Phenoxy compound comprising fluoroalkyl group-substituted tetrazole and uses thereof as herbicide

Abstract

The present invention relates to a compound selected from the group consisting of a phenoxy compound containing a fluoroalkyl group-substituted tetrazole, represented by Chemical Formula 1, and an agrochemically acceptable salt thereof; and a herbicide comprising, as an active ingredient, the compound of Chemical Formula 1, an agrochemically acceptable salt thereof, or a mixture thereof.

Description

Phenoxy compounds containing fluoroalkyl substituted tetrazoles and their use as herbicides

[0001] The present invention relates to a novel phenoxy compound comprising a fluoroalkyl group substituted tetrazole and its use as a herbicide.

[0002] This work was supported by the "Development of Eco-Friendly Herbicides and Fungicides Candidate Materials for Solving Global Issues (Project Numbers: 1415178056 and 1415184920)" project, a bio-industry technology development project of the Korea Industrial Technology Evaluation and Planning Institute under (or affiliated with) the Ministry of Trade, Industry and Energy, and the "Development of Leading Crop Protection Agent Materials (Project Number: 0000236120)" project of the Korea Research Institute of Chemical Technology under (or affiliated with) the Ministry of Science and ICT.

[0003] Herbicides are crop protection agents that do not harm crops but suppress or kill weeds. These herbicides can be classified by chemical structure, mechanism of action, application site, target weeds, and application timing. Understanding their mechanism of action is crucial to understanding the chemical and biological properties of herbicides. Based on their mechanism of action, herbicides are classified as lipid biosynthesis inhibitors, amino acid biosynthesis inhibitors, photosynthesis inhibitors, pigment biosynthesis inhibitors, folate biosynthesis inhibitors, cell division inhibitors, cell wall synthesis inhibitors, energy metabolism inhibitors, and auxin inhibitors.

[0004] Pigment biosynthesis inhibitors can be classified into chlorophyll biosynthesis inhibitors, carotenoid biosynthesis inhibitors, and plastoquinone biosynthesis inhibitors. Representative examples of carotenoid biosynthesis inhibitors include norflurazon, fluridone, flurochloridone, diflufenican, flurtamone, picolinafen, or beflubutamid. Existing herbicides have high treatment doses, complex production processes for herbicidal active substances, and high production costs, so there is a continuous need for research and development of new herbicides.

[0005] Many phenoxy compounds and their herbicidal activity properties have been disclosed in the art, and recently, many heterocyclic substituted phenoxy compounds and their herbicidal activity have been reported. International Patent Publication Nos. WO2015-089003 and WO2015-108779 disclose pyrimidinyloxybenzene compounds as herbicides, respectively, and International Patent Publication Nos. WO2020-094524 and WO2020-126746 disclose the herbicidal activity of pyridinyloxybenzene compounds, respectively. Meanwhile, International Patent Publication Nos. WO2021-028419 and WO2021-028421 disclose substituted (2-heteroaryloxyphenyl)isoxazolines and their use as herbicidal agents, respectively, and International Patent Publication No. WO2021-204706 discloses 5-haloalkoxy-pyrimidine compounds as herbicides. The above prior art is similar in that it is an oxybenzene or oxyphenyl compound as a herbicide, but does not disclose a phenoxy compound containing a fluoroalkyl group-substituted tetrazole of the present invention.

[0006] The present invention was derived from the above-mentioned needs, and the present invention completed the present invention by confirming that any one compound selected from the group consisting of a phenoxy compound containing a fluoroalkyl group-substituted tetrazole represented by the chemical formula 1 and an agrochemically acceptable salt thereof has selectivity for cultivated crops, does not cause any harm to useful crops such as wheat, corn or rice, and has an excellent herbicidal effect before / after weed emergence for the removal of broadleaf weeds.

[0007] To achieve the above purpose, the present invention provides a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group-substituted tetrazole represented by the chemical formula 1 and an agrochemically acceptable salt thereof.

[0008] In addition, the present invention provides a herbicide comprising a compound of chemical formula 1, an agrochemically acceptable salt thereof, or a mixture thereof as an active ingredient.

[0009] In addition, the present invention provides a herbicidal composition characterized in that it comprises, as an active ingredient, 0.1 to 99.9 wt% of a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group-substituted tetrazole represented by Chemical Formula 1 and an agrochemically acceptable salt thereof, or a mixture thereof; and 0.1 to 99.9 wt% of one or more additives selected from a surfactant, a solid diluent, or a liquid diluent.

[0010] The present invention relates to a herbicide comprising a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group-substituted tetrazole represented by Chemical Formula 1 and an agrochemically acceptable salt thereof; and a compound of Chemical Formula 1, an agrochemically acceptable salt thereof, or a mixture thereof as an active ingredient, which has selectivity for cultivated crops and thus does not cause any harm to useful crops such as wheat, corn, or rice, and has an excellent herbicidal effect when treating broadleaf weeds before / after emergence.

[0011] The present invention relates to a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group-substituted tetrazole represented by the following chemical formula 1 and an agrochemically acceptable salt thereof.

[0012]

[0013] In the above chemical formula 1,

[0014] R1 represents a halogen group, a (C1-C3)alkyl group, a (C1-C3)haloalkyl group, a (C1-C3)alkoxy group or a (C1-C3)haloalkoxy group;

[0015] R2 represents H, a halogen group, a (C1-C3)alkyl group, or a (C1-C3)alkoxy group;

[0016] R3 represents a (C1-C3)fluoroalkyl group;

[0017] It is preferable that A represents CF or N,

[0018] More preferably, R1 represents a halogen group, a (C1-C3)haloalkyl group or a (C1-C3)haloalkoxy group;

[0019] R2 represents H, a halogen group or a (C1-C3)alkoxy group;

[0020] R3 represents a (C1-C3)fluoroalkyl group;

[0021] A represents CF or N,

[0022] Even more preferably

[0023] R1 represents Cl, CF3 or OCF2H;

[0024] R2 represents H, F, Cl or OCH3;

[0025] R3 represents CF2H, CFH2, or CH2CF2H;

[0026] A represents CF or N.

[0027] Among the phenoxy compounds containing a tetrazole ring substituted with fluoroalkyl represented by the above chemical formula 1, more preferred compounds are as follows.

[0028] 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-3-fluoropyridine;

[0029] 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-3-fluoropyridine;

[0030] 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0031] 5-chloro-2-(2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0032] 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine;

[0033] 5-chloro-2-(3-fluoro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0034] 2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine;

[0035] 5-(Difluoromethoxy)-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine;

[0036] 5-chloro-2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine;

[0037] 2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine;

[0038] 5-chloro-2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0039] 5-chloro-2-(3-chloro-2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0040] 2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-5-(difluoromethoxy)pyrimidine;

[0041] 5-chloro-2-(4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0042] 5-chloro-2-(5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine;

[0043] 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine;

[0044] 2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine;

[0045] 5-(Difluoromethoxy)-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine;

[0046] 5-chloro-2-(4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)pyrimidine;

[0047] 5-chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine; and

[0048] Any one compound selected from the group consisting of their pesticide-acceptable salts.

[0049] Agrochemically acceptable salts of phenoxy compounds containing a fluoroalkyl substituted tetrazole represented by the above chemical formula 1 may include, for example, salts with inorganic acids, salts with organic acids, salts with acidic amino acids, etc.

[0050] Salts with preferred inorganic acids may include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, or phosphoric acid, etc. Salts with preferred organic acids may include salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, or p-toluenesulfonic acid, etc. Salts with preferred acidic amino acids may include salts with aspartic acid or glutamic acid, etc.

[0051] In addition, the present invention relates to a herbicide comprising the compound of the above chemical formula 1, an agrochemically acceptable salt thereof, or a mixture thereof as an active ingredient.

[0052] The above herbicide has selectivity for cultivated crops and can be used for weed control by treating weeds before emergence (pre-emergence) or after emergence (post-emergence).

[0053] The above crop is preferably corn, wheat or rice, but is not limited thereto, and the above weed is preferably a broadleaf weed, and the above broadleaf weed is preferably roundleaf rhododendron, dwarf rhododendron, hairy rhododendron or kudzu, but is not limited thereto.

[0054] In addition, the present invention relates to a herbicidal composition characterized in that it comprises, as an active ingredient, 0.1 to 99.9 wt% of a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl substituted tetrazole represented by the following chemical formula 1 and an agrochemically acceptable salt thereof, or a mixture thereof; and 0.1 to 99.9 wt% of one or more additives selected from a surfactant, a solid diluent, or a liquid diluent.

[0055] [Chemical Formula 1]

[0056]

[0057] In the above chemical formula 1,

[0058] R1 represents a halogen group, a (C1-C3)alkyl group, a (C1-C3)haloalkyl group, a (C1-C3)alkoxy group or a (C1-C3)haloalkoxy group;

[0059] R2 represents H, a halogen group, a (C1-C3)alkyl group, or a (C1-C3)alkoxy group;

[0060] R3 represents a (C1-C3)fluoroalkyl group;

[0061] A represents CF or N.

[0062] The above herbicidal composition is preferably formulated in one dosage form selected from among a wettable powder, a suspension, an emulsion, an emulsifier, a turbidity agent, a liquid, a dispersible liquid, a granular wettable powder, a granule, a powder, a liquid wettable powder, a floating granule, and a tablet, but is not limited thereto.

[0063] In addition to the effective ingredients of the above herbicidal composition, one selected from the group consisting of an acetyl-CoA carboxylase (ACCase) inhibitor, an acetolactate synthase (ALS) inhibitor, a cell division inhibitor, an auxin-type herbicide, a photosynthetic system 1, 2 inhibitor, a 5-enolpyruvylshikimate 3-phosphate synthase (ESPS) inhibitor, a glutamine synthetase inhibitor, a carotenoid biosynthesis inhibitor, a protoporphyrinogen oxidase inhibitor, a lipid biosynthesis inhibitor, a plastoquinone biosynthesis inhibitor, a cell wall biosynthesis inhibitor, an auxin transport inhibitor, an oxidative phosphorylation process inhibitor by uncoupler, a serine-threonine protein phosphatase inhibitor, a dihydrooresinol dehydrogenase (DHODH) inhibitor, a herbicide with an unknown point of action, and a known herbicide It may contain additional ingredients.

[0064] The compound represented by Chemical Formula 1 of the present invention can be prepared by a general method known in the field of synthetic organic chemistry. The compound represented by Chemical Formula 1 can be prepared using a method as described in Schemes 1 to 3. Unless otherwise specified, all substituents for Chemical Formulas 1 to 4 are as defined in Chemical Formula 1 above.

[0065] As shown in Scheme 1, the compound represented by Chemical Formula 1 ([1]) can be prepared by reacting the tetrazole-substituted phenol compound represented by Chemical Formula 2 ([2]) with the compound represented by Chemical Formula 3 ([3]) under basic conditions. Specific examples of the base include triethylamine, diisopropylethylamine, potassium carbonate, cesium carbonate, sodium hydride, sodium hydroxide, and the like. The reaction solvent may include tetrahydrofuran, dimethylformamide, toluene, 1,4-dioxane, pyridine, acetonitrile, dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, and the like. The reaction temperature is preferably 50 to 100°C. After the reaction is completed, the organic layer obtained by diluting with water and extracting with an organic solvent can be concentrated under reduced pressure and purified by silica gel column chromatography.

[0066] [Reaction Formula 1]

[0067]

[0068] (In the above reaction scheme 1, X is defined as fluorine, chlorine, bromine, iodine or methanesulfonyl.)

[0069] As shown in Scheme 2, the compound represented by Chemical Formula 2 ([2]) can be prepared by a fluoroalkylation reaction of the compound represented by Chemical Formula 4 ([4]) under basic conditions. However, the compound represented by R3 as CF2H can be prepared using ethyl 2-bromo-2,2-difluoroacetate or (bromodifluoromethyl)trimethylsilane. Specific examples of the base may include triethylamine, diisopropylethylamine, potassium carbonate, cesium carbonate, sodium carbonate, sodium hydride, potassium hydroxide, etc. The reaction solvent may include tetrahydrofuran, dimethylformamide, toluene, 1,4-dioxane, pyridine, acetonitrile, dichloromethane, chloroform, 1,2-dichloroethane, ethyl acetate, etc. The reaction temperature is preferably 0 to 60°C. After the reaction is complete, the organic layer obtained by diluting with water and extracting with an organic solvent can be concentrated under reduced pressure and purified using silica gel column chromatography.

[0070] [Reaction Formula 2]

[0071]

[0072] (In the above reaction formula 2, Y is defined as chlorine, bromine, iodine or trifluoromethanesulfonate.)

[0073] As shown in Scheme 3, the compound represented by Chemical Formula 4 ([4]) can be prepared by reacting a substituted benzonitrile compound with sodium azide (NaN3) under basic conditions. Specific examples of the base include ammonium chloride (NH4Cl), triethylamine hydrochloride (Et3N·HCl), diethylammonium chloride (Et2NH·HCl), hydroxyl ammonium chloride (NH2OH·HCl), etc. The reaction solvent may include toluene, dimethylformamide, dimethyl sulfoxide, etc. The reaction temperature is preferably 80 to 140°C. After the reaction is completed, an aqueous hydrogen chloride solution is added, and the obtained solid can be dried to obtain the product.

[0074] [Reaction Formula 3]

[0075]

[0076] Specific examples of the compounds represented by the above chemical formula 1 synthesized through this example are as shown in Table 1 below. Those skilled in the art can easily synthesize the compounds exemplified in Table 1 below by using or applying the synthetic method specified in this example.

[0077]

[0078]

[0079] The results of structural analysis of the compounds specified in Tables 1 and 2 above are as shown in Table 3 below.

[0080] Compound No. 1 H NMR1 1 H NMR (300MHz, CDCl3) δ 8.38 (s, 1H), 7.76 (d,J= 7.6 Hz, 1H), 7.66 (t,J= 7.9 Hz, 1H), 7.61 - 7.45 (m, 3H), 7.39 (d,J= 9.1 Hz, 1H)3 1 H NMR (400MHz, CDCl3) δ 7.82 (s, 1H), 7.64 (t,J= 57.3 Hz, 1H), 7.62 (d,J= 6.8 Hz, 1H), 7.52 (d,J= 9.0 Hz, 1H), 7.25 - 7.17 (m, 2H)15 1 H NMR (400MHz, CDCl3) δ 8.46 (s, 2H), 8.36 (dd,J= 7.8, 1.6 Hz, 1H), 7.67 (td,J= 8.0, 1.7 Hz, 1H), 7.57 (t,J= 56.1 Hz, 1H) 7.51 (td,J= 7.7, 1.0 Hz, 1H), 7.39 (dd,J= 7.8, 1.6 Hz, 1H)16 1NMR (300MHz, CDCl3) δ 8.44 (s, 2H), 8.34 (dd,J= 7.7, 1.6 Hz, 1H), 7.68 - 7.58 (m, 1H), 7.53 - 7.44 (m, 1H), 7.35 (dt,J= 8.1, 1.1 Hz, 1H), 6.44 (s, 1H), 6.27 (s, 1H)17 1 H NMR (500MHz, CDCl3) δ 8.49 (s, 2H), 7.65 (d,J= 8.4 Hz, 1H), 7.63 (t,J= 57.2 Hz, 1H), 7.30 - 7.24 (m, 1H), 7.22 (d,J= 8.2 Hz, 1H)18 1 H NMR (300MHz, CDCl3) δ 8.46 (s, 2H), 7.68 - 7.52 (m, 1H), 7.29 - 7.22 (m, 1H), 7.22 - 7.13 (m, 1H), 6.50 (s, 1H), 6.34 (s, 1H)19 1 H NMR (400MHz, CDCl3) δ 8.78 (s, 2H), 7.67- 7.62 (m, 1H), 7.74 - 7.45 (m, 1H), 7.32 - 7.25 (m, 1H), 7.22 (d,J= 8.3 Hz, 1H)20 1 H NMR (400MHz, CDCl3) δ 8.40 (s, 2H), 7.76 - 7.42 (m, 2H), 7.29 - 7.18 (m, 2H), 6.53 (t,J= 71.7 Hz, 1H)21 1 H NMR (400MHz, CDCl3) δ 8.44 (s, 2H), 7.58 (td,J= 8.4, 6.1 Hz, 1H), 7.23 (ddd,J= 9.5, 8.5, 1.0 Hz, 1H), 7.17 (dt,J= 8.3, 1.1 Hz, 1H), 6.21 (tt,J= 54.5, 4.3 Hz, 1H), 4.95 (td,J= 12.6, 4.3 Hz, 2H)22 1H NMR (400MHz, CDCl3) δ 8.75 (d,J= 0.9 Hz, 2H), 7.61 (td,J= 8.4, 6.0 Hz, 1H), 7.33 - 7.23 (m, 1H), 7.19 (dt,J= 8.3, 1.1 Hz, 1H), 6.18 (tt,J= 54.4, 4.2 Hz, 1H), 4.94 (td,J= 12.7, 4.2 Hz, 2H)23 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 7.63 (t,J= 56.2 Hz, 1H), 7.62 - 7.51 (m, 2H), 7.30 (d,J= 8.9 Hz, 1H)24 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 7.63 - 7.50 (m, 2H), 7.29 (d,J= 6.5 Hz, 1H), 6.45 (d,J= 49.8 Hz, 2H)25 1 H NMR (400MHz, CDCl3) δ 8.40 (s, 2H), 7.76 - 7.43 (m, 3H), 7.30 (dd,J= 8.1, 1.2 Hz, 1H), 6.53 (t,J= 71.6 Hz, 1H)26 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 8.36 (s, 1H), 7.62 (dd,J= 8.7, 2.6 Hz, 1H), 7.71 - 7.42 (m, 1H), 7.34 (d,J= 8.7 Hz, 1H)27 1 H NMR (400MHz, CDCl3) δ 8.44 (s, 2H), 8.27 (d,J= 8.4 Hz, 1H), 7.75 - 7.47 (m, 1H), 7.46 - 7.44 (m, 1H), 7.39 (s, 1H)28 1 H NMR (300MHz, CDCl3) δ 8.47 (s, 2H), 7.86 - 7.85 (m, 1H), 7.74 - 7.36 (m, 1H), 7.32 - 7.29 (m, 1H), 7.20 - 7.16 (m, 1H), 3.95 (s, 3H)29 1H NMR (400MHz, CDCl3) δ 7.86 (s, 1H), 7.77 - 7.69 (m, 2H), 7.57 - 7.53 (m, 1H), 7.53 (t,J= 56.2 Hz, 1H), 7.49 (t,J= 7.6 Hz, 1H), 7.33 (d,J=8.7 Hz, 1H)47 1 H NMR (400MHz, CDCl3) δ 8.79 (s, 2H), 7.70 - 7.64 (m, 1H), 7.25 (d,J= 7.1 Hz, 1H), 7.22 - 7.19 (m, 1H), 6.87 (t,J= 56.9 Hz, 1H)48 1 H NMR (400MHz, CDCl3) δ 8.37 (s, 2H), 7.72 (td,J= 8.4, 6.3 Hz, 1H), 7.46 (t,J= 57.6 Hz, 1H), 7.30 - 7.19 (m, 2H), 6.53 (t,J= 71.5 Hz, 1H)54 1 H NMR (400 MHz, CDCl3) δ 8.43 (s, 2H), 7.75 - 7.46 (m, 1H), 7.69 - 7.66 (m, 2H), 7.38 - 7.35 (m, 1H)56 1 H NMR (300 MHz, CDCl3) δ 8.43 (s, 2H), 7.76 - 7.38 (m, 1H), 7.34 - 7.16 (m, 3H), 3.91 (s, 3H)

[0081] Representative synthetic methods for the compounds specified in Tables 1 and 2 above are as follows.

[0082]

[0083] Example 1. 5-Chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-3-fluoropyridine (Compound No. 1)

[0084] Step 1) 2-(1H-tetrazol-5-yl)phenol

[0085] To a solution of 2-hydroxybenzonitrile (5.0 g, 41.97 mmol) in toluene (50 ml) were added triethylamine hydrochloride (17.33 g, 125.92 mmol) and sodium azide (8.19 g, 125.92 mmol), and the reaction solution was stirred at 120°C for 18 hours. After completion of the reaction, the reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for 18 hours to obtain 6.88 g (quant.) of the target compound in the form of a white solid.

[0086] 1 H NMR (400 MHz, CD3OD) δ 8.08 (dd,J= 7.8, 1.7 Hz, 1H), 7.44 (ddd,J= 8.7, 7.3, 1.7 Hz, 1H), 7.12 - 7.00 (m, 2H).

[0087]

[0088] Step 2) 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol

[0089] To a solution of 2-(1H-tetrazol-5-yl)phenol (300 mg, 1.85 mmol) in N,N-dimethylformamide (6.0 mL) were added potassium carbonate (306.8 mg, 2.22 mmol) and ethyl 2-bromo-2,2-difluoroacetate (0.36 mL, 2.78 mmol), and the reaction solution was stirred at room temperature for 1 day. Then, it was stirred at 60°C for 1 hour. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 5 / 95) to obtain 60.2 mg (15%) of the title compound as a white solid.

[0090] 1H NMR (400MHz, CDCl3) δ 9.26 (br s, 1H), 8.15 (dd,J= 7.9, 1.7 Hz, 1H), 7.75 (t,J= 57.3 Hz, 1H), 7.47 (ddd,J= 8.7, 7.2, 1.7 Hz, 1H), 7.14 (dd,J= 8.4, 1.1 Hz, 1H), 7.06 (ddd,J= 8.3, 7.3, 1.1 Hz, 1H).

[0091] Step 3) 5-chloro-2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-3-fluoropyridine

[0092] To a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol (60.2 mg, 0.28 mmol) in N,N-dimethylformamide (2.0 mL) were added potassium carbonate (116.1 mg, 1.84 mmol) and 5-chloro-2,3-difluoropyridine (0.04 mL, 0.36 mmol), and the reaction solution was stirred at 90°C for 2 hours. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed with a 1 N aqueous hydrochloric acid solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 5 / 95) to obtain 18.7 mg (20%) of the title compound as a white solid.

[0093] 1 H NMR (300MHz, CDCl3) δ 8.38 (s, 1H), 7.76 (d,J= 7.6 Hz, 1H), 7.66 (t,J= 7.9 Hz, 1H), 7.61 - 7.45 (m, 3H), 7.39 (d,J= 9.1 Hz, 1H).

[0094]

[0095] Example 2. 5-Chloro-2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-3-fluoropyridine (Compound No. 3)

[0096] Step 1) 3-Fluoro-2-(1H-tetrazol-5-yl)phenol

[0097] To a solution of 2-fluoro-6-hydroxybenzonitrile (1.37 g, 10.00 mmol) in toluene (12 ml) were added triethylamine hydrochloride (4.13 g, 30.00 mmol) and sodium azide (1.95 g, 30.00 mmol), and the reaction solution was stirred at 120°C for 18 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for 18 hours to obtain 1.546 g (86%) of the target compound as a brown solid.

[0098] 1 H NMR (300 MHz, CD3OD) δ 7.46 (td,J= 8.4, 6.6 Hz, 1H), 6.93 (dt,J= 8.5, 1.0 Hz, 1H), 6.86 (ddd,J= 10.6, 8.4, 1.0 Hz, 1H).

[0099]

[0100] Step 2) 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenol

[0101] To a solution of 3-fluoro-2-(1H-tetrazol-5-yl)phenol (4.0 g, 22.2 mmol) in ethyl acetate (80 mL) was slowly added diisopropylethylamine (11.6 mL, 66.6 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (5.18 mL, 33.3 mmol) and the mixture was stirred for 1 hour. After the reaction was complete, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 4.24 g (83%) of the title compound as a white solid.

[0102] 1 H NMR (300MHz, CDCl3) δ 10.02 (br s, 1H), 7.79 (t,J= 57.3 Hz, 1H), 7.45 - 7.37 (m, 1H), 6.96 (d,J= 8.5 Hz, 1H), 6.82 (dd,J= 10.6, 8.3 Hz, 1H).

[0103]

[0104] Step 3) 5-chloro-2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)fluorophenoxy)-3-fluoropyridine

[0105] To a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenol (94.4 mg, 0.41 mmol) in N,N-dimethylformamide (2 mL) were added potassium carbonate (170.0 mg, 1.23 mmol) and 5-chloro-2,3-difluoropyridine (0.06 mL, 0.53 mmol), and the reaction solution was stirred at 90°C for 1 hour. When the reaction was complete, the reaction mixture was diluted with water and extracted with diethyl ether. The obtained organic layer was washed twice more with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 7.7 mg (5%) of the title compound as a yellow oil.

[0106] 1 H NMR (400MHz, CDCl3) δ 7.82 (s, 1H), 7.64 (t,J= 57.3 Hz, 1H), 7.62 (d,J= 6.8 Hz, 1H), 7.52 (d,J= 9.0 Hz, 1H), 7.25 - 7.17 (m, 2H).

[0107]

[0108] Example 3. 5-Chloro-2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 15)

[0109] To a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-phenol (45.0 mg, 0.21 mmol) in N,N-dimethylformamide (2 mL) were added potassium carbonate (87.1 mg, 0.63 mmol) and 2,5-dichloropyrimidine (41.7 mg, 0.28 mmol), and the reaction solution was stirred at 90°C for 1 hour. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed once with a 1 N aqueous hydrochloric acid solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 36.2 mg (53%) of the title compound as a white solid.

[0110] 1 H NMR (400MHz, CDCl3) δ 8.46 (s, 2H), 8.36 (dd,J= 7.8, 1.6 Hz, 1H), 7.67 (td,J= 8.0, 1.7 Hz, 1H), 7.57 (t,J= 56.1 Hz, 1H) 7.51 (td,J= 7.7, 1.0 Hz, 1H), 7.39 (dd,J= 7.8, 1.6 Hz, 1H).

[0111]

[0112] Example 4. 5-Chloro-2-(2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 16)

[0113] Step 1) 2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol

[0114] To a solution of 2-(1H-tetrazol-5-yl)phenol (243 mg, 1.51 mmol) in acetonitrile (5.0 mL) were added cesium carbonate (541 mg, 1.66 mmol) and fluoroiodomethane solution (2 M in acetonitrile, 0.83 mL, 1.66 mmol) at 0°C, and the reaction solution was stirred at room temperature for 5 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 91.0 mg (31%) of the title compound as a white solid.

[0115] 1 H NMR (500MHz, CDCl3) δ 9.40 (s, 1H), 8.11 (dd,J= 7.9, 1.7 Hz, 1H), 7.43 (ddd,J= 8.7, 7.2, 1.7 Hz, 1H), 7.12 (dd,J= 8.4, 1.2 Hz, 1H), 7.08 - 6.96 (m, 1H), 6.59 (s, 1H), 6.49 (s, 1H).

[0116]

[0117] Step 2) 5-chloro-2-(2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0118] To a solution of 2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol (91.0 mg, 0.47 mmol) in N,N-dimethylformamide (2.0 mL) were added potassium carbonate (195 mg, 1.41 mmol) and 2,5-dichloropyrimidine (91.0 mg, 0.61 mmol), and the reaction solution was stirred at 90°C for 1 hour. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 142 mg (99%) of the title compound as a white solid.

[0119] 1 H NMR (300MHz, CDCl3) δ 8.44 (s, 2H), 8.34 (dd,J= 7.7, 1.6 Hz, 1H), 7.68 - 7.58 (m, 1H), 7.53 - 7.44 (m, 1H), 7.35 (dt,J= 8.1, 1.1 Hz, 1H), 6.44 (s, 1H), 6.27 (s, 1H).

[0120]

[0121] Example 5. 5-Chloro-2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine (Compound No. 17)

[0122] To a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenol (82.0 mg, 0.36 mmol) in N,N-dimethylformamide (2 mL) were added potassium carbonate (149 mg, 1.08 mmol) and 2,5-dichloropyrimidine (68.5 mg, 0.46 mmol), and the reaction solution was stirred at 90°C for 1 hour. When the reaction was complete, the reaction mixture was diluted with water and extracted with diethyl ether. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 27.1 mg (22%) of the title compound as a clear oil.

[0123] 1 H NMR (500 MHz, CDCl3) δ 8.49 (s, 2H), 7.65 (d,J= 8.4 Hz, 1H), 7.63 (t,J= 57.2 Hz, 1H), 7.30 - 7.24 (m, 1H), 7.22 (d,J= 8.2 Hz, 1H).

[0124]

[0125] Example 6. 5-Chloro-2-(3-fluoro-2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 18)

[0126] Step 1) 3-Fluoro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol

[0127] To a solution of 3-fluoro-2-(1H-tetrazol-5-yl)phenol (333 mg, 1.85 mmol) in acetonitrile (8.0 mL) were added cesium carbonate (665 mg, 2.01 mmol) and fluoroiodomethane solution (2 M in acetonitrile, 1.02 mL, 2.04 mmol) at 0°C, and the reaction solution was stirred at room temperature for 6 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 43.6 mg (11%) of the title compound as a white solid.

[0128] 1 H NMR (500MHz, CDCl3) δ 10.23 (s, 1H), 7.44 - 7.30 (m, 1H), 6.94 (dt,J= 8.5, 1.1 Hz, 1H), 6.81 (ddd,J= 10.6, 8.2, 1.1 Hz, 1H), 6.65 (s, 1H), 6.55 (s, 1H).

[0129]

[0130] Step 2) 5-chloro-2-(3-fluoro-2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0131] To a solution of 3-fluoro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol (43.6 mg, 0.206 mmol) in N,N-dimethylformamide (1.0 mL) were added potassium carbonate (85.4 mg, 0.618 mmol) and 2,5-dichloropyrimidine (40.0 mg, 0.268 mmol), and the reaction solution was stirred at 90°C for 1 hour. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 43.3 mg (65%) of the title compound as a white solid.

[0132] 1 H NMR (300 MHz, CDCl3) δ 8.46 (s, 2H), 7.68 - 7.52 (m, 1H), 7.29 - 7.22 (m, 1H), 7.22 - 7.13 (m, 1H), 6.50 (s, 1H), 6.34 (s, 1H).

[0133]

[0134] Example 7. 2-(2-(2-difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine (Compound No. 19)

[0135] To a solution of 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenol (100 mg, 0.43 mmol) in N,N-dimethylformamide (3 mL) were added 2-chloro-5-(trifluoromethyl)pyrimidine (102.2 mg, 0.56 mmol) and potassium carbonate (178.3 mg, 1.29 mmol) at room temperature, and the reaction solution was stirred at 90°C for 3 hours. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 34.0 mg (21%) of the title compound as a white solid.

[0136] 1 H NMR (400MHz, CDCl3) δ 8.78 (s, 2H), 7.67- 7.62 (m, 1H), 7.74 - 7.45 (m, 1H), 7.32 - 7.25 (m, 1H), 7.22 (d,J= 8.3 Hz, 1H).

[0137]

[0138] Example 8. 5-(Difluoromethoxy)-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine (Compound No. 20)

[0139] Step 1) 5-(difluoromethoxy)-2-(methylthio)pyrimidine

[0140] To a solution of 2-chloro-5-(difluoromethoxy)pyrimidine (2.49 g, 13.79 mmol) in N,N-dimethylformamide (15.0 mL) was slowly added sodium thiomethoxide (1.16 g, 16.55 mmol) at 0°C, and the reaction solution was stirred at room temperature for 2 hours. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 2.10 g (79%) of the title compound as a clear oil.

[0141] 1 H NMR (300 MHz, CDCl3) δ 8.43 (s, 2H), 6.54 (t, J= 71.8 Hz, 1H), 2.57 (s, 3H).

[0142]

[0143] Step 2) 5-(difluoromethoxy)-2-(methylsulfonyl)pyrimidine

[0144] To a solution of 5-(difluoromethoxy)-2-(methylthio)pyrimidine (1.73 g, 9.00 mmol) in dichloromethane (25 mL) was slowly added m-chloroperoxybenzoic acid (4.03 g, 18.00 mmol) at 0°C, and the reaction solution was stirred at room temperature for 2 hours. The reaction was quenched with a 10% aqueous sodium thiosulfate solution, and the obtained organic layer was washed with a 1 N aqueous sodium hydroxide solution and water. The organic layer was dried over anhydrous sodium sulfate and dried under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 1.40 g (69%) of the target compound as a white solid.

[0145] 1 H NMR (400 MHz, CDCl3) δ 8.80 (s, 2H), 6.73 (t, J= 70.4 Hz, 1H), 3.38 (s, 3H).

[0146]

[0147] Step 3) 5-(difluoromethoxy)-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine

[0148] To a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenol (100 mg, 0.43 mmol) in acetonitrile (2.0 mL) were added potassium carbonate (118.9 mg, 0.86 mmol) and 5-(difluoromethoxy)-2-(methylsulfonyl)pyrimidine (146.1 mg, 0.65 mmol), and the reaction solution was stirred at 60°C for 15 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 110.5 mg (69%) of the title compound as a white solid.

[0149] 1 H NMR (400MHz, CDCl3) δ 8.40 (s, 2H), 7.76 - 7.42 (m, 2H), 7.29 - 7.18 (m, 2H), 6.53 (t,J= 71.7 Hz, 1H).

[0150]

[0151] Example 9. 5-Chloro-2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine (Compound No. 21)

[0152] Step 1) 2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenol

[0153] To a solution of 3-fluoro-2-(2H-tetrazol-5-yl)phenol (1.0 g, 5.55 mmol) in ethyl acetate (25 mL) were slowly added diisopropylamine (2.90 mL, 16.65 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (1.78 g, 8.33 mmol) at 0°C, and the reaction solution was stirred for 1 hour. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 480.0 mg (35%) of the title compound as a white solid.

[0154] 1 H NMR (400MHz, CDCl3) δ 10.34 (br s, 1H), 7.36 (td,J= 8.4, 6.2 Hz, 1H), 6.93 (d,J= 8.5 Hz, 1H), 6.78 (dd,J= 11.6, 8.3 Hz, 1H), 6.39 (tt,J= 54.5, 4.3 Hz, 1H), 5.13 (td,J= 12.5, 4.3 Hz, 2H).

[0155] Step 2) 5-chloro-2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine

[0156] To a solution of 2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenol (100 mg, 0.41 mmol) in acetonitrile (2 mL) were added potassium carbonate (113.3 mg, 0.82 mmol) and 5-chloro-2-(methylsulfonyl)pyrimidine (117.5 mg, 0.61 mmol), and the reaction solution was stirred at 60°C for 17 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 148.5 mg (quant) of the title compound as a clear oil.

[0157] 1 H NMR (400MHz, CDCl3) δ 8.44 (s, 2H), 7.58 (td,J= 8.4, 6.1 Hz, 1H), 7.23 (ddd,J= 9.5, 8.5, 1.0 Hz, 1H), 7.17 (dt,J= 8.3, 1.1 Hz, 1H), 6.21 (tt,J= 54.5, 4.3 Hz, 1H), 4.95 (td,J= 12.6, 4.3 Hz, 2H).

[0158]

[0159] Example 10. 2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine (Compound No. 22)

[0160] To a solution of 2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenol (100 mg, 0.41 mmol) in N,N-dimethylformamide (2 mL) were added potassium carbonate (113.3 mg, 0.82 mmol) and 2-chloro-5-(trifluoromethyl)pyrimidine (111.3 mg, 0.61 mmol), and the reaction solution was stirred at 80°C for 1 hour. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 148.2 mg (93%) of the title compound as a clear oil.

[0161] 1 H NMR (400MHz, CDCl3) δ 8.75 (d,J= 0.9 Hz, 2H), 7.61 (td,J= 8.4, 6.0 Hz, 1H), 7.33 - 7.23 (m, 1H), 7.19 (dt,J= 8.3, 1.1 Hz, 1H), 6.18 (tt,J= 54.4, 4.2 Hz, 1H), 4.94 (td,J= 12.7, 4.2 Hz, 2H).

[0162]

[0163] Example 11. 5-Chloro-2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 23)

[0164] Step 1) 3-chloro-2-(1H-tetrazol-5-yl)phenol

[0165] To a solution of 2-chloro-6-hydroxybenzonitrile (1.54 g, 10.00 mmol) in toluene (15 ml) were added triethylamine hydrochloride (4.13 g, 30.00 mmol) and sodium azide (1.95 g, 30.00 mmol), and the reaction solution was stirred at 120°C for 20 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for 15 hours to obtain 1.70 g (73%) of the target compound as a white solid.

[0166] 1 H NMR (300 MHz, CD3OD) δ 7.40 (t,J= 8.2 Hz, 1H), 7.10 (d,J= 8.1 Hz, 1H), 6.97 (d,J= 8.4 Hz, 1H).

[0167]

[0168] Step 2) 3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol

[0169] To a solution of 3-chloro-2-(1H-tetrazol-5-yl)phenol (896.3 mg, 3.00 mmol) in dichloromethane (8 mL) was slowly added a 20 wt% aqueous potassium hydroxide solution (3.4 mL, 12.00 mmol) and (bromodifluoromethyl)trimethylsilane (0.93 mL, 6.00 mmol) at 0°C and stirred for 1 hour. The mixture was then stirred at room temperature for 2.5 hours. After completion of the reaction, the reaction mixture was diluted with water and extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 169.2 mg (23%) of the title compound as a white solid.

[0170] 1H NMR (400MHz, CDCl3) δ 9.90 (br s, 1H), 7.78 (t,J= 57.3 Hz, 1H), 7.38 - 7.34 (m, 1H), 7.16 (d,J= 8.0 Hz, 1H), 7.09 (d,J= 8.4 Hz, 1H).

[0171]

[0172] Step 3) 5-chloro-2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0173] To a solution of 3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol (97.6 mg, 0.40 mmol) dissolved in N,N-dimethylformamide (2 mL) were added potassium carbonate (164.1 mg, 1.19 mmol) and 2,5-dichloropyrimidine (77.5 mg, 0.52 mmol), and the reaction solution was stirred at 90°C for 1 hour. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 30.0 mg (21%) of the title compound as a white solid.

[0174] 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 7.63 (t,J= 56.2 Hz, 1H), 7.62 - 7.51 (m, 2H), 7.30 (d,J= 8.9 Hz, 1H).

[0175]

[0176] Example 12. 5-Chloro-2-(3-chloro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 24)

[0177] Step 1) 3-chloro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol

[0178] To a solution of 3-chloro-2-(1H-tetrazol-5-yl)phenol (521.8 mg, 1.50 mmol) in acetonitrile (6 mL) were slowly added cesium carbonate (586.5 mg, 1.80 mmol) and fluoroiodomethane (2 M in acetonitrile, 0.90 mL, 1.80 mmol) at 0°C, and the reaction solution was stirred at room temperature for 30 minutes. Then, the mixture was stirred at 45°C for one day. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 65.5 mg (19%) of the title compound as a clear oil.

[0179] 1 H NMR (400 MHz, CDCl3) δ 10.14 (br s, 1H), 7.34 - 7.30 (m, 1H), 7.13 (d,J= 8.0 Hz, 1H), 7.06 (d,J= 8.4 Hz, 1H), 6.62 (d,J= 49.5 Hz, 2H).

[0180] Step 2) 5-chloro-2-(3-chloro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0181] To a solution of 3-chloro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenol (65.5 mg, 0.29 mmol) dissolved in N,N-dimethylformamide (2 mL) were added potassium carbonate (118.9 mg, 0.86 mmol) and 2,5-dichloropyrimidine (56.2 mg, 0.38 mmol), and the reaction solution was stirred at 90°C for 1 hour. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 93.0 mg (94%) of the title compound as a clear oil.

[0182] 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 7.63 - 7.50 (m, 2H), 7.29 (d,J= 6.5 Hz, 1H), 6.45 (d,J= 49.8 Hz, 2H).

[0183]

[0184] Example 13. 2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-5-(difluoromethoxy)pyrimidine (Compound No. 25)

[0185] To a solution of 3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol (150 mg, 0.61 mmol) in acetonitrile (3 mL) were added potassium carbonate (168.6 mg, 1.22 mmol) and 5-(difluoromethoxy)-2-(methylsulfonyl)pyrimidine (204.5 mg, 0.91 mmol), and the reaction solution was stirred at 60°C for 16 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 192.2 mg (81%) of the title compound as a white solid.

[0186] 1 H NMR (400 MHz, CDCl3) δ 8.40 (s, 2H), 7.76 - 7.43 (m, 3H), 7.30 (dd,J= 8.1, 1.2 Hz, 1H), 6.53 (t,J= 71.6 Hz, 1H).

[0187]

[0188] Example 14. 5-Chloro-2-(4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 26)

[0189] Step 1) 4-chloro-2-(1H-tetrazol-5-yl)phenol

[0190] To a solution of 5-chloro-2-hydroxybenzonitrile (3.0 g, 19.54 mmol) in toluene (55 ml) were added triethylamine hydrochloride (8.07 g, 58.62 mmol) and sodium azide (3.81 g, 58.62 mmol), and the reaction solution was stirred at 120°C for 20 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for one day to obtain 3.51 g (91%) of the target compound as a white solid.

[0191] 1 H NMR (400MHz, CD3OD) δ 8.08 (s, 1H), 7.42 (d,J=8.9 Hz, 1H), 7.06 (d,J=8.9 Hz, 1H).

[0192]

[0193] Step 2) 4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol

[0194] To a solution of 4-chloro-2-(1H-tetrazol-5-yl)phenol (1.0 g, 5.09 mmol) in ethyl acetate (25 mL) was slowly added diisopropylethylamine (1.19 mL, 7.64 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (2.66 mL, 15.27 mmol) and the mixture was stirred for 2 hours. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 730 mg (58%) of the title compound as a white solid.

[0195] 1H NMR (300MHz, CDCl3) δ 9.27 (s, 1H), 8.14 (d,J= 2.6 Hz, 1H), 7.94 - 7.56 (t,J= 57.2 Hz, 1H), 7.42 (dd,J= 8.9, 2.6 Hz, 1H), 7.10 (d,J= 8.9 Hz, 1H).

[0196]

[0197] Step 3) 5-chloro-2-(4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0198] To a solution of 4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol (200 mg, 0.81 mmol) in acetonitrile (5 mL) were added potassium carbonate (134.05 mg, 0.97 mmol) and 5-chloro-2-(methylsulfonyl)pyrimidine (235.00 mg, 1.22 mmol), and the reaction solution was stirred at 60°C for 18 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 257.8 mg (89%) of the title compound as a white solid.

[0199] 1 H NMR (400MHz, CDCl3) δ 8.47 (s, 2H), 8.36 (s, 1H), 7.62 (dd,J= 8.7, 2.6 Hz, 1H), 7.71 - 7.42 (m, 1H), 7.34 (d,J= 8.7 Hz, 1H).

[0200]

[0201] Example 15. 5-chloro-2-(5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 27)

[0202] Step 1) 5-chloro-2-(1H-tetrazol-5-yl)phenol

[0203] To a solution of 4-chloro-2-hydroxybenzonitrile (3.0 g, 19.54 mmol) in toluene (55 ml) were added triethylamine hydrochloride (8.07 g, 58.62 mmol) and sodium azide (3.81 g, 58.62 mmol), and the reaction solution was stirred at 120°C for 18 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for 18 hours to obtain 3.62 g (94%) of the target compound as a white solid.

[0204] 1 H NMR (400 MHz, CD3OD) δ 8.07 (d, J= 8.4 Hz, 1H), 7.16 - 6.97 (m, 2H).

[0205]

[0206] Step 2) 5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol

[0207] To a solution of 5-chloro-2-(1H-tetrazol-5-yl)phenol (1.0 g, 5.09 mmol) dissolved in ethyl acetate (25 mL) was slowly added diisopropylethylamine (1.19 mL, 7.64 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (2.66 mL, 15.27 mmol) and the mixture was stirred for 2 hours. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 756.1 mg (60%) of the title compound as a white solid.

[0208] 1H NMR (400MHz, CDCl3) δ 9.41 (d,J= 7.5 Hz, 1H), 8.29 - 8.00 (m, 1H), 8.00 - 7.49 (m, 1H), 7.37 - 6.82 (m, 1H).

[0209]

[0210] Step 3) 5-chloro-2-(5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine

[0211] To a solution of 5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenol (200 mg, 0.81 mmol) in acetonitrile (5 mL) were added 5-chloro-2-(methylsulfonyl)pyrimidine (235 mg, 1.22 mmol) and potassium carbonate (134 mg, 0.97 mmol) at room temperature, and the reaction solution was stirred at 60°C for 18 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 257.6 mg (89%) of the title compound as a white solid.

[0212] 1 H NMR (400MHz, CDCl3) δ 8.44 (s, 2H), 8.27 (d,J= 8.4 Hz, 1H), 7.75 - 7.47 (m, 1H), 7.46 - 7.44 (m, 1H), 7.39 (s, 1H).

[0213]

[0214] Example 16. 5-Chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine (Compound No. 28)

[0215] Step 1) 4-methoxy-2-(1H-tetrazol-5-yl)phenol

[0216] To a solution of 2-hydroxy-5-methoxybenzonitrile (2.0 g, 13.41 mmol) in toluene (40 ml) were added triethylamine hydrochloride (5.54 g, 40.23 mmol) and sodium azide (2.61 g, 40.23 mmol), and the reaction solution was stirred at 120°C for 18 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 2 with concentrated hydrochloric acid, and filtered. The residue was washed with water several times and dried in an oven (60°C) for 18 hours to obtain 2.43 g (94%) of the target compound as a white solid.

[0217] 1 H NMR (300 MHz, CD3OD) δ 7.65 - 7.59 (m, 1H), 7.08 - 6.96 (m, 2H), 3.84 (s, 3H).

[0218]

[0219] Step 2) 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenol

[0220] To a solution of 4-methoxy-2-(1H-tetrazol-5-yl)phenol (2.43 g, 12.64 mmol) dissolved in ethyl acetate (63 mL) was slowly added diisopropylethylamine (6.61 mL, 37.92 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (2.95 mL, 18.96 mmol) and the mixture was stirred for 3 hours and 30 minutes. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 5) to obtain 1.63 g (53%) of the target compound as a white solid.

[0221] 1H NMR (300MHz, CDCl3) δ 8.90 (s, 1H), 7.94 - 7.56 (m, 1H), 7.63 - 7.61 (m, 1H), 7.08 (d,J= 1.7 Hz, 2H), 3.88 (s, 3H).

[0222]

[0223] Step 3) 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine

[0224] 5-Chloro-2-(methylsulfonyl)pyrimidine (595.20 mg, 3.09 mmol) and potassium carbonate (341.35 mg, 2.47 mmol) were added to a solution of 2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenol (500 mg, 2.06 mmol) in acetonitrile (10 mL) at room temperature, and the reaction solution was stirred at 60°C for 22 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 741.70 mg (quant) of the title compound as a white solid.

[0225] 1 H NMR (300 MHz, CDCl3) δ 8.47 (s, 2H), 7.86 - 7.85 (m, 1H), 7.74 - 7.36 (m, 1H), 7.32 - 7.29 (m, 1H), 7.20 - 7.16 (m, 1H), 3.95 (s, 3H).

[0226]

[0227] Example 17. 5-Chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)-3-fluoropyridine (Compound No. 29)

[0228] Step 1) 5-(2-(difluoromethoxy)phenyl)-1-(difluoromethyl)-1H-tetrazole

[0229] To a solution of 2-(1H-tetrazol-5-yl)phenol (200 mg, 1.23 mmol) in dichloromethane (4 mL) was added a 20% wt aqueous potassium hydroxide solution (0.9 mL, 3.69 mmol) and a solution of (bromodifluoromethyl)trimethylsilane (0.29 mL, 1.85 mmol) in dichloromethane (1 mL) at 0°C, and the mixture was stirred at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was diluted with water and extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 76.4 mg (24%) of the title compound as a clear oil.

[0230] 1 H NMR (400MHz, CDCl3) δ 9.26 (br s, 1H), 8.16 (d,J= 7.9 Hz, 1H), 7.75 (t,J= 57.3 Hz, 1H), 7.47 (t,J= 7.8 Hz, 1H), 7.15 (d,J= 8.4 Hz, 1H), 7.07 (t,J= 7.6 Hz, 1H).

[0231] Step 2) 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenol

[0232] To a solution of 5-(2-(difluoromethoxy)phenyl)-1-(difluoromethyl)-1H-tetrazole (76.4 mg, 0.29 mmol) dissolved in anhydrous dichloromethane (3 mL) was added boron tribromide (1 M in dichloromethane, 0.32 mL, 0.32 mmol) at -78°C, and the reaction solution was stirred at -78°C for 1 hour. Additionally, boron tribromide (1 M in dichloromethane, 0.26 mL, 0.526 mmol) was added and stirred for 2.5 hours until the temperature reached 13°C. After completion of the reaction, the reaction mixture was diluted with aqueous sodium bicarbonate solution and extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 61.5 mg (quant.) of the target compound as a white solid.

[0233] 1 H NMR (300MHz, CDCl3) δ 7.68 (d,J= 5.7 Hz, 1H), 7.55 - 7.38 (m, 3H), 7.26 (d,J= 5.4 Hz, 1H).

[0234]

[0235] Step 3) 5-chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)-3-fluoropyridine

[0236] To a solution of 2-(1-(difluoromethyl)-1H-tetrazol-5-)phenol (69.6 mg, 0.33 mmol) in N,N-dimethylformamide (3 mL) were added potassium carbonate (136.8 mg, 0.99 mmol) and 5-chloro-2,3-difluoropyridine (0.04 mL, 0.43 mmol), and the reaction solution was stirred at 90°C for 1 hour. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice more with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 15.0 mg (13%) of the title compound as a clear oil.

[0237] 1 H NMR (400MHz, CDCl3) δ 7.86 (s, 1H), 7.77 - 7.69 (m, 2H), 7.57 - 7.53 (m, 1H), 7.53 (t,J= 56.2 Hz, 1H), 7.49 (t,J= 7.6 Hz, 1H), 7.33 (d,J=8.7 Hz, 1H).

[0238]

[0239] Example 18. 2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine (Compound No. 47)

[0240] Step 1) 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenol

[0241] To a solution of 3-fluoro-2-(1H-tetrazol-5-yl)phenol (4.0 g, 22.2 mmol) dissolved in ethyl acetate (80 mL) was slowly added diisopropylethylamine (11.6 mL, 66.6 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (5.18 mL, 33.3 mmol) and the mixture was stirred for 1 hour. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 480.6 mg (9%) of the target compound as a white solid.

[0242] 1 H NMR (400MHz, CDCl3) δ 9.00 (br s, 1H), 7.70 - 7.34 (m, 2H), 7.02 (d,J= 8.5 Hz, 1H), 6.86 (dd,J= 11.4, 8.4 Hz, 1H).

[0243]

[0244] Step 2) 2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine

[0245] To a solution of 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenol (100 mg, 0.43 mmol) in N,N-dimethylformamide (3 mL) were added 2-chloro-5-(trifluoromethyl)pyrimidine (102.2 mg, 0.56 mmol) and potassium carbonate (178.3 mg, 1.29 mmol) at room temperature, and the reaction solution was stirred at 90°C for 3 hours. When the reaction was complete, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed twice with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 9) to obtain 13.7 mg (8%) of the title compound as a white solid.

[0246] 1 H NMR (400MHz, CDCl3) δ 8.79 (s, 2H), 7.70 - 7.64 (m, 1H), 7.25 (d,J= 7.1 Hz, 1H), 7.22 - 7.19 (m, 1H), 6.87 (t,J= 56.9 Hz, 1H).

[0247]

[0248] Example 19. 5-(Difluoromethoxy)-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine (Compound No. 48)

[0249] To a solution of 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenol (150 mg, 0.65 mmol) in acetonitrile (3 mL) were added potassium carbonate (179.7 mg, 1.30 mmol) and 5-(difluoromethoxy)-2-(methylsulfonyl)pyrimidine (219.2 mg, 0.98 mmol), and the reaction solution was stirred at 60°C for 16 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 1) to obtain 194.1 mg (80%) of the title compound as a white solid.

[0250] 1 H NMR (400MHz, CDCl3) δ 8.37 (s, 2H), 7.72 (td,J= 8.4, 6.3 Hz, 1H), 7.46 (t,J= 57.6 Hz, 1H), 7.30 - 7.19 (m, 2H), 6.53 (t,J= 71.5 Hz, 1H).

[0251]

[0252] Example 20. 5-Chloro-2-(4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)pyrimidine (Compound No. 54)

[0253] Step 1) 4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenol

[0254] To a solution of 4-chloro-2-(1H-tetrazol-5-yl)phenol (1.0 g, 5.09 mmol) in ethyl acetate (25 mL) was slowly added diisopropylethylamine (1.19 mL, 7.64 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (2.66 mL, 15.27 mmol) and the mixture was stirred for 2 hours. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 261.7 mg (16%) of the title compound as a white solid.

[0255] 1 H NMR (400MHz, CDCl3) δ 10.46 (s, 1H), 8.07 - 7.69 (m, 2H), 7.51 (dd,J= 8.8, 2.3 Hz, 1H), 7.18 (d,J= 9.0 Hz, 1H).

[0256]

[0257] Step 2) 5-chloro-2-(4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)pyrimidine

[0258] To a solution of 4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenol (100 mg, 0.41 mmol) in acetonitrile (2.5 mL) were added 5-chloro-2-(methylsulfonyl)pyrimidine (119.42 mg, 0.62 mmol) and potassium carbonate (67.72 mg, 0.49 mmol) at room temperature, and the reaction solution was stirred at 60°C for 17 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 4) to obtain 140 mg (95%) of the title compound as a white solid.

[0259] 1 H NMR (400 MHz, CDCl3) δ 8.43 (s, 2H), 7.75 - 7.46 (m, 1H), 7.69 - 7.66 (m, 2H), 7.38 - 7.35 (m, 1H).

[0260]

[0261] Example 21. 5-Chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine (Compound No. 56)

[0262] Step 1) 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenol

[0263] To a solution of 4-methoxy-2-(1H-tetrazol-5-yl)phenol (2.43 g, 12.64 mmol) in ethyl acetate (63 mL) was slowly added diisopropylethylamine (6.61 mL, 37.92 mmol) at 0°C, followed by the addition of (bromodifluoromethyl)trimethylsilane (2.95 mL, 18.96 mmol) and the mixture was stirred for 3 hours and 30 minutes. After completion of the reaction, a 5% aqueous hydrochloric acid solution was added to the reaction mixture at room temperature and the mixture was stirred for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 1.24 g (41%) of the target compound as a white solid.

[0264] 1 H NMR (300MHz, CDCl3) δ 9.86 (s, 1H), 8.07 - 7.68 (m, 1H), 7.34 - 7.33 (m, 1H), 7.18 - 7.13 (m, 2H), 3.85 (s, 3H).

[0265]

[0266] Step 2) 5-chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine

[0267] 5-Chloro-2-(methylsulfonyl)pyrimidine (595.2 mg, 3.09 mmol) and potassium carbonate (341.4 mg, 2.47 mmol) were added to a solution of 2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenol (500 mg, 2.06 mmol) in acetonitrile (10 mL) at room temperature, and the reaction solution was stirred at 60°C for 22 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1 / 3) to obtain 720.2 mg (99%) of the target compound as a white solid.

[0268] 1 H NMR (300 MHz, CDCl3) δ 8.43 (s, 2H), 7.76 - 7.38 (m, 1H), 7.34 - 7.16 (m, 3H), 3.91 (s, 3H).

[0269] [Serjee]

[0270] The phenoxy compound comprising a fluoroalkyl-substituted tetrazole represented by the above chemical formula 1 according to the present invention can be usefully used as a herbicide. Therefore, the present invention includes a herbicide comprising, as an active ingredient, a compound selected from the group consisting of the compound represented by the above chemical formula 1 and an agrochemically acceptable salt thereof.

[0271] The herbicide of the present invention can be applied to the whole plant or a part of a plant, and in the present invention, 'plant' means all plants and plant populations, such as desired or unwanted wild plants or crops (including wild crops). 'Crops' can be plants obtained by conventional breeding and optimization methods, by biotechnological and recombinant methods, or by a combination of these methods, including plant varieties and transgenic plants that may or may not be protected by plant breeder's guarantees. 'Parts of plants' means all above-ground and underground parts and organs of plants, such as shoots, leaves, flowers, and roots, which may include, for example, leaves, needles, stalks, trunks, flowers, fruit bodies, fruits, seeds, roots, tubers, and rhizomes. Parts of plants also include vegetative and reproductive propagation materials, such as seedlings, tubers, rhizomes, cuttings, and seeds. The herbicide of the present invention can be applied to the whole plant or a part of the plant directly or by a conventional treatment method such as spraying, incorporation, soaking, coating, or fumigation.

[0272] When preparing a herbicidal composition containing the compound represented by the above chemical formula 1 as an active ingredient, carriers, surfactants, diluents, dispersants, and adjuvants commonly used in pesticide formulations may be blended to prepare a formulation in various liquid or solid forms. These formulations may be used directly or may be diluted in an appropriate medium for treatment. The spraying volume may range from several hundred liters to several thousand liters per hectare (ha).

[0273] The herbicidal composition of the present invention may comprise 0.1 to 99.9 wt% of one or more compounds represented by the above chemical formula 1 and their pesticide-acceptable salts as active ingredients; and 0.1 to 99.9 wt% of one or more additives selected from surfactants and solid or liquid diluents. In addition, the herbicidal composition of the present invention may be formulated as a wettable powder, a suspension, an emulsion, an emulsifying agent, a turbidity agent, a liquid, a dispersible liquid, a granular wettable powder, a granule, a powder, a liquid wettable powder, a surface-floating granule, or a tablet.

[0274] Table 4 below exemplifies the contents of the active ingredient and the surfactant and diluent as additives constituting the herbicidal composition of the present invention by type of formulation, but the composition ratio of the herbicidal composition according to the present invention is not limited by Table 4 below.

[0275] Composition ratio of the herbicide composition according to the present invention Formulation content ratio (unit: weight %) Active ingredient Diluent Surfactant Wetting agent 10 ∼ 900 ∼ 801 ∼ 10 Suspension agent 3 ∼ 50 40 ∼ 950 ∼ 15 Emulsion / liquid agent 3 ∼ 50 40 ∼ 950 ∼ 15 Granular agent 0.1 ∼ 955 ∼ 99.51 ∼ 15

[0276] The content of the active ingredient included in the herbicidal composition of the present invention can be adjusted depending on the use, and there are times when it is necessary to use a surfactant at a higher ratio than the active ingredient. The surfactant included in the herbicidal composition of the present invention is a substance with high surface activity, and is an amphiphilic substance having hydrophilic and lipophilic molecular groups in the molecule, and has excellent cleaning power, dispersing power, emulsifying power, solubilizing power, wetting power, sterilizing power, foaming power, and penetrating power, and thus has the function of wetting, disintegrating, dispersing, and emulsifying so that the active ingredient can effectively exhibit its efficacy. The surfactant is (C8~C 12 alkyl)benzenesulfonate, (C3~C6 alkyl)naphthalenesulfonate, di(C3~C6 alkyl)naphthalenesulfonate, di(C8~C 12Alkyl)sulfosuccinate, lignin sulfonate, naphthalene sulfosuccinate formalin condensate, (C8~C 12 Alkyl)naphthalene sulfonate formalin condensate, polyoxyethylene (C8~C 12 Sodium or calcium salts of sulfonates such as alkyl)phenylsulfonate; (C8~C 12 Alkyl) sulfate, polyoxyethylene (C8~C 12 Alkyl) sulfate, polyoxyethylene (C8~C 12 Anionic surfactants may be included, such as sodium or calcium salts of sulfates such as alkyl)phenyl sulfate; sodium or calcium salts of succinates such as polyoxyalkylene succinate; and the like. In addition, the surfactants may include polyoxyethylene (C8~C 12 Alkyl) ether, polyoxyethylene (C8~C 12 Alkyl)phenyl ether, polyoxyethylene (C8~C 12 Nonionic surfactants such as alkyl)phenyl polymers may be included. The above surfactants may be used alone or in combination of two or more, and the surfactants that may be used in the present invention are not limited to the compounds exemplified above.

[0277] The diluents included in the herbicidal composition of the present invention can be classified into solid diluents and liquid diluents based on their properties. Solid diluents with high absorbency are particularly advantageous when preparing wettable powders. Liquid diluents and solvents should be stable and not undergo phase separation even at 0°C. Liquid diluents include water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxytol, alkylpyrrolidone, ethyl acetate. 2-Ethyl hexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene Chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG 400), propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol,Xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and high molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc. can be used. Solid diluents such as talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheatmeal, soybean meal, pumice stone, wood flour, walnut shells, lignin, etc. can be used.

[0278] Additionally, when formulating the herbicidal composition of the present invention, a small amount of other additives may be added to prevent foaming, caking, corrosion, microbial growth, etc. The formulation process is performed by conventional methods. In the case of liquid formulations, the components simply need to be mixed, and fine solid compositions can be mixed and ground in a hammer or fluidized bed mill. Suspensions can be prepared by mixing in a wet mill, and granules can be prepared by spraying the active ingredient onto a granule carrier.

[0279] An example of manufacturing a representative formulation using a compound according to the present invention is as follows.

[0280] Preparation 1: Wetting agent

[0281] The following ingredients were thoroughly mixed and the liquid surfactant was sprayed onto the solid ingredients while mixing. The mixture was pulverized in a hammer mill to a particle size of 100 μm or less.

[0282] - 20% by weight of active compound

[0283] - 2% by weight of dodecylphenol polyethylene glycol ether

[0284] - 4% by weight of sodium lignin sulfonate

[0285] - 6 wt% sodium silicon aluminate

[0286] - 68 wt% montmorillonite

[0287] Preparation 2: Wetting agent

[0288] The following ingredients were mixed and ground in a hammer mill until the particle size was 25㎛ or less, and then packaged.

[0289] - 80% by weight of active compound

[0290] - 2 wt% sodium alkyl naphthalene sulfonate

[0291] - 2% by weight of sodium lignin sulfonate

[0292] - 3 wt% synthetic amorphous silica

[0293] - 13% by weight of kaolinite

[0294] Formulation 3: Milk

[0295] The following ingredients were mixed and dissolved evenly to make an emulsion.

[0296] - 30% by weight of active compound

[0297] - 20% by weight of cyclohexanone

[0298] - 11% by weight of polyoxyethylene alkyl aryl ether

[0299] - 4% by weight of calcium alkylbenzenesulfonate

[0300] - 35 wt% methylnaphthalene

[0301] Preparation 4: Injection

[0302] After uniformly mixing and grinding the following ingredients, 20 parts by weight of water was added to 100 parts by weight of the mixture, mixed, and processed into granules of 14 to 32 mesh using an extrusion granulator, and then dried to produce granules.

[0303] - 5% by weight of active compound

[0304] - 2% by weight of sodium lauryl alcohol sulfate ester salt

[0305] - 5 wt% sodium lignin sulfonate

[0306] - 2% by weight of carboxymethyl cellulose

[0307] - 16% by weight of potassium sulfate

[0308] - 70% gypsum by weight

[0309] The formulation of the present invention was diluted to an appropriate concentration and sprayed for actual use.

[0310] [use]

[0311] The phenoxy compound containing a tetrazole substituted with a fluoroalkyl according to the present invention exhibits high selectivity for corn, wheat or rice during soil treatment and foliar treatment, and is particularly useful for corn, wheat or rice farming because it has an excellent effect in selectively controlling weeds such as round-leafed rhizome, common rhizome, hairy amaranth and kudzu.

[0312] The herbicidal composition of the present invention can be used at a dosage of 200 g to 1 kg per hectare (ha) based on the active ingredient. Preferably, the dosage is 200 g to 400 g, but this is not a limitation. The dosage may be determined by factors such as weed growth rate, weed growth rate, and formulation.

[0313] In addition, the herbicidal composition of the present invention may contain the compound of the above chemical formula 1 alone as an active ingredient, but may also use a conventional active ingredient known to have activity as an agrochemical, if necessary. Known active ingredients that can be used together in the herbicidal composition of the present invention include acetyl-CoA carboxylase (ACCase) inhibitors, acetolactate synthase (ALS) inhibitors, cell division inhibitors, auxin-type herbicides, photosynthetic system 1, 2 inhibitors, 5-enolpyruvylshikimate 3-phosphate synthase (ESPS) inhibitors, glutamine synthetase inhibitors, carotenoid biosynthesis inhibitors, protoporphyrinogen oxidase inhibitors, lipid biosynthesis inhibitors, plastoquinone biosynthesis inhibitors, cell wall biosynthesis inhibitors, auxin transport inhibitors, inhibitors of oxidative phosphorylation process by uncoupler, serine-threonine protein phosphatase inhibitors, dihydrooresinol dehydrogenase (DHODH) inhibitors, herbicides with unknown action sites and known herbicides. It is also useful to use it in combination with one or more herbicidal active compounds selected from the group consisting of:

[0314] The above acetyl-CoA carboxylase (ACCase) inhibitors include cyclohexanediones such as clethodim, cycloxydim, profoxydim, sethoxydim, tepraloxydim, or tralkoxydim; aryloxphenoxy-propionates such as clodinafop-propargyl, cyhalofop-butyl, diclofop-methyl, fenoxaprop-ethyl, fenthiaprop, fluazifop-butyl, haloxyfop-methyl, metamifop, or quizalofop-ethyl; Phenylpyrazoline such as pinoxaden can be used.

[0315] The above acetolactate synthase (ALS) inhibitors include imidazolinones such as imazamethabenz-methyl, imazamox, imazapyr, imazapyr, imazapyr, imazethapyr; triazolopyrimidines such as cloransulam-methyl, diclosulam, flurasulam, flumetsulam, metosulam, penoxsulam, or pyroxsulam; triazolinones such as flucarbazone-Na, propoxycarbarzone-Na, or thiencarbazone-methyl; and sulfonylureas such as amidosulfuron, azimsulfuron, bensulfuron-methyl, chlorimuron-ethyl, chlorsulfuron, cinosulfuron, cyclosulfamuron, ethametsulfuron-methyl, ethoxysulfuron, plazasulfuron, flucetosulfuron, flupyrsulfuron-methyl-Na, foramsulfuron, halosulfuron-methyl, imazosulfuron, iodosulfuron-methyl-Na, mesosulfuron-methyl, metazosulfuron, metsulfuron-methyl, nicosulfuron, orthosulfamuron,Pyrimisulfuron-methyl, propyrisulfuron, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron, sulfometuron-methyl, sulfosulfuron, triasulfuron, tribenuron-methyl, thifensulfuron-methyl, trifloxysulfuron-Na, triflusulfuron-methyl, or tritosulfuron, bispyribac-Na as pyrimidinyl benzoate, pyribenzoxim, pyriftalid, Pyriminobac-methyl, pyrithiobac-Na, sulfonanilides such as pyrimisulfan or triafamone can be used.

[0316] As the above mitotic inhibitors, carbamates such as asulam, barban, carbetamide, or chlorpropham, dinitroanilines such as benfluralin, butralin, ethalfluralin, prodiamine, oryzalin, pendimethalin, or trifluralin, pyridines such as dithiopyr or thiazopyr, phosphoramidates such as butamifos or DMPA, benzoic acid such as chlorthaldimethyl, and benzamide such as pronamide can be used.

[0317] The above auxin-type herbicides include 2,4,5-T, 2,4-D, 2,4-DB, clomeprop, dichlorporp, MCPA, MCPB, or mecoprop as phenoxy-carboxylates, aminopyralid, clopyralid, florpyrauxifen, halauxifen, or picloram as pyridine-carboxylates, quinclorac or quinmerac as quinoline-carboxylates, chloramben or dicamba as benzoates, fluroxypyr or triclopyr as pyridyloxy-carboxylates, and pyrimidinecarboxylates. Aminocyclopyrachlor, benazoline-ethyl, etc., which are not included in the chemical series, can be used.

[0318] The photosynthetic type 1 inhibitors include pyridinium such as diquat or paraquat, the photosynthetic type 2 inhibitors include triazines such as ametryne, atrazine, cyanazine, dimethametryn, prometon, prometryne, propazine, simazine, terbuthylazine, or terbutryne, and the ureas such as chlorotoluron, diuron, fluometuron, isoproturon, linuron, metobromuron, metabenzthiazuron, monuron, or Examples of such agents include tebuthiuron, haxazinone, metamitron, or metribuzin as a triazinone, bromacil, lenacil, or terbacil as a uracil, desmedipham or phenmedipham as a phenylcarbamate, chloranocryl or propanil as an amide, bromoxynil or ioxynil as a nitrile, bentazon as a benzothiadaazinon, pyridate as a phenylpyridazine, pyrazon as a pyridazinone, and amicarbazone as a triazolinone.

[0319] As the above 5-enolpyruvylshikimate-3-phosphate synthase (ESPS) inhibitor, glyphosate or the like can be used as glycine, and as the above glutamine synthetase inhibitor, bialaphos or glufosinate-ammonium or the like can be used as phosphinic acid.

[0320] The carotenoid biosynthesis inhibitors mentioned above may include phenyl ethers such as beflubutamid, diflufenican, or picolinafen, N-phenyl heterocycles such as flurochloridone or norflurazone, diphenyl heterocycles such as fluridone or flurtamone, isoxazolidinones such as bixlozone or clomazone, and triazoles such as amitrole.

[0321] The plastoquinone biosynthesis inhibitors may include triketones such as benzobicyclon, bicyclopyrone, fenquinotrione, mesotrione, sulcotrione, tembotrione, or tefuryltrione; pyrazoles such as benzofenap, pyrasulfotole, pyrazolynate, pyrazoxyfen, tolpyralate, or topramezone; isoxaflutole as isoxazole; phenoxypyridazine such as cyclopyrimorate; and diphenyl ethers such as aclomifen.

[0322] The above protoporphyrinogen IX oxidase inhibitors are N-phenylimides such as butafenacil, cinidon-ethyl, epirifenacil, flumiclorac-pentyl, flumioxazin, fluthiacet-methyl, pentoxazone, saflufencacil, tiafenacil, or trifludimoxazin; diphenyl ethers such as acifluorfen, bifenox, fomesafen, lactofen, or oxyfluorfen; N-phenyl-triazolinones such as azafenidin, carfentrazone-ethyl, Alternatively, sulfentrazone, oxadiargyl or oxadiazon as N-phenyl-oxadiazolones, pyraflufen-ethyl as phenylpyrazole, and pyraclonil, which does not belong to the chemical series, can be used.

[0323] The lipid biosynthesis inhibitors include chloroacetamides such as acetochlor, alachlor, butachlor, dimethachlor, dimethenamid, metazachlor, metolachlor, pethoxamid, pretilachlor, propachlor, thenylchlor, or propisochlor; thiocarbamates such as cycloate, dimepiperate, EPTC, esprocarb, molinate, orbencarb, prosulfocarb, thiobencarb, triallate, or vernolate; and benzofurans such as Benfuresate or ethofumesate, azolylcarboxamides such as capenstrole, fentrazamide, or ipfencarbazone, thioacetamides such as anilofos or piperophos, oxyacetamides such as mefenacet or flufenacet, oxiranes such as indanofan or tridiphane, isoxazoline such as fenoxasulfone or pyroxasulfone, and benzyl esters such as cinmethylin or methiozolin can be used.

[0324] As the above cell wall biosynthesis inhibitor, indaziflam or triaziflam can be used as an alkylazine, chlorthiamid or dichlobenil can be used as a nitrile, flupoxam can be used as a triazolocarboxamide, isoxaben can be used as a benzamide, and as an auxin transport inhibitor, diflufenzopyr or naptalam can be used as an arylcarboxylate.

[0325] As an inhibitor of the oxidative phosphorylation process by the above uncoupler, dinitrophenol such as dinosec or DNOC, as a serine-threonine protein phosphatase inhibitor, endothal, as a dehydrooresinol dehydrogenase (DHODH) inhibitor, arylpyrrolidine anilide such as Tetflupyrolimet can be used.

[0326] Herbicides with unknown action sites include bensulide, bromobutide, cumyluron, difenzoquat, pyributicarb, DSMA, MSMA, dymron, etobenzanid, flamprop-m, fosamine, oxaziclomefone, pelargonic acid, diphenamid, naproanilide, or naproamide.

[0327] The compound according to the present invention possesses herbicidal activity against weeds. Weeds are unwanted plants that occur in crop fields and require control. Weeds are numerous and their classification methods are quite diverse.

[0328] In a common weed classification method, weeds are classified into grasses, cypresses, and broadleaf weeds according to their shapes. The grasses include water parsley, barnyard grass, sorghum, common foxtail, rye, wheatgrass, American foxtail, foxtail, Chinese yam, autumn dog grass, deungsae, binori, large binori, garakjijo, poa grass, or king poa grass, etc. The cypresses include goldenrod, tadpole gorangi, hyangbuja, neodobangdongsani, soetolgol, olbangae, and maejagi, etc. The broadleaf weeds include roundleaf gypsophila, albino, hairy amaranth, kochia, water parsley, blackcurrant, cocklebur, dandelion, and bindweed, etc.

[0329] Also, depending on the number of leaves, weeds are classified as monocotyledonous or dicotyledonous weeds. Monocotyledonous weed species may include grasses such as barnacles, wheatgrass, rice paddy, American dandelion, common barnacles, king barnacles, foxtail, sedge, autumn dog grass, deureungsae, binori, large binori, garakjijo, poa grass or king poa grass. Dicotyledonous weed species include Asteraceae weeds such as yeoncho, hairy jindeukchal, middle head grass, crown daisy, mugwort, American cicada, western dandelion, common forget-me-not, forget-me-not, hairy starch, jijigae, barley weed, mugwort, wild wormwood, goby needle, jindeukchal, maple leaf ragweed, sseumbaegi, godulppaegi, king godulppaegi, American aster, jobangi, dandelion, ragweed, aster, red sedge, etc. Weeds of the Lamiaceae family, such as honeysuckle, dandelion, perilla, and motherwort; weeds of the Euphorbiaceae family, such as sesame, large ground beetle, and baby ground beetle; weeds of the Scrophulariaceae family, such as wrinkled leaf and field ridge grass; weeds of the Solanaceae family, such as black nightshade and American black nightshade; weeds of the Amaranthaceae family, such as common amaranth and fine hairy amaranth; weeds of the Oxalis family, such as sorrel and oxalis; weeds of the Clematis family, such as European primrose and schisandra; weeds of the Malvaceae family, such as watermelon plant and ablution; weeds of the Hemlock family, such as ginseng and hemp; weeds of the Arrhenius family, such as perilla and double evening primrose; weeds of the Purslane family, such as purslane; weeds of the Equisetum family, such as horsetail; weeds of the Araceae family, such as pinellia; weeds of the Umbelliferae family, such as sasa; weeds of the Pomegranate family, such as pomegranate; weeds of the Commelinaceae family, such as Commelinae; weeds of the Crassulaceae family, such as Sedum; This may include weeds from the Papaveraceae family, such as celandine; weeds from the Asteraceae family, such as milk vetch; weeds from the Violaceae family, such as violet; weeds from the Caryophyllaceae family, such as starflower; weeds from the Nettle family, such as mosimultongi; weeds from the Boraginaceae family, such as flower daisy; weeds from the Plantain family, such as plantago; weeds from the Rosaceae family, such as dog's sedge; and weeds from the Water Hyacinth family, such as water dandelion.

[0330]

[0331] Test Example 1. Pre-emergence treatment herbicidal activity test

[0332] Surface area 300cm 2A square plastic pot was filled with a soil mixture of sandy loam and compost mix in a 1:1 ratio, and seeds of three crops, including corn, wheat, and rice, were sown. Another pot made in the same manner was sown with seeds of four weeds, including round-leafed iris, common daisy, hairy amaranth, and kudzu. The pot was irrigated, and pesticides were sprayed after 1 day. Spraying was done using a track sprayer (R&D Sprayer, USA) equipped with a Teejet 8002EVS (Spraying Systems Co., USA) nozzle, and the spraying amount was adjusted to 1000 L / ha. The spraying solution was prepared by dissolving the materials of each example in acetone and then adding the same amount of 0.1% (v / v) Tween 20 aqueous solution. The spraying amount was 200 g ai / ha to 1000 g ai / ha. The pots were placed in a greenhouse maintained at 25–30°C during the day and 15–25°C at night, and watered regularly. Two to three weeks after spraying the test or control substances, the efficacy and toxicity of each weed and crop were assessed on a scale of 0 to 10 (0: no effect, 10: complete death), and the results are presented in Table 5 below.

[0333] Pre-emergence treatment herbicidal activity test Compound number Dosage (g ai / ha) Crop Weed Corn Wheat Rice Roundleaf Ilex quasi-Hermitage Amaranth Amaranth 110000000104033000046101061630000081010101720020210101010183000008101010193002310101010320200000410103212000001 01010102220003410101023400625101010102430000010101032520000001010026300000010100273000003870283000000700292000000450543000000270563000002600

[0334]

[0335] Test Example 2. Post-emergence treatment herbicidal activity test. Pots of crops and weeds were prepared in the same manner as in Test Example 1. After 2 weeks, when the crops and weeds reached approximately 3-leaf stage, the test substances were sprayed in the same manner as above. The spraying dose was 200 g ai / ha to 1000 g ai / ha. 2 to 3 weeks after spraying the test substances, the efficacy and damage to each weed and crop were evaluated on a scale of 0 to 10 (0: no effect, 10: complete death). The results are presented in Table 6 below.

[0336] Post-emergence treatment herbicidal activity test Compound number Dosage (g ai / ha) Crop Weed Corn Wheat Rice Roundleaf Ilex rhizome Amaranth Amaranth rhizome 110003005101010330000010109101630002973107172000006101010183000029310101930011310810102020000025502120003 5106107222001431071022340041410101062430010862105252000000540263000000510102730000005105283000000460292000003493543000000073563000000460

Claims

1. Any one compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group substituted tetrazole represented by the following chemical formula 1 and an agrochemically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, R1 represents a halogen group, a (C1-C3)alkyl group, a (C1-C3)haloalkyl group, a (C1-C3)alkoxy group or a (C1-C3)haloalkoxy group; R2 represents H, a halogen group, a (C1-C3)alkyl group, or a (C1-C3)alkoxy group; R3 represents a (C1-C3)fluoroalkyl group; A represents CF or N.

2. In paragraph 1, R1 represents a halogen group, a (C1-C3)haloalkyl group or a (C1-C3)haloalkoxy group; R2 represents H, a halogen group or a (C1-C3)alkoxy group; R3 represents a (C1-C3)fluoroalkyl group; A compound characterized in that A represents CF or N.

3. In paragraph 1, R1 represents Cl, CF3 or OCF2H; R2 represents H, F, Cl or OCH3; R3 represents CF2H, CFH2, or CH2CF2H; A compound characterized in that A represents CF or N.

4. In paragraph 1, 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-3-fluoropyridine; 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-3-fluoropyridine; 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine; 5-chloro-2-(3-fluoro-2-(2-(fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine; 5-(Difluoromethoxy)-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine; 5-chloro-2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine; 2-(2-(2-(2,2-difluoroethyl)-2H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine; 5-chloro-2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(3-chloro-2-(2-fluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 2-(3-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)-5-(difluoromethoxy)pyrimidine; 5-chloro-2-(4-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(5-chloro-2-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(2-(2-(difluoromethyl)-2H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine; 2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)-5-(trifluoromethyl)pyrimidine; 5-(Difluoromethoxy)-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-3-fluorophenoxy)pyrimidine; 5-chloro-2-(4-chloro-2-(1-(difluoromethyl)-1H-tetrazol-5-yl)phenoxy)pyrimidine; 5-chloro-2-(2-(1-(difluoromethyl)-1H-tetrazol-5-yl)-4-methoxyphenoxy)pyrimidine; and Any one compound selected from the group consisting of their pesticide-acceptable salts.

5. A herbicide comprising a compound of any one of clauses 1 to 4, an agrochemically acceptable salt thereof, or a mixture thereof as an active ingredient.

6. In the fifth paragraph, the herbicide is a herbicide characterized in that it has selectivity for cultivated crops and is used for weed removal by treating weeds before emergence (pre-emergence) or after emergence (post-emergence).

7. A herbicide according to claim 6, characterized in that the crop is corn, wheat or rice, and the weed is a broadleaf weed.

8. A herbicidal composition comprising, as an active ingredient, 0.1 to 99.9 wt% of a compound selected from the group consisting of a phenoxy compound comprising a fluoroalkyl group-substituted tetrazole represented by the following chemical formula 1 and an agrochemically acceptable salt thereof, or a mixture thereof; and 0.1 to 99.9 wt% of one or more additives selected from a surfactant, a solid diluent, and a liquid diluent: [Chemical Formula 1] In the above chemical formula 1, R1 represents a halogen group, a (C1-C3)alkyl group, a (C1-C3)haloalkyl group, a (C1-C3)alkoxy group or a (C1-C3)haloalkoxy group; R2 represents H, a halogen group, a (C1-C3)alkyl group, or a (C1-C3)alkoxy group; R3 represents a (C1-C3)fluoroalkyl group; A represents CF or N.

9. In the 8th paragraph, the herbicidal composition is characterized in that it is formulated into any one formulation selected from among a wettable powder, a suspension, an emulsion, an emulsifier, a turbidity agent, a liquid, a dispersible liquid, a granular wettable powder, a granule, a powder, a liquid wettable powder, a floating granule, and a tablet.

10. In the 8th paragraph, in addition to the above effective ingredient, it further comprises an acetyl-CoA carboxylase (ACCase) inhibitor, an acetolactate synthase (ALS) inhibitor, a cell division inhibitor, an auxin-type herbicide, a photosynthetic system 1, 2 inhibitor, a 5-enolpyruvylshikimate 3-phosphate synthase (ESPS) inhibitor, a glutamine synthetase inhibitor, a carotenoid biosynthesis inhibitor, a protoporphyrinogen oxidase inhibitor, a lipid biosynthesis inhibitor, a plastoquinone biosynthesis inhibitor, a cell wall biosynthesis inhibitor, an auxin transport inhibitor, an oxidative phosphorylation process inhibitor by uncoupler, a serine-threonine protein phosphatase inhibitor, a dihydrooresinol dehydrogenase (DHODH) inhibitor, a herbicide with an unknown point of action, and a known herbicide. A herbicidal composition characterized in that it further comprises one or more components selected from the group.

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