Azo oxide compound as well as preparation method and application thereof

Abstract

The preparation method comprises the following steps: reacting a compound shown in a formula (II) with triphosgene to obtain a compound shown in a formula (IV), dropwise adding an acid-binding agent B into the compound shown in the formula (V), and reacting with the compound shown in the formula (IV) to obtain a compound shown in a formula (VI); adding the compound shown in the formula (VI) into an oxidizing agent D, and reacting to obtain a compound shown in a formula (VII); adding the compound as shown in the formula (VII) into an oxidizing agent F, and reacting to obtain a compound as shown in a formula (I); the reaction formula is as follows: in a # imgabs0 # formula, H on a benzene ring is substituted or not substituted by a substituent group R1, during substitution, R1 is methyl, methoxy, cyano, halogen, trifluoromethyl, trifluoromethoxy, methylthio, methylamino or dimethylamino, m is an integer, m is more than or equal to 0 and less than or equal to 9, and a substituent group R2 is alkyl, naphthenic base, substituted alkyl, halogen, fluorenyl, phenyl or substituted phenyl. The compound disclosed by the invention also shows excellent nematicidal activity and antibacterial activity at low concentration.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and specifically relates to an azoxy compound, a preparation method thereof, and an application thereof. Background Art

[0002] Pine wilt disease, also known as pine wilt blight and pine blight, is a worldwide quarantine disease of plants. This disease is caused by the pine wood nematode, which has strong pathogenicity and a long incubation period. Pine trees can die 40 days after being infected, and an entire pine forest can be destroyed in 3 - 5 years. It is known as the "cancer" of pine trees.

[0003] Agricultural nematode diseases are plant diseases caused by the invasion and parasitism of crop parasitic nematodes. The affected plants can be affected in their normal growth and development due to the nematodes absorbing nutrients in the body. The secretions during the metabolic process of nematodes can also stimulate the cells and tissues of the host plants, resulting in plant deformities, etc. Relatively serious agricultural nematode diseases include root - knot nematode disease of various crops such as peanuts, soybean cyst nematode disease, wheat grain nematode disease, sweet potato stem nematode disease, rice white - tip nematode disease, millet nematode disease, citrus semi - puncture nematode disease, etc. Nematode damage during the crop production process seriously affects the yield and quality.

[0004] The nematicidal activity of azoxy compounds has been reported. For example, CN1034580A discloses the long - chain compounds jiehumycin A and jiehumycin B, and patent CN107501131A discloses a class of jiehumycin analogs, which have good nematicidal activity against pine wood nematodes. However, the chemical synthesis route of this type of compound is long and the conditions are harsh, and further optimization is needed to achieve the nematicidal effect on pine wood nematodes. The excellent biological activity of this type of long - chain compound has good guiding significance for the research of azoxy - based compounds. CN115197103A discloses a class of azo and azoxy compounds, which have good control effects on pine wood nematodes, Meloidogyne incognita, hickory dry rot, and rice sheath blight. Summary of the Invention

[0005] In view of the above situation, the purpose of the present invention is to provide an azoxy compound, a preparation method thereof, and an application thereof.

[0006] The specific technical solutions are as follows:

[0007] An azoxy compound, the structural formula of which is shown in formula (Ⅰ),

[0008]

[0009] In the formula, H on the benzene ring is substituted or unsubstituted by the substituent R 1 When substituted, R 1 is methyl, methoxy, cyano, halogen, trifluoromethyl or trifluoromethoxy, m is an integer, 0 ≤ m ≤ 9, and the substituent R 2is an alkyl group, cycloalkyl group, substituted alkyl group, halogen, fluorenyl group, phenyl group or substituted phenyl group, and the substituent of the substituted phenyl group is a nitro group, methyl group, methoxy group, halogen or isopropyl group.

[0010] Further, the substituent R 1 is 2-methoxy, 3-methoxy, 4-methoxy, 4-methyl, 4-cyano, 4-trifluoromethyl, 4-trifluoromethoxy, 4-chloro, 4-fluoro, 4-bromo, 4-methylthio, 4-methylamino or 4-dimethylamino; the substituent R 2 is a methyl group, propyl group, heptyl group, isopropyl group, sec-butyl group, tert-butyl group, pentacyclo group, chlorine, trifluoromethyl group, chloroethyl group, fluorenyl group, phenyl group or substituted phenyl group, and the substituent of the substituted phenyl group is a nitro group, methyl group, fluorine, methoxy group, isopropyl group, methylthio group, methylamino group or dimethylamino group.

[0011] A method for preparing an azoxy compound, comprising the following steps:

[0012] 1) Under the condition of 0 °C, the compound shown in formula (II) is dissolved in dichloromethane, phosgene shown in formula (III) is added, and after 15 min, it is transferred to room temperature and left overnight. After the reaction is complete, water is added for quenching, and dichloromethane is used for extraction, followed by washing with water and saturated sodium chloride in sequence, and anhydrous Na 2 SO 4 is dried, column chromatography is carried out using petroleum ether as the eluent, and solvent is removed under reduced pressure to obtain the compound shown in formula (IV);

[0013] 2) The compound shown in formula (V) is dissolved in solvent A, a deacidifying agent B is added dropwise, cooled to 0 °C, the compound shown in formula (IV) is added dropwise, stirred and then transferred to room temperature. After 2 h, TLC monitoring is carried out until the reaction ends. After the reaction ends, extraction, washing, drying, solvent removal under reduced pressure and column chromatography are carried out to obtain the compound shown in formula (VI); 3) Under the condition of room temperature, the compound shown in formula (VI) is dissolved in solvent C, an oxidant D is added under stirring, and the reaction continues. TLC monitoring is carried out. After the reaction ends, extraction, washing, drying, solvent removal under reduced pressure and column chromatography are carried out to obtain the compound shown in formula (VII);

[0014] 4) Under the condition of room temperature, the compound shown in formula (VII) is dissolved in solvent E, an oxidant F is added under stirring, and the reaction is heated. TLC monitoring is carried out. After the reaction ends, after-treatment is carried out to obtain the compound shown in formula (I);

[0015] The reaction formula is as follows:

[0016]

[0017] In the formula, the H on the benzene ring is substituted or unsubstituted by the substituent R 1 When substituted, R 1is 2-methoxy, 3-methoxy, 4-methoxy, 4-methyl, 4-cyano, 4-trifluoromethyl, 4-trifluoromethoxy, 4-chloro, 4-fluoro, 4-bromo, 4-methylthio, 4-methylamino or 4-dimethylamino; the substituent R 2 is methyl, propyl, heptyl, isopropyl, sec-butyl, tert-butyl, pentyl ring, chloro, trifluoromethyl, chloroethyl, fluorenyl, phenyl or substituted phenyl, and the substituents of the substituted phenyl are nitro, methyl, fluoro, methoxy, isopropyl, methylthio, methylamino or dimethylamino.

[0018] Further, the solvent A in step 2) is tetrahydrofuran or acetonitrile, and the acid-binding agent B is triethylamine or pyridine; the solvent C in step 3) is dichloromethane or acetonitrile, and the oxidant D is iodobenzene diacetate or a sodium hydroxide solution of potassium ferricyanide; the solvent E in step 4) is dichloromethane, chloroform or ethyl acetate, and the oxidant F is m-chloroperbenzoic acid, hydrogen peroxide or sodium acetate.

[0019] Further, after the reaction in step 2) is completed, it is extracted with ethyl acetate or dichloromethane, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (VI).

[0020] Further, in step 3), when the oxidant D is iodobenzene diacetate, after the reaction is completed, it is extracted with dichloromethane, washed successively with saturated sodium carbonate, water and saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (VII); when the oxidant D is a sodium hydroxide solution of potassium ferricyanide, after the reaction is completed, it is extracted with dichloromethane, washed with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (VII).

[0021] Further, in step 4), when the oxidant F is m-chloroperbenzoic acid, the reaction is heated at 40 °C and monitored by TLC. After the reaction is completed, it is extracted, washed, dried, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (I); when the oxidant F is hydrogen peroxide, the catalyst maleic anhydride is added, hydrogen peroxide is added after stirring, and the reaction is refluxed at 65 °C for 5 h. After the reaction is complete, it is extracted, washed, dried, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (I); when the oxidant F is sodium acetate, the catalyst glacial acetic acid is added, sodium acetate is added after stirring, and the reaction is heated under reflux for 5 h. After the reaction is complete, it is extracted, washed, dried, concentrated under reduced pressure, and purified by column chromatography to obtain the compound shown in formula (I).

[0022] Further, in step 1), the molar ratio of triphosgene to the compound shown in formula (II) is 1:1; in step 2), the molar ratio of acid-binding agent B to the compound shown in formula (IV) is 2:1.1; in step 3), when the oxidizing agent D is iodobenzenedicarboxylic acid, the molar ratio of iodobenzenedicarboxylic acid to the compound shown in formula (VI) is 1.1:1; when the oxidizing agent D is a sodium hydroxide solution of potassium ferricyanide, the molar ratio of potassium ferricyanide to the compound shown in formula (VI) is 3:1; in step 4), when the oxidizing agent F is m-chloroperbenzoic acid, the molar ratio of m-chloroperbenzoic acid to the compound shown in formula (VII) is 1.35:1; when the oxidizing agent F is hydrogen peroxide, the molar ratio of hydrogen peroxide to the compound shown in formula (VII) is 3:1; when the oxidizing agent F is sodium acetate, the molar ratio of sodium acetate to the compound shown in formula (VII) is 2:1.

[0023] Use of an azoxy compound in the preparation of a nematicide and a fungicide, wherein the nematodes are Bursaphelenchus xylophilus, Meloidogyne incognita, Aphelenchoides besseyi or Ditylenchus destructor, and the fungi are Rhizoctonia solani, Botryosphaeria dothidea, Colletotrichum gloeosporioides, Fusarium graminearum, Fusarium solani or Botrytis cinerea; the concentration of the compound in the nematicide is 10-40 μg·mL -1 , and the concentration in the fungicide is 50 μg·mL -1 .

[0024] Further, the compound is used in combination with at least one other component selected from surfactants, solid diluents and liquid diluents.

[0025] The beneficial effects of the present invention are as follows: Using alcohol and triphosgene as raw materials, after generating chloroformate, through condensation and two-step oxidation reactions with phenylhydrazine hydrochloride, an azoxy compound is obtained. The reaction route is short, the conditions are mild, and it is easy to prepare. It shows excellent nematicidal activity against Bursaphelenchus xylophilus, Meloidogyne incognita, Aphelenchoides besseyi and Ditylenchus destructor at low concentrations. Through formulation of the compound, it also has good nematicidal activity and good fungicidal activity. Description of the Drawings

[0026] Figure 1 Shows the effects of some compounds on the body surface structure of Bursaphelenchus xylophilus. Detailed Embodiments

[0027] The following further illustrates the present invention with reference to examples, but the protection scope of the present invention is not limited thereto.

[0028] Examples 1-28

[0029] 1) Under the condition of 0 °C, 1 mmol (1 eq.) of compounds 1-1 to 1-18 (m is an integer from 0 to 9, substituent R 2(wherein the substituent R is methyl, propyl, heptyl, isopropyl, sec-butyl, tert-butyl, cyclopentyl, chlorine, trichloromethyl or chloroethyl) was dissolved in dichloromethane, and 1 mmol of triphosgene (1 eq.) was added under stirring. After 15 min, the mixture was transferred to room temperature and reacted overnight. After the reaction was complete, the reaction was quenched with water, extracted with dichloromethane, washed successively with water and saturated sodium chloride, and dried over anhydrous Na 2 SO 4 dried, and column chromatography was carried out using petroleum ether as the eluent to obtain compounds 3-1 to 3-18;

[0030] 2) 10 mmol (1 eq.) of compounds 4-1 to 4-8 (substituent R 1 is 4-methoxy, 4-chloro, 4-fluoro, 4-bromo, 4-trifluoromethyl, 4-trifluoromethoxy, 4-methylthio or 4-dimethylamino) was dissolved in tetrahydrofuran. 20 mmol (2 eq.) of triethylamine was added dropwise to the above solution, and the mixture was cooled to 0 °C. 11 mmol (1.1 eq.) of compounds 3-1 to 3-18 was slowly added dropwise. After stirring for 15 min, the mixture was transferred to room temperature. After 2 h, TLC was used to monitor the reaction until it ended. After the reaction ended, it was extracted with ethyl acetate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and column chromatography was carried out to obtain compounds 5-1 to 5-28;

[0031] 3) Method A: At room temperature, 5 mmol (1 eq.) of compounds 5-1 to 5-28 was dissolved in dichloromethane. 5.5 mmol (1.1 eq.) of iodobenzenedicarboxylic acid was added under stirring, and the reaction was continued for 15 min. TLC was used to monitor the reaction. After the reaction ended, it was extracted with dichloromethane, washed with saturated sodium carbonate, washed with water, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and column chromatography was carried out to obtain compounds 6-1 to 6-28;

[0032] Method B: At room temperature, 1 mmol (1 eq.) of compounds 5-1 to 5-28 was dissolved in dichloromethane. 3 mmol of K 3 Fe(CN) 6 (3 eq.) was dissolved in 2 mol / L sodium hydroxide (10 mL) solution, and it was added to the dichloromethane solution of compounds 5-1 to 5-24. The reaction was carried out for 5 min. After the reaction was complete, it was extracted with dichloromethane, washed twice with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and column chromatography was carried out to obtain compounds 6-1 to 6-28;

[0033] 4) Method A: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-1 to 6-28 in dichloromethane. Slowly add a dichloromethane solution of 4.05 mmol (1.35 eq.) of m-chloroperbenzoic acid dropwise under stirring. Heat the reaction at 40 °C for 2 h and monitor by TLC. After the reaction is completed, extract with dichloromethane, wash with saturated sodium sulfite, wash with saturated sodium chloride, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and perform column chromatography to obtain compounds 7-1 to 7-28;

[0034] Method B: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-1 to 6-28 in chloroform. Add 3 mmol (1 eq.) of maleic anhydride and stir for 10 min. Add 9 mmol (3 eq.) of hydrogen peroxide, heat to reflux at 65 °C, and react for 5 h. After the reaction is complete, stop heating and cool to room temperature. Dissolve in dichloromethane and wash successively with saturated Na 2 CO 3 ,H 2 O, saturated NaCl solution, and dry over anhydrous Na 2 SO 4 . Remove the solvent under reduced pressure. Perform column chromatography on the crude mixture using ethyl acetate and petroleum ether at a ratio of 1:20 as the eluent, and remove the solvent under reduced pressure to obtain compounds 7-1 to 7-28;

[0035] Method C: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-1 to 6-28 in ethyl acetate. Add 3 mmol (1 eq.) of glacial acetic acid and stir for 10 min. Add 6 mmol (2 eq.) of sodium acetate, heat to reflux, and react for 5 h. After the reaction is complete, stop heating and cool to room temperature. Dissolve in ethyl acetate and wash successively with saturated Na 2 CO 3 ,H 2 O, saturated NaCl solution, and dry over anhydrous Na 2 SO 4 . Remove the solvent under reduced pressure. Perform column chromatography on the crude mixture using ethyl acetate and petroleum ether at a ratio of 1:20 as the eluent, and remove the solvent under reduced pressure to obtain compounds 7-1 to 7-28;

[0036] Substituents R 1 and R 2 are shown in Table 1. The reaction formula is as follows:

[0037]

[0038] Table 1 1 1H NMR spectroscopic data of compounds 7-1 to 7-28

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047] Examples 29 - 55

[0048] 1) Under the condition of 0 °C, 1 mmol (1 eq.) of Compounds 1 - 19 to 1 - 44 (m is an integer from 0 to 4, and the substituent R 2 is fluorenyl, phenyl or substituted phenyl, and the substituents of the substituted phenyl are 4 - nitro, 4 - methyl, 2 - methoxy, 3 - methoxy, 4 - methoxy, 4 - isopropyl, 4 - fluoro, 4 - methylthio, 4 - methylamino or 4 - dimethylamino) is dissolved in dichloromethane. Under stirring, 1 mmol triphosgene (1 eq.) is added. After 15 min, it is transferred to room temperature and the reaction is carried out overnight. After the reaction is complete, water is added for quenching, and it is extracted with dichloromethane, washed successively with water and saturated sodium chloride, and dried over anhydrous Na 2 SO 4 and column chromatography is carried out using petroleum ether as the eluent to obtain Compounds 3 - 19 to 3 - 44;

[0049] 2) 10 mmol (1 eq.) of Compound 4 - 1 or 4 - 7 to 4 - 14 (the substituent R 1 is 4 - methoxy, 3 - methoxy, 2 - methoxy, H, cyano, 4 - methyl, 4 - methylthio, 4 - methylamino or 4 - dimethylamino) is dissolved in acetonitrile. 20 mmol (2 eq.) of pyridine is added dropwise to the above solution, cooled to 0 °C, and 11 mmol (1.1 eq.) of Reactants 3 - 19 to 3 - 44 is slowly added dropwise. After stirring for 15 min, it is transferred to room temperature. After 2 h, TLC monitoring is carried out until the reaction ends. After the reaction ends, it is extracted with dichloromethane, washed with clear water and saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and column chromatography is carried out to obtain Compounds 5 - 29 to 5 - 55;

[0050] 3) Method A: At room temperature, dissolve 5 mmol (1 eq.) of compounds 5-29 to 5-55 in dichloromethane. Under stirring conditions, add 5.5 mmol (1.1 eq.) of iodobenzenediacetic acid and continue the reaction for 15 min, monitored by TLC. After the reaction is completed, extract with dichloromethane, wash with saturated sodium carbonate, wash with water, wash with saturated sodium chloride, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and perform column chromatography to obtain compounds 6-29 to 6-55;

[0051] Method B: At room temperature, dissolve 1 mmol (1 eq.) of compounds 5-29 to 5-55 in dichloromethane. Dissolve 3 mmol of K 3 Fe(CN) 6 (3 eq.) in 2 mol / L sodium hydroxide (10 mL) solution, and add it to the dichloromethane solution of compounds 3-1 to 3-24. React for 5 min. After the reaction is complete, extract with dichloromethane, wash twice with water, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and perform column chromatography to obtain compounds 6-29 to 6-55;

[0052] 4) Method A: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-29 to 6-55 in dichloromethane,

[0053] Slowly add dropwise a dichloromethane solution of 4.5 mmol (1.35 eq.) of m-chloroperbenzoic acid under stirring conditions. Heat the reaction at 40 °C for 2 h, monitored by TLC. After the reaction is completed, extract with dichloromethane, wash with saturated sodium sulfite, wash with saturated sodium chloride, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and perform column chromatography to obtain compounds

[0054] 7-29 to 7-55;

[0055] Method B: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-29 to 6-55 in chloroform, add 3 mmol (1 eq.) of maleic anhydride, stir for 10 min, add 9 mmol (3 eq.) of hydrogen peroxide, heat to reflux at 65 °C, react for 5 h. After the reaction is complete, stop heating, cool to room temperature, dissolve in dichloromethane, and wash successively with saturated Na 2 CO 3 , H 2 O, saturated NaCl solution, and dry over anhydrous Na 2 SO 4 Dry. Remove the solvent under reduced pressure. Use ethyl acetate and petroleum ether 1:20 as the eluent for column chromatography of the crude mixture, and remove the solvent under reduced pressure to obtain compounds 7-29 to 7-55;

[0056] Method C: At room temperature, dissolve 3 mmol (1 eq.) of compounds 6-25 to 6-48 in ethyl acetate, add 3 mmol (1 eq.) of glacial acetic acid, stir for 10 min, add 6 mmol (2 eq.) of sodium acetate, heat to reflux, and react for 5 h. After the reaction is complete, stop heating, cool to room temperature, dissolve in ethyl acetate, and wash successively with saturated Na 2 CO 3 ,H 2 O, saturated NaCl solution, and dry over anhydrous Na 2 SO 4 . Remove the solvent under reduced pressure. Chromatograph the crude mixture on a column using ethyl acetate and petroleum ether at a ratio of 1:20 as the eluent, and remove the solvent under reduced pressure to obtain compounds 7-29 to 7-55;

[0057] Substituent R 1 and R 2 are shown in Table 2, and the reaction formula is as follows:

[0058]

[0059] Table 2 1 1H NMR spectroscopic data of compounds 7-29 to 7-55

[0060]

[0061]

[0062]

[0063]

[0064]

[0065] Example 49

[0066] Activity test against Bursaphelenchus xylophilus: Dissolve compounds 7-1 to 7-55 in a mixed solution of dimethyl sulfoxide and an aqueous solution of 0.1% Tween-80 to form a homogeneous solution, and dilute it with water to any desired concentration when in use. In a 96-well plate, add 10 μL of the sample dilution and 90 μL of the Bursaphelenchus xylophilus suspension to prepare a mixed solution with a final concentration of 10 μg·mL -1 . Incubate in an incubator at 25 °C. After 24 h, observe the poisoning and death of the nematodes, and calculate the mortality rate and corrected mortality rate. If the control mortality rate < 5%, no correction is required; if the control mortality rate is between 5% and 20%, correction is required.

[0067]

[0068] Table 3 Bioactivity assay results of compounds 7-1 to 7-48 against Bursaphelenchus xylophilus

[0069]

[0070]

[0071] *Nematicidal activity grade in the table: Grade A is 100%-90%; Grade B is 90%-70%; Grade C is 70%-50%; Grade D is 50%-0%.

[0072] It can be seen from the nematicidal activity of Bursaphelenchus xylophilus in Table 3 that compounds 7-1 to 7-10 all have high nematicidal activity. However, when the number of C atoms in the substituted long chain increases to 16, the nematicidal activity of compound 7-11 decreases significantly. Compounds 7-12 to 7-14 show that introducing a branched chain in the alkyl group can effectively maintain the nematicidal activity, but the introduction of a tert-butyl group is not conducive to the activity. For compound 7-15, introducing a cycloalkyl group in the R 2 group shows better nematicidal activity. Compounds 7-16 to 7-18 show that when a halogen is introduced into the R 2 group, the presence of a branched chain is not conducive to maintaining the activity. To sum up, introducing an electron-donating group into the R 1 group is beneficial to increasing the activity. Similarly, introducing a benzene ring or a substituted benzene ring into the R 2 group. It can be seen from the nematicidal activity of 7-29 to 7-55 that no substitution or substitution with an electron-donating group on the right benzene ring is beneficial to increasing the activity.

[0073] The effects of some compounds on the body surface structure of Bursaphelenchus xylophilus are as Figure 1As shown, after 72 hours of treatment, a comprehensive observation and comparison were made: The body of Bursaphelenchus xylophilus treated with CK was plump and curved naturally; the body shrank and twisted after treatment with abamectin; the body shrank and twisted after treatments with 7-2, 7-12, and 7-36, and the body was thinner and the curvature was more obvious compared with the positive control. Observation and comparison of the head: The connection position between the head and the body trunk of CK was obvious, and the circular protrusion at the junction was obvious; the connection position between the head and the body trunk was blurred after treatment with abamectin, and a circular protrusion appeared on the body surface at the connection; the connection position between the head and the body trunk was blurred after treatment with 7-2, and a vein-like protrusion appeared on the body surface at the connection; a circular protrusion appeared on the head skin after treatment with 7-12, and the body shrank more obviously at the connection; the connection position between the head and the body trunk was blurred after treatment with 7-36, the body shrank obviously at the connection, and holes appeared on the skin. Observation and comparison of the tail: The tail of the CK was smooth and plump; the surface of the tail shrank and circular protrusions appeared on the surface after treatment with abamectin; the surface of the tail shrank severely and the tail shape changed, resembling a needle after treatment with 7-2; the surface of the tail shrank severely and strip-shaped protrusions appeared on the surface after treatment with 7-12; the surface of the tail shrank severely and strip-shaped protrusions appeared on the surface after treatment with 7-36. Observation and comparison of the trunk: The body wall pattern of the trunk of CK was clear and the body surface was smooth; the body pattern was blurred and the body wall shrank slightly after treatment with abamectin; the body pattern was blurred and uneven, the body wall shrank severely, and holes appeared on the skin after treatment with 7-2; the body pattern was blurred and uneven, and there were obvious concave shrinkages on the body wall after treatment with 7-12; the body was shriveled, the pattern was blurred and uneven, and there were obvious concave shrinkages on the body wall after treatment with 7-36. Different symptoms appeared after the worms of different treatments died. Among them, 7-2 caused the most serious damage to the body of Bursaphelenchus xylophilus, especially the tail and the trunk of the body. The scanning electron microscope results showed that the azoxy group compounds represented by 7-2, 7-12, and 7-36 may have a different mechanism of action from abamectin.

[0074] Example 50

[0075] Activity test of Meloidogyne incongnita: Compounds 7-1 to 7-55 were dissolved in an aqueous solution of dimethyl sulfoxide and 0.1% Tween-80 to form a homogeneous solution, and diluted with water to any required concentration when used. In a 96-well plate, 50 μL of the sample dilution and 50 μL of the nematode suspension were added to prepare a mixed solution with a final concentration of 40 μg·mL -1 and cultured in an incubator at 25°C. After 72 hours, the poisoning and death of the nematodes were observed, and the mortality or corrected mortality was calculated. The test results are shown in Table 3.

[0076] Based on the test results of the activity of Bursaphelenchus xylophilus and preliminary experiments, azoxy compounds were selected for the nematicidal activity test against Meloidogyne incognita. It can be seen from the data in Table 4 that when the number of long-chain carbon atoms increases to 16, the nematicidal activities of compounds 7-1 to 7-13, 7-15, 7-17, 7-25 to 7-28 can still maintain more than 90% activity. When the R 2 group is introduced into the benzene ring or substituted benzene ring, compounds 7-29, 7-33, 7-35 to 7-42, 7-44, 7-46, 7-47, 7-49 to 7-55 still have more than 90% nematicidal activity. Therefore, the compounds that show good nematicidal activity against Bursaphelenchus xylophilus also show excellent nematicidal activity against Meloidogyne incognita. Although the activity level of compound 7-11 against Bursaphelenchus xylophilus is D at a concentration of 10 μg·mL -1 , its activity level against Meloidogyne incognita is A at a concentration of 40 μg·mL -1 . It can be speculated that azoxy compounds with nematicidal activity levels B-D against Bursaphelenchus xylophilus may have good nematicidal activity against Meloidogyne incognita at a concentration of 40 μg·mL -1 .

[0077] Table 4 Determination results of the biological activities of some compounds against Meloidogyne incognita

[0078]

[0079]

[0080] *Nematicidal activity levels in the table: A level is 100%-90%; B level is 90%-70%; C level is 70%-50%; D level is 50%-0%.

[0081] Examples 51 to 52

[0082] Activity test of Aphelenchoides besseyi and Ditylenchus destructor: Select the test compound and dissolve it in an aqueous solution of dimethyl sulfoxide and 0.1% Tween-80 to form a homogeneous solution, and dilute it with water to any required concentration when in use. In a 96-well plate, add 50 μL of the sample dilution and 50 μL of the nematode suspension to prepare a mixed solution with a final concentration of 10 μg·mL -1 . Place it in an incubator at 25 °C for cultivation. After 24 h, observe the poisoning and death of the nematodes, and calculate the mortality or corrected mortality. The test results are shown in Table 5.

[0083] Based on the test results of the activity of Bursaphelenchus xylophilus and preliminary experiments, oxidative azo compounds with relatively high nematicidal activity were selected for the nematicidal activity test against Aphelenchoides besseyi and Ditylenchus destructor. It can be seen from the data in Table 5 that when the number of long-chain carbon atoms increases to 16, the nematicidal activity of compounds 7-1 to 7-10, 7-12, 7-13, 7-15, 7-17, 7-25 to 7-28 can still maintain an activity of more than 90%. When the R 2 group is introduced into the benzene ring or substituted benzene ring, compounds 7-29, 7-35 to 7-42, 7-44, 7-46, 7-47, 7-49 to 7-55 still have a nematicidal activity of more than 90%. Therefore, compounds that show good nematicidal activity against Bursaphelenchus xylophilus also show excellent nematicidal activity against Aphelenchoides besseyi and Ditylenchus destructor.

[0084] Table 5 Determination results of the biological activities of some compounds against Aphelenchoides besseyi and Ditylenchus destructor

[0085] Number <![CDATA[Activity level a > Number <![CDATA[Activity level a > Number <![CDATA[Activity level a > 7-1 A 7-25 A 7-46 A 7-2 A 7-26 A 7-47 A 7-3 A 7-27 A 7-49 A 7-4 A 7-28 A 7-50 A 7-5 A 7-29 A 7-51 A 7-6 A 7-35 A 7-52 A 7-7 A 7-36 A 7-53 A 7-8 A 7-37 A 7-54 A 7-9 A 7-38 A 7-55 A 7-10 A 7-39 A Emamectin benzoate <![CDATA[D b and c > 7-12 A 7-40 A Abamectin <![CDATA[D b and c > 7-13 A 7-41 A Fludioxonil <![CDATA[D b or C c > 7-15 A 7-42 A / / 7-17 A 7-44 A / /

[0086] *a: Nematicidal activity grades in the table: Grade A is 100%-90%; Grade B is 90%-70%; Grade C is 70%-50%; Grade D is 50%-0%; b: The test concentrations of emamectin benzoate, abamectin, and fluxapyroxad against Aphelenchoides besseyi are 100 μg·mL -1 ; c: The test concentrations of emamectin benzoate, abamectin, and fluxapyroxad against Ditylenchus destructor are 10 μg·mL -1 .

[0087] Example 53

[0088] Determination of bactericidal activity: Using the poisoned medium method, dissolve the compound to be tested in DMF to prepare a 2% stock solution, and then dilute it to 500 μg·mL with 1‰ Tween water -1 , and mix it with PDA at a volume ratio of 1:9. The final determination concentration is 50 μg·mL -1 . Azoxystrobin and tebuconazole are used as positive controls, and the final determination concentration is 25 μg·mL -1 , distilled water containing 0.5% DMF is used as the solvent control, and 1‰ Tween water is used as the blank control. Each treatment is repeated 3 times. Incubate in an incubator at 25°C, and observe the inhibitory effect of the treatment group after the diameter of the blank control grows to 7 cm. The inhibition rate is calculated according to the following formula:

[0089]

[0090] At 50 μg·mL -1, the inhibitory effects of Compounds 7-2 to 7-7 against Rhizoctonia solani (R. solani), Botryosphaeria dothidea (B. dothidea), and Botrytis cinerea (B. cinerea) reached over 70%. The inhibitory activities of Compounds 7-2 to 7-10 against 6 pathogenic fungi showed a downward trend, indicating that the number of carbon atoms in the fatty chain affects the inhibitory effect of the compound on pathogenic fungi. The inhibitory activity decreased with the increase in the number of carbon atoms in the fatty chain. The best-performing compound, 7-2, had an inhibitory effect of over 70% against Rhizoctonia solani (R. solani), Botryosphaeria dothidea (B. dothidea), Colletotrichum gloeosporioides (C. gloeosporioides), Fusarium graminearum (F. graminearum), and Botrytis cinerea (B. cinerea). In the R 2 When the R group was introduced into the benzene ring or substituted benzene ring, Compounds 7-31 and 7-32 still had a bactericidal activity of over 70% against Rhizoctonia solani (R. solani) and Botryosphaeria dothidea (B. dothidea).

[0091] Table 6 Determination Results of Bactericidal Activities of Some Compounds

[0092] Compound R.s. B.d. C.g. F.g. F.s. B.c. 7-2 A A B B C A 7-3 A B C B C A 7-4 A B C C D A 7-5 A B C C D B 7-6 A B D C D B 7-7 A B D C D B 7-8 B C D D D C 7-9 C B C D D D 7-10 D C D D D D 7-31 B C C D D D 7-32 C C D D D D Tebuconazole B A A A A A Azoxystrobin B D B C D D

[0093] * Grades of bactericidal activities in the table: Grade A is 100% - 90%; Grade B is 90% - 70%; Grade C is 70% - 50%; Grade D is 50% - 0%. R.s.: Rhizoctonia solani; B.d.: Botryosphaeria dothidea; C.g.: Colletotrichum gloeosporioides; F.g.: Fusarium graminearum; F.s.: Fusarium solani; B.c.: Botrytis cinerea.

[0094] Example 54

[0095] Dosage Form / Application

[0096] The compounds of the present invention are generally applied as dosage forms or compositions together with agriculturally suitable carriers, and the suitable carriers include at least one of liquid diluents, solid diluents or surfactants. The selection of the components of the dosage form or composition should be consistent with the physical properties of the active ingredient, the application method and environmental factors. Useful dosage forms include liquid agents such as solutions, suspensions, emulsions, etc., which can optionally be thickened into gels. Useful dosage forms also include solids such as granules, tablets, pills, powders, dusts, films, etc., which can be water-dispersible or water-soluble. The active ingredient can be microencapsulated and then made into a suspension or solid dosage form; alternatively, the entire dosage form of the active ingredient can also be encapsulated. Encapsulation can control or delay the release of the active ingredient.

[0097] Each dosage form generally contains an effective amount of the active ingredient, diluent and surfactant, in the following approximate ranges, up to 100% (by weight).

[0098] All dosage forms may contain a small amount of additives to reduce foaming, caking, corrosion, microbial growth, etc., or a thickening agent to increase viscosity.

[0099] Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilanes, N,N-dialkyl taurates, lignin sulfonates, naphthalene sulfonate-aldehyde condensates, polycarboxylates and polyoxyethylene / polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and sodium bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzene, alkylnaphthalene, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and cocoa butter, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, dodecanol and tetrahydrofurfuryl alcohol.

[0100] All percentages are by weight, and all dosage forms are prepared by conventional methods.

[0101] Table 7 Formulation ratio table of microemulsion

[0102] Microemulsion Weight percentage Compound 7-7 5％ Polyoxyethylene fatty alcohol phosphate 15％ Ethanol 40％ Isopropanol 40％

[0103] Table 8 Formulation ratio table of emulsifiable concentrate

[0104] Emulsifiable concentrate Weight percentage (%) Compound 7-7 1％ Nonylphenol polyoxyethylene ether 6％ Methanol 93％

[0105] Table 9 Formulation ratio table of suspension concentrate

[0106] Suspension concentrate Weight percentage (%) Compound 7-7 5％ Terpene resin 90％ Polyoxyethylene lauryl ether 5％

[0107] Table 10 Formulation Table of Aqueous Agent

[0108] Aqueous solution Weight percentage (%) Compound 7-7 5％ Tween 80 27％ Water 68％

[0109] Table 11 Formulation Table of Nano-dispersion

[0110] Nanodispersion Weight percentage (%) Compound 7-7 2％ Silica nanoparticles 4％ Water 94％

[0111] Table 12 Formulation Table of Water-dispersible Granules

[0112] Water dispersible granule Weight percentage (%) Compound 7-7 5％ Tea saponin 15％ Anhydrous glucose 6％ Diatomaceous earth 48％ Ammonium sulfate 26％

[0113] Table 13 Formulation Table of Granules

[0114] Granule Weight percentage (%) Compound 7-7 2％ Attapulgite 98％

[0115] Using the above-mentioned method for determining the biological activity of Bursaphelenchus xylophilus, the biological activity of Bursaphelenchus xylophilus was determined for the dosage forms in Tables 6 to 12. The results are shown in Table 13. At the concentration of 5 μg·mL -1 and after 24 h of treatment, the nematicidal activities were all 100%, showing good application prospects. The research and development of such compounds can provide an effective means for controlling Bursaphelenchus xylophilus disease.

[0116] Table 14 Activity Determination Results of Different Dosage Forms

[0117]

[0118]

[0119] Corrected mortality rate grades in the table: Grade A is 100% - 90%; Grade B is 90% - 70%; Grade C is 70% - 50%; Grade D is 50% - 0%.

[0120] It can be seen from the test results that at the concentration of 10 μg·mL -1 , the azoxy group-containing compounds showed excellent nematicidal activities against Bursaphelenchus xylophilus. In addition, the compounds showing excellent nematicidal activities against Bursaphelenchus xylophilus also showed excellent nematicidal activities against Meloidogyne incognita, Aphelenchoides besseyi and Ditylenchus destructor. During the bactericidal activity test, some compounds also showed good bactericidal activities against Rhizoctonia solani, Botryosphaeria dothidea, Colletotrichum gloeosporioides, Fusarium graminearum, Fusarium solani and Botrytis cinerea. In summary, the compounds in Examples 1 - 55 not only showed excellent nematicidal activities against Bursaphelenchus xylophilus, Meloidogyne incognita, Aphelenchoides besseyi and Ditylenchus destructor, but also had certain bactericidal activities, and can be used for controlling agricultural and forestry pests and diseases.

Claims

1. An azoxy compound, characterized in that: Its structural formula is shown in formula (I). In the formula, the H on the benzene ring is replaced by a substituent R 1 Replacement or non-replacement, when replaced R 1 is methyl, methoxy, cyano, halogen, trifluoromethyl, trifluoromethoxy, methylthio, methylamino or dimethylamino, m is an integer, 0≤m≤9, and the substituent R 2 It is alkyl, cycloalkyl, substituted alkyl, halogen, fluorenyl, phenyl or substituted phenyl, and the substituent of the substituted phenyl is nitro, methyl, methoxy, halogen, isopropyl, methylthio, methylamino or dimethylamino.

2. An azoxy compound according to claim 1, characterized in that: Substituent R 1 is 2-methoxy, 3-methoxy, 4-methoxy, 4-methyl, 4-cyano, 4-trifluoromethyl, 4-trifluoromethoxy, 4-chloro, 4-fluoro, 4-bromo, 4-methylthio, 4-methylamino or 4-dimethylamino; the substituent R 2 It is methyl, propyl, heptyl, isopropyl, sec-butyl, tert-butyl, pentyl, chloro, trifluoromethyl, chloroethyl, fluorenyl, phenyl or substituted phenyl, and the substituent of the substituted phenyl is nitro, methyl, fluoro, methoxy, isopropyl, methylthio, methylamino or dimethylamino.

3. A method for preparing an oxyazolyl compound as claimed in claim 2, characterized in that: The steps include: 1) At 0°C, the compound represented by formula (II) is dissolved in dichloromethane, and triphosgene represented by formula (III) is added. After 15 minutes, the mixture is transferred to room temperature overnight. After the reaction is complete, water is added to quench the mixture, and the mixture is extracted with dichloromethane. The mixture is washed with water and saturated sodium chloride in sequence, dried over anhydrous Na2SO4, and subjected to column chromatography using petroleum ether as the eluent. The mixture is desolvated under reduced pressure to obtain a compound represented by formula (IV); 2) dissolving the compound represented by formula (V) in solvent A, adding acid-binding agent B dropwise, cooling to 0°C, adding the compound represented by formula (IV) dropwise, stirring and transferring to room temperature, monitoring by TLC after 2 hours until the reaction is completed, extracting, washing, drying, desolventizing under reduced pressure, and column chromatography after the reaction is completed to obtain the compound represented by formula (VI); 3) Under room temperature, the compound represented by formula (VI) is dissolved in solvent C, and an oxidant D is added under stirring, and the reaction is continued, and TLC is monitored. After the reaction is completed, extraction, washing, drying, desolventizing, and column chromatography are performed to obtain a compound represented by formula (VII); 4) Under room temperature, the compound represented by formula (VII) is dissolved in solvent E, and oxidant F is added under stirring, and the reaction is heated and monitored by TLC. After the reaction is completed, the compound represented by formula (I) is obtained by post-treatment; The reaction formula is as follows: In the formula, the H on the benzene ring is replaced by a substituent R 1 Replacement or non-replacement, when replaced R 1 is 2-methoxy, 3-methoxy, 4-methoxy, 4-methyl, 4-cyano, 4-trifluoromethyl, 4-trifluoromethoxy, 4-chloro, 4-fluoro, 4-bromo, 4-methylthio, 4-methylamino or 4-dimethylamino; the substituent R 2 It is methyl, propyl, heptyl, isopropyl, sec-butyl, tert-butyl, pentyl, chloro, trifluoromethyl, chloroethyl, fluorenyl, phenyl or substituted phenyl, and the substituent of the substituted phenyl is nitro, methyl, fluoro, methoxy, isopropyl, methylthio, methylamino or dimethylamino.

4. The method for preparing an azoxy compound according to claim 3, characterized in that: The solvent A in step 2) is tetrahydrofuran or acetonitrile, and the acid-binding agent B is triethylamine or pyridine; the solvent C in step 3) is dichloromethane or acetonitrile, and the oxidant D is a sodium hydroxide solution of iodophenyl diacetic acid or potassium ferrocyanide; the solvent E in step 4) is dichloromethane, chloroform or ethyl acetate, and the oxidant F is m-chloroperbenzoic acid, hydrogen peroxide or sodium acetate.

5. The method for preparing an azoxy compound according to claim 4, characterized in that: Step 2) After the reaction is completed, extract with ethyl acetate or dichloromethane, wash with water, wash with saturated sodium chloride, dry with anhydrous sodium sulfate, desolventize under reduced pressure, and perform column chromatography to obtain a compound represented by formula (VI).

6. The method for preparing an azoxy compound according to claim 4, characterized in that: In step 3), when the oxidant D is iodophenyldiacetic acid, after the reaction is completed, dichloromethane is used for extraction, saturated sodium carbonate, water and saturated sodium chloride are washed in sequence, dried over anhydrous sodium sulfate, desolventized under reduced pressure, and column chromatography is performed to obtain the compound represented by formula (VII); when the oxidant D is a sodium hydroxide solution of potassium ferrocyanide, after the reaction is completed, dichloromethane is used for extraction, water is washed, dried over anhydrous sodium sulfate, desolventized under reduced pressure, and column chromatography is performed to obtain the compound represented by formula (VII).

7. The method for preparing an azoxy compound according to claim 4, characterized in that: In step 4), when the oxidant F is m-chloroperbenzoic acid, the reaction is heated at 40°C and monitored by TLC. After the reaction is completed, extraction, washing, drying, desolventizing under reduced pressure, and column chromatography are performed to obtain the compound shown in formula (I); when the oxidant F is hydrogen peroxide, maleic anhydride is added as a catalyst, hydrogen peroxide is added after stirring, and the reaction is refluxed at 65°C for 5 hours. After the reaction is complete, extraction, washing, drying, desolventizing under reduced pressure, and column chromatography are performed to obtain the compound shown in formula (I); when the oxidant F is sodium acetate, glacial acetic acid is added as a catalyst, sodium acetate is added after stirring, and the reaction is heated under reflux for 5 hours. After the reaction is complete, extraction, washing, drying, desolventizing under reduced pressure, and column chromatography are performed to obtain the compound shown in formula (I).

8. The method for preparing an azoxy compound according to claim 5, characterized in that: In step 1), the molar ratio of triphosgene to the compound represented by formula (II) is 1:1; in step 2), the molar ratio of the acid-binding agent B to the compound represented by formula (IV) is 2:1.1; in step 3), when the oxidant D is iodophenyldiacetic acid, the molar ratio of iodophenyldiacetic acid to the compound represented by formula (VI) is 1.1:1; when the oxidant D is a sodium hydroxide solution of potassium ferrocyanide, the molar ratio of potassium ferrocyanide to the compound represented by formula (VI) is 3:1; in step 4), when the oxidant F is meta-chloroperbenzoic acid, the molar ratio of meta-chloroperbenzoic acid to the compound represented by formula (VII) is 1.35:1; when the oxidant F is hydrogen peroxide, the molar ratio of hydrogen peroxide to the compound represented by formula (VII) is 3:1; when the oxidant F is sodium acetate, the molar ratio of sodium acetate to the compound represented by formula (VII) is 2:

1.

9. Use of the azoxy compound as claimed in claim 1 or 2 in the preparation of nematicides and fungicides, characterized in that: The nematode is pine wood nematode, southern root knot nematode, rice stem tip nematode or stem nematode, and the fungus is Rhizoctonia solani, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Fusarium solani or Botrytis cinerea; the concentration of the compound in the nematicide is 10-40 μg·mL -1 , the concentration in the fungicide is 50 μg mL -1 .

10. Use of an azoxy compound according to claim 9 in the preparation of nematicides and fungicides, characterized in that: The compound is used in combination with at least one other component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

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