Arylpyridine compounds and preparation methods and uses thereof

Abstract

The present invention discloses an arylpyridine compound and a preparation method and use thereof. The arylpyridine compound is as shown in formula (I). The present invention uses an acetophenone compound as a raw material and obtains the arylpyridine compound through reactions such as condensation, cyclization, halogenation and condensation. The compound of general formula (I) has a good control effect on agricultural diseases, especially a good control effect on plant downy mildew, rust and harmful mites, and can be used as an agricultural fungicide and acaricide to control diseases and harmful mites.

Description

Technical Field

[0001] The invention relates to the field of agricultural fungicides and acaricides, and in particular to an aryl pyridine compound and a preparation method thereof, as well as use of the aryl pyridine compound as a fungicide and acaricide in agriculture or other fields. Background Art

[0002] Chinese patent CN1938292 discloses a cyclic amine compound with the general formula shown below as a miticide:

[0003]

[0004] R2 represents a halogen atom, a nitro group, a C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 a haloalkoxy group, a heterocyclic group which may be substituted by G4 (a 5- or 6-membered heterocyclic group having at least one heteroatom selected from an oxygen atom, a nitrogen atom and a sulfur atom) or C 1-6 In the haloalkoxy group, k represents 0 or an integer of 1 to 4; and X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group.

[0005] The structures of the compounds reported in the prior art are very different from those of the compounds of the present invention, and there are no reports on the use of the compounds having the structure as shown in the general formula I of the present invention as agricultural fungicides and miticides. Summary of the invention

[0006] The present invention aims to provide an aryl pyridine compound and a preparation method thereof. The aryl pyridine compound can be used as an agricultural fungicide and acaricide to control diseases and harmful mites.

[0007] The technical solution of the present invention is as follows:

[0008] An aryl pyridine compound represented by formula (I):

[0009]

[0010] In formula (I):

[0011] R 1 Selected from H, halogen, CN, NO 2 , alkyl, haloalkyl, alkoxy, alkynyloxy, cycloalkyl or haloalkoxy; m is selected from an integer from 0 to 5; when m is greater than 1, R 1 Can be the same or different;

[0012] R 2 Selected from H, CN, C(=O)R 4 , CO 2 H, CO 2 Na or alkoxycarbonyl; R 4 Selected from alkylamino, NH2 , alkoxyamino, cyanoalkylamino, cyclopropylamino or cyclopropylmethylamino;

[0013] R 3 Selected from alkoxy, R 1 Substituted phenyl, R 1 substituted heteroaryl or 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl;

[0014] X is selected from CO, SO 2 or CH 2 .

[0015] Preferably, in formula (I):

[0016] R 1 Selected from H, F, Cl, Br, I, CN, NO 2 , C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 1 -C 4 Alkoxy, C 3 -C 4 Alkynyloxy, C 3 -C 6 Cycloalkyl or halogenated C 1 -C 4 Alkoxy; m is an integer selected from 0 to 5; when m is greater than 1, R 1 Can be the same or different;

[0017] R 2 Selected from H, CN, C(=O)R 4 , CO 2 H, CO 2 Na or C 1 -C 4 Alkoxycarbonyl; R 4 Selected from alkylamino, NH 2 , alkoxyamino, cyanoalkylamino, cyclopropylamino or cyclopropylmethylamino;

[0018] R 3 Selected from C 1 -C 4 Alkoxy, R 1 Substituted phenyl, R 1 substituted heteroaryl or 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl;

[0019] X is selected from CO, SO 2 or CH 2 .

[0020] Further preferably, in formula (I):

[0021] R 1 Selected from H, F, Cl, Br, I, CN, NO 2 , CH 3 、OCH 3 CF 3 、OCF 3 , OCHF 2 , CHF 2 , C 2 H 5 , n-propyl, tert-butyl, propynyloxy or cyclopropyl; m is selected from an integer from 0 to 5; when m is greater than 1, R 1 Can be the same or different;

[0022] R 2 Selected from H, CN, C(=O)R 4 , methoxycarbonyl or ethoxycarbonyl; R 4 Selected from methylamino, ethylamino, NH 2 , cyclopropylamino, methoxyamino, cyanomethylamino or cyclopropylmethylamino;

[0023] R 3 Selected from n-butoxy, tert-butoxy, R 1 Substituted phenyl, R 1 Substituted pyridyl, R 1 Substituted pyrazolyl, R 1 substituted thiazolyl or 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl;

[0024] X is selected from CO, SO 2 or CH 2 .

[0025] Some of the compounds of the general formula (I) of the present invention can be illustrated by the specific compounds listed in the following table, but the present invention is not limited to the following specific compounds.

[0026] When in the general formula (I), (R 1 ) m =H, R 2 =H, X = CO, the substituent R 3 See Table 1, the representative compounds are numbered 1-46, corresponding to 1-46 in Table 1.

[0027] Table 1

[0028] Serial number <![CDATA[R 3 ]]> Serial number <![CDATA[R 3 ]]> 1 Phenyl 24 <![CDATA[1-CH 3 -3-CF 3 -4-pyrazolyl]]> 2 2-Cl-phenyl 25 <![CDATA[1,3-2CH 3 -4-pyrazolyl]]> 3 3-Cl-phenyl 26 <![CDATA[1-CH 3 -3-CHF 2 -4-pyrazolyl]]> 4 4-Cl-phenyl 27 <![CDATA[1-CH 3 -3-CF 3 -5-Cl-4-pyrazolyl]]> 5 2-F-phenyl 28 <![CDATA[1,3-2CH 3 -5-Cl-4-pyrazolyl]]> 6 3-F-phenyl 29 <![CDATA[1-CH 3 -3-CHF 2 -5-Cl-4-pyrazolyl]]> 7 4-F-phenyl 30 <![CDATA[1-CH 3 -3-CF 3 -5-OCH 3 -4-pyrazolyl]]> 8 <![CDATA[2-CF 3 -phenyl]]> 31 <![CDATA[1,3-2CH 3 -5-OCH 3 -4-pyrazolyl]]> 9 <![CDATA[3-CF 3 -phenyl]]> 32 <![CDATA[1,3-2CH 3 -5-F-4-pyrazolyl]]> 10 <![CDATA[4-CF 3 -phenyl]]> 33 <![CDATA[1,3-2CH 3 -5-I-4-pyrazolyl]]> 11 2,4-2Cl-phenyl 34 <![CDATA[1,3-2CH 3 -5-NH 2 -4-pyrazolyl]]> 12 2,4-2F-phenyl 35 <![CDATA[1-CH 3 -3-CF 3 -5-pyrazolyl]]> 13 2,5-2Cl-phenyl 36 <![CDATA[1,3-2CH 3 -5-pyrazolyl]]> 14 2,6-2Cl-phenyl 37 <![CDATA[1-CH 3 -3-CHF 2 -5-pyrazolyl]]> 15 2,6-2F-phenyl 38 <![CDATA[1-CH 3 -3-C 2 H 5 -5-pyrazolyl]]> 16 2-Cl-3-pyridyl 39 <![CDATA[1-CH 3 -3-CF 3 -4-Cl-5-pyrazolyl]]> 17 6-Cl-3-pyridyl 40 <![CDATA[1,3-2CH 3 -4-Cl-5-pyrazolyl]]> 18 4-Cyanophenyl 41 <![CDATA[1-CH 3 -3-CHF 2 -4-Cl-5-pyrazolyl]]> 19 3-Cl-2-pyridyl 42 <![CDATA[1-CH 3 -3-C 2 H 5 -4-Cl-5-pyrazolyl<!-- 2 --> ]]> 20 4-tert-Butylphenyl 43 2-Cl-5-pyridyl 21 6-Methyl-2-pyridyl 44 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl 22 2-Br-phenyl 45 n-Butoxy 23 4-Methoxyphenyl 46 tert-Butoxy

[0029] Table 2: When in the general formula (I), (R 1 ) m =H, R 2=H, X = CH 2 When the substituent R 3 See 1-44 in Table 1, representing compound numbers 47-90.

[0030] Table 3: When in the general formula (I), (R 1 ) m =H, R 2 =CO 2 C 2 H 5 , when X=CO, the substituent R 3 See 1-46 in Table 1, representing compound numbers 91-136.

[0031] Table 4: When in the general formula (I), (R 1 ) m =4-Cl, R 2 =H, X = CO, the substituent R 3 See 1-44 in Table 1, representing compound numbers 137-180.

[0032] Table 5: When in the general formula (I), (R 1 ) m =4-Cl, R 2 =H, X = CH 2 When the substituent R 3 See 1-44 in Table 1, representing compound numbers 181-224.

[0033] When the substituents in the general formula (I) are as shown in Table 6, the representative compound numbers are 225-261.

[0034] Table 6

[0035]

[0036]

[0037] Table 7: When in the general formula (I), R 2 =H, X = CH 2 , R 3 When it is 4-tert-butylphenyl, the substituent (R 1 ) m See Table 7, representative compound numbers are 270-323.

[0038] Table 7

[0039] Serial number <![CDATA[(R 1 ) m ]]> Serial number <![CDATA[(R 1 ) m ]]> Serial number <![CDATA[(R 1 ) m ]]> 270 2-F 288 <![CDATA[2-CF 3 ]]> 306 <![CDATA[2,6-Cl 2 ]]> 271 3-F 289 <![CDATA[2-OCF 3 ]]> 307 <![CDATA[3,4-Cl 2 ]]> 272 4-F 290 <![CDATA[3-OCF 3 ]]> 308 <![CDATA[3,5-Cl 2 ]]> 273 2-Cl 291 <![CDATA[2-CH 3 ]]> 309 <![CDATA[2,4-Cl 2 ]]> 274 3-Cl 292 <![CDATA[3-CH 3 ]]> 310 <![CDATA[2-C(CH 3 ) 3 ]]> 275 2-Br 293 <![CDATA[4-CH 3 ]]> 311 <![CDATA[3-C(CH 3 ) 3 ]]> 276 3-Br 294 <![CDATA[2-OCH 3 ]]> 312 <![CDATA[4-C(CH 3 ) 3 ]]> 277 4-Br 295 <![CDATA[3-OCH 3 ]]> 313 <![CDATA[2-Cl-4-CF 3 ]]> 278 2-CN 296 <![CDATA[4-OCH 3 ]]> 314 <![CDATA[2-Cl-4-NO 2 ]]> 279 3-CN 297 <![CDATA[2,3-Cl 2 ]]> 315 2-Cl-4-F 280 4-CN 298 <![CDATA[2,5-Cl 2 ]]> 316 2-Cl-4-Br 281 <![CDATA[2-Cl-3-CH 3 ]]> 299 <![CDATA[2-F-4-CF 3 ]]> 317 <![CDATA[2-Cl-4-CH 3 ]]> 282 <![CDATA[2-Cl-5-CH 3 ]]> 300 <![CDATA[2-Br-4-CF 3 ]]> 318 2-Cl-4-CN 283 <![CDATA[2-Cl-6-CH 3 ]]> 301 <![CDATA[2-CH 3 -4-CF 3 ]]> 319 2-F-4-Cl 284 2-Cl-3-CN 302 <![CDATA[2-NO 2 -4-CF 3 ]]> 320 2-Br-4-Cl 285 2-Cl-5-CN 303 <![CDATA[2-CN-4-CF 3 ]]> 321 <![CDATA[2-CH 3 -4-Cl]]> 286 2-Cl-6-CN 304 2-CN-4-Cl 322 <![CDATA[2-NO 2 -4-Cl]]> 287 <![CDATA[2-F-4-NO 2 ]]> 305 <![CDATA[2-Br-4-NO 2 ]]> 323 <![CDATA[2-NO 2 -4-AND 3 ]]>

[0040] The preparation method of the aryl pyridine compound represented by formula (I) of the present invention is:

[0041] (1) Compound (II), a condensation reagent and a solvent are mixed, reacted at 30 to 150° C. for 0.5 to 15 h, and then post-treated to obtain compound (III);

[0042] The condensation reagent is selected from one or a mixture of any proportion of N,N-dimethylformamide dimethyl acetal, trimethyl orthoformate, and triethyl orthoformate;

[0043] The molar ratio of the compound (II) to the condensation reagent is 1:1 to 4;

[0044] The solvent is selected from one or a mixed solvent of any proportion of N,N-dimethylformamide, N,N-dimethylacetamide, N,N-dimethylformamide dimethyl acetal, dimethyl sulfoxide, ethanol, toluene, acetone, acetonitrile, and acetic anhydride;

[0045] The volume amount of the solvent is 1 to 20 mL / g based on the mass of compound (II);

[0046] (2) Compound (III), a cyclization reagent, a solvent, and an alkaline substance are mixed, reacted at 20 to 100° C. for 0.5 to 25 h, and then post-treated to obtain compound (IV);

[0047] The cyclization reagent is selected from cyanoacetamide or malononitrile;

[0048] The alkaline substance is selected from sodium methoxide, sodium ethoxide, triethylamine or sodium hydride;

[0049] The molar ratio of the compound (III), the cyclization reagent and the alkaline substance is 1:1-4:0.1-3;

[0050] The solvent is selected from one or a mixed solvent of two or more of methanol, ethanol, acetic acid, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide in any proportion;

[0051] The volume amount of the solvent is 1 to 10 mL / g based on the mass of compound (III);

[0052] (3) Compound (IV), a halogenating agent, a solvent, and a catalyst are mixed, reacted at 20 to 130° C. for 0.5 to 25 h, and then post-treated to obtain compound (V);

[0053] The halogenating agent is selected from one or a mixture of any proportion of thionyl chloride, phosphorus oxybromide, phosphorus tribromide, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, N-bromosuccinimide, and N-chlorosuccinimide;

[0054] The catalyst is selected from N,N-dimethylformamide, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, thiourea or dimethylthiourea;

[0055] The molar ratio of the compound (IV), the halogenating agent and the catalyst is 1:1-8:0.001-3;

[0056] The solvent is selected from one or a mixed solvent of two or more of toluene, acetonitrile, xylene, chlorobenzene, dichloromethane and dichloroethane in any proportion;

[0057] The volume amount of the solvent is 0 to 10 mL / g based on the mass of compound (IV);

[0058] (4) Compound (V), piperazine, a solvent, and an acid-binding agent are mixed, reacted at 20 to 130° C. for 0.5 to 20 h, and then post-treated to obtain compound (VI);

[0059] The acid binding agent is selected from sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate or sodium carbonate;

[0060] The molar ratio of the compound (V), piperazine and acid-binding agent is 1:1-1.5:0.5-3;

[0061] The solvent is selected from toluene, xylene, trimethylbenzene, chlorobenzene, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, dimethyl sulfone, N-methylpyrrolidone, N,N-dimethylacetamide, sulfolane or hexamethylphosphoramide;

[0062] The volume amount of the solvent is 1 to 10 mL / g based on the mass of compound (V);

[0063] (5) Compound (VI) and R 3 -X-Cl, a solvent and an acid-binding agent are mixed, reacted at 20 to 130°C for 0.5 to 20 hours, and then post-treated to obtain compound (I);

[0064] The acid binding agent is selected from sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, cesium carbonate, sodium bicarbonate, sodium methoxide, sodium ethoxide, potassium bicarbonate, sodium carbonate or triethylamine;

[0065] The compound (VI), R 3 The molar ratio of -X-Cl and acid-binding agent is 1:0.8~1.2:0.5~3;

[0066] The solvent is selected from toluene, xylene, trimethylbenzene, chlorobenzene, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, dimethyl sulfone, N-methylpyrrolidone, N,N-dimethylacetamide, cyclopentane, dichloromethane, dichloroethane or hexamethylphosphoramide;

[0067] The volume amount of the solvent is 1 to 10 mL / g based on the mass of compound (VI);

[0068] R 3 -X-Cl, R 3 , X is defined the same as in formula (I);

[0069] The reaction formula is as follows:

[0070]

[0071] In formula (II), (III), (IV), (V) or (VI), R 1 , R 2 , m are defined as in formula (I);

[0072] In formula (III), Y 1 Selected from N,N-dimethylamino, methoxy or ethoxy;

[0073] In formula (V), Y 2 Selected from chlorine or bromine.

[0074] The present invention relates to the use of the aryl pyridine compound represented by formula (I) or a salt thereof as a fungicide or acaricide in the fields of agriculture, forestry or sanitation, and is used for preventing and treating plant downy mildew, rust or harmful mites, including downy mildew of melon and fruit plants, downy mildew of sugarcane, downy mildew of leguminous plants, downy mildew of vegetable plants, rust of leguminous plants, wheat rust, corn rust, rust of fruit and vegetable plants, rust of flowers, Tarsonemidae, Tetranychus family (Panonychus apple, Tetranychus cinnabarinus, Tetranychus twospotted, Panonychus citrus, etc.), Tetranychus family, etc.

[0075] For practical application in agriculture, the aryl pyridine compounds represented by formula (I) or their salts can be compounded with acaricides and fungicides commonly used in existing agriculture to delay resistance, while broadening the control spectrum of pathogenic bacteria and mites and improving the efficacy.

[0076] Therefore, the present invention also relates to a mite-killing and fungicidal composition, which contains an aryl pyridine compound represented by formula (I) or its salt and an agriculturally acceptable carrier as an active component; the weight percentage of the active component in the composition is 0.5-99%.

[0077] The composition can be prepared into a formulation permitted by pesticides, such as wettable powder, emulsifiable concentrate, microemulsion, granule, solution, suspension, etc. The selection of the composition type depends on the specific application.

[0078] The beneficial effects of the present invention are:

[0079] The present invention discloses an aryl pyridine compound represented by formula (I), a preparation method and application thereof. The present invention uses an acetophenone compound as a raw material, and obtains the aryl pyridine compound through reactions such as condensation, cyclization, halogenation and condensation. The compound represented by general formula (I) has a good control effect on agricultural diseases, especially a good control effect on plant downy mildew, rust and harmful mites. DETAILED DESCRIPTION

[0080] The present invention is further described below by means of specific embodiments, but the protection scope of the present invention is not limited thereto.

[0081] Synthesis Example

[0082] Example 1: Select (R 1 ) m When is H, the preparation process of aryl pyridine compounds is described, and other compounds can be synthesized by similar methods.

[0083]

[0084] 1) Preparation of intermediate III-1

[0085] 60.0 g (0.5 mol) of acetophenone was placed in a 1000 mL single-mouth bottle, 200 mL of DMFDMA and 100 mL of DMF were added thereto, the temperature was raised to 110° C. and refluxed. After the reaction was completed under TLC monitoring, the mixture was cooled to room temperature, the solvent was evaporated under reduced pressure at 100° C., and a large amount of solid was precipitated when it was cooled to 0° C. The solid was filtered, the filter cake was washed with petroleum ether 2-3 times, and dried to obtain 70 g of solid with a yield of 80.1%.

[0086] 2) Preparation of Intermediate IV-1

[0087] 35 g (0.2 mol) of intermediate III-1 was placed in a 1000 mL single-mouth bottle, 300 mL of DMF was added thereto, and then 21.6 g of sodium methoxide and 20 g of cyanoacetamide were added thereto. The temperature was raised to 100 ° C for reaction. After the reaction was completed as monitored by TLC, it was cooled to room temperature, the reaction solution was poured into water, the pH was adjusted to about 5 with 30% hydrochloric acid, and the filter cake was dried to obtain 19.6 g of a yellow solid with a yield of 50%, which can be directly used in the next step without purification.

[0088] 3) Preparation of intermediate V-1

[0089] 9.8 g (0.05 mol) of intermediate IV-1 was placed in a 250 mL single-mouth bottle, 100 mL of phosphorus oxychloride and 1 drop of DMF were added thereto, the temperature was raised to 110°C for reflux reaction, after the reaction was completed as monitored by TLC, the phosphorus oxychloride was recovered under reduced pressure at 100°C until no liquid flowed out, cooled to room temperature, the residue was poured into ice water, the solid was precipitated, filtered, and dried to obtain 7.5 g of brown solid, yield: 70%.

[0090] 4) Preparation of intermediate VI-1

[0091] 1.1 g (5 mmol) of intermediate V-1 was placed in a 250 mL single-mouth bottle, 100 mL of DMF was added thereto, and then 0.69 g (5 mmol) of potassium carbonate and 0.43 g (5 mmol) of piperazine were added thereto, and the temperature was raised to 90°C for reaction. After the reaction was completed as monitored by TLC, the mixture was cooled to room temperature, and the reaction solution was poured into water. After extraction with ethyl acetate, hydrogen chloride gas was introduced, and solid precipitated. 0.63 g of light yellow solid was obtained by suction filtration. The yield was 42.2%, and the solid was directly used in the next step without purification.

[0092] 5) Preparation of Compound 20

[0093] 1 g (3.33 mmol) of intermediate VI-1 was placed in a 50 mL three-necked flask, 10 mL of DMF was added thereto, and then 0.61 g (3.33 mmol) of p-tert-butylbenzyl chloride and 0.91 g (6.66 mmol) of potassium carbonate were added thereto. The temperature was raised to 85°C for reaction. After the reaction was completed by monitoring by TLC, the mixture was cooled to room temperature, poured into water, extracted with ethyl acetate, washed with water, washed with a saturated sodium chloride solution, dried, concentrated under reduced pressure, and then column chromatography (eluent: ethyl acetate / 60-90°C petroleum ether) was performed to obtain 0.92 g of a brown oil with a yield of 68.1%.

[0094] Embodiment 2:

[0095] 1) Preparation of Compound 46

[0096] 10.7 g (0.05 mol) of intermediate V was placed in a 250 mL three-necked flask, 100 mL of DMF was added thereto, and then 6.9 g (0.05 mol) of potassium carbonate and 9.3 g (0.05 mol) of 1-tert-butyloxycarbonylpiperazine were added thereto. The temperature was raised to 80° C. for reaction. After the reaction was completed as monitored by TLC, the reaction was cooled to room temperature, the reaction solution was poured into water, filtered, and the filter cake was dried to obtain 13.65 g of a gray solid with a yield of 70.5%.

[0097] 2) Preparation of Compound 161

[0098]

[0099] 0.8 g (2.5 mmol) of 6-(4-chlorophenyl)-2-(piperazine-1-yl)nicotinonitrile hydrochloride was placed in a 250 mL three-necked flask, 100 mL of DCM was added thereto, and then 0.5 g (5 mmol) of triethylamine and 0.4 g (2.5 mmol) of 1,3-dimethyl-4-pyrazole acid chloride were added thereto, and the mixture was reacted at 35° C. After the reaction was completed as monitored by TLC, the reaction solution was poured into water, extracted with dichloromethane, washed with water, washed with a saturated sodium chloride solution, dried, concentrated under reduced pressure, and then subjected to column chromatography (eluent: ethyl acetate / 60-90° C. petroleum ether) to obtain 0.53 g of a brown solid, with a yield of 50%.

[0100] Example 3: Select (R 1 ) m When is H, the preparation process of aryl pyridine compounds is described, and other compounds can be synthesized by similar methods.

[0101]

[0102] 1) Preparation of intermediate III-2

[0103] 19.2g (0.1mol) of ethyl benzoyl acetate was placed in a 500mL single-mouth bottle, 20mL of DMFDMA and 20mL of DMF were added thereto, the temperature was raised to 110°C, after the reaction was completed by TLC monitoring, the mixture was cooled to room temperature, DMFDMA and DMF were removed under reduced pressure at 110°C, and a large amount of solid was precipitated when the mixture was cooled to 0°C. The solid was filtered, the filter cake was washed with petroleum ether for 2-3 times, and dried to obtain 17.50g of solid, with a yield of 70.5%. The crude intermediate III-2 was directly used in the next step without purification.

[0104] 2) Preparation of Intermediate IV-2

[0105] 8.5 g (0.125 mol) of sodium ethoxide was poured into a 500 mL four-necked bottle, 100 mL of ethanol was added thereto, and then 6.3 g (0.075 mol) of cyanoacetamide was added thereto. After reacting at 25°C for 1 hour, 12.35 g (0.05 mol) of an ethanol solution of the intermediate III-2 was added dropwise. After the addition was completed, the reaction was continued. After the reaction was completed as monitored by TLC, the reaction solution was poured into water, the pH was adjusted to about 5 with 30% hydrochloric acid, and the filter cake was dried to obtain 6.7 g of a yellow solid with a yield of 50%. The solid was directly used in the next step without purification.

[0106] 3) Preparation of intermediate V-2

[0107] 13.4 g (0.05 mol) of intermediate IV-2 was placed in a 250 mL single-mouth bottle, 50 mL of phosphorus oxychloride and 1 drop of DMF were added thereto, the temperature was raised to 110 ° C and refluxed for reaction, after the reaction was completed under TLC monitoring, the phosphorus oxychloride was recovered under reduced pressure at 100 ° C until no liquid flowed out, cooled to room temperature, the residue was poured into ice water, the solid was precipitated, filtered, and dried to obtain 8.6 g of brown solid, yield: 60%, which can be directly used in the next step reaction without purification.

[0108] 4) Preparation of intermediate VI-2

[0109] 14.3 g (0.05 mol) of intermediate V-2 was placed in a 250 mL single-mouth bottle, 100 mL of DMF was added thereto, and then 6.9 g (0.05 mol) of potassium carbonate and 4.3 g (0.05 mol) of piperazine were added thereto. The temperature was raised to 90°C for reaction. After the reaction was completed as monitored by TLC, the reaction was cooled to room temperature. The reaction solution was poured into water, extracted with ethyl acetate, and hydrogen chloride gas was introduced. Solid precipitated and 7.5 g of light yellow solid was obtained by suction filtration. The yield was 40.2%. The solid was directly used in the next step without purification.

[0110] 5) Preparation of Compound 114

[0111] 1 g (2.7 mmol) of intermediate VI-2 was placed in a 50 mL single-mouth bottle, 50 mL of DCM was added thereto, and then 0.54 g (5.4 mmol) of triethylamine and 0.57 g (2.7 mmol) of 1-methyl-3-trifluoromethyl-4-pyrazole acid chloride were added thereto. The reaction was carried out at room temperature. After the reaction was completed as monitored by TLC, the reaction mixture was cooled to room temperature, poured into water, extracted with DCM, and then washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered under reduced pressure to remove the solid residue. The solvent was removed from the filtrate, and then separated and purified by silica gel column chromatography (eluent: ethyl acetate / 60-90°C petroleum ether) to obtain 0.48 g of solid, with a yield of 35%.

[0112] Embodiment 4:

[0113] Preparation of Compound 262

[0114]

[0115] 1 g (3.07 mmol) of 2-phenyl-6-(piperazine-1-yl)-3,5-dicyanopyridine hydrochloride was placed in a 50 mL three-necked flask, 10 mL of DMF was added thereto, and then 0.56 g (3.07 mmol) of p-tert-butylbenzyl chloride and 0.85 g (6.14 mmol) of potassium carbonate were added thereto, and the temperature was raised to 85°C for reaction. After the reaction was completed as monitored by TLC, the reaction solution was cooled to room temperature, poured into water, extracted with ethyl acetate, washed with water, washed with a saturated sodium chloride solution, dried, concentrated under reduced pressure, and then column chromatography (eluent: ethyl acetate / 60-90°C petroleum ether) was performed to obtain 0.47 g of a brown solid, with a yield of 35%.

[0116] The melting points and NMR data of some compounds are as follows:

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124] Biological Activity Assay Example

[0125] The activity test of the compound of the present invention on the adult of Tetranychus cinnabarinus was carried out. The test method is as follows:

[0126] Example 5: Indoor toxicity determination against adult mites

[0127] After the compound is weighed, acetone is used to make a mother solution, and a series of concentrations are diluted with standing tap water containing 0.1% Tween 80 according to the experimental design. Take two true leaf bean seedlings, inoculate adult mites of Tetranychus cinnabarinus and investigate the base number, then spray with a handheld sprayer, repeat 3 times for each treatment, place in a standard observation room after treatment, investigate the number of surviving mites after 72 hours, and calculate the mortality rate. Then use the toxicity statistics software SPSS to perform toxicity statistics and calculate the LC of each agent 50 etc., to compare the toxicity of the test agent with that of the standard agent.

[0128] The mortality rates for Tetranychus cinnabarinus are as follows:

[0129] When the concentration of the drug solution was 600 mg / L, the mortality rate of compound 46 to Tetranychus cinnabarinus was 100%; the mortality rate of compounds 25, 160, and 161 to Tetranychus cinnabarinus was 90%; the mortality rate of compounds 26 and 231 to Tetranychus cinnabarinus was 80%; when the concentration of the drug solution was 100 mg / L, the mortality rate of compounds 25, 26, 46, and 161 to Tetranychus cinnabarinus was 50%.

[0130] Example 6: Determination of in vivo protective activity against soybean rust

[0131] Select 2-leaf soybean seedlings in pots that grow in a uniform pattern. Use an Airbrush to spray the leaves with the agent at the designed concentration, and set up a blank control of spraying water, and repeat 3 times. The next day after treatment, inoculate with a soybean rust spore suspension, place in an artificial climate chamber (temperature: 20℃-25℃, relative humidity: >95%) for moisturizing culture, and place in a greenhouse (25℃±1℃) for normal management after 8-16 hours. Investigate the control effect 10 days after inoculation. The results were investigated with reference to the "A Manual of Assessment Keys for Plant Diseases" compiled by the American Society of Plant Pathology. According to the degree of disease in the control, the fungicidal activity of the test samples was investigated by visual inspection.

[0132] When the concentration of the drug solution was 400 mg / L, the protective effect of compound 20 on soybean rust was 90%; the protective effect of compounds 67 and 161 on soybean rust was 80%; when the concentration of the drug solution was 12.5 mg / L, the protective effect of compound 161 on soybean rust was 50%.

[0133] Example 7: Determination of in vivo protective activity against cucumber downy mildew

[0134] Select potted cucumber seedlings at the 2-leaf stage with uniform growth. Use Airbrush to spray the agent on the leaves according to the designed concentration, and set up a blank control of spraying water, and repeat 3 times. The next day after treatment, inoculate with a suspension of cucumber downy mildew spores. After inoculation, place the seeds in an artificial climate chamber (temperature: 20℃-25℃, relative humidity: >95%) for moisturizing culture. After 8-16 hours, place them in a greenhouse (25℃±1℃) for normal management. Investigate the control effect 10 days after inoculation. The results were investigated with reference to "A Manual of Assessment Keys for Plant Diseases" compiled by the American Society of Plant Pathology. According to the degree of disease in the control, the fungicidal activity of the test samples was investigated by visual inspection.

[0135] When the concentration of the drug solution is 400 mg / L, the control effect of compounds 8, 20, 161, 200, 240, 245, 246, and 247 on cucumber downy mildew is not less than 90%; the control effect of compounds 25, 26, 42, 67, 114, 115, 116, 162, 178, 225, 238, 239, 242, and 244 on cucumber downy mildew is 70% to 85%; when the concentration of the drug solution is 25 mg / L, the control effect of compounds 8, 20, 161, and 240 on cucumber downy mildew is not less than 70%.

Claims

1. An aryl pyridine compound represented by formula (I): In formula (I): R1 is selected from H, halogen, C1-C4 alkyl or halogenated C1-C4 alkyl; m is selected from an integer from 0 to 5; when m is greater than 1, R1 may be the same or different; R2 is selected from H or C1-C4 alkoxycarbonyl; R3 is selected from C1-C4 alkoxy, R1-substituted phenyl, R1-substituted pyridyl, R1-substituted pyrazolyl or 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl; X is selected from CO or CH2.

2. The aryl pyridine compound of formula (I) according to claim 1, characterized in that: R1 is selected from H, F, Cl, Br, I, CH3, CF3, CHF2, C2H5, n-propyl, tert-butyl; m is selected from an integer from 0 to 5; when m is greater than 1, R1 may be the same or different; R2 is selected from H, methoxycarbonyl or ethoxycarbonyl; R3 is selected from n-butoxy, tert-butoxy, R1-substituted phenyl, R1-substituted pyridyl, R1-substituted pyrazolyl or 1-(3-Cl-pyridin-2-yl)-3-bromo-5-pyrazolyl; X is selected from CO or CH2.

3. The method for preparing the aryl pyridine compound represented by formula (I) according to claim 1, characterized in that: The preparation method is: (1) Compound (II), a condensation reagent and a solvent are mixed, reacted at 30 to 150° C. for 0.5 to 15 h, and then post-treated to obtain compound (III); The condensation reagent is selected from one or a mixture of any proportion of N,N-dimethylformamide dimethyl acetal, trimethyl orthoformate, and triethyl orthoformate; The molar ratio of the compound (II) to the condensation reagent is 1:1 to 4; The solvent is selected from one or a mixed solvent of any proportion of N,N-dimethylformamide, N,N-dimethylacetamide, N,N-dimethylformamide dimethyl acetal, dimethyl sulfoxide, ethanol, toluene, acetone, acetonitrile, and acetic anhydride; (2) Compound (III), a cyclization reagent, a solvent, and an alkaline substance are mixed, reacted at 20 to 100° C. for 0.5 to 25 h, and then post-treated to obtain compound (IV); The cyclization reagent is selected from cyanoacetamide or malononitrile; The alkaline substance is selected from sodium methoxide, sodium ethoxide, triethylamine or sodium hydride; The molar ratio of the compound (III), the cyclization reagent and the alkaline substance is 1:1-4:0.1-3; The solvent is selected from one or a mixed solvent of two or more of methanol, ethanol, acetic acid, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide in any proportion; (3) Compound (IV), a halogenating agent, a solvent, and a catalyst are mixed, reacted at 20 to 130° C. for 0.5 to 25 h, and then post-treated to obtain compound (V); The halogenating agent is selected from one or a mixture of any proportion of thionyl chloride, phosphorus oxybromide, phosphorus tribromide, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, N-bromosuccinimide, and N-chlorosuccinimide; The catalyst is selected from N,N-dimethylformamide, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, thiourea or dimethylthiourea; The molar ratio of the compound (IV), the halogenating agent and the catalyst is 1:1-8:0.001-3; The solvent is selected from one or a mixed solvent of two or more of toluene, acetonitrile, xylene, chlorobenzene, dichloromethane and dichloroethane in any proportion; (4) Compound (V), piperazine, a solvent, and an acid-binding agent are mixed, reacted at 20 to 130° C. for 0.5 to 20 h, and then post-treated to obtain compound (VI); The acid binding agent is selected from sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate or sodium carbonate; The molar ratio of the compound (V), piperazine and acid-binding agent is 1:1-1.5:0.5-3; The solvent is selected from toluene, xylene, trimethylbenzene, chlorobenzene, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, dimethyl sulfone, N-methylpyrrolidone, N,N-dimethylacetamide, sulfolane or hexamethylphosphoramide; (5) Compound (VI) is mixed with R3-X-Cl, a solvent and an acid binding agent, reacted at 20-130° C. for 0.5-20 h, and then post-treated to obtain compound (I); The acid binding agent is selected from sodium hydride, potassium hydroxide, sodium hydroxide, potassium carbonate, cesium carbonate, sodium bicarbonate, sodium methoxide, sodium ethoxide, potassium bicarbonate, sodium carbonate or triethylamine; The molar ratio of the compound (VI), R3-X-Cl and the acid-binding agent is 1:0.8-1.2:0.5-3; The solvent is selected from toluene, xylene, trimethylbenzene, chlorobenzene, tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, dimethyl sulfone, N-methylpyrrolidone, N,N-dimethylacetamide, cyclopentane, dichloromethane, dichloroethane or hexamethylphosphoramide; In R3-X-Cl, R3 and X are the same as those in formula (I); The reaction formula is as follows: In formula (II), (III), (IV), (V) or (VI), R1, R2, and m are the same as those in formula (I); In formula (III), Y1 is selected from N,N-dimethylamino, methoxy or ethoxy; In formula (V), Y2 is selected from chlorine or bromine.

4. Use of the arylpyridine compound represented by formula (I) or its salt as claimed in claim 1 as a fungicide or acaricide in agriculture, forestry or health fields; the fungicide is used to control soybean rust and cucumber downy mildew, and the acaricide is used to control cinnabarinus spider mite.

5. A mite-killing and fungicidal composition comprising an arylpyridine compound of formula (I) or a salt thereof and an agriculturally acceptable carrier as an active ingredient; the weight percentage of the active ingredient in the composition is 0.5 to 99%.

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