-1-yl 92 CF 3 H H H Cl CH 2 cPr pyrazol-1-yl 93 CF 3 H H H Cl CH 2 cPr 3-methyl--2-thienyl 94 CF 3 H H H Cl CH 2 cPr 4-methyl--2-thienyl 95 CF 3 H H H Cl CH 2 cPr 5-methyl--2-thienyl 96 CF 3 H H H Cl CH 2 cPr 2-thienyl 47-49 97 CF 3 H H H Cl CH 2 cPr 4-methyl--3-thienyl 98 CF 3 H H H Cl CH 2 cPr 5-methyl--3-thienyl 99 CF 3 H H H Cl CH 2 cPr 3-thienyl 74-76 100 CF 3 H H H Cl CH 2 cPr Ph-2,4-F 2 101 CF 3 H H H Cl CH 2 cPr Ph-2-F 102 CF 3 H H H Cl CH 2 cPr Ph-2-F-3-Me 103 CF 3 H H H Cl CH 2 cPr Ph-2-F-4-OMe 104 CF 3 H H H Cl CH 2 cPr Ph-2-F-4-OMe--5-Me 105 CF 3 H H H Cl CH 2 cPr Ph-2-F-5-Me n 23.8 / D 1.5323 106 CF 3 H H H Cl CH 2 cPr Ph-3,5-Me 2 107 CF 3 H H H Cl CH 2 cPr Ph-3-Me 108 CF 3 H H H Cl CH 2 cPr Ph-3-Me-4-F 109 CF 3 H H H Cl CH 2 cPr Ph-3-Me-4-OMe 110 CF 3 H H H Cl CH 2 cPr Ph-4-F 111 CF 3 H H H Cl CH 2 cPr Ph-4-Me 112 CF 3 H H H Cl CH 2 cPr Ph-4-OMe 65-67 113 CF 3 H H H Cl CH 2 cPr Ph 63-65 114 CF 3 H H H Cl CH 2 C≡CH Ph-4-OMe 76-78 115 CF 3 H H H Cl CH 2 C≡CH Ph 96-97 116 CF 3 H H H Cl CH 2 C≡Cl Ph-4-OMe 117 CF 3 H H H Cl iPr Ph-4-OMe 118 CF 3 H H H Cl nBu Ph-4-OMe 119 CF 3 H H H Cl nPr Ph-4-OMe 120 CF 3 H H H Cl tBu Ph-4-OMe 121 CF 3 H H H CF 3 CH 2 CH=CH 2 Ph-4-OMe 122 CF 3 H H H CF 3 CH(CH 3 )CH=CH 2 Ph-4-OMe 123 CF 3 H H H CF 3 CH 2 CH=CHCl Ph-4-OMe 124 CF 3 H H H CF 3 CH 2 CH=CCl 2 Ph-4-OMe 125 CF 3 H H H CF 3 CH 2 CH=CHCH 3 Ph-4-OMe 126 CF 3 H H H CF 3 Et Ph-4-OMe 127 CF 3 H H H CF 3 CH 2 CH 2 Cl Ph-4-OMe 128 CF 3 H H H CF 3 CH 2 CHF 2 Ph-4-OMe 129 CF 3 H H H CF 3 Me Ph-4-OMe 130 CF 3 H H H CF 3 CH 2 C(Cl)=CH 2 Ph-4-OMe 131 CF 3 H H H CF 3 CH 2 C(CH 3 )=CH 2 Ph-4-OMe 132 CF 3 H H H CF 3 CH 2 CN Ph-4-OMe 133 CF 3 H H H CF 3 CH 2 OMe Ph-4-OMe 134 CF 3 H H H CF 3 CH 2 cPr 3-methyl--pyrazol-1-yl 135 CF 3 H H H CF 3 CH 2 cPr 4-methyl- 136 CF 3 H H H CF 3 CH 2 cPr -pyrazol-1-yl Ph 137 CF 3 H H H CF 3 CH 2 cPr pyrazol-1-yl 3-methyl--2-thienyl 138 CF 3 H H H CF 3 CH 2 cPr 4-methyl-- 2-thienyl 139 CF 3 H H H CF 3 CH 2 cPr 5-methyl--2-thienyl 140 CF 3 H H H CF 3 CH 2 cPr 2-thienyl n 22.4 / D 1.5082 141 CF 3 H H H CF 3 CH 2 cPr 4-methyl--3-thienyl 142 CF 3 H H H CF 3 CH 2 cPr 5-methyl--3-thienyl 143 CF 3 H H H CF 3 CH 2 cPr 3-thienyl 144 CF 3 H H H CF 3 CH 2 cPr Ph-2,4-F 2 145 CF 3 H H H CF 3 CH 2 cPr Ph-2-F 146 CF 3 H H H CF 3 CH 2 cPr Ph-2-F-3-Me 147 CF 3 H H H CF 3 CH 2 cPr Ph-2-F-4-OMe 148 CF 3 H H H CF 3 CH 2 cPr Ph-2-P-4-OMe--5-Me 149 CF 3 H H H CF 3 CH 2 cPr Ph-2-F-5-Me 74 -75 150 CF 3 H H H CF 3 CH 2 cPr Ph-3,5-Me 2 151 CF 3 H H H CF 3 CH 2 cPr Ph-3-Me 152 CF 3 H H H CF 3 CH 2 cPr Ph-3-Me-4-F 153 CF 3 H H H CF 3 CH 2 cPr Ph-3-Me-4-OMe 154 CF 3 H H H CF 3 CH 2 cPr Ph-4-F 155 CF 3 H H H CF 3 CH 2 cPr Ph-4-Me 156 CF 3 H H H CF 3 CH 2 cPr Ph-4-OMe n 22.6 / D 1.5031 157 CF 3 H H H CF 3 CH 2 cPr Ph 68-69 158 CF 3 H H H CF 3 CH 2 C≡CH Ph-4-OMe 159 CF 3 H H H CF 3 CH 2 C≡Cl Ph-4-OMe 160 CF 3 H H H CF 3 iPr Ph-4-OMe 161 CF 3 H H H CF 3 nBu Ph-4-OMe 162 CF 3 H H H CF 3 nPr Ph-4-OMe 163 CF 3 H H H CF 3 tBu Ph-4-OMe 164 CF 3 H H H OMe CH 2 CH=CH 2 Ph-4-OMe 165 CF 3 H H H OMe CH(CH 3 )CH=CH 2 Ph-4-OMe 166 CF 3 H H H OMe CH 2 CH=CHCl Ph-4-OMe 167 CF 3 H H H OMe CH 2 CH=CCl 2 Ph-4-OMe 168 CF 3 H H H OMe CH 2 CH=CHCH 3 Ph-4-OMe 169 CF 3 H H H OMe Et Ph-4-OMe 95-96 170 CF 3 H H H OMe CH 2 CH 2 Cl Ph-4-OMe 171 CF 3 H H H OMe CH 2 CHF 2 Ph-4-OMe 172 CF 3 H H H OMe Me Ph-4-OMe 173 CF 3 H H H OMe CH 2 C(Cl)=CH 2 Ph-4-OMe 174 CF 3 H H H OMe CH 2 C(CH 3 )=CH 2 Ph-4-OMe 175 CF 3 H H H OMe CH 2 CN Ph-4-OMe 176 CF 3 H H H OMe CH 2 OMe Ph-4-OMe 177 CF 3 H H H OMe CH 2 cPr 3-methyl--pyrazol-1-yl 178 CF 3 H H H OMe CH 2 cPr 4-methyl--pyrazol-1-yl 179 CF 3 H H H OMe CH 2 cPr pyrazol-1-yl 180 CF 3 H H H OMe CH 2 cPr 3-methyl-- 2-thienyl 181 CF 3 H H H OMe CH 2 cPr 4-methyl-- 2-thienyl 182 CF 3 H H H OMe CH 2 cPr 5-methyl-- 2-thienyl 183 CF 3 H H H OMe CH 2 cPr 2-thienyl 4-methyl- 184 CF 3 H H H OMe CH 2 cPr -3-thienyl 185 CF 3 H H H OMe CH 2 cPr 5-methyl-- 3-thienyl 186 CF 3 H H H OMe CH 2 cPr 3-thienyl 187 CF 3 H H H OMe CH 2 cPr Ph-2,4-F 2 188 CF 3 H H H OMe CH 2 cPr Ph-2-F 189 CF 3 H H H OMe CH 2 cPr Ph-2-F-3-Me 190 CF 3 H H H OMe CH 2 cPr Ph-2-F-4-OMe 191 CF 3 H H H OMe CH 2 cPr Ph-2-F-4-OMe-- 5-Me 192 CF 3 H H H OMe CH 2 cPr Ph-2-F-5-Me 193 CF 3 H H H OMe CH 2 cPr Ph-3,5-Me 2 194 CF 3 H H H OMe CH 2 cPr Ph-3-Me 195 CF 3 H H H OMe CH 2 cPr Ph-3-Me-4-F 196 CF 3 H H H OMe CH 2 cPr Ph-3-Me-4-OMe 197 CF 3 H H H OMe CH 2 cPr Ph-4-F 198 CF 3 H H H OMe CH 2 cPr Ph-4-Me 199 CF 3 H H H OMe CH 2 cPr Ph-4-OMe 92-93 200 CF 3 H H H OMe CH 2 cPr Ph-3-Cl-4-OMe 201 CF 3 H H H OMe CH 2 cPr Ph-3-Cl-4-OMe-- 5-Me 202 CF 3 H H H OMe CH 2 cPr Ph 203 CF 3 H H H OMe CH 2 C≡CH Ph-4-OMe 204 CF 3 H H H OMe CH 2 C≡Cl Ph-4-OMe 205 CF 3 H H H OMe iPr Ph-4-OMe 206 CF 3 H H H OMe nBu Ph-4-OMe 207 CF 3 H H H OMe nPr Ph-4-OMe 208 CF 3 H H H OMe tBu Ph-4-OMe 209 CF 3 H H H SMe Et Ph-4-OMe 89-90 210 CF 3 H H H SMe Me Ph-4-OMe 211 CF 3 H H H SMe CH 2 cPr Ph-4-OMe 73-75 212 CF 3 H H H SMe CH 2 cPr Ph 106-109 213 CF 3 H H H SMe nBu Ph-4-OMe 214 CF 3 H H H SMe tBu Ph-4-OMe 215 CF 3 H H Cl H CH 2 CH=CH 2 Ph-4-OMe 216 CF 3 H H Cl H Et Ph-4-OMe 217 CF 3 H H Cl H Me Ph-4-OMe 218 CF 3 H H Cl H CH 2 cPr 3-methyl--pyrazol-1-yl 219 CF 3 H H Cl H CH 2 cPr 4-methyl--pyrazol-1-yl 220 CF 3 H H Cl H CH 2 cPr pyrazol-1-yl 221 CF 3 H H Cl H CH 2 cPr 3-methyl--2-thienyl 222 CF 3 H H Cl H CH 2 cPr 4-methyl-- 2-thienyl 223 CF 3 H H Cl H CH 2 cPr 5-methyl--2-thienyl 224 CF 3 H H Cl H CH 2 cPr 2-thienyl 225 CF 3 H H Cl H CH 2 cPr 4-methyl--3-thienyl 226 CF 3 H H Cl H CH 2 cPr 5-methyl--3-thienyl 227 CF 3 H H Cl H CH 2 cPr 3-thienyl 228 CF 3 H H Cl H CH 2 cPr Ph-4-OMe 229 CF 3 H H Cl H CH 2 C ≡CH Ph-4-OMe 230 CF 3 H H Cl H iPr Ph-4-OMe 231 CF 3 H H Cl H nBu Ph-4-OMe 232 CF 3 H H Cl H nPr Ph-4-OMe 233 CF 3 H H Cl H tBu Ph-4-OMe 234 CF 3 H H Cl F CH 2 CH=CH 2 Ph-4-OMe 81-83 235 CF 3 H H Cl F CH(CH 3 )CH=CH 2 Ph-4-OMe 236 CF 3 H H Cl F CH 2 CH=CHCl Ph-4-OMe 237 CF 3 H H Cl F CH 2 CH=CCl 2 Ph-4-OMe 238 CF 3 H H Cl F CH 2 CH=CHCH 3 Ph-4-OMe 239 CF 3 H H Cl F Et Ph-4-OMe 99- 100 240 CF 3 H H Cl F CH 2 CH 2 Cl Ph-4-OMe n 24.0 / D 1.5301 241 CF 3 H H Cl F CH 2 CH 2 Cl Ph 90-91 242 CF 3 H H Cl F CH 2 CH 2 Cl Ph-2-F-5-Me n 24.0 / D 1.5241 243 CF 3 H H Cl F CH 2 CHF 2 Ph-4-OMe 244 CF 3 H H Cl F Me Ph-4-OMe 245 CF 3 H H Cl F CH 2 C(Cl)=CH 2 Ph-4-OMe 246 CF 3 H H Cl F CH 2 C(CH 3 )=CH 2 Ph-4-OMe 247 CF 3 H H Cl F CH 2 CN Ph-4-OMe 248 CF 3 H H Cl F CH 2 OMe Ph-4-OMe 249 CF 3 H H Cl F CH 2 cPr 3-methyl--pyrazol-1-yl 250 CF 3 H H Cl F CH 2 cPr 4-methyl--pyrazol-1-yl 251 CF 3 H H Cl F CH 2 cPr pyrazol-1-yl 252 CF 3 H H Cl F CH 2 cPr 3-methyl-- 2-thienyl 253 CF 3 H H Cl F CH 2 cPr 4-methyl-- 2-thienyl 254 CF 3 H H Cl F CH 2 cPr 5-methyl--2-thienyl 255 CF 3 H H Cl F CH 2 cPr 2-thienyl 112-113 256 CF 3 H H Cl F CH 2 cPr 4-methyl--3-thienyl 257 CF 3 H H Cl F CH 2 cPr 5-methyl--3-thienyl 258 CF 3 H H Cl F CH 2 cPr 3-thienyl 125-126 259 CF 3 H H Cl F CH 2 cPr Ph-2,4-F 2 260 CF 3 H H Cl F CH 2 cPr Ph-2-F 57-59 261 CF 3 H H Cl F CH 2 cPr Ph-2-F-3-Me 262 CF 3 H H Cl F CH 2 cPr Ph-2F-4-OMe n 26.7 / D 1.5200 263 CF 3 H H Cl F CH 2 cPr Ph-2-F-4-OMe-- 5-Me 73-74 264 CF 3 H H Cl F CH 2 cPr Ph-2-F-5-Me 60-62 265 CF 3 H H Cl F CH 2 cPr Ph-3,5-Me 2 266 CF 3 H H Cl F CH 2 cPr Ph-3-Me 92-93 267 CF 3 H H Cl F CH 2 cPr Ph-3-Me-4-F 98-99 268 CF 3 H H Cl F CH 2 cPr Ph-3-Me-4-OMe 86-87 269 CF 3 H H Cl F CH 2 cPr Ph-4-F 94-95 270 CF 3 H H Cl F CH 2 cPr Ph-4-Me 75-76 271 CF 3 H H Cl F CH 2 cPr Ph-4OMe 98 272 CF 3 H H Cl F CH 2 cPr Ph 112 273 CF 3 H H Cl F CH 2 C≡CH Ph 54-58 274 CF 3 H H Cl F CH 2 C≡CH Ph-2-F-5-Me 91-92 275 CF 3 H H Cl F CH 2 C≡CH Ph-4-OMe 102-103 276 CF 3 H H Cl F CH 2 C≡Cl Ph-4-OMe 112-114 277 CF 3 H H Cl F iPr Ph-4-OMe 124-125 278 CF 3 H H Cl F nBu Ph-4-OMe 279 CF 3 H H Cl F nPr Ph-4-OMe 90-91 280 CF 3 H H Cl F tBu Ph-4-OMe 281 CF 3 H H Cl Cl CH 2 CH=CH 2 Ph-4-OMe 80-81 282 CF 3 H H Cl Cl CH(CH 3 )CH=CH 2 Ph-4-OMe 283 CF 3 H H Cl Cl CH 2 CH=CHCl Ph-4-OMe 284 CF 3 H H Cl Cl CH 2 CH=CCl 2 Ph-4-OMe 285 CF 3 H H Cl Cl CH 2 CH=CHCH 3 Ph-4-OMe 286 CF 3 H H Cl Cl Et Ph 123-124 287 CF 3 H H Cl Cl Et Ph-2-F-5-Me 78-81 288 CF 3 H H Cl Cl Et Ph-4-OMe 90-91 289 CF 3 H H Cl Cl CH 2 CH 2 Cl Ph 104-105 290 CF 3 H H Cl Cl CH 2 CH 2 Cl Ph-2-F-5-Me n 26.5 / D 1.5309 291 CF 3 H H Cl Cl CH 2 CH 2 Cl Ph-4-OMe 292 CF 3 H H Cl Cl CH 2 CHF 2 Ph-4-OMe 293 CF 3 H H Cl Cl Me Ph-4-OMe 77-79 294 CF 3 H H Cl Cl CH 2 C(Cl)=CH 2 Ph-4-OMe 295 CF 3 H H Cl Cl CH 2 C(CH 3 )=CH 2 Ph-4-OMe 296 CF 3 H H Cl Cl CH 2 CN Ph-4-OMe 297 CF 3 H H Cl Cl CH 2 OMe Ph-4-OMe 298 CF 3 H H Cl Cl CH 2 cPr 3-methyl--pyrazol-1-yl 299 CF 3 H H Cl Cl CH 2 cPr 4-methyl--pyrazol-1-yl 300 CF 3 H H Cl Cl CH 2 cPr pyrazol-1-yl 301 CF 3 H H Cl Cl CH 2 cPr 3-methyl--2-thienyl 302 CF 3 H H Cl Cl CH 2 cPr 4-methyl--2-thienyl 303 CF 3 H H Cl Cl CH 2 cPr 5-methyl--2-thienyl 304 CF 3 H H Cl Cl CH 2 cPr 2-thienyl 139-141 305 CF 3 H H Cl Cl CH 2 cPr 4-methyl-- 3-thienyl 306 CF 3 H H Cl Cl CH 2 cPr 5-methyl-- 3-thienyl 307 CF 3 H H Cl Cl CH 2 cPr 3-thienyl 140-141 308 CF 3 H H Cl Cl CH 2 cPr Ph-2,4-F 2 309 CF 3 H H Cl Cl CH 2 cPr Ph-2-F n 23.0 / D 1.5404 310 CF 3 H H Cl Cl CH 2 cPr Ph-2-F-3-Me 311 CF 3 H H Cl Cl CH 2 cPr Ph-2-F-4-OMe n 22.5 / D 1.5371 312 CF 3 H H Cl Cl CH 2 cPr Ph-2F-4-OMe--5-Me n 23.5 / D 1.5287 313 CF 3 H H Cl Cl CH 2 cPr Ph-2-F-5-Me 56-57 314 CF 3 H H Cl Cl CH 2 cPr Ph-3,5-Me 2 315 CF 3 H H Cl Cl CH 2 cPr Ph-3-Me 111-114 316 CF 3 H H Cl Cl CH 2 cPr Ph-3-Me-4-F 113-114 317 CF 3 H H Cl Cl CH 2 cPr Ph-3-Me-4-OMe 318 CF 3 H H Cl Cl CH 2 cPr Ph-4-F 319 CF 3 H H Cl Cl CH 2 cPr Ph-4-Me 93-95 320 CF 3 H H Cl Cl CH 2 cPr Ph-4-OMe 97-98 321 CF 3 H H Cl Cl CH 2 cPr Ph 134-135 322 CF 3 H H Cl Cl CH 2 C≡CH Ph 96-98 323 CF 3 H H Cl Cl CH 2 C≡CH Ph-2-F-5-Me 77-79 324 CF 3 H H C l Cl CH 2 C≡CH Ph-4-OMe 94-96 325 CF 3 H H Cl Cl CH 2 C≡CI Ph-4-OMe 326 CF 3 H H Cl Cl iPr Ph-4-OMe 123-124 327 CF 3 H H Cl Cl nBu Ph-4-OMe 328 CF 3 H H Cl Cl nPr Ph-4-OMe 88-89 329 CF 3 H H Cl Cl tBu Ph-4-OMe 330 CF 3 H H SMe F CH 2 cPr Ph-4-OMe 114-115 331 CF 3 H H OMe F CH 2 cPr Ph-4-OMe 125-126 332 CF 3 H H OMe F CH 2 cPr Ph-4-OMe 135-136 333 CF 3 H H Me F CH 2 cPr Ph-4-OMe 71-72 334 CF 3 H F H H Et Ph-4-OMe 70-72 335 CF 3 H F H H Me Ph-4-OMe 336 CF 3 H F H H CH 2 cPr Ph-4-OMe 97-99 337 CF 3 H F H H CH 2 cPr Ph 117-119 338 CF 3 H F H H nBu Ph-4-OMe 339 CF 3 H F H H tBu Ph 340 CF 3 H Cl H H Et Ph-4-OMe 89-91 341 CF 3 H Cl H H Me Ph-4-OMe 342 CF 3 H Cl H H CH 2 cPr Ph-4-OMe 97-99 343 CF 3 H Cl H H CH 2 cPr Ph 91-92 344 CF 3 H Cl H H nBu Ph-4-OMe 345 CF 3 H Cl H H tBu Ph 346 CF 3 Cl H H F CH 2 cPr Ph-4-OMe Oil, ‡l 347 CF 3 Cl H H Cl CH 2 cPr 2-thienyl 74 348 CF 3 Cl H H Cl CH 2 cPr Ph-4-OMe 100 349 CF 3 Cl H H Cl CH 2 cPr Ph 95-96 350 CF 3 H H F F CH 2 CH=CH 2 Ph-4-OMe 351 CF 3 H H F F Et Ph 81-83 352 CF 3 H H F F Et Ph-2-F-5-Me 79-80 353 CF 3 H H F F Et Ph-4-OMe 78-79 354 CF 3 H H F F CH 2 CH 2 Cl Ph n 23.5 / D 1.5245 355 CF 3 H H F F CH 2 CH 2 Cl Ph-2-F-5-Me 356 CF 3 H H F F CH 2 CH 2 Cl Ph-4-OMe 357 CF 3 H H F F Me Ph-4-OMe 358 CF 3 H H F F CH 2 OMe Ph-4-OMe 359 CF 3 H H F P CH 2 cPr 3-methyl--pyrazol-1-yl 360 CF 3 H H F F CH 2 cPr 4-methyl--pyrazol-1-yl 361 CF 3 H H F F CH 2 cPr pyrazol-1-yl 362 CF 3 H H F F CH 2 cPr 3-methyl-- 2-thienyl 363 CF 3 H H F F CH 2 cPr 4-methyl--2-thienyl 364 CF 3 H H F F CH 2 cPr Ph-2-F 56-58 365 CF 3 H H F F CH 2 cPr Ph-2-F-3-Me 366 CF 3 H H F F CH 2 cPr Ph-2F-4-OMe 367 CF 3 H H F F CH 2 cPr Ph-2F-4-OMe--5-Me 70-73 368 CF 3 H H F F CH 2 cPr Ph-2F-5-Me 67-69 369 CF 3 H H F F CH 2 cPr Ph-3,5-Me 2 370 CF 3 H H F F CH 2 cPr Ph-3-Me 70-72 371 CF 3 H H F F CH 2 cPr Ph-3-Me-4-F 51-53 372 CF 3 H H F F CH 2 cPr Ph-3-Me-4-OMe 56-57 373 CF 3 H H F F CH 2 cPr Ph-4-F 70-72 374 CF 3 H H F F CH 2 cPr Ph-4-Me 64-66 375 CF 3 H H F F CH 2 cPr Ph-4-OMe 73-74 376 CF 3 H H F F CH 2 cPr Ph 61-62 377 CF 3 H H F F CH 2 C≡CH Ph 76-78 378 CF 3 H H F F CH 2 C≡CH Ph-2-F-5-Me 84-86 379 CF 3 H H F F CH 2 C≡CH Ph-4-OMe 100-102 380 CF 3 H H F F CH 2 C≡Cl Ph-4-OMe 381 CF 3 H H F F iPr Ph-4-OMe 65-66 382 CF 3 H H F F nBu Ph-4-OMe 383 CF 3 H H F F nPr Ph-4-OMe 67-69 384 CF 3 H H F F tBu Ph-4-OMe 385 CF 3 H H F F CH 2 cPr 5-methyl--2-thienyl 386 CF 3 H H F F CH 2 cPr 2-thienyl 69-71 387 CF 3 H H F F CH 2 cPr 4-methyl--3-thienyl 388 CF 3 H H F F CH 2 cPr 5-methyl--3-thienyl 389 CF 3 H H F F CH 2 cPr 3-thienyl 79-81 390 CF 3 H H F F CH 2 cPr Ph-2,4-F 2 391 CF 3 H H Cl F nPr Ph 113-114 392 CF 3 H H Cl F nPr Ph-2-F-5-Me 60-61 393 CF 3 H H Cl F iPr Ph 111-112 394 CF 3 H H Cl F iPr Ph-2-F-5-Me 395 CF 3 H H Cl F CH 2 CH=CH 2 Ph 107-108 396 CF 3 H H Cl F CH 2 CH=CH 2 Ph-2-F-5-Me 68-70 397 CF 3 H H Cl F CH 3 Ph 398 CF 3 H H Cl F CH 3 Ph-2-F-5-Me 399 CF 3 H H Cl F CH 2 C=CI Ph 90-91 400 CF 3 H H Cl F CH 2 C≡CI Ph-2-F-5-Me n 25.0 / D 1.5491 401 CF 3 H H Cl F CH 2 CH 3 Ph 101-102 402 CF 3 H H Cl F CH 2 CH 3 Ph-2-F-5-Me 60-62 403 CF 3 H H Cl Cl nPr Ph 128-129 404 CF 3 H H Cl Cl nPr Ph-2-F-5-Me n 24.0 / D 1.5212 405 CF 3 H H Cl Cl iPr Ph 125-127 406 CF 3 H H Cl Cl iPr Ph-2-P-5-Me n 24.7 / D 1.5245 407 CF 3 H H Cl Cl CH 2 CH=CH 2 Ph 115-116 408 CF 3 H H Cl Cl CH 2 CH=CH 2 Ph-2-F-5-Me 62-63 409 CF 3 H H Cl Cl CH 3 Ph 111-113 410 CF 3 H H Cl Cl CH 3 Ph-2-P-5-Me 80-81 411 CF 3 H H Cl Cl CH 2 C≡CI Ph 412 CF 3 H H Cl Cl CH 2 C≡CI Ph-2-F-5-Me 413 CF 3 H H F F nPr Ph 56-58 414 CF 3 H H F F nPr Ph-2-F-5-Me 38-40 415 CF 3 H H F F iPr Ph 81-82.5 416 CF 3 H H F F iPr Ph-2-F-5-Me 417 CF 3 H H F F CH 2 CH=CH 2 Ph 418 CF 3 H H F F CH 2 CH=CH 2 Ph-2-F-5-Me 419 CF 3 H H F F CH 3 Ph 420 CF 3 H H F F CH 3 Ph-2-F-5-Me 421 CF 3 H H F F CH 2 C≡Cl Ph 422 CF 3 H H F F CH 2 C≡CI Ph-2-F-5-Me 423 CF 3 H H F Cl CH 2 CH=CH 2 Ph 424 CF 3 H H F Cl CH 2 CH=CH 2 Ph-4-OMe 425 CF 3 H H F Cl CH 2 CH=CH 2 Ph-2-F-5-Me 426 CF 3 H H F Cl CH 2 CH 3 Ph 427 CF 3 H H F Cl CH 3 CH 3 Ph-4-OMe 428 CF 3 H H F Cl CH 2 CH 3 Ph-2-F-5-Me 429 CF 3 H H F Cl CH 2 CH 2 Cl Ph n 24.5 / D 1.5344 430 CF 3 H H F Cl CH 2 CH 2 Cl Ph-4-OMe n 24.5 / D 1.5294 431 CF 3 H H F Cl CH 2 CH 2 Cl Ph-2-F-5-Me 432 CF 3 H H F Cl CH 3 Ph 433 CF 3 H H F Cl CH 3 Ph-4-OMe 434 CF 3 H H F Cl CH 3 Ph-2-F-5-Me 435 CF 3 H H F Cl CH 2 OMe Ph-4-OMe 436 CF 3 H H F Cl CH 2 cPr 3-methyl--pyrazol-1-yl 437 CF 3 H H F Cl CH 2 cPr 4-methyl--pyrazol-1-yl 438 CF 3 H H F Cl CH 2 cPr pyrazol-1-yl 439 CF 3 H H F Cl CH 2 cPr 3-methyl--2-thienyl 440 CF 3 H H F Cl CH 2 cPr 4-methyl--2-thienyl 441 CF 3 H H F Cl CH 2 cPr 5-methyl--2-thienyl 442 CF 3 H H F Cl CH 2 cPr 2-thienyl 104-106 443 CF 3 H H F Cl CH 2 cPr 4-methyl--3-thienyl 444 CF 3 H H F Cl CH 2 cPr 5-methyl--3-thienyl 445 CF 3 H H F Cl CH 2 cPr 3-thienyl 113-115 446 CF 3 H H F Cl CH 2 cPr Ph-2,4-F 2 447 CF 3 H H F Cl CH 2 cPr Ph-2-F n 23.8 / D 1.5262 448 CF 3 H H F Cl CH 2 cPr Ph-2-F-3-Me 449 CF 3 H H F Cl CH 2 cPr Ph-2-F-4-OMe 450 CF 3 H H F Cl CH 2 cPr Ph-2-F-4-OMe-- 5-Me 451 CF 3 H H F Cl CH 2 cPr Ph-2-F-5-Me 62-63 452 CF 3 H H F Cl CH 2 cPr Ph-3,5-Me 2 453 CF 3 H H F Cl CH 2 cPr Ph-3-Me 96-98 454 CF 3 H H F Cl CH 2 cPr Ph-3-Me-4-F 82-83 455 CF 3 H H F Cl CH 2 cPr Ph-3-Me-4-OMe 72-73 456 CF 3 H H F Cl CH 2 cPr Ph-4-F 76-77 457 CF 3 H H F Cl CH 2 cPr Ph-4-Me 75-76 458 CF 3 H H F Cl CH 2 cPr Ph-4-OMe 68-69 459 CF 3 H H F Cl CH 2 cPr Ph 102-104 460 CF 3 H H F Cl CH 2 C ≡CH Ph 461 CF 3 H H F Cl CH 2 C ≡CH Ph-4-OMe 462 CF 3 H H F Cl CH 2 C ≡CH Ph-2-F-5-Me 463 CF 3 H H F Cl CH 2 C ≡Cl Ph-4-OMe 464 CF 3 H H F Cl iPr Ph 465 CF 3 H H F Cl iPr Ph-4-OMe 466 CF 3 H H F Cl iPr Ph-2-F-5-Me 467 CF 3 H H F Cl nPr Ph 468 CF 3 H H F Cl nPr Ph-4-OMe 469 CF 3 H H F Cl nPr Ph-2-F-5-Me 470 CF 3 H H F Cl nBu Ph-4-OMe 471 CF 3 H H F Cl tBu Ph-4-OMe 472 CF 3 H H CF 3 Cl CH 2 CH=CH 2 Ph 473 CF 3 H H CF 3 Cl CH 2 CH=CH 2 Ph-4-OMe 474 CF 3 H H CF 3 Cl CH 2 CH=CH 2 Ph-2-F-5-Me 475 CF 3 H H CF 3 Cl CH 2 CH 3 Ph 476 CF 3 H H CF 3 Cl CH 2 CH 3 Ph-4-OMe 477 CF 3 H H CF 3 Cl CH 2 CH 3 Ph-2-F-5-Me 478 CF 3 H H CF 3 Cl CH 2 CH 2 Cl Ph 479 CF 3 H H CF 3 Cl CH 2 CH 2 Cl Ph-4-OMe 480 CF 3 H H CF 3 Cl CH 2 CH 2 Cl Ph-2-F-5-Me 481 CF 3 H H CF 3 Cl CH 3 Ph 482 CF 3 H H CF 3 Cl CH 3 Ph-4-OMe 483 CF 3 H H CF 3 Cl CH 3 Ph-2-F-5-Me 484 CF 3 H H CF 3 Cl CH 2 OMe Ph-4-OMe 485 CF 3 H H CF 3 Cl CH 2 cPr 3-methyl--pyrazol-1-yl 486 CF 3 H H CF 3 Cl CH 2 cPr 4-methyl--pyrazol-1-yl 487 CF 3 H H CF 3 Cl CH 2 cPr pyrazol-1-yl 488 CF 3 H H CF 3 Cl CH 2 cPr 3-methyl-- 2-thienyl 489 CF 3 H H CF 3 Cl CH 2 cPr 4-methyl-- 2-thienyl 490 CF 3 H H CF 3 Cl CH 2 cPr 5-methyl-- 2-thienyl 491 CF 3 H H CF 3 Cl CH 2 cPr 2-thienyl 492 CF 3 H H CF 3 Cl CH 2 cPr 4-methyl--3-thienyl 493 CF 3 H H CF 3 Cl CH 2 cPr 5-methyl-- 3-thienyl 494 CF 3 H H CF 3 Cl CH 2 cPr 3-thienyl 495 CF 3 H H CF 3 Cl CH 2 cPr Ph-2,4-F 2 496 CF 3 H H CF 3 Cl CH 2 cPr Ph-2-F 497 CF 3 H H CF 3 Cl CH 2 cPr Ph-2-F-3-Me 498 CF 3 H H CF 3 Cl CH 2 cPr Ph-2-F-4-OMe 499 CF 3 H H CF 3 Cl CH 2 cPr Ph-2-F-4-OMe--5-Me 500 CF 3 H H CF 3 Cl CH 2 cPr Ph-2-F-5-Me 501 CF 3 H H CF 3 Cl CH 2 cPr Ph-3,5-Me 2 502 CF 3 H H CF 3 Cl CH 2 cPr Ph-3-Me 503 CF 3 H H CF 3 Cl CH 2 cPr Ph-3-Me-4-F 504 CF 3 H H CF 3 Cl CH 2 cPr Ph-3-Me-4-OMe 505 CF 3 H H CF 3 Cl CH 2 cPr Ph-4-F 506 CF 3 H H CF 3 Cl CH 2 cPr Ph-4-Me 507 CF 3 H H CF 3 Cl CH 2 cPr Ph-4-OMe 508 CF 3 H H CF 3 Cl CH 2 cPr Ph 65-67 509 CF 3 H H CF 3 Cl CH 2 C≡CH Ph 510 CF 3 H H CF 3 Cl CH 2 C≡CH Ph-4-OMe 511 CF 3 H H CF 3 Cl CH 2 C≡CH Ph-2-F-5-Me 512 CF 3 H H CF 3 Cl CH 2 C≡CI Ph 513 CF 3 H H CF 3 Cl iPr Ph 514 CF 3 H H CF 3 Cl iPr Ph-4-OMe 515 CF 3 H H CF 3 Cl iPr Ph-2-F-5-Me 516 CF 3 H H CF 3 Cl nPr Ph 517 CF 3 H H CF 3 Cl nPr Ph-4-OMe 518 CF 3 H H CF 3 Cl nPr Ph-2-F-5-Me 519 CF 3 H H CF 3 Cl nBu Ph-4-OMe 520 CF 3 H H CF 3 Cl tBu Ph-4-OMe 521 CF 3 H H CF 3 F CH 2 CH=CH 2 Ph 522 CF 3 H H CF 3 F CH 2 CH=CH 2 Ph-4-OMe 523 CF 3 H H CF 3 F CH 2 CH=CH 2 Ph-2-F-5-Me 524 CF 3 H H CF 3 F CH 2 CH 3 Ph 525 CF 3 H H CF 3 F CH 2 CH 3 Ph-4-OMe 526 CF 3 H H CF 3 F CH 2 CH 3 Ph-2-F-5-Me 527 CF 3 H H CF 3 F CH 2 CH 2 Cl Ph 528 CF 3 H H CF 3 F CH 2 CH 2 Cl Ph-4-OMe 529 CF 3 H H CF 3 F CH 2 CH 2 Cl Ph-2-F-5-Me 530 CF 3 H H CF 3 F CH 3 Ph 531 CF 3 H H CF 3 F CH 3 Ph-4-OMe 532 CF 3 H H CF 3 F CH 3 Ph-2-F-5-Me 533 CF 3 H H CF 3 F CH 2 OMe Ph-4-OMe 534 CF 3 H H CF 3 F CH 2 cPr 3-methyl--2-thienyl 535 CF 3 H H CF 3 F CH 2 cPr 4-methyl-- 2-thienyl 536 CF 3 H H CF 3 F CH 2 cPr 5-methyl-- 2-thienyl 537 CF 3 H H CF 3 F CH 2 cPr 2-thienyl 538 CF 3 H H CF 3 F CH 2 cPr 4-methyl--3-thienyl 539 CF 3 H H CF 3 F CH 2 cPr 5-methyl--3-thienyl 540 CF 3 H H CF 3 F CH 2 cPr 3-thienyl 541 CF 3 H H CF 3 F CH 2 cPr 4-methyl--3-thienyl 542 CF 3 H H CF 3 F CH 2 cPr 5-methyl--3-thienyl 543 CF 3 H H CF 3 F CH 2 cPr 3-thienyl 544 CF 3 H H CF 3 F CH 2 cPr Ph-2,4-F 2 545 CF 3 H H CF 3 F CH 2 cPr Ph-2-F 546 CF 3 H H CF 3 F CH 2 cPr Ph-2-F-3-Me 547 CF 3 H H CF 3 F CH 2 cPr Ph-2-F-4-OMe 548 CF 3 H H CF 3 F CH 2 cPr Ph-2-F-4-OMe-- 5-Me 549 CF 3 H H CF 3 F CH 2 cPr Ph-2-F-5-Me 550 CF 3 H H CF 3 F CH 2 cPr Ph-3,5-Me 2 551 CF 3 H H CF 3 F CH 2 cPr Ph-3-Me 552 CF 3 H H CF 3 F CH 2 cPr Ph-3-Me-4-F 553 CF 3 H H CF 3 F CH 2 cPr Ph-3-Me-4-OMe 554 CF 3 H H CF 3 F CH 2 cPr Ph-4-F 555 CF 3 H H CF 3 F CH 2 cPr Ph-4-Me 556 CF 3 H H CF 3 F CH 2 cPr Ph-4-OMe 557 CF 3 H H CF 3 F CH 2 cPr Ph 558 CF 3 H H CF 3 F CH 2 C≡CH Ph 559 CF 3 H H CF 3 F CH 2 C≡CH Ph-4-OMe 560 CF 3 H H CF 3 F CH 2 C≡CH Ph-2-F-5-Me 561 CF 3 H H CF 3 F CH 2 C≡Cl Ph-4-OMe 562 CF 3 H H CF 3 F iPr Ph 563 CF 3 H H CF 3 F iPr Ph-4-OMe 564 CF 3 H H CF 3 F iPr Ph-2-F-5-Me 565 CF 3 H H CF 3 F nPr Ph 566 CF 3 H H CF 3 F nPr Ph-4-OMe 567 CF 3 H H CF 3 F nPr Ph-2-F-5-Me 568 CF 3 H H CF 3 F nBu Ph-4-OMe 569 CF 3 H H CF 3 F tBu Ph-4-OMe 570 CF 3 F H H Cl CH 2 cPr Ph 571 CF 3 F H H Cl CH 2 cPr Ph-4-OMe 572 CF 3 F H H Cl CH 2 cPr Ph-2-F-5-Me 573 CF 3 F H H F CH 2 cPr Ph 574 CF 3 F H H F CH 2 cPr Ph-4-OMe 575 CF 3 F H H F CH 2 cPr Ph-2-F-5-Me 576 CF 3 CF 3 H H Cl CH 2 cPr Ph 577 CF 3 CF 3 H H Cl CH 2 cPr Ph-4-OMe 578 CF 3 CF 3 H H Cl CH 2 cPr Ph-2-F-5-Me 579 CF 3 CF 3 H H F CH 2 cPr Ph 580 CF 3 CF 3 H H F CH 2 cPr Ph-4-OMe 581 CF 3 CF 3 H H F CH 2 cPr Ph-2-F-5-Me 582 CF 3 Cl H H CF 3 CH 2 cPr Ph 583 CF 3 Cl H H CF 3 CH 2 cPr Ph-4-OMe 584 CF 3 Cl H H CF 3 CH 2 cPr Ph-2-F-5-Me 585 CF 3 F H H CF 3 CH 2 cPr Ph 586 CF 3 F H H CF 3 CH 2 cPr Ph-4-OMe 587 CF 3 F H H CF 3 CH 2 cPr Ph-2-F-5-Me 588 CF 3 CF 3 H H CF 3 CH 2 cPr Ph 589 CF 3 CF 3 H H CF 3 CH 2 cPr Ph-4-OMe 590 CF 3 CF 3 H H CF 3 CH 2 cPr Ph-2-F-5-Me 591 CF 3 H H H CH 3 CH 2 cPr Ph 592 CF 3 H H H CH 3 CH 2 cPr Ph-4-OMe 593 CF 3 H H H CH 3 CH 2 cPr Ph-2-F-5-Me 594 CF 3 H H F CH 3 CH 2 cPr Ph 595 CF 3 H H F CH 3 CH 2 cPr Ph-4-OMe 596 CF 3 H H F CH 3 CH 2 cPr Ph-2-F-5-Me 597 CF 3 H H Cl CH 3 CH 2 cPr Ph 598 CF 3 H H Cl CH 3 CH 2 cPr Ph-4-OMe 599 CF 3 H H Cl CH 3 CH 2 cPr Ph-2-F-5-Me 600 CF 3 F H F F CH 2 cPr Ph 601 CF 3 F H F F CH 2 cPr Ph-4-OMe 602 CF 3 F H F F CH 2 cPr Ph-2-F-5-Me 603 CF 3 F H F Cl CH 2 cPr Ph 604 CF 3 F H F Cl CH 2 cPr Ph-4-OMe 605 CF 3 F H F Cl CH 2 cPr Ph-2-F-5-Me 606 CF 3 F H Cl F CH 2 cPr Ph 607 CF 3 F H Cl F CH 2 cPr Ph-4-OMe 608 CF 3 F H Cl F CH 2 cPr Ph-2-F-5-Me 609 CF 3 F H Cl Cl CH 2 cPr Ph 610 CF 3 F H Cl Cl CH 2 cPr Ph-4-OMe 611 CF 3 F H Cl Cl CH 2 cPr Ph-2-F-5-Me 612 CF 3 Cl H F F CH 2 cPr Ph 613 CF 3 Cl H F F CH 2 cPr Ph-4-OMe 614 CF 3 Cl H F F CH 2 cPr Ph-2-F-5-Me 615 CF 3 Cl H F Cl CH 2 cPr Ph 616 CF 3 Cl H F Cl CH 2 cPr Ph-4-OMe 617 CF 3 Cl H F Cl CH 2 cPr Ph-2-F-5-Me 618 CF 3 Cl H Cl F CH 2 cPr Ph 619 CF 3 Cl H Cl F CH 2 cPr Ph-4-OMe 620 CF 3 Cl H Cl F CH 2 cPr Ph-2-F-5-Me 621 CF 3 Cl H Cl Cl CH 2 cPr Ph 622 CF 3 Cl H Cl Cl CH 2 cPr Ph-4-OMe 623 CF 3 Cl H Cl Cl CH 2 cPr Ph-2-F-5-Me 624 CF 3 Cl H Cl CF 3 CH 2 cPr Ph 625 CF 3 Cl H F CF 3 CH 2 cPr Ph 626 CF 3 F H Cl CF 3 CH 2 cPr Ph 627 CF 3 F H F CF 3 CH 2 cPr Ph 628 CF 3 CF 3 H Cl Cl CH 2 cPr Ph 629 CF 3 CF 3 H Cl P CH 2 cPr Ph 630 CF 3 CF 3 H F Cl CH 2 cPr Ph 631 CF 3 CF 3 H F F CH 2 cPr Ph 632 CF 3 Cl H CF 3 Cl CH 2 cPr Ph 633 CF 3 F H CF 3 Cl CH 2 cPr Ph 634 CF 3 Cl H CF 3 F CH 2 cPr Ph 635 CF 3 F H CF 3 F CH 2 cPr Ph 636 CF 3 CF 3 H Cl CF 3 CH 2 cPr Ph 637 CF 3 CF 3 H F CF 3 CH 2 cPr Ph 638 CF 3 CF 3 H CF 3 CF 3 CH 2 cPr Ph 639 CF 3 F F F F CH 2 cPr Ph 640 CF 3 F F F Cl CH 2 cPr Ph 641 CF 3 F F Cl F CH 2 cPr Ph 642 CF 3 F F Cl Cl CH 2 cPr Ph 643 CF 3 Cl H Cl CF 3 CH 2 cPr Ph-4-OMe 644 CF 3 Cl H F CF 3 CH 2 cPr Ph-4-OMe 645 CF 3 F H Cl CF 3 CH 2 cPr Ph-4-OMe 646 CF 3 F H F CF 3 CH 2 cPr Ph-4-OMe 647 CF 3 CF 3 H Cl Cl CH 2 cPr Ph-4-OMe 648 CF 3 CF 3 H Cl F CH 2 cPr Ph-4-OMe 649 CF 3 CF 3 H F Cl CH 2 cPr Ph-4-OMe 650 CF 3 CF 3 H F F CH 2 cPr Ph-4-OMe 651 CF 3 Cl H CF 3 Cl CH 2 cPr Ph-4-OMe 652 CF 3 F H CF 3 Cl CH 2 cPr Ph-4-OMe 653 CF 3 Cl H CF 3 F CH 2 cPr Ph-4-OMe 654 CF 3 F H CF 3 F CH 2 cPr Ph-4-OMe 655 CF 3 CF 3 H Cl CF 3 CH 2 cPr Ph-4-OMe 656 CF 3 CF 3 H F CF 3 CH 2 cPr Ph-4-OMe 657 CF 3 CF 3 H CF 3 CF 3 CH 2 cPr Ph-4-OMe 658 CF 3 F F F F CH 2 cPr Ph-4-OMe 659 CF 3 F F F Cl CH 2 cPr Ph-4-OMe 660 CF 3 F F Cl F CH 2 cPr Ph-4-OMe 661 CF 3 F F Cl Cl CH 2 cPr Ph-4-OMe 662 CF 3 H H H F CH 2 -1-F-cPr Ph 663 CF 3 H H H F CH 2 -2-F-cPr Ph 664 CF 3 H H H F CH 2 -2-F 2 -cPr Ph 665 CF 3 H H H F CH 2 -1-F-cPr Ph-4-OMe 666 CF 3 H H H F CH 2 -2-F-cPr Ph-4-OMe 667 CF 3 H H H F CH 2 -2-F 2 -cPr Ph-4-OMe 668 CF 3 H H Cl Cl CH 2 -1-F-cPr Ph 669 CF 3 H H Cl Cl CH 2 -2-F-cPr Ph 670 CF 3 H H Cl Cl CH 2 -2-F 2 -cPr Ph 671 CF 3 H H Cl Cl CH 2 -1-F-cPr Ph-4-OMe 672 CF 3 H H Cl Cl CH 2 -2-F-cPr Ph-4-OMe 673 CF 3 H H Cl Cl CH 2 -2-F 2 -cPr Ph-4-OMe 674 CF 3 H H Cl F CH 2 -1-F-cPr Ph 675 CF 3 H H Cl F CH 2 -2-F-cPr Ph 676 CF 3 H H Cl F CH 2 -2-F 2 -cPr Ph 677 CF 3 H H Cl F CH 2 -1-F-cPr Ph-4-OMe 678 CF 3 H H Cl F CH 2 -2-F-cPr Ph-4-OMe 679 CF 3 H H Cl F CH 2 -2-F 2 -cPr Ph-4-OMe 680 CF 3 H H F Cl CH 2 -1-F-cPr Ph 681 CF 3 H H F Cl CH 2 -2-F-cPr Ph 682 CF 3 H H F Cl CH 2 -2-F 2 -cPr Ph 683 CF 3 H H F Cl CH 2 -1-F-cPr Ph-4-OMe 684 CF 3 H H F Cl CH 2 -2-F-cPr Ph-4-OMe 685 CF 3 H H F Cl CH 2 -2-F 2 -cPr Ph-4-OMe 686 CF 3 H H F F CH 2 -1-F-cPr Ph 687 CF 3 H H F F CH 2 -2-F-cPr Ph 688 CF 3 H H F F CH 2 -2-F 2 -cPr Ph 689 CF 3 H H F F CH 2 -1-F-cPr Ph-4-OMe 690 CF 3 H H F F CH 2 -2-F-cPr Ph-4-OMe 691 CF 3 H H F F CH 2 -2-F 2 -cPr Ph-4-OMe 692 CF 3 H H H Br CH 2 CH 3 Ph 693 CF 3 H H H Br CH 2 CH 3 Ph-4-OMe 694 CF 3 H H H Br CH 2 -cPr Ph n 23.5 / D 1.5343 695 CF 3 H H H Br CH 2 -cPr Ph-4-OMe n 23.5 / D 1.5330 696 CF 3 H H H Br CH 2 -cPr Ph-2-F-5-Me 697 CF 3 H H F Br CH 2 CH 3 Ph 698 CF 3 H H F Br CH 2 CH 3 Ph-4-OMe 699 CF 3 H H F Br CH 2 -cPr Ph 114-115 700 CF 3 H H F Br CH 2 -cPr Ph-4-OMe n 23.1 / D 1.5304 701 CF 3 H H F Br CH 2 -cPr Ph-4-F 81-82 702 CF 3 H H Cl Br CH 2 CH 3 Ph 703 CF 3 H H Cl Br CH 2 CH 3 Ph-4-OMe 704 CF 3 H H Cl Br CH 2 -cPr Ph 705 CF 3 H H Cl Br CH 2 -cPr Ph-4-OMe 706 CF 3 H H Cl Br CH 2 -cPr Ph-2-F-5-Me 707 CF 3 H H Br F CH 2 CH 3 Ph 708 CF 3 H H Br F CH 2 CH 3 Ph-4-OMe 709 CF 3 H H Br F CH 2 -cPr Ph 710 CF 3 H H Br F CH 2 -cPr Ph-4-OMe 711 CF 3 H H Br F CH 2 -cPr Ph-2-F-5-Me 712 CF 3 H H Br Cl CH 2 CH 3 Ph 713 CF 3 H H Br Cl CH 2 CH 3 Ph-4-OMe 714 CF 3 H H Br Cl CH 2 -cPr Ph 715 CF 3 H H Br Cl CH 2 -cPr Ph-4-OMe 716 CF 3 H H Br Cl CH 2 -cPr Ph-2-F-5-Me 717 CF 3 H H F H CH 2 CH 3 Ph 718 CF 3 H H F H CH 2 CH 3 Ph-4-OMe 719 CF 3 H H F H CH 2 -cPr Ph 91-92 720 CF 3 H H F H CH 2 -cPr Ph-4-OMe 109-110 721 CF 3 H H F H CH 2 -cPr Ph-2-F-5-Me 722 CF 3 H H Cl H CH 2 CH 3 Ph 723 CF 3 H H F H CH 2 -cPr Ph-2-F 94-95 724 CF 3 H H Cl H CH 2 -cPr Ph 99-100 725 CF 3 H H F H CH 2 -cPr Ph-4-F 110-111 726 CF 3 H H Cl H CH 2 -cPr Ph-2-F-5-Me 727 CF 3 H H H I CH 2 CH 3 Ph 728 CF 3 H H H I CH 2 CH 3 Ph-4-OMe 729 CF 3 H H H I CH 2 -cPr Ph 730 CF 3 H H H I CH 2 -cPr Ph-4-OMe 731 CF 3 H H H I CH 2 -cPr Ph-2-F-5-Me 732 CF 3 H H Cl Cl CH 2 -cHxe-3 Ph 106-107 733 CF 3 H H Cl Cl CH 2 -cHex--3,4-Br 2 Ph 124-125 734 CP 3 H H Cl Cl CH 2 -cHex Ph 106-109 735 C 2 F 5 H H F F CH 2 -cPr Ph 736 C 2 F 5 H H F F CH 2 -cPr Ph-4-OMe 737 C 2 F 5 H H F F CH 2 -cPr Ph-2-F-5-Me 738 C 2 F 5 H H F F CH 2 CH 2 Cl Ph 739 C 2 F 5 H H F F CH 2 CH 3 Ph 740 C 2 F 5 H H F F CH 2 C≡CH Ph 741 C 2 F 5 H H Cl Cl CH 2 -cPr Ph 742 C 2 F 5 H H Cl Cl CH 2 -cPr Ph-4-OMe 743 C 2 F 5 H H Cl Cl CH 2 -cPr Ph-2-F-5-Me 744 C 2 F 5 H H Cl Cl CH 2 CH 2 Cl Ph 745 C 2 F 5 H H Cl Cl CH 2 CH 3 Ph 746 C 2 F 5 H H Cl Cl CH 2 C≡CH Ph 747 C 2 F 5 H H F Cl CH 2 -cPr Ph 748 C 2 F 5 H H F Cl CH 2 -cPr Ph-4-OMe 749 C 2 F 5 H H F Cl CH 2 -cPr Ph-2-F-5-Me 750 C 2 F 5 H H F Cl CH 2 CH 2 Cl Ph 751 C 2 F 5 H H F Cl CH 2 CH 3 Ph 752 C 2 F 5 H H F Cl CH 2 C≡CH Ph 753 C 2 F 5 H H Cl F CH 2 -cPr Ph 754 C 2 F 5 H H Cl F CH 2 -cPr Ph-4-OMe 755 C 2 F 5 H H Cl F CH 2 -cPr Ph-2-P-5-Me 756 C 2 F 5 H H Cl F CH 2 CH 2 Cl Ph 757 C 2 F 5 H H Cl F CH 2 CH 3 Ph 758 C 2 F 5 H H Cl F CH 2 C≡CH Ph 759 CCl 3 H H F F CH 2 -cPr Ph 760 CCl 3 H H F F CH 2 -cPr Ph-4-OMe 761 CCl 3 H H F F CH 2 -cPr Ph-2-F-5-Me 762 CCl 3 H H F F CH 2 CH 2 Cl Ph 763 CCl 3 H H F F CH 2 CH 3 Ph 764 CCl 3 H H F F CH 2 C≡CH Ph 765 CCl 3 H H Cl Cl CH 2 -cPr Ph 766 CCl 3 H H Cl Cl CH 2 -cPr Ph-4-OMe 767 CCl 3 H H Cl Cl CH 2 -cPr Ph-2-F-5-Me 768 CCl 3 H H Cl Cl CH 2 CH 2 Cl Ph 769 CCl 3 H H Cl Cl CH 2 CH 3 Ph 770 CCl 3 H H Cl Cl CH 2 C≡CH Ph 771 CCl 3 H H F Cl CH 2 -cPr Ph 772 CCl 3 H H F Cl CH 2 -cPr Ph-4-OMe 773 CCl 3 H H F Cl CH 2 -cPr Ph-2-F-5-Me 774 CCl 3 H H F Cl CH 2 CH 2 Cl Ph 775 CCl 3 H H F Cl CH 2 CH 3 Ph 776 CCl 3 H H F Cl CH 2 C≡CH Ph 777 CCl 3 H H Cl F CH 2 -cPr Ph 778 CCl 3 H H Cl F CH 2 -cPr Ph-4-OMe 779 CCl 3 H H Cl F CH 2 -cPr Ph-2-F-5-Me 780 CCl 3 H H Cl F CH 2 CH 2 Cl Ph 781 CCl 3 H H Cl F CH 2 CH 3 Ph 782 CCl 3 H H Cl F CH 2 C≡CH Ph 783 CHF 2 H H F F CH 2 cPr Ph 784 CHF 2 H H F F CH 2 cPr Ph-4-OMe 785 CHF 2 H H F F CH 2 cPr Ph-2-F-5-Me 786 CHF 2 H H F F CH 2 CH 2 Cl Ph 787 CHF 2 H H F F CH 2 CH 3 Ph 788 CHF 2 H H F F CH 2 C≡CH Ph 789 CHF 2 H H Cl Cl CH 2 cPr Ph 790 CHF 2 H H Cl Cl CH 2 cPr Ph-4-OMe 791 CHF 2 H H Cl Cl CH 2 cPr Ph-2-F-5-Me 792 CHF 2 H H Cl Cl CH 2 CH 2 Cl Ph 793 CHF 2 H H Cl Cl CH 2 CH 3 Ph 794 CHF 2 H H Cl Cl CH 2 C≡CH Ph 795 CHF 2 H H F Cl CH 2 cPr Ph 796 CHF 2 H H F Cl CH 2 cPr Ph-4-OMe 797 CHF 2 H H F Cl CH 2 cPr Ph-2-F-5-Me 798 CHF 2 H H F Cl CH 2 CH 2 Cl Ph 799 CHF 2 H H F Cl CH 2 CH 3 Ph 800 CHF 2 H H F Cl CH 2 C≡CH Ph 801 CHF 2 H H Cl F CH 2 cPr Ph 802 CHF 2 H H Cl F CH 2 cPr Ph-4-OMe 803 CHF 2 H H Cl F CH 2 cPr Ph-2-F-5-Me 804 CHF 2 H H Cl F CH 2 CH 2 Cl Ph 805 CHF 2 H H Cl F CH 2 CH 3 Ph 806 CHF 2 H H Cl F CH 2 C≡CH Ph 807 CF 3 H H H F CH 2 CF 3 Ph 808 CF 3 H H H F CH 2 Cl Ph 809 CF 3 H H H F CH 2 CH 2 Br Ph 810 CF 3 H H H F CH 2 OEt Ph 811 CF 3 H H H F CH 2 CH 2 OMe Ph 812 CF 3 H H H F CH 2 cPent Ph 813 CF 3 H H H F CH 2 cHex Ph 814 CF 3 H H H F CH 2 cPr-2,2--Cl 2 Ph 815 CF 3 H H H F CH 2 cPr-2,2-- Brz Ph 816 CF 3 H H H F CH 2 SMe Ph n 23.2 / D 1.5469 817 CF 3 H H H F CH 2 SOMe Ph n 26.0 / D 1. 5462 818 CF 3 H H H F CH 2 SO 2 Me Ph 116-117 819 CF 3 H H H F CH 2 CO 2 Me Ph n 22.8 / D 1.5194 820 CF 3 H H H F CH 2 CO 2 Et Ph n 22.8 / D 1.5167 821 CF 3 H H H F CH 2 CH 2 CO 2 Me Ph 822 CF 3 H H H F CH 2 NMe 2 Ph 823 CF 3 H H H F CH 2 NHMe Ph 824 CF 3 H H H F CH 2 CH 2 NMe 2 Ph 825 CF 3 H H H F CH 2 CONH 2 Ph n 24.5 / D 1.5380 826 CF 3 H H H F CH 2 CONHMe Ph 827 CF 3 H H H F CH 2 CONMe 2 Ph n 23.3 / D 1.5302 828 CF 3 H H H F CH 2 CH=CHCF 3 Ph 829 CF 3 H H H F CH 2 CH=CF 2 Ph 830 CF 3 H H H F CH 2 C(Br)=CH 2 Ph 831 CF 3 H H H F CH 2 C ≡CCH 3 Ph 832 CF 3 H H H F CH 2 CH 2 C≡CH Ph 833 CF 3 H H H F CH 2 C ≡CCF 3 Ph 834 CF 3 H H F F CH 2 CF 3 Ph 835 CF 3 H H F F CH 2 Cl Ph 836 CF 3 H H F F CH 2 CH 2 Br Ph 837 CF 3 H H F F CH 2 OEt Ph 838 CF 3 H H F F CH 2 CH 2 OMe Ph 839 CF 3 H H F F CH 2 cPent Ph 840 CF 3 H H F F CH 2 cHex Ph 841 CF 3 H H F F CH 2 -2,2-Cl 2 -- cPr Ph 842 CF 3 H H F F CH 2 -2,2-Br 2 -- cPr Ph 843 CF 3 H H F F CH 2 SMe Ph 844 CF 3 H H F F CH 2 SOMe Ph 845 CF 3 H H F F CH 2 SO 2 Me Ph 846 CF 3 H H F F CH 2 CO 2 Me Ph 847 CF 3 H H F F CH 2 CO 2 Et Ph n 24.0 / D 1.5066 848 CF 3 H H F F CH 2 CH 2 CO 2 Me Ph 849 CF 3 H H F F CH 2 NMe 2 Ph 850 CF 3 H H F F CH 2 NHMe Ph 851 CF 3 H H F F CH 2 CH 2 NMe 2 Ph 852 CF 3 H H F F CH 2 CONH 2 Ph 853 CF 3 H H F F CH 2 CONHMe Ph 854 CF 3 H H F F CH 2 CONMe 2 Ph 855 CF 3 H H F F CH 2 CH=CHCF 3 Ph 856 CF 3 H H F F CH 2 CH=CF 2 Ph 857 CF 3 H H F F CH 2 C(Br)=CH 2 Ph 858 CF 3 H H F F CH 2 C≡CCH 3 Ph 859 CF 3 H H F F CH 2 CH 2 C≡CH Ph 860 CF 3 H H F F CH 2 C≡CCF 3 Ph 861 CF 3 H H H F CH 2 cPr Ph-2-Cl 82-83 862 CF 3 H H H F CH 2 cPr Ph-4-Br 89-90 863 CF 3 H H H F CH 2 cPr Ph-2-Cl-4-F 864 CF 3 H H H F CH 2 cPr Ph-2-Br-4-Me 865 CF 3 H H H F CH 2 cPr Ph-4-Et 866 CF 3 H H H F CH 2 cPr Ph-4-OEt 867 CF 3 H H H F CH 2 cPr Ph-4-OiPr 868 CF 3 H H H F CH 2 cPr Ph-4-OCH 2 CH=CH 2 65-67 869 CF 3 H H H F CH 2 cPr Ph-4-OCH 2 C≡CH 77-78 870 CF 3 H H H F CH 2 cPr Ph-3-CF 3 77-78 871 CF 3 H H H F CH 2 cPr Ph-4-CF 3 124-125 872 CF 3 H H H F CH 2 cPr Ph -4-CF 2 CF 2 H 873 CF 3 H H H F CH 2 cPr Ph-4-OCF 3 96-97 874 CF 3 H H H F CH 2 cPr Ph-4-OCF 2 H 875 CF 3 H H H F CH 2 cPr Ph-4-OCF 2 CF 3 876 CF 3 H H H F CH 2 cPr Ph-4-OCF 2 CF 2 H 877 CF 3 H H H F CH 2 cPr 1-Me-2-Pyrrolyl 878 CF 3 H H H F CH 2 cPr 1-Me-3-Pyrrolyl 879 CF 3 H H H F CH 2 cPr 2-Pyrrolyl 880 CF 3 H H H F CH 2 cPr 3-Pyrrolyl 881 CF 3 H H F F CH 2 cPr Ph-2-Cl 882 CF 3 H H F F CH 2 cPr Ph-4-Br 883 CF 3 H H F F CH 2 cPr Ph-2-Cl-4-F 884 CF 3 H H F F CH 2 cPr Ph-2-Br-4-CH 3 885 CF 3 H H F F CH 2 cPr Ph-4-Et 886 CF 3 H H F F CH 2 cPr Ph-4-OEt 887 CF 3 H H F F CH 2 cPr Ph-4-OiPr 888 CF 3 H H F F CH 2 cPr Ph-4-OCH 2 CH=CH 2 889 CF 3 H H F F CH 2 cPr Ph-4-OCH 2 C≡CH 890 CF 3 H H F F CH 2 cPr Ph-3-CF 3 891 CF 3 H H F F CH 2 cPr Ph-4-CF 3 892 CF 3 H H F F CH 2 cPr Ph-4-CF 2 CF 2 H 893 CF 3 H H F F CH 2 cPr Ph-4-OCF 3 894 CF 3 H H F F CH 2 cPr Ph-4-OCF 2 H 895 CF 3 H H F F CH 2 cPr Ph-4-OCF 2 CF 3 896 CF 3 H H F F CH 2 cPr Ph-4-OCF 2 CF 2 H 897 CF 3 H H F F CH 2 cPr 1-Me-2-Pyrrolyl 898 CF 3 H H F F CH 2 cPr 1-Me-3-Pyrrolyl 899 CF 3 H H F F CH 2 cPr 2-Pyrrolyl 900 CF 3 H H F F CH 2 cPr 3-Pyrrolyl 901 CF 3 H H F Br CH 2 cPr Ph n 22.0 / D 1. 5349 902 CF 3 H H H Et CH 2 cPr Ph 903 CF 3 H H H nPr CH 2 cPr Ph 904 CF 3 H H H nBu CH 2 cPr Ph 905 CF 3 H H H tBu CH 2 cPr Ph 906 CF 3 H H H C 2 F 5 CH 2 cPr Ph 907 CF 3 H H H OEt CH 2 cPr Ph 908 CF 3 H H H OnPr CH 2 cPr Ph 909 CF 3 H H H OiPr CH 2 cPr Ph 910 CF 3 H H H OtBu CH 2 cPr Ph 911 CF 3 H H OEt F CH 2 cPr Ph 912 CF 3 H H OnPr F CH 2 cPr Ph 913 CF 3 H H OiPr F CH 2 cPr Ph 914 CF 3 H H OtBu F CH 2 cPr Ph 915 CF 3 H H H SOMe CH 2 cPr Ph n 23.3 / D 1.5450 916 CF 3 H H H SO 2 Me CH 2 cPr Ph 144-146 917 CF 3 H H H SEt CH 2 cPr Ph 918 CF 3 H H H S-iPr CH 2 cPr Ph 919 CF 3 H H SOMe F CH 2 cPr Ph 920 CF 3 H H SO 2 Me F CH 2 cPr Ph 921 CF 3 H H SEt F CH 2 cPr Ph 922 CF 3 H H S-iPr F CH 2 cPr Ph 923 CF 3 H H OCF 3 F CH 2 cPr Ph-4-OMe 924 CF 3 H H OCF 3 F CH 2 cPr Ph-2-F 925 CF 3 H H OCF 3 F CH 2 cPr Ph-4-F 926 CF 3 H H OCF 3 F CH 2 cPr Ph 927 CF 3 H H NO 2 OCH 3 CH 2 cPr Ph 928 CF 3 H H NHAc F CH 2 cPr Ph 929 CF 3 H H NH 2 F CH 2 cPr Ph 930 CF 3 H H F F CH 2 COOH Ph 113-120 931 CF 3 H H F F CH 2 cPr 2-imidazolyl 1-methyl-2- 932 CF 3 H H F F CH 2 cPr -imidazolyl 1-methyl-2- 933 CF 3 H H F F CH 2 cPr -oxazolyl 934 CF 3 H H F F CH 2 cPr 2-isoxazolyl 1-methyl-2- 935 CF 3 H H F F CH 2 cPr -isoxazolyl 936 CF 3 H H F F CH 2 cPr 2-pyrimidinyl 937 CF 3 H H F F CH 2 cPr 4,6-dimethyl-2 -pyrimidinyl 938 CF 3 H H F F CH 2 cPr 2-thiazolyl 939 CF 3 H H F F CH 2 cPr 3-chloro-2--thiazolyl 940 CF 3 H H F F CH 2 cPr 1-pyrazinyl 941 CF 3 H H F F CH 2 cPr 3-mrthyl-1-- pyrazinyl 942 CF 3 H H F F CH 2 cPr 3-pyridazinyl 943 CF 3 H H F F CH 2 cPr 3-methyl-4-- pyridazinyl 944 CF 3 H H F F CH 2 cPr 2-furyl 945 CF 3 H H F F CH 2 cPr 3-bromo-2--furyl 946 CF 3 H H F F CH 2 cPr 4-thiazolyl The compounds of the present invention can show excellent fungicidal activity against wide varieties of fungi, and therefore, the compounds can be useful for plant disease control in the farming of agricultural and horticultural crops including ornamental flowers, turf and forage crops. The examples for the plant diseases to be controlled with the compounds of the present invention are given in the following. Paddy rice Blast (Pyricularia oryzae) Sheath blight (Rhizoctonia solani) Bakanae disease (Gibberella fujikuroi) Heiminthosporium leaf spot (Cochliobolus miyabeanus) Barley Loose smut (Ustilago nuda) Wheat Scab (Gibberella zeae) Leaf rust (Puccinia recondita) Eye spot (Pseudocercosporella herpotrichoides) Glume blotch (Leptosphaeria nodorum) Powdery mildew (Erysiphe graminis f. sp. tritici) Fusarium snow blight (Micronectriella nivalis) Potato Late blight (Phytophthora infestans) Ground nut Leaf spot (Mycosphaerella aradius) Sugar beat Cercospora leaf spot (Cercospora beticola) Cucumber Powdery mildew (Sphaerotheca fuliginea) Sclerotinia rot (Sclerotinia sclerotiorum) Gray mold (Botrytis cinerea) Downy mildew (Pseudoperonospora cubensis) Tomato Leaf mold (Cladosporium fulvum) Late blight (Phytophthora infestans) Egg plant Onion Black rot (Corynespora melongenae) Gray-mold neck rot (Botrytis allii) Strawberry Powdery mildew (Sphaerotheca humuli) Apple Powdery mildew (Podosphaera leucotricha) Scab (Venturia inaequalis) Blossom blight (Monilinia mali) Persimmon Anthracnose (Gloeosporium kaki) Peach Brown rot (Monilinia fructicola) Grape Powdery mildew (Uncinula necator) Downy mildew (Plasmopara viticola) Pear Rust (Gymnosporangium asiaticum) Black spot (Alternaria kikuchiana) Tea-plant Leaf spot (Pestalotia theae) Anthracnose (Colletotrichum theae-sinensis) Orange Scab (Elsinoe fawcetti) Blue mold (Penicillium italicum) Turf Sclerotinia snow blight (Sclerotinia borealis) In recent years, it is known that various pathogenic fungi have developed their resistance to benzimidazole fungicides and ergosterol biosynthesis inhibitors and that such fungicides have been insufficient in their fungicidal effectiveness. Therefore, it is required to provide new compounds useful as a fungicide which are effective to the resistant-strain of such pathogenic fungi as well. The compounds of the present invention are the ones which can be a fungicide having excellent fungicidal effectiveness not only to the susceptible-strains of pathogenic fungi but also to the resistant-strains of pathogenic fungi to benzimidazole fungicides and ergosterol biosynthesis inhibitors. For the preferable examples of plant diseases to be applied with the compounds of the present invention, powdery mildew on wheat, powdery mildew on cucumber, powdery mildew on strawberries, etc. can be given. The compounds of the present invention can be utilized as an antifouling agent for preventing the adhesion of aqueous organisms to structures, such as the bottom of a ship and fishing nets, in water and sea. Also, the compounds of the present invention can be contained in paints and fibers and thereby used as an antimicrobial agent for walls, bathtubs, shoes and clothes. Furthermore, some of the compounds of the present invention can show insecticidal, acaricidal and herbicidal activities. In the practical application of the compounds of the present invention obtained as described above, the compounds can be used in the state as it is without formulation, or, for the use as agricultural plant protection chemicals, the compounds can be applied in forms of general formulations for agricultural plant protection chemicals, such as wettable powders, granules, powders, emulsifiable concentrates, aqueous solutions, suspensions and flowables. For the additives and carriers to be used in the formulations described above, vegetable powders, such as soybean powder and wheat powder, mineral fine powders, such as diatomaceous earth, apatite, gypsum, talc, bentonite. pyrophyllite and clay. and organic and inorganic compounds, such as sodium benzoate, urea and Glauber's salt, can be used, when the compounds are formulated into solid formulations. Whereas, when the compounds are formulated into liquid formulations, petroleum fractions. such as kerosine. xylene and solvent naphtha, cyclohexane, cyclohexanone, dimethyl formamide, dimethyl sulfoxide, alcohols, acetone, trichloro ethylene. methylisobutyl ketone, mineral oils. vegetable oils and water, can be used as the solvent. In these formulations, surface active agents may be added to the formulations in order to make the formulations homogeneous and stable, if appropriate. The content of the compound of the present invention as the active principle in the formulations is preferably in a range of from 5 to 70%. The wettable powders, the emulsifiable concentrates and the flowable formulation comprising the compound of the present invention prepared as described above can be applied in a form prepared by diluting the formulations with water to the suspension or the emulsion at a desired concentrations, while the powders and the granules of the said compound can be directly applied to plants without dilution. The compounds of the present invention can demonstrate sufficient effectiveness on plant diseases independently, however, it is also possible to use the said compound in admixing with 1 or more of other fungicides, insecticides, acaricides or synergists. The followings are the examples for the fungicides, insecticides, acaricides, nematocides and plant growth regulators, those which are usable in admixing with the compounds of the present invention. Fungicides: Copper-based fungicides: Basic copper chloride, basic copper sulfate, etc. Sulphur-based fungicides: Thiram, maneb, mancozeb, polycarbamate, propineb. ziram, zineb, etc. Polyhaloalkylthio fungicides: Captan. dichlofluanid, folpet, etc. Organochlorine fungicides: Chlorothalonil, fthalide, etc. Organophosphorous fungicides: IBP, EDDP, tolclofos-methyl, pyrazophos. fosetyl-Al, etc. Benzimidazole fungicides: Thiophanate-methyl, benomyl, carbendazim, thiabendazole, etc. Dicarboxyimide fungicides: Oxycarboxine, mepronyl, flutolanil, techlofthalam, trichlamide, pencycuron, etc. Acyl alanine fungicides: Metalaxyl, oxadixyl, furalaxyl etc. EBI fungicides: Triadimefon, triadomenol, bitertanol, microbutanil, hexaconazol, propiconazole, triflumizole, procloraz, peflazoate, fenarimol, pyrifenox, trifolin, flusilazole, etaconazole, diclobutrazol, fluotrimazole, flutriafen, penconazole, diniconazole, cyproconazole, imazalil, tridemorph, fenpropimorph, buthiobate, etc. Antibiotics: Polyoxin, blasticidin-S, kasugamycin, validamycin, streptomycin sulfate, etc. Others: Propamocarb hydrochloride salt, quintozene, hydroxyisoxazole, metasulfocarb, anilazine, isoprothiolane, probenazole, quinomethionate, dithianone, dinocap, dichlomezine, mepaniprim, ferimzone, fluazinam, pyroquilon, tricyclazole, oxolinic acid, dithianone, iminoctazine acetate salt, cymoxanil, pyrrolenitrine, metasulfocarb, diethofencarb, binapacryl, lecithin, sodium hydrogencarbonate, fenaminosulf, dodine, dimethomorph, fenazine oxide, etc. Insecticides and Acaricides: Organophosphorous and carbamate insecticides: Fenthion, fenitrothion, diazinon, chlorpyrifos. ESP, vamidothion, fenthoate, dimethoate. formothion, malathon, trichlorfon. thiometon, phosmet, dichlorvos, acephate. EPBP, methyl parathion, oxydimeton methyl. ethion, salithion, cyanophos, isoxathion, pyridafenthion, phosalon, methydathion, sulprofos, chlorfenvinphos, tetrachlorvinphos, dimethylvinphos. propaphos, isofenphos, ethylthiometon, profenofos. pyraclophos, monocrotophos, azinphos methyl, aldicarb, methomyl, thiodicarb. carbofuran, carbosulfan, benfuracarb. furathiocarb. propoxur. BPMC, MTMC, MIPC, carbaryl, pirimicarb, ethiofencarb, fenoxycarb, cartap. thiocyclam, bensultap, etc. Pyrethroid insecticides: Permethrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, pyrethrin. allethrin, tetramethrin, resmethrin, dimethrin, propathrin, fenothrin, prothrin, fluvalinate, cyfluthrin, cyhalothrin, flucythrinate, ethofenprox, cycloprothrin, tralomethrin, silafluophen, brofenprox, acrinathrin, etc. Benzoyl urea-based insecticides and others: Diflubenzuron, chlorfluazuron, hexaflumuron, triflumuron, tetrabenzuron, flufenoxuron. flucycloxuron, buprofezin, pyriproxyfen, methoprene, benzoepin, diaphenthiuron, imidacloprid, fipronil, nicotine sulfate, rotenone, meta-aldehyde, machine oil, Bacillus thuringiensis, microbial insecticides such as insect-pathogenic viruses. etc. Nematocides: Fenamiphos, phosthiazate, etc. Acaricides: Chlorbenzilate, phenisobromolate, dicofol, amitraz, BPPS, benzomate, hexythiazox, fenbutatin oxide, polynactin, quinomethionate, CPCBS, tetradifon, avermectin. milbemectin, chlofentezin, cyhexatin, pyridaben, fenpyroxymate. tebufenpyrad, pyrimidifen, fenothiocarb, dienochlor, etc. Plant Growth Regulators: Gibberellines (Gibberelline A 3 , Gibberelline A 4 , Gibberelline A 7 , etc.). IAA, and NAA. Now, the examples of the formulations comprising the compound of the present invention are described hereinbelow, however. it should be noted that the type and the rate of the additives shall not be limited to the ones described in the examples and can be replaced by wide range of other additives and/or carriers. In the examples hereinbelow, a part mentioned in each of the formulation examples represents a part by weight. Example 3 : Wettable Powder The compound of the present invention 40 parts Diatomaceous earth 53 parts Sulfuric acid ester of higher alcohol 4 parts Alkyl naphthalene sulfonate 3 parts All components are admixed and micronized to fine powder, thereby affording the wettable powder formulation containing the active principle at a concentration of 40%. Example 4 : Emulsifiable Concentrate The compound of the present invention 30 parts Xylene 33 parts Dimethyl formamide 30 parts Polyoxy ethlene alkylally ether 7 parts All components are admixed and then dissolved into a solution, thereby affording the emulsifiable concentrate formulation containing the active principle at a concentration of 30%. Example 5 : Dust Formulation The compound of the present invention 10 parts Talc 89 parts Polyoxy ethlene alkylally ether 1 parts All components are admixed and pulverized to fine dusting powder. thereby affording the dust formulation containing the active principle at a concentration of 10%. Example 6 : Granular Formulation The compound of the present invention 5 parts Clay 73 parts Bentonite 20 parts Sodium salt of dioctylsulfosuccinate 1 part Sodium phosphate 1 part All components are admixed, pulverized and then kneaded thoroughly while adding water, and then further granulated and dried, thereby affording the granular formulation containing the active principle at a concentration of 5%. Example 7 : Suspension The compound of the present invention 10 parts Sodium lignin sulfonate 4 parts Sodium dodecyl benzene sulfonate 1 part Xanthane Gum 0.2 part Water 84.8 parts All components are admixed and subjected to wet grinding up to the particle size of less than 1µ, thereby affording the suspension containing the active principle at a concentration of 10%. Now, the usefulness of the compounds of the present invention as the active principle of a plant protection chemical for controlling various plant diseases is shown in Test Examples described hereinbelow. The effectiveness of the compounds on plant disease control were assessed basing on the pathological changes in the state of plants provided, namely the degree of disease-induced lesion on leaves, stems and other parts of the plants was visually observed, respectively. The assessment was conducted by giving scores in effectiveness on plant diseases to each test plots as the following. Score, 5; If no lesion were observed. Score, 4; If the degree of the lesion observed were approximately 10% of the degree in the untreated plot. Score, 3; If the degree of the lesion observed were approximately 25% of the degree in the untreated plot. Score, 2; If the degree of the lesion observed were approximately 50% of the degree in the untreated plot. Score. 1; If the degree of the lesion observed were approximately 75% of the degree in the untreated plot. Score. 0; If the degree of the lesion observed were almost same as the degree in the untreated plot. Test Example 1 : Preventive Control Efficacy Test on Wheat Powdery Mildew To young seedlings of wheat (Variety: Chihoku) grown in an unglazed pot, the emulsion at a concentration of 12.5 ppm prepared from the emulsifiable concentrate comprising the compound of the present invention were sprayed throughly. After the spraying, the seedlings were dried under natural condition and then inoculated by means of sprinkling with the conidia of the fungus causing wheat powdery mildew (Erysiphe graminia f. sp. tritici) and placed in a greenhouse maintained at around 20 °C for 7 days in order to complete the infection. Appearance of the lesion on leaves cause by the disease was assessed and compared with the lesion on leaves in the untreated plot, thereby evaluating the preventive efficacy of the compound to the disease. The results are shown in Table 5. Test Example 2 : Preventive Control Efficacy Test on Cucumber Powdery Mildew To young seedlings of cucumber (Variety: Sagami-Hanjiro) grown in an unglazed pot, the emulsion at a concentration of 12.5 ppm prepared from the emulsifiable concentrate comprising the compound of the present invention were sprayed. After the spraying, the seedlings were dried under natural condition and then inoculated by means of sprinkling with the conidia of the fungus causing cucumber powdery mildew (Sphaerotheca fuliginea) and placed in a temperature-controlled room maintained at around 25°C for 11 days in order to complete the infection. Appearance of powdery mildew-causing lesion on the leaves whereto the compound was sprayed was assessed and compared with the lesion appeared on leaves in the untreated plot, thereby evaluating the preventive efficacy of the compound to the disease. The results are shown in Table 5. As shown in Table 5, it is demonstrated that the compounds of the present invention can show superior preventive control efficacy to not only wheat powdery mildew but also cucumber powdery mildew in comparison with other compounds tested. Test Example 3 : Test on Cucumber Powdery Mildew Control with Vapour 10 µI of the emulsion at a concentration of 500 ppm prepared from the emulsifiable concentrate comprising the compound of the present invention were fed dropwise onto round aluminium foils each having a diameter of 1 cm and dried at room temperature under natural condition. The aluminium foils were then fixed on the upper side of the leaves of cucumber seedlings (Variety: Sagami-Hanjiro) grown in an unglazed pot. After 24 hours, the cucumber leaves were inoculated by means of sprinkling with the conidia of the fungus causing cucumber powdery mildew (Sphaerotheca fuliginea) and placed in a temperature-controlled room maintained at around 25°C for 11 days in order to complete the infection. Appearance of powdery mildew-causing lesion on the leaves placed with the aluminium foil was assessed and compared with the lesion appeared on the leaves in the untreated plot. The control efficacy with the vapour of the compound to the disease was confirmed in case that disease lesion-free circle having a diameter of more than 2 cm is formed around the aluminium foil fixed on a leaf. The results are shown in Table 5. On the other hand, other compounds for the comparison, which are disclosed in Japanese Patent Laid-opened No. Hei 2-6453 (see Table 5), did not show the control efficacy with the vapour to the disease. Since the compounds of the present invention have vapour action, it is suggested that the compound of the present invention can show plant disease control efficacy even in the inner space of leaves and fruits of crops whereto spraying of a fungicide in even condition is generally rather difficult. Industrial Applicability: The compounds of the present invention have excellent fungicidal effectiveness, and therefore, are useful as a fungicide for agricultural and horticultural use.

Claims: Benzamidoxime derivatives represented by the formula (I); wherein R 1 is unsubstituted or substituted C 1 -C 4 alkyl, unsubstituted or substituted C 2 -C 4 alkenyl or unsubstituted or substituted C 2 -C 4 alkynyl, R 2 is phenyl optionally having substituents or heterocycle optionally having substituents, X 2 , X 3 , X 4 and X 5 are each independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 - C 4 alkyoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, nitro, amino or C 1 -C 4 alkylcarbonylamino, and r 1 and r 2 are each independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or amino, or r 1 and r 2 together may form a carbonyl. Benzamidoxime derivatives represented by the formula (I'); wherein R 1 is straight-chain or branched C 1 -C 4 alkyl; a group represented by a general formula, R 3 CH 2 , wherein R 3 is a group selected from the group consisting of C 3 -C 8 cycloalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 1 -C 3 alkoxycarbonyl, cyano, amino, C 1 -C 3 monoalkylamino, C 1 -C 3 dialkylamino, acylamino and cyano C 2 -C 4 alkenyl or C 2 -C 4 alkynyl, R 2 is phenyl optionally having one or more substituents selected from the group consisting of halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl and C 1 -C 3 haloalkoxy; or 5- or 6-membered aromatic heterocycle containing 1 to 4 heteroatoms or one or more species selected from a group consisting of nitrogen, oxygen and sulphur, those which are optionally having one or more substituents selected from a group consisting of halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl and C 1 -C 3 haloalkoxy, X 2 , X 3 , X 4 and X 5 are each independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 ahloakyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, nitro, amino or C 1 -C 4 alkylcarbonylamino, and r 1 and r 2 are each independently hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio or amino, or r 1 and r 2 together may form carbonyl. A process for preparation of benzamidoxime derivatives represented by the formula (I); wherein R 1 , X 2 , X 3 , X 4 , X 5 , R 2 , r 1 and r 2 are as described above, which comprises reacting a compound represented by the formula (II) wherein R 1 , X 3 , X 4 and X 5 are as described above, with a compound represented by the formula (III); wherein Hal represents halogen, and R 2 , r 1 and r 2 are as described above. A fungicide for agricultural and horticultural use, comprising one or more of the benzamidoxime derivatives as defined in claim 1 or 2.

Inventors: HOSOKAWA HIROYASU, KASAHARA ISAMU, OOKA HIROHITO, SANO SHINSUKE, YAMANAKA HOMARE, HOSOKAWA, HIROYASU, KASAHARA, ISAMU, OOKA, HIROHITO, SANO, SHINSUKE, YAMANAKA, HOMARE, HOSOKAWA, Hiroyasu Odawara Research Center, KASAHARA, Isamu Odawara Research Center, OOKA, Hirohito Odawara Research Center, SANO, Shinsuke Odawara Research Center, YAMANAKA, Homare Odawara Research Center
Applicants: NIPPON SODA CO, NIPPON SODA CO., LTD.
Application year: 1995
Main classification: C07C259
IPC codes: A01N43, C07C317, C07C259, C07C319, C07C323, C07D333, A01N37, C07D521, C07D231, C07D207