DIARYL-AZOLE COMPOUND AND FORMULATION FOR CONTROLLING HARMFUL ORGANISM

Abstract

A compound represented by Formula (I), or a salt thereof:

##STR00001##

wherein, R.sup.1 represents an unsubstituted or substituted C1-6 alkylthio group, or the like; A.sup.1 represents a nitrogen atom or CH; A.sup.2 represents a nitrogen atom or CR.sup.2; R.sup.2 and R.sup.3 each independently represents a hydrogen atom, an unsubstituted or substituted C6-10 aryl group, an unsubstituted or substituted 3- to 6-membered heterocyclyl group, or the like; B.sup.1 and B.sup.2 each independently represents a nitrogen atom or CR.sup.5, with the proviso that B.sup.1 and B.sup.2 do not represent CR.sup.5 at the same time, wherein R.sup.5 represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, or the like; R.sup.4 represents an unsubstituted or substituted C1-6 alkyl group, or the like, and R.sup.4 binds to any one of nitrogen atoms forming an imidazole ring or a triazole ring; and Ar represents an unsubstituted or substituted C6-10 aryl group or the like.

Claims

1. A compound represented by Formula (I) or a salt thereof. ##STR00038## wherein R.sup.1 represents an unsubstituted or substituted C1-6 alkylthio group, an unsubstituted or substituted C1-6 alkylsulfinyl group, an unsubstituted or substituted C1-6 alkylsulfonyl group, a halogeno group, or a group represented by —S(═O)(═N—R.sup.a)—R.sup.b, in which each of R.sup.a and R.sup.b independently represents an unsubstituted or substituted C1-6 alkyl group, A1 represents a nitrogen atom, A.sup.2 represents CR.sup.2, each of R.sup.2 and R.sup.3 independently represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C2-6 alkenyl group, an unsubstituted or substituted C2-6 alkynyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C1-6 alkylamino group, an unsubstituted or substituted C1-6 alkyl carbonylamino group, an unsubstituted or substituted C1-6 alkoxy carbonyl group, an unsubstituted or substituted C1-6 alkyl aminocarbonyl group, an unsubstituted or substituted C1-6 alkylthio group, an unsubstituted or substituted C1-6 alkylsulfinyl group, an unsubstituted or substituted C1-6 alkylsulfonyl group, an unsubstituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C6-10 aryl group, an unsubstituted or substituted, 3- to 6-membered heterocyclyl group, a 2-(propan-2-ylidene)hydrazinyl group, a benzyloxy group, a halogeno group, a cyano group, or a nitrile group, or R.sup.2 and R.sup.3 may form an unsubstituted or substituted, 5- to 6-membered ring, together with the carbon atoms to which R.sup.2 and R.sup.3 are bonded, each of B.sup.1 and B.sup.2 independently represents a nitrogen atom or CR.sup.5, with the proviso that both B.sup.1 and B.sup.2 do not simultaneously represent CR.sup.5, in which R.sup.5 represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C6-10 aryl group, a halogeno group, a cyano group, or a nitro group, R.sup.4 represents an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C2-6 alkenyl group, an unsubstituted or substituted C2-6 alkynyl group, an unsubstituted or substituted C3-8 cycloalkyl group, a hydroxyl group, an unsubstituted or substituted C1-6 alkoxy group, a formyl group, an unsubstituted or substituted C1-6 alkyl carbonyl group, an unsubstituted or substituted C1-6 alkoxy carbonyl group, or an unsubstituted or substituted C1-6 alkylsulfonyl group, and R.sup.4 bonds to any one of nitrogen atoms forming an imidazole ring or a triazole ring, and Ar represents an unsubstituted or substituted C6-10 aryl group, or an unsubstituted or substituted, 5- to 10-membered heteroaryl group.

2. The compound according to claim 1, or a salt thereof, wherein Ar represents an unsubstituted or substituted, 5-membered heteroaryl group.

3. The compound according to claim 1, or a salt thereof, wherein Formula (I) is represented by Formula (IV). ##STR00039## wherein R.sup.1 and R.sup.4 indicate the same meanings as those of Formula (I), R.sup.2′ represents an unsubstituted or substituted phenyl group, or an unsubstituted or substituted, 5- to 6-membered heteroaryl group, and R.sup.6 represents a C1-6 haloalkyl group.

4. A formulation for controlling harmful organisms, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

5. An insecticidal formulation or an acaricidal formulation, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

6. A formulation for controlling ectoparasites, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

7. A formulation for controlling endoparasites or for expelling endoparasites, comprising at least one compound selected from the group consisting of the compounds as recited in claim 1, and salts thereof, as an active ingredient.

Description

EXAMPLES

Formulation Examples

[0485] Some examples of the formulations for controlling harmful organisms, insecticides, acaricides, formulations for controlling ectoparasites, or formulations for controlling or expelling endoparasites of the present invention are described below. The additives and the addition ratios are not limited to those in the examples and can be modified over a wide range. The term “part” in the formulation examples indicates “part by weight”.

[0486] The formulation examples for agricultural and horticultural use and for paddy rice are described below.

[0487] (Formulation 1: Wettable Powder)

[0488] 40 parts of diaryl-azole compound of the present invention, 53 parts of diatomaceous earth, 4 parts of a higher alcohol sulfuric ester, and 3 parts of an alkylnaphthalene sulfonic acid salt were uniformly mixed and finely pulverized to obtain a wettable powder including 40% of an active ingredient.

[0489] (Formulation 2: Emulsion)

[0490] 30 parts of the diaryl-azole compound of the present invention, 33 parts of xylene, 30 parts of dimethylformamide and 7 parts of a polyoxyethylene alkyl aryl ether were mixed and dissolved to obtain an emulsion including 30% of an active ingredient.

[0491] (Formulation 3: Granules)

[0492] 5 parts of the diaryl-azole compound of the present invention, 40 parts of talc, 38 parts of clay, 10 parts of bentonite and 7 parts of sodium alkylsulfate were uniformly mixed and finely pulverized, followed by granulating into a granular shape having a diameter of 0.5 to 1.0 mm to obtain granules containing 5% of an active ingredient.

[0493] (Formulation 4: Granules)

[0494] 5 parts of the diaryl-azole compound of the present invention, 73 parts of clay, 20 parts of bentonite, 1 part of sodium dioctyl sulfosuccinate and 1 part of potassium phosphate were thoroughly pulverized and mixed. Water was added thereto, and the mixture was kneaded well, followed by granulating and drying to obtain granules containing 5% of an active ingredient.

[0495] (Formulation 5: Suspension)

[0496] 10 parts of the diaryl-azole compound according to the present invention, 4 parts of polyoxyethylene alkyl allyl ether, 2 parts of sodium polycarboxylate, 10 parts of glycerol, 0.2 parts of xanthan gum and 73.8 parts of water were mixed and wet-pulverized so as to have a grain size of 3 microns or less. Thereby, a suspension containing 10% of an active ingredient was obtained.

[0497] The formulation examples of the formulation for controlling ectoparasites, or the formulation for controlling or expelling endoparasites are described below.

[0498] (Formulation 6: Granulated Powder)

[0499] 5 parts of the diaryl-azole compound of the present invention was dissolved in an organic solvent to obtain a solution. The solution mentioned above was sprayed on 94 parts of kaolin and 1 part of white carbon, followed by evaporating the solvent under reduced pressure. This type of granulated powder may be mixed with animal food.

[0500] (Formulation 7: Impregnating Formulation)

[0501] 0.1 to 1 parts of the diaryl-azole compound of the present invention and 99 to 99.9 parts of peanut oil were uniformly mixed, and then filter-sterilized by means of a sterilizing filter.

[0502] (Formulation 8: Pour-on Formulation)

[0503] 5 parts of the diaryl-azole compound of the present invention, 10 parts of a myristic ester and 85 parts of isopropanol were uniformly mixed to obtain a pour-on formulation.

[0504] (Formulation 9: Spot-on Formulation)

[0505] 10 to 15 parts of the diaryl-azole compound of the present invention, 10 parts of a palmitic ester and 75 to 80 parts of isopropanol were uniformly mixed to obtain a spot-on formulation.

[0506] (Formulation 10: Spray Formulation)

[0507] 1 part of the diaryl-azole compound of the present invention, 10 parts of propylene glycol and 89 parts of isopropanol were uniformly mixed to obtain a spray formulation.

[0508] Next, Examples of compounds are described to explain the present invention more specifically. It should be understood that the present invention is not limited to the following examples.

Example 1

Synthesis of 5-(ethylsulfonyl)-4-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyrimidine (Compound No. 3)

(Step 1) Synthesis of 5-(ethylthio)uracil

[0509] ##STR00017##

[0510] 5-Bromouracil (10 g) was dissolved in dimethylsulfoxide (100 ml), and then stirred at room temperature. Ethylmercaptan sodium salt (80%, 10 g) was added thereto, and then stirred for 2 hours at 100° C. The obtained liquid was poured into water at about 5° C., and neutralized with diluted hydrochloric acid. Precipitated crude crystals were obtained by filtration, and the obtained residue was concentrated under reduced pressure. Thereby, the objective product was obtained in an amount of 6.7 g (yield 75%).

[0511] .sup.1H-NMR of the objective product obtained is shown below.

[0512] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 11.20 (br s, 1H), 10.47 (br s, 1H), 5.24 (s, 1H), 2.91 (q, 2H), 1.20 (t, 3H).

(Step 2) Synthesis of 2,4-dichloro-5-(ethylthio)pyrimidine

[0513] ##STR00018##

[0514] 5-(Ethylthio)uracil (6.7 g) was suspended to phosphorus oxychloride (20 ml), and stirred at 0° C. N,N-dimethylaniline (7.9 ml) was added thereto, and then stirred for 3 hours at 100° C. The obtained liquid was poured into water at about 60° C., and stirred for 2 hours. Subsequently, the reaction mixture was subjected to extraction with dichloromethane. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 1.7 g (yield 21%).

[0515] .sup.1H-NMR of the obtained objective product is shown below.

[0516] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 8.37 (s, 1H), 3.03 (q, 2H), 1.40 (t, 3H).

(Step 3) Synthesis of 1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazole

[0517] ##STR00019##

[0518] 5-Bromoimidazole (5 g) was dissolved in a solvent mixture of toluene (150 ml) and ethanol (50 ml). 4-(Trifluoromethoxy)phenylboronic acid (9.6 g), tetrakis(triphenylphosphine)palladium (0) (3.6 g), and sodium carbonate (6.6 g) were added thereto. The mixture was stirred under an argon atmosphere for 3 hours at 100° C. The resultant liquid was added to water, and subsequently, the mixture was subjected to extraction with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 5.8 g (yield 77%).

[0519] .sup.1H-NMR of the obtained objective product is shown below.

[0520] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 7.54 (s, 1H), 7.42 (m, 2H), 7.30 (m, 2H), 7.16 (s, 1H), 3.68 (s, 3H).

(Step 4) Synthesis of 2-chloro-5-(ethylthio)-4-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)pyrimidine

[0521] ##STR00020##

[0522] Tetrahydrofuran (44 ml) was placed in a reactor, and subsequently, 1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazole (2.0 g) was added thereto and dissolved therein. The inside of the reaction reactor was replaced with argon. Subsequently, the solution was cooled to −70° C. n-Butyl lithium (2.69 M, n-hexanal solution, 3.3 ml) was dropwise added thereto, and then stirred for 30 minutes at −70° C. Zinc chloride (II) (2.2 g) was added thereto, and the mixture was warmed to room temperature, and stirred for 1 hour at room temperature. Subsequently, 2,4-dichloro-5-(ethylthio)pyrimidine (1.7 g), tetrakis(triphenylphosphine)palladium (0) (0.96 g), and toluene (44 ml) were added thereto, and the mixture was stirred overnight under heating and refluxing. Water was added to the obtained liquid, and the mixture was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.6 g (yield 17%).

[0523] .sup.1H-NMR of the obtained objective product is shown below.

[0524] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 8.52 (1H, s), 7.50 (2H, m), 7.38 (s, 1H), 7.35 (2H, m), 3.95 (3H, s), 3.05 (2H, q), 1.44 (3H, t)

(Step 5) Synthesis of 5-(ethylthio)-4-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyrimidine

[0525] ##STR00021##

[0526] Sodium hydride (60%, 0.044 g) was suspended in N,N-dimethylformamide (10 ml), and then stirred at 0° C. 1,2,4-Triazole was added thereto, and then stirred for 30 minutes at 0° C. Subsequently, 2-chloro-5-(ethylthio)-4-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)pyrimidine (0.35 g) was added thereto, and then stirred overnight at room temperature. Water was added to the obtained liquid, and subsequently extraction with ethyl acetate was carried out. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.25 g (yield 67%).

[0527] .sup.1H-NMR of the obtained objective product is shown below.

[0528] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 9.19 (1H, s), 8.71 (1H, s), 8.19 (1H, s), 7.53 (2H, m), 7.42 (s, 1H), 7.37 (m, 2H), 4.05 (s, 3H), 3.12 (q, 2H), 1.47 (3H, t).

(Step 6) Synthesis of 5-(ethylsulfonyl)-4-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyrimidine

[0529] ##STR00022##

[0530] 5-(Ethylthio)-4-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)pyrimidine (0.20 g) was dissolved in dichloromethane (5 ml), and then stirred at 0° C. Meta-chloroperbenzoic acid (70%, 0.24 g) was added thereto, and then stirred overnight at room temperature. The obtained liquid was added to a mixed liquid of a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium thiosulfate, and then subjected to extraction with dichloromethane. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.16 g (yield 74%).

[0531] .sup.1H-NMR of the obtained objective product is shown below.

[0532] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 9.44 (s, 1H), 9.33 (s, 1H), 8.24 (s, 1H), 7.54 (m, 2H), 7.37 (m, 2H), 7.35 (s, 1H), 4.24 (q, 2H), 3.96 (s, 3H), 1.46 (t, 3H).

Example 2

Synthesis of 3-(ethylsulfonyl)-6-(3-methyl-1H-1,2,4-triazol-1-yl)-2-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)pyridine (Compound No. a-8)

(Step 1) Synthesis of 2-bromo-6-chloro-3-(ethylthio)pyridine

[0533] ##STR00023##

[0534] t-Butyl nitrite (5.15 g, 45 mmol, 1.5 eq) was added to a solution of diethyldisulfide (7.3 g, 60 mmol, 2 eq) dissolved in dichloroethane (100 ml), and then heated to 40° C. 3-Amino-2-bromo-6-chloropyridine (6.18 g, 30 mmol, 1.0 eq) was dropwise added thereto, and then stirred overnight at room temperature. Water was added to the reaction solution mentioned above, and then extraction with chloroform was carried out. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 4.02 g (yield 53%).

[0535] .sup.1H-NMR of the obtained objective product is shown below.

[0536] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 7.42 (1H, d), 7.26 (1H, d), 2.95 (2H, q), 1.39 (3H, t).

(Step 2) Synthesis of 6-chloro-3-(ethylthio)-2-(1-methyl-1H-imidazol-2-yl) pyridine

[0537] ##STR00024##

[0538] 1-Methyl-1H-imidazole (1.19 g, 14.5 mmol, 1.0 eq) was dissolved in tetrahydrofuran (50 ml), and the inside of the reactor was substituted with nitrogen. Subsequently, the solution was cooled to −70° C. A solution of n-butyllithium dissolved in n-hexane (2.67 M) (6 ml, 16 mmol, 1.1 eq) was dropwise added thereto, and then stirred for 30 minutes at −70° C. Zinc (II) chloride (5.92 g, 43.5 mmol, 3 eq) was added thereto, then warmed to room temperature, and stirred for 1 hour. Subsequently, a solution of 2-bromo-6-chloro-3-(ethylthio)pyridine (4.02 g, 16 mmol, 1.1 eq) dissolved in tetrahydrofuran (50 ml), and tetrakis(triphenylphosphine)palladium (0) (335 mg, 0.29 mmol, 0.02 eq) were added thereto. The inside of the reactor was replaced with nitrogen, and subsequently, the reaction mixture was stirred overnight under heating and refluxing. Water was added to the aforementioned reaction solution, and then the mixture was subjected to extraction with ethyl acetate. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 2.04 g (yield 55%).

[0539] .sup.1H-NMR of the obtained objective product is shown below.

[0540] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 7.61 (1H, d), 7.27-7.20 (2H, m), 6.99 (1H, m), 3.90 (3H, s), 2.91 (2H, q), 1.35 (3H, t).

(Step 3) Synthesis of 2-(5-bromo-1-methyl-1H-imidazol-2-yl)-6-chloro-3-(ethylthio)pyridine

[0541] ##STR00025##

[0542] 6-Chloro-3-(ethylthio)-2-(1-methyl-1H-imidazol-2-yl) pyridine (2.04 g, 8.06 mmol, 1.0 eq) was dissolved in 50 ml of dichloromethane, and then cooled to 0° C. N-bromosuccinimide (1.36 g, 7.66 mmol, 0.95 eq) was added thereto, and the mixture was stirred for 3 hours at room temperature. Water was added to the aforementioned reaction solution, and then extraction with dichloromethane was carried out. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 1.43 g (yield 53%).

[0543] .sup.1H-NMR of the obtained objective product is shown below.

[0544] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 7.63 (1H, d), 7.26 (1H, d), 7.22 (1H, s), 3.82 (3H, s), 2.92 (2H, q), 1.34 (3H, t).

(Step 4) Synthesis of 2-(5-bromo-1-methyl-1H-imidazol-2-yl)-6-chloro-3-(ethylsulfonyl)pyridine

[0545] ##STR00026##

[0546] 2-(5-Bromo-1-methyl-1H-imidazol-2-yl)-6-chloro-3-(ethylthio)pyridine (1.41 g, 4.25 mmol, 1.0 eq) was dissolved in chloroform (20 ml), and then cooled to 0° C. 70% meta-chloroperbenzoic acid (9.34 mmol, 2.2 eq) was added thereto, and the mixture was stirred overnight at room temperature. The aforementioned reaction solution was added to a saturated aqueous solution of sodium hydrogen carbonate, and extraction with chloroform was carried out. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 1.16 g (yield 75%).

[0547] .sup.1H-NMR of the obtained objective product is shown below.

[0548] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 8.41 (1H, d), 7.57 (1H, d), 7.14 (1H, s), 3.86 (2H, q), 3.66 (3H, s), 1.33 (3H, t).

(Step 5) Synthesis of 2-(5-bromo-1-methyl-1H-imidazol-2-yl)-3-(ethylsulfonyl)-6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridine

[0549] ##STR00027##

[0550] 2-(5-Bromo-1-methyl-1H-imidazol-2-yl)-6-chloro-3-(ethylsulfonyl)pyridine (200 mg, 0.55 mmol, 1.0 eq) was dissolved in dimethylformamide (5 ml), and 50% sodium hydride (32 mg, 0.66 mmol, 1.1 eq) was added. Subsequently, the mixture was cooled to 0° C. 3-Methyl-1H-1,2,4-triazole (50 mg, 0.61 mmol, 1.1 eq) was added thereto, and then stirred overnight at room temperature. The aforementioned reaction solution was added to a saturated aqueous solution of sodium hydrogen carbonate, and extraction with ethyl acetate was carried out. The obtained organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 91 mg (yield 40%).

[0551] .sup.1H-NMR of the obtained objective product is shown below.

[0552] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 9.04 (OH, s), 8.61 (OH, d), 8.07 (1H, d), 7.17 (1H, s), 3.84 (2H, q), 3.65 (3H, s), 2.53 (3H, s), 1.35 (3H, t).

(Step 6) Synthesis of 3-(ethylsulfonyl)-6-(3-methyl-1H-1,2,4-triazol-1-yl)-2-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)pyridine

[0553] ##STR00028##

[0554] 2-(5-Bromo-1-methyl-1H-imidazol-2-yl)-3-(ethylsulfonyl)-6-(3-methyl-1H-1,2,4-triazol-1-yl)pyridine (90 mg, 0.22 mmol, 1.0 eq) was dissolved in 10 ml of dioxane, and then stirred at room temperature. Water (1 ml), 4-(trifluoromethoxy)phenylboronic acid (50 mg, 0.24 mmol, 1.1 eq), tetrakis(triphenylphosphine)palladium (0) (13 mg, 0.05 mmol, 0.05 eq), and cesium carbonate (110 mg, 0.33 mmol, 1.5 eq) were added thereto, and the inside of the reactor was replaced with nitrogen. The mixture was stirred overnight at 100° C. The aforementioned reaction solution was added to water, and extraction with ethyl acetate was carried out. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 108 mg (yield quant.).

[0555] .sup.1H-NMR of the obtained objective product is shown below.

[0556] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ: 9.09 (OH, s), 8.64 (1H, d), 8.08 (1H, d), 7.55 (2H, d), 7.35 (2H, d), 7.23 (1H, s), 3.90 (2H, q), 3.64 (3H, s), 2.54 (3H, s), 1.37 (3H, t).

Example 3

Synthesis of 5-(ethylsulfonyl)-4-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)-2,2′-bipyrimidine (Compound No. 7)

(Step 1) Synthesis of 1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazole

[0557] ##STR00029##

[0558] 1-Methyl-1H-imidazole (0.681 g, 8.30 mmol, 2.0 eq) was dissolved in N,N-dimethylacetamide (21 ml), and the inside of the reactor was replaced with argon. Subsequently, the mixture was stirred at room temperature. 1-Bromo-4-(trifluoromethoxy)benzene (1.0 g, 4.15 mmol, 1.0 eq), palladium (II) acetate (4.7 mg, 0.021 mmol, 0.005 eq), potassium acetate (0.814 g, 8.30 mmol, 2.0 eq) were added thereto, and then stirred for 64 hours at 150° C. The obtained liquid was naturally cooled to room temperature, and the solvent was removed by distillation under reduced pressure. Water was added to the obtained residue, and extraction with chloroform was carried out. The obtained organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.51 g (yield 51%).

[0559] .sup.1H-NMR of the obtained objective product is shown below.

[0560] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ7.54 (s, 1H), 7.41 (m, 2H), 7.29 (m, 2H), 7.10 (s, 1H), 3.67 (s, 3H).

(Step 2) Synthesis of 2-chloro-1-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)ethan-1-one

[0561] ##STR00030##

[0562] 1-Methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazole (0.50 g, 2.06 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 ml), and the inside of the reactor was replaced with nitrogen. Subsequently, the mixture was cooled to −70° C. n-Butyllithium (2.65 M, n-hexane solution) (0.95 ml) was dropwise added thereto, and the mixture was stirred for 30 minutes at −70° C. 2-Chloro-N-methoxy-N-methylacetamide (0.34 g, 2.48 mmol, 1.2 eq) was added thereto, and then stirred for 1 hour at −70° C. A saturated aqueous solution of ammonium chloride was added to the resultant liquid, and extraction with chloroform was carried out. The obtained organic layer was dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.38 g (yield 58%).

[0563] .sup.1H-NMR of the obtained objective product is shown below.

[0564] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 7.45 (m, 2H), 7.36 (m, 2H), 7.12 (s, 1H), 4.98 (s, 2H), 3.97 (s, 3H).

(Step 3) Synthesis of 2-(ethylthio)-1-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)ethan-1-one

[0565] ##STR00031##

[0566] 2-Chloro-1-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)ethan-1-one (0.187 g, 0.59 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5.9 ml), and then stirred at room temperature. Ethylmercaptan sodium salt (80%) (0.068 g, 0.65 mmol, 1.1 eq) was added thereto, and then stirred overnight at room temperature. A saturated aqueous solution of ammonium chloride was added to the resultant liquid, and extraction with ethyl acetate was carried out. The obtained organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.138 g (yield 68%).

[0567] .sup.1H-NMR of the obtained objective product is shown below.

[0568] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 7.44 (m, 2H), 7.35 (m, 2H), 7.23 (s, 1H), 4.00 (s, 2H), 3.95 (s, 3H), 2.69 (q, 2H), 1.31 (t, 3H).

(Step 4) Synthesis of 2-(ethylsulfonyl)-1-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)ethan-1-one

[0569] ##STR00032##

[0570] 2-(Ethylthio)-1-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl) ethan-1-one (0.138 g, 0.40 mmol, 1.0 eq) was dissolved in dichloromethane (2 ml), and then stirred at 0° C. Meta-chloroperbenzoic acid (70/a) (0.217 g, 0.88 mmol, 2.2 eq) was added thereto, and then stirred overnight at room temperature. A saturated aqueous solution of sodium hydrogen carbonate was added to the resultant liquid, and extraction with chloroform was carried out. The obtained organic layer was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.113 g (yield 75%).

[0571] .sup.1H-NMR of the obtained objective product is shown below.

[0572] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 7.45 (m, 2H), 7.36 (m, 2H), 7.30 (s, 1H), 4.87 (s, 2H), 3.96 (s, 3H), 3.33 (q, 2H), 1.49 (t, 3H).

(Step 5) Synthesis of 3-(dimethylamino)-2-(ethylsulfonyl)-1-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)prop-2-en-1-one

[0573] ##STR00033##

[0574] 2-(Ethylsulfonyl)-1-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)ethan-1-one (0.374 g, 0.99 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 ml), and then stirred at room temperature. N,N-Dimethylformamide dimethylacetal (0.592 g, 4.97 mmol, 5.0 eq) was added thereto, and the mixture was stirred for 3 hours under heating and refluxing. The resultant liquid was concentrated under reduced pressure, and the obtained residue was used in the next step, without carrying out purification.

(Step 6) Synthesis of 5-(ethylsulfonyl)-4-(1-methyl-5-(4-(trifluoromethoxy) phenyl)-1H-imidazol-2-yl)-2,2′-bipyrimidine

[0575] ##STR00034##

[0576] The aforementioned 3-(dimethylamino)-2-(ethylsulfonyl)-1-(1-methyl-5-(4-(trifluoromethoxy)phenyl)-1H-imidazol-2-yl)prop-2-en-1-one obtained in Step 5 was dissolved in ethanol (5 ml), and then stirred at room temperature. Triethylamine (0.453 g, 4.47 mmol, 4.5 eq) and 2-amidinopyridine hydrochloride (0.36 g, 1.49 mmol, 1.5 eq) were added thereto, and then stirred for 1 hour under heating and refluxing. The resultant liquid was naturally cooled, and the solvent was removed by distillation under reduced pressure. Water was added to the obtained residue, and extraction with chloroform was carried out. The obtained organic layer was dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography with silica gel. Thereby, the objective product was obtained in an amount of 0.53 g (yield 92%, 2 steps).

[0577] .sup.1H-NMR of the obtained objective product is shown below.

[0578] .sup.1H-NMR (400 MHz, CDCl.sub.3): δ 9.65 (s, 1H), 9.09 (d, 2H), 7.54 (m, 3H), 7.36 (m, 2H), 7.31 (s, 1H), 4.23 (q, 2H), 3.93 (s, 3H), 1.46 (t, 3H).

[0579] The compounds according to the present invention prepared by the same methods as those described in the aforementioned Examples are shown in Table 1 to Table 3. Table 1 and Table 2 show the compounds represented by Formula (b-2-1-a) wherein R.sup.5 in Formula (b-2-1) is a hydrogen atom, having various substituents. The physical data of the compounds are described in the columns of “Physical property”. As the physical property data, the property or the melting point (m. p.) are described. In the Tables, Me represents a methyl group, Et represents an ethyl group, Bn represents a benzyl group, .sup.tBu represents a tertiary butyl group, and Ac represents an acetyl group.

##STR00035##

TABLE-US-00001 TABLE 1 Compound Physical No. R.sup.1 R.sup.3 R.sup.4 Ar A.sup.1 A.sup.2 property a-1 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-CF.sub.2CF.sub.3-phenyl N CH m.p. 163-165° C. a-2 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-OCF.sub.3-phenyl N CH m.p. 190-192° C. a-3 SO.sub.2Et 4-OCF.sub.3-phenyl CH.sub.3 4-OCF.sub.3-phenyl N CH m.p. 168-170° C. a-4 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-CF.sub.2CF.sub.3-phenyl CH CH m.p. 121-123° C. a-5 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-OCF.sub.3-phenyl CH CH m.p. 177-180° C. a-6 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-SCF.sub.3-phenyl CH CH m.p. 216-218° C. a-7 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 6-CF.sub.3-pyridin-3-yl CH CH m.p. 100-103° C. a-8 SO.sub.2Et 3-methyl-1H-1,2,4- CH.sub.3 4-OCF.sub.3-phenyl N CH m.p. 160-163° C. triazol-1-yl a-9 SO.sub.2Et Cl CH.sub.3 4-OCF.sub.3-phenyl CH CH amorphous a-10 SO.sub.2Et OH CH.sub.3 4-OCF.sub.3-phenyl N CH amorphous a-11 SO.sub.2Et CN CH.sub.3 4-OCF.sub.3-phenyl CH CH m.p. 158-160° C. a-12 SO.sub.2Et F CH.sub.3 4-OCF.sub.3-phenyl CH C—CF.sub.3 m.p. 136-138° C. a-13 SO.sub.2Et 1H-1,2,4-triazol-1-yl CH.sub.3 4-OCF.sub.3-phenyl CH C—CF.sub.3 m.p. 186-188° C. a-14 SO.sub.2Et cyclopropyl CH.sub.3 4-OCF.sub.3-phenyl CH CH viscous oil a-15 SO.sub.2Et 5-methyl-1,3,4- CH.sub.3 4-OCF.sub.3-phenyl CH CH m.p. 187-189° C. oxadiazol-2-yl a-16 SO.sub.2Et 3-methyl-1H-1,2,4- CH.sub.3 4-OCF.sub.3-phenyl CH CH m.p. 138-140° C. triazol-1-yl

TABLE-US-00002 TABLE 2 Compound Physical No. R.sup.1 R.sup.3 R.sup.4 A.sup.1 A.sup.2 Ar property 1 SO.sub.2Et H Me N N 4-OCF.sub.3-phenyl m.p. 107-109° C. 2 SEt 1H-1,2,4-triazol-1-yl Me N N 4-OCF.sub.3-phenyl m.p. 150-152° C. 3 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me N N 4-OCF.sub.3-phenyl m.p. 153-156° C. 4 SO.sub.2Et 3-Cl-1H-1,2,4-triazol-1-yl Me N N 4-OCF.sub.3-phenyl m.p. 190-192° C. 5 SO.sub.2Et 3-NHCOO.sup.tBu-1H- Me N N 4-OCF.sub.3-phenyl m.p. 235-238° C. 1,2,4-triazol-1-yl 6 SO.sub.2Et 3-NH.sub.2-1H-1,2,4- Me N N 4-OCF.sub.3-phenyl m.p. 194-197° C. triazol-1-yl 7 SO.sub.2Et pyrimidin-2-yl Me N N 4-OCF.sub.3-phenyl m.p. 186-188° C. 8 SO.sub.2Et pyrimidin-2-yl Me N N 4-CF.sub.2CF.sub.3-phenyl m.p. 207-209° C. 9 SO.sub.2Et pyrimidin-2-yl Me N N 6-CF.sub.3-pyridin-3-yl m.p. 234-236° C. 10 SO.sub.2Et 3-NH.sub.2-1H-1,2,4- Me N CH 4-OCF.sub.3-phenyl m.p. 148-151 triazol-1-yl 11 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me N CH 6-OCHF.sub.2-pyridin-3-yl m.p. 214-216° C. 12 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me N CH 3-OCF.sub.3-phenyl m.p. 165-166° C. 13 SO.sub.2Et OEt Me N CH 4-OCF.sub.3-phenyl viscous oil 14 SO.sub.2Et OBn Me N CH 4-OCF.sub.3-phenyl viscous oil 15 SO.sub.2Et 3,5-F.sub.2-phenyl Me N CH 4-OCF.sub.3-phenyl m.p. 182-183° C. 16 SO.sub.2Et 3-Cl-1H-1,2,4- Me N CH 4-OCF.sub.3-phenyl m.p. 219-220° C. triazol-1-yl 17 SO.sub.2Et pyrimidin-2-yl Me N CH 4-OCF.sub.3-phenyl m.p. 205-207° C. 18 SO.sub.2Et 4-Me-1H-imidazol-1-yl Me N CH 4-OCF.sub.3-phenyl m.p. 136-137° C. 19 SO.sub.2Et 4-NO.sub.2-1H-imidazol-1-yl Me N CH 4-OCF.sub.3-phenyl m.p. 231-233° C. 20 SO.sub.2Et 3-NHCOO.sup.tBu-1H- Me N CH 4-OCF.sub.3-phenyl m.p. 156-157° C. 1,2,4-triazol-1-yl 21 SO.sub.2Et 3-NMeCOO.sup.tBu-1H- Me N CH 4-OCF.sub.3-phenyl amorphous 1,2,4-triazol-1-yl 22 SO.sub.2Et 3-NHMe-1H-1,2,4- Me N CH 4-OCF.sub.3-phenyl m.p. 123-125° C. triazol-1-yl 23 SO.sub.2Et 3-NHAc-1H-1,2,4- Me N CH 4-OCF.sub.3-phenyl m.p. 300° C. up triazol-1-yl 24 SO.sub.2Et NHN═CMe.sub.2 Me N CH 4-OCF.sub.3-phenyl m.p. 145-146° C. 25 SO.sub.2Et 6-CF.sub.3-pyridin-3-yl Me N CH 4-OCF.sub.3-phenyl m.p. 189-190° C. 26 SO.sub.2Et 3-F-phenyl Me N CH 4-OCF.sub.3-phenyl m.p. 195-196° C. 27 SO.sub.2Et CN Me N CH 4-OCF.sub.3-phenyl m.p. 156-158° C. 28 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me CH N 4-OCF.sub.3-phenyl m.p. 207-209° C. 29 SO.sub.2Et OMe Me CH N 4-OCF.sub.3-phenyl m.p. 133-135° C. 30 SO.sub.2Et OH Me CH N 4-OCF.sub.3-phenyl m.p. 208-212° C. 31 SO.sub.2Et pyrimidin-2-yl Me CH N 4-OCF.sub.3-phenyl m.p. 185-187° C. 32 SO.sub.2Et 3-NH.sub.2-1H-1,2,4- Me CH N 4-OCF.sub.3-phenyl m.p. 262-266° C. triazol-1-yl 33 SO.sub.2Et 3-NHAc-1H-1,2,4- Me CH N 4-OCF.sub.3-phenyl m.p. 253-255° C. triazol-1-yl 34 SO.sub.2Et 3-NHCOCF.sub.3-1H-1,2,4- Me CH N 4-OCF.sub.3-phenyl m.p. 159-163° C. triazol-1-yl 35 SO.sub.2Et H Me CH C—CF.sub.3 4-(2,5-Me.sub.2-1H-pyrrol- m.p. 74-80° C. 1-yl)-1H-pyrazol-1-yl 36 SO.sub.2Et H Me CH C—CF.sub.3 4-CF.sub.2CF.sub.3-1H- m.p. 139-141° C. pyrazol-1-yl 37 SO.sub.2Et H Me CH C—CF.sub.3 4-CF.sub.3-1H-pyrazol-1-yl m.p. 155-157° C. 38 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me N CH 1-CF.sub.3-1H-pyrazol-4-yl m.p. 181-184° C. 39 SO.sub.2Et H Me N C—CF.sub.3 1-CF.sub.3-1H-pyrazol-4-yl m.p. 87-90° C. 40 SO.sub.2Et H Me N C—CF.sub.3 1-SO.sub.2CF.sub.3-1H- m.p. 163-165° C. pyrazol-4-yl 41 SO.sub.2Et H Me CH C—CF.sub.3 1-SO.sub.2CF.sub.3-1H- m.p. 105-107° C. pyrazol-4-yl 42 SO.sub.2Et H Me N C-(3,5-F.sub.2- 1H-pyrazol-4-yl m.p. 230° C. up phenyl) 43 SO.sub.2Et H Me N C-(3,5-F.sub.2- 1-SO.sub.2CF.sub.3-1H- m.p. 178-180° C. phenyl) pyrazol-4-yl 44 SO.sub.2Et 3-NHCOO.sup.tBu-1H- Me N CH 1-SO.sub.2CF.sub.3-1H- m.p. 186-190° C. 1,2,4-triazol-1-yl pyrazol-4-yl 45 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me N CH 1-SO.sub.2CF.sub.3-1H- amorphous pyrazol-4-yl 46 SO.sub.2Et H Me CH C—CF.sub.3 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 197-199° C. 47 SO.sub.2Et H Me N C-(pyrimidin- 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 179-181° C. 2-yl 48 SO.sub.2Et H Me CH C-CF.sub.3 2-CF.sub.3-thiazol-5-yl m.p. 166-168° C. 49 SO.sub.2Et H Me N C-(1H-1,2,4- 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 186-188° C. triazol-1-yl) 50 SO.sub.2Et H Me CH C-(pyrimidin- 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 193-194° C. 2-yl) 51 SO.sub.2Et H Me N C-(3,5-F.sub.2- 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 184-185° C. phenyl) 52 SO.sub.2Et H Me N C-(pyrimidin- 1-CF.sub.3-1H-pyrazol-4-yl m.p. 155-157° C. 2-yl) 53 SO.sub.2Et H Me N C—CH═CH.sub.2 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 133-135° C. 54 SO.sub.2Et H Me N C-(pyrimidin- 1-CH.sub.2CF.sub.3-1H-pyrazol-4-yl m.p. 176-178° C. 2-yl) 55 SO.sub.2Et H Me N C-(pyrimidin- 2-CF.sub.3-thiazol-5-yl m.p. 167-169° C. 2-yl) 56 SO.sub.2Et pyrimidin-2-yl Me N N 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 126-128° C. 57 SO.sub.2Et H Me CH C-(3,5-F.sub.2- 1-CHF.sub.2-1H-pyrazol-4-yl m.p. 155-156° C. phenyl) 58 SO.sub.2Et H Me CH C-(pyrimidin- 1-CH.sub.2CF.sub.3-1H-pyrazol-4-yl m.p. 197-199° C. 2-yl) 59 SO.sub.2Et 3-Cl-1H-1,2,4-triazol-1-yl Me CH CH 4-OCF.sub.3-phenyl m.p. 108-110° C. 60 SO.sub.2Et F Me CH C—F 4-OCF.sub.3-phenyl m.p. 150-152° C. 61 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me CH C—F 4-OCF.sub.3-phenyl m.p. 163-164° C. 62 SO.sub.2Et 1H-1,2,4-triazol-1-yl Me CH C-(1H-1,2,4- 4-OCF.sub.3-phenyl m.p. 257-259° C. triazol-1-yl)

TABLE-US-00003 TABLE 3 Compound Physical No. Structural formula property b-1 [00036] m.p. 202-204° C. b-2 [00037] m.p. 176-178° C.

[0580] The .sup.1H-NMR data (400 MHz, CDCl.sub.3) of the compounds of which the physical property is a viscous oil or amorphous in Table 1 to Table 3 are shown in Table 4.

TABLE-US-00004 TABLE 4 Compound No. .sup.1H-NMR (CDCl.sub.3-d.sub.6, δ ppm) a-9  8.12 (1H, d), 7.68 (1H, dd), 7.57 (1H), 7.52-7.47 (2H, m), 7.35-7.28 (2H, m), 7.18-7.15 (1H, m), 3.44-3.34 (5H, m), 3.42 (5H, s), 1.23 (3H, t). a-10 7.97 (1H, d), 7.50-7.45 (2H, m), 7.33 (2H, d), 7.17 (1H, s), 6.67 (1H, d), 3.58 (3H, s), 3.40 (2H, q), 1.65 (1H, br), 1.31 (3H, t). a-14 8.02 (1H, d), 7.53-7.47 (2H, m), 7.36-7.27 (3H, m), 7.19 (1H, d), 7.16 (1H, s), 3.39 (3H, s), 3.32 (2H, q), 2.04-1.97 (1H, m), 1.20 (3H, t), 1.18-1.11 (2H, m), 0.87-0.81 (2H, m). 13 8.28 (1H, d), 7.57-7.48 (2H, m), 7.35-7.28 (2H, m), 7.18 (1H, s), 6.91 (1H, d), 4.47 (2H, q), 3.79 (2H, q), 3.59 (3H, s), 1.42 (3H, t), 1.33 (3H, t). 14 8.32 (1H, d), 7.53-7.46 (2H, m), 7.44-7.27 (7H, m), 7.18 (1H, s), 7.02 (1H, d), 5.48 (2H, s), 3.80 (2H, q), 3.44 (3H, s), 1.33 (3H, t). 21 9.04 (1H, s), 8.63 (1H, d), 8.08 (1H, d), 7.57-7.50 (2H, m), 7.37-7.32 (2H, m), 7.24 (1H, s), 3.89 (2H, q), 3.63 (3H, s), 3.45 (3H, s), 1.57 (9H, s), 1.37 (3H, t). 45 9.18 (1H, s), 8.68 (1H, d), 8.25 (1H, s), 8.20 (3H, d), 7.38 (1H, s), 3.84 (2H, q), 3.70 (3H, s), 1.37 (3H, t).

[0581] [Biological Tests]

[0582] The following Test Examples demonstrate that the diaryl-azole compounds of the present invention (hereinafter, referred to as “compounds of the present invention”) are useful as active ingredients of the formulations for controlling harmful organisms, and of the formulations for controlling ectoparasites. The term “part” is based on weight.

[0583] (Preparation of Emulsion for Test)

[0584] 5 parts of the compound of the present invention, 93.6 parts of dimethylformamide and 1.4 parts of polyoxyethylene alkyl aryl ether were mixed and dissolved to prepare Emulsion (1) including 5% of an active ingredient.

[0585] An insect mortality rate and a controlling rate were calculated by the numerical equations shown below.

Insect mortality rate (%)=(Number of dead insects)/(Number of sample insects)×100

Controlling rate={1−(Nt)/(Nc)}×100

[0586] wherein Nt: number of parasites in spray-treated area; and

[0587] Nc: number of parasites in non-treated area

(Test Example 1) Efficacy Test Against Mythimna separata

[0588] 0.8 g of a commercially available artificial feed (Insecta LFS, manufactured by Nosan Corporation) and 1 μl of Emulsion (I) were mixed thoroughly, and 0.2 g of the resulting mixture was placed in each of the treatment areas of a plastic test container (volume: 1.4 ml) to complete preparation of a test feed.

[0589] Two second-instar larvae of Mythimna separata were inoculated into each treatment area, and the test container was sealed with a plastic lid. The sealed container was placed in a thermostatic chamber at 25° C., and the mortality rate and the amount of feed consumed were determined on the fifth day. The test was performed twice. In addition, a test performed under the same conditions, but with the exception of excluding the compound of the present invention from the aforementioned Emulsion (I), was used as a control.

[0590] Efficacy tests against Mythimna separata were conducted for the compounds having the compound numbers shown in Table 5. For all of the compounds, the mortality rate against Mythimna separata was 100%, or the amount of feed consumed was 10% or less of the amount of feed consumed in the control.

TABLE-US-00005 TABLE 5 a-1 a-9 6 15 24 33 48 60 a-2 a-11 7 16 25 34 50 61 a-3 a-13 8 17 26 36 51 62 a-4 a-14 9 18 27 37 52 a-5 a-15 10 19 28 38 53 a-6 a-16 11 20 29 39 54 a-7 1 12 21 31 46 55 a-8 5 13 23 32 47 59

(Test Example 2) Efficacy Test Against Spodoptera litura

[0591] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Cabbage leaves were soaked in the diluted liquid for 30 seconds. Subsequently, the cabbage leaves were put on Petri dishes, followed by inoculating 5 second-instar larvae of Spodoptera litura. The Petri dishes were placed in a thermostatic chamber at a temperature of 25° C. and humidity of 60%. Mortality was investigated 6 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0592] The efficacy test against Spodoptera litura was carried out for the compounds according to the compound numbers shown in Table 6. All of the compounds demonstrated an 80% or more insect mortality rate against Spodoptera litura.

TABLE-US-00006 TABLE 6 a-4  10 59 a-11 28 61 8 48

(Test Example 3) Efficacy Test Against Plutella xylostella

[0593] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Cabbage leaves were soaked in the diluted liquid for 30 seconds. Subsequently, the cabbage leaves were put on Petri dishes, followed by inoculating 5 second-instar larvae of Plutella xylostella. The Petri dishes were placed in a thermostatic chamber at a temperature of 25° C. and humidity of 60%. Mortality was investigated 3 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0594] The efficacy test against Plutella xylostella was carried out for the compounds according to the compound numbers shown in Table 7. All of the compounds demonstrated an 80% or more mortality rate against Plutella xylostella.

TABLE-US-00007 TABLE 7 a-1  7 17 31 39 51 61 a-2  8 23 32 43 52 62 a-4 10 27 33 46 54 a-5 13 28 34 47 55 a-8 16 29 36 48 59

(Test Example 4) Efficacy Test Against Aphis craccivora

[0595] Black-eyed pea plants were raised in No. 3 pots and the primary leaves were inoculated with nymphs of Aphis craccivora. Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Subsequently, the aforementioned diluted liquid was sprayed on the black-eyed pea plants on which the nymphs of Aphis craccivora were parasitic. The aforementioned black-eyed pea plants were then placed in a thermostatic chamber with a temperature of 25° C. and humidity of 60%. Mortality was investigated 4 days after spraying was carried out, and the insect mortality rate of Aphis craccivora was calculated. The test was performed twice.

[0596] The efficacy test against Aphis craccivora was carried out for the compounds according to the compound numbers shown in Table 8. All of the compounds demonstrated an 80% or more mortality rate against Aphis craccivora.

TABLE-US-00008 TABLE 8 a-2   1 16 46 55 a-5   7 22 47 56 a-8   8 36 48 62 a-9  10 37 49 a-16 13 39 54

(Test Example 5) Efficacy Test Against Bemisia tabaci

[0597] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm, and subsequently, the diluted liquid was sprayed on young seedlings of tomato, followed by air-drying. On the day of the spraying, adult Bemisia tabaci were released to the seedlings so as to lay eggs. The number of parasitic larvae was calculated 12 days after the spraying. The controlling (prevention) rate was calculated. The test was performed twice.

[0598] The efficacy test against Bemisia tabaci was carried out for the compounds of the compound numbers shown in Table 9. All of the compounds demonstrated an 80% or more next-generation controlling rate.

TABLE-US-00009 TABLE 9 a-4 a-7 62 a-5 36 a-6 39

(Test Example 6) Efficacy Test Against Nilaparvata lugens

[0599] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. Rice seedlings were soaked in the diluted liquid for 30 seconds, and subjected to air-drying. Subsequently, the rice seedlings were placed in plastic cases, followed by inoculating 5 second-instar larvae of Nilaparvata lugens. The plastic cases were placed in a thermostatic chamber at a temperature of 25° C. and humidity of 65%. Mortality was investigated 7 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0600] The efficacy test against Nilaparvata lugens was carried out for the compounds according to the compound numbers shown in Table 10. All of the compounds demonstrated an 80% or more mortality rate against Nilaparvata lugens.

TABLE-US-00010 TABLE 10 a-1 a-8 10 47 62 a-2 1 13 54 a-5 7 38 55 a-6 8 39 56 a-7 9 46 61

(Test Example 7) Efficacy Test Against Phyllotreta striolata

[0601] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm, to prepare a diluted liquid for testing. The aforementioned diluted liquid was sprayed on bok-choi seedlings (7.sup.th major leaf-development period) planted in No. 3 pots. After the bok-choi seedlings were subjected to air-drying, the seedlings were placed in plastic cups, followed by inoculating 10 adult Phyllotreta striolata. The plastic cups were stored in a thermostatic chamber at a temperature of 25° C. and humidity of 65%. Mortality was investigated 7 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0602] The efficacy test against adult Phyllotreta striolata was carried out for the compounds according to the compound numbers shown in Table 11. All of the compounds demonstrated an 80% or more mortality rate against adult Phyllotreta striolata.

TABLE-US-00011 TABLE 11 a-1 a-7   8 18 36 54 a-2 a-8  10 19 39 55 a-4 a-11 12 23 47 59 a-5 6 16 28 51 61 a-6 7 17 31 52 62

(Test Example 8) Efficacy Test Against Thrips palmi (125 ppm)

[0603] Inoculation of 10 adult Thrips palmi on cucumber seedlings was carried out. Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 125 ppm. The aforementioned diluted liquid was sprayed on the cucumber seedlings, followed by air-drying. The number of parasitic larvae was calculated 7 days after the spraying, and the controlling (prevention) rate was calculated. The test was performed twice.

[0604] The efficacy test against Thrips palmi was carried out for the compounds of the compound numbers shown in Table 12. All of the compounds demonstrated an 80% or more next-generation controlling rate.

TABLE-US-00012 TABLE 12 7 10 61 8 31 62 9 59

(Test Example 9) Efficacy Test Against Thrips palmi (31 ppm)

[0605] Inoculation of 10 Adult Thrips palmi on Cucumber Seedlings was Carried Out. Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 31 ppm. The aforementioned diluted liquid was sprayed on the cucumber seedlings, followed by air-drying. The number of parasitic larvae was calculated 7 days after the spraying, and the controlling (prevention) rate was calculated. The test was performed twice.

[0606] The efficacy test against Thrips palmi was carried out for the compounds of the compound numbers shown in Table 13. All of the compounds demonstrated an 80% or more next-generation controlling rate.

TABLE-US-00013 TABLE 13 7 10 61 8 31 62 9 59

(Test Example 10) Efficacy Test Against Culex pipiens Molestus

[0607] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 10 ppm, to prepare a chemical liquid for testing. 20 first-instar larvae of Culex pipiens molestus were released in 100 mL of the chemical liquid. After one day, the number of dead insects was counted, and the insect mortality rate was calculated. The test was performed twice.

[0608] The efficacy test against first-instar larvae of Culex pipiens molestus was carried out for the compounds according to the compound numbers shown in Table 14. All of the compounds demonstrated a 100% mortality rate against the first-instar larvae of Culex pipiens molestus.

TABLE-US-00014 TABLE 14 a-2  a-14  6 21 32 50 a-4  a-15 10 22 34 51 a-5  a-16 14 23 39 52 a-6  1 16 24 43 53 a-7  2 17 27 46 54 a-8  3 18 28 47 59 a-9  4 19 29 48 61 a-13 5 20 30 49 62

(Test Example 11) Efficacy Test Against Mythimna separata (Pseudaletia separate) (Seed Treatment Test)

[0609] 0.1 g of each of the compounds of the present invention was diluted with 2 mL of acetone to prepare a chemical liquid for test. 10 g of wheat seeds were added to the chemical liquid for test and air-dried, followed by seedling 100 seeds in a planter. After keeping the planter in a warm room with a temperature of 25° C. for 7 days, 100 first-instar larvae of Mythimna separata (Pseudaletia separata) (Psedaletia separata) were released in the planter. The planter was kept in a warm room with a temperature of 25° C., the number of living Mythimna separata (Pseudaletia separata) was investigated after 3 days had passed, and the controlling (prevention) rate was calculated by the following equation. The test was performed twice.

[0610] The efficacy test against the first-instar larvae of Mythimna separata (Pseudaletia separate) was carried out for the compounds according to Compound Nos. a-2 and a-8. As a result, both the compounds demonstrated an 80% or more the controlling rate against the first-instar larvae of Mythimna separata (Pseudaletia separate).

(Test Example 12) Efficacy Test Against Rhopalosiphum padi (Seed Treatment Test)

[0611] 0.1 g of each of the compounds of the present invention was diluted with 2 mL of acetone to prepare a chemical liquid for test. 10 g of wheat seeds were added to the chemical liquid for test and air-dried, followed by seedling 100 seeds in a planter. After keeping the planter in a warm room with a temperature of 25° C. for 7 days, 50 adult Rhopalosiphum padi were released in the planter. The number of living Rhopalosiphum padi was investigated after 6 days had passed, and the controlling rate was obtained. The test was repeated twice.

[0612] The efficacy test against Rhopalosiphum padi was carried out for the compounds according to Compound Nos. a-5, a-6, and a-7. As a result, all of the compounds demonstrated an 80% or more controlling rate against Rhopalosiphum padi.

(Test Example 13) Efficacy Test Against Nilaparvata lugens

[0613] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 8 ppm. Rice seedlings were soaked in the diluted liquid for 30 seconds, and subjected to air-drying. Subsequently, the rice seedlings were placed in plastic cases, followed by inoculating 5 second-instar larvae of Nilaparvata lugens. The plastic cases were placed in a thermostatic chamber at a temperature of 25° C. and humidity of 65%. Mortality was investigated 7 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0614] The efficacy test against Nilaparvata lugens was carried out for the compounds according to the compound numbers shown in Table 15. All of the compounds demonstrated an 80% or more mortality rate against Nilaparvata lugens.

TABLE-US-00015 TABLE 15  7 17 51 56  8 38 52 62  9 40 54 10 47 55

(Test Example 14) Efficacy Test Against Phyllotreta Striolata

[0615] Emulsion (1) was diluted with water so that the concentration of the compound of the present invention was 8 ppm, to prepare a diluted liquid for testing. The aforementioned diluted liquid was sprayed on bok-choi seedlings (7.sup.th major leaf-development period) planted in No. 3 pots. After the bok-choi seedlings were subjected to air-drying, the seedlings were placed in plastic cups, followed by inoculating 10 adult Phyllotreta striolata. The plastic cups were stored in a thermostatic chamber at a temperature of 25° C. and humidity of 65%. Mortality was investigated 7 days after inoculation, and the insect mortality rate was calculated. The test was performed twice.

[0616] The efficacy test against adult Phyllotreta striolata was carried out for the compounds according to the compound numbers shown in Table 16. All of the compounds demonstrated an 80% or more mortality rate against adult Phyllotreta striolata.

TABLE-US-00016 TABLE 16  6 11 47 59  7 17 52 61  8 23 54 62 10 28 55

[0617] The compounds selected at random among the compounds according to the present invention exhibit the effects described above. For this reason, it can be understood that the compounds of the present invention including those which cannot be demonstrated above have effects of controlling harmful organisms, and in particular, acaricidal effects, insecticidal effects and the like. In addition, it can also be understood that the compounds of the present invention have effects on ectoparasites and the like which harm humans and animals.

INDUSTRIAL APPLICABILITY

[0618] A diaryl-azole compound which has superior activity for controlling harmful organisms, and in particular, superior insecticidal activity and/or acaricidal activity, which exhibits superior safety, and can be industrially-advantageously synthesized can be provided, and also a formulation for controlling harmful organisms containing the same as an active ingredient can be provided. In addition, a formulation for controlling ectoparasites or a formulation for controlling or expelling endoparasites which contains the same as an active ingredient can be provided.