A heterocyclic oxime compound, a preparation method and application thereof, and a composition

Abstract

The application belongs to the technical field of pesticides, and particularly relates to a heterocyclic oxime compound, a preparation method and application thereof, and a composition. The application provides a heterocyclic oxime compound with a structure shown in formula 1. The heterocyclic oxime compound provided by the application takes a heterocyclic diaromatic oxime structure as a skeleton structure, and one heteroaromatic group connected with the oxime group is a substituted or substituted benzothiazole group. The benzothiazole oxime compound obtained through the oxime group on the skeleton structure and the heterocyclic group jointly acting can have a good inhibitory effect on plant fungal diseases, and has a positive significance for the creation of new pesticides.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticides, and particularly relates to a heterocyclic oxime compound, a preparation method and application thereof, and a composition. BACKGROUND

[0002] Fungicides play an important role in crop protection and plant disease control, and the use of agricultural fungicides is related to food output and people's food safety. At present, chemical synthesis of agricultural fungicides accounts for more than 80% of the market share, and has a long history and a variety of products.

[0003] However, with the widespread and long-term use of existing agricultural fungicides, the resistance and tolerance of pests to existing agricultural fungicides occur frequently.

[0004] Therefore, it is urgent to develop new structure fungicides for effective protection of crops. SUMMARY

[0005] The present application aims to provide a heterocyclic oxime compound, a preparation method and application thereof, and the heterocyclic oxime compound provided by the present application can have a good inhibitory effect on plant fungal diseases, and has a positive significance for the creation of new pesticides.

[0006] In order to achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0007] The present application provides a heterocyclic oxime compound having the structure shown in formula 1:

[0008]

[0009] In formula 1, the configuration of the oxime group is E type or Z type; R1 is H, halogen, substituted or unsubstituted C1-C4 alkyl, cyano, alkynyl, alkoxy, -NO2, -NH2, -OH or -SH;

[0010] Ar is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, naphthyl, thienyl, thiazolyl, furanyl, pyrrolyl, benzothiazolyl, benzofuranyl, pyrimidinyl, pyrazinyl or imidazolyl.

[0011] Preferably, R1 is H, C1-C4 alkyl, C1-C4 alkoxy or halogen.

[0012] Preferably, Ar is R3 in the above-mentioned is H, halogen, phenyl, -OH, C1-C4 alkyl, C1-C4 alkoxy, CF3 or

[0013] R3 in the above-mentioned is pyrazinyl or any of the following structures:

[0014]

[0015] Preferably, R1 is H or Cl; Ar is 2-methylphenyl, 3-methylphenyl, 2-CF3-phenyl, 2-Cl phenyl, 2-F phenyl, 2-I phenyl, 2-Br phenyl, 3-Br phenyl, 4-Br phenyl, 2-hydroxyphenyl, 2 phenyl-phenyl, 2 methoxyphenyl,

[0016] Preferably, it has any one of the following structures:

[0017]

[0018] The application provides a preparation method of the heterocyclic oxime compound.

[0019] The compound shown in the structure of formula 2, hydroxylamine hydrochloride, an alkali metal salt of an organic acid and an organic solvent are subjected to an oxime group reaction under heating to obtain the heterocyclic oxime compound shown in the structure of formula 1.

[0020]

[0021] Preferably, the preparation method of the compound shown in the structure of formula 2 comprises the following steps.

[0022] The compound shown in the structure of formula 3, the compound shown in the structure of formula 4, an inorganic strong base, iodine, an organic solvent and water are subjected to a nucleophilic substitution reaction under heating to obtain the compound shown in the structure of formula 2.

[0023]

[0024] Alternatively, the compound shown in the structure of formula 4, the compound shown in the structure of formula 5, iodine and an organic solvent are mixed and heated to perform a ring-forming-substitution reaction to obtain the compound shown in the structure of formula 2.

[0025]

[0026] The application provides application of the heterocyclic oxime compound or the heterocyclic oxime compound prepared by the preparation method in prevention and treatment of plant pathogenic fungi.

[0027] Preferably, the plant pathogenic fungi include one or more of rice sheath blight fungus, wheat sheath blight fungus, sclerotinia sclerotiorum, fusarium graminearum, fusarium cerealis, botrytis cinerea, phytophthora infestans, phytophthora capsici, alternaria solani, xanthomonas oryzae, fusarium oxysporum, cucumis sativus and pyricularia oryzae.

[0028] The application provides a composition comprising a bacteriostatic active component and a pesticide-accepted auxiliary material; the bacteriostatic active component is the heterocyclic oxime compound or the pesticide-acceptable salt thereof as described in the above technical solution or the heterocyclic oxime compound prepared by the preparation method as described in the above technical solution or the pesticide-acceptable salt thereof.

[0029] The application provides a heterocyclic oxime compound with the structure shown in formula 1. The heterocyclic oxime compound provided by the application takes a heterocyclic diaromatic oxime structure as a skeleton structure, and one heteroaromatic group connected with the oxime group is a substituted or unsubstituted benzothiazole group, so that the benzothiazole oxime compound obtained by the joint action of the oxime group on the skeleton structure and the heterocyclic group can have a good inhibitory effect on plant fungal diseases, and has a positive significance for the creation of new pesticides.

[0030] The preparation method of the heterocyclic oxime compound provided by the application has simple and practical synthesis steps, raw materials are easy to obtain, and is suitable for industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 The preparation flowchart of the heterocyclic oxime compound provided by the application is shown in the following table.

[0032] Figure 2 The preparation flowchart of the heterocyclic oxime compound provided by the application is shown in the following table.

[0033] Figure 3 The preparation flowchart of the heterocyclic oxime compound HXD-47 provided by the application is shown in the following table.

[0034] Figure 4 The preparation flowchart of the heterocyclic oxime compound HXD-144a provided by the application is shown in the following table.

[0035] Figure 5 The preparation flowchart of the heterocyclic oxime compound HXD-88 provided by the application is shown in the following table.

[0036] Figure 6 The preparation flowchart of the heterocyclic oxime compound HXD-90a provided by the application is shown in the following table.

[0037] Figure 7 The preparation flowchart of the heterocyclic oxime compound HXD-76 provided by the application is shown in the following table.

[0038] Figure 8 The preparation flowchart of the heterocyclic oxime compound HXD-123a provided by the application is shown in the following table.

[0039] Figure 9The preparation flow chart of the heterocyclic oxime compound HXD-110a provided for the embodiment 13 of the present application is shown in the figure;

[0040] Figure 10 The preparation flow chart of the heterocyclic oxime compound HXD-111a provided for the embodiment 14 of the present application is shown in the figure;

[0041] Figure 11 The preparation flow chart of the heterocyclic oxime compound HXD-43a provided for the embodiment 15 of the present application is shown in the figure;

[0042] Figure 12 The preparation flow chart of the heterocyclic oxime compound HXD-55a provided for the embodiment 16 of the present application is shown in the figure;

[0043] Figure 13 The preparation flow chart of the heterocyclic oxime compound HXD-108a provided for the embodiment 17 of the present application is shown in the figure;

[0044] Figure 14 The preparation flow chart of the heterocyclic oxime compound HXD-70 provided for the embodiment 18 of the present application is shown in the figure;

[0045] Figure 15 The preparation flow chart of the heterocyclic oxime compound HXD-288a provided for the embodiment 19 of the present application is shown in the figure;

[0046] Figure 16 The preparation flow chart of the heterocyclic oxime compound HXD-150a provided for the embodiment 20 of the present application is shown in the figure;

[0047] Figure 17 The preparation flow chart of the heterocyclic oxime compound HXD-162a provided for the embodiment 21 of the present application is shown in the figure

[0048] Figure 18 The preparation flow chart of the heterocyclic oxime compound HXD-183a provided for the embodiment 22 of the present application is shown in the figure.

[0049] Figure 19 The preparation flow chart of the heterocyclic oxime compound HXD-282a provided for the embodiment 23 of the present application is shown in the figure;

[0050] Figure 20 The preparation flow chart of the heterocyclic oxime compound HXD-269a provided for the embodiment 24 of the present application is shown in the figure;

[0051] Figure 21 The preparation flow chart of the heterocyclic oxime compound HXD-169a provided for the embodiment 25 of the present application is shown in the figure;

[0052] Figure 22 The preparation flow chart of the heterocyclic oxime compound HXD-281b provided for the embodiment 7 of the present application is shown in the figure. DETAILED DESCRIPTION

[0053] The present application provides a heterocyclic oxime compound having the structure shown in Formula 1:

[0054]

[0055] In Formula 1, the configuration of the oxime group is E or Z; R1 is H, halogen, substituted or unsubstituted C1-C4 alkyl, cyano, alkynyl, alkoxy, -NO2, -NH2, -OH or -SH;

[0056] Ar is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, naphthyl, thienyl, thiazolyl, furanyl, pyrrolyl, benzothiazolyl, benzofuranyl, pyrimidinyl, pyrazinyl or imidazolyl.

[0057] In the present application, all the raw materials / components are commercially available products well known to those skilled in the art, unless otherwise specified.

[0058] In the present application, R1 is preferably H, C1-C4 alkyl, C1-C4 alkoxy or halogen, more preferably H, methyl, methoxy or halogen, and further preferably H or Cl.

[0059] In the present application, Ar is preferably: R3 in the above-mentioned is preferably H, halogen, phenyl, -OH, C1-C4 alkyl, C1-C4 alkoxy, CF3 or The C1-C4 alkyl is particularly preferably methyl. The C1-C4 alkoxy is particularly preferably methoxy.

[0060] R3 in the above-mentioned is preferably pyrazinyl or any of the following structures:

[0061]

[0062] In the present application, Ar is more preferably 2-methylphenyl, 3-methylphenyl, 2-CF3-phenyl, 2-Cl phenyl, 2-F phenyl, 2-I phenyl, 2-Br phenyl, 3-Br phenyl, 4-Br phenyl, 2-hydroxyphenyl, 2-phenyl-phenyl, 2-methoxyphenyl,

[0063] In the present application, the Ar preferably does not include 4-Br phenyl, 2-hydroxyphenyl, 2-methoxyphenyl,

[0064] In the present application, the heterocyclic oxime compound has the structure shown in Formula 1-1 or Formula 1-2:

[0065]

[0066] In the formula 1-1, R2 is preferably H, F, Cl, Br or Me; R3 is preferably H, F, Cl, Br, I, Me, OMe, CF3, OMe or

[0067] In the formula 1-2, R4 is preferably H, F, Cl, Br, Me or OMe;

[0068] In specific embodiments of the present application, the heterocyclic oxime compound has any one of the following structures:

[0069]

[0070] In specific embodiments of the present application, the heterocyclic oxime compound preferably does not include HXD-218a, HXD-227c, HXD-111a, HXD-169a, HXD-281b.

[0071] In specific embodiments of the present application, the heterocyclic oxime compound is further preferably specifically HXD-47, HXD-46, HXD-144a, HXD-88, HXD-114a, HXD-233a, HXD-90a, HXD-76, HXD-123a, HXD-110a, HXD-55a, HXD-108a, HXD-288a, HXD-183a, HXD-282a, HXD-269a, HXD-70, HXD-150a or HXD-162a.

[0072] The present application provides a preparation method of the heterocyclic oxime compound described in the above technical solution, comprising the following steps:

[0073] The compound shown in the formula 2, hydroxylamine hydrochloride, an organic acid alkali metal salt and an organic solvent (hereinafter referred to as the first organic solvent) are mixed (hereinafter referred to as the first mixing), and an oxime group reaction is carried out by heating to obtain a heterocyclic oxime compound shown in the formula 1;

[0074]

[0075] In the present application, as shown in the synthesis flow chart: Figure 1 The preparation method of the compound shown in the formula 2 preferably comprises the following steps:

[0076] The compound shown in the formula 3, the compound shown in the formula 4, an inorganic strong base, iodine, an organic solvent (hereinafter referred to as the second organic solvent) and water are mixed (hereinafter referred to as the second mixing), and a nucleophilic substitution reaction is carried out by heating to obtain the compound shown in the formula 2;

[0077]

[0078] In the present application, the inorganic strong base is preferably potassium hydroxide.

[0079] In the present application, the second organic solvent is preferably dimethyl sulfoxide.

[0080] In the present application, the volume ratio of the second organic solvent and water is preferably 3:1.

[0081] In the present application, the molar ratio of the compound of formula 3 and the compound of formula 4 is preferably 3:2.

[0082] In the present application, the molar ratio of the compound of formula 3 and the inorganic strong base is preferably 3:2.

[0083] In the present application, the molar ratio of the compound of formula 3 and iodine is preferably 1:1.

[0084] The present application does not have special requirements for the amount of the second organic solvent and water, as long as the nucleophilic substitution reaction can proceed smoothly.

[0085] In the present application, the second mixing is preferably: pre-mixing the second organic solvent and water to obtain a mixed solvent; dissolving the compound of formula 3, the compound of formula 4, the inorganic strong base and iodine in the mixed solvent. In the present application, the temperature of the nucleophilic substitution reaction is preferably 100°C.

[0086] In the present application, the nucleophilic substitution reaction is preferably detected by TLC. The present application preferably dilutes the reaction liquid obtained after the nucleophilic substitution reaction with water, extracts with ethyl acetate, washes the organic extraction phase, and then dries to obtain a dry extraction organic phase. The dry extraction organic phase is purified by column chromatography to obtain a pure compound of formula 2. In the present application, the washing is preferably washed with sodium thiosulfate, and the drying reagent used is preferably anhydrous sodium sulfate. The eluent used in the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably (7-50):1, and more preferably 7:1, 10:1, 40:1, 50:1, 30:1, 15:1 or 20:1.

[0087] In the present application, the preparation method of the compound of formula 2 preferably comprises the following steps: Figure 2

[0088] Mixing (hereinafter referred to as third mixing) the compound of formula 4, the compound of formula 5, iodine and an organic solvent (hereinafter referred to as a third organic solvent), and heating to perform a ring-forming-substitution reaction to obtain the compound of formula 2; ​

[0089]

[0090] In this invention, the third organic solvent is preferably dimethyl sulfoxide.

[0091] In this invention, the molar ratio of the compound with the structure shown in Formula 4 to the compound with the structure shown in Formula 5 is preferably 2:2.4.

[0092] In this invention, the molar ratio of the compound with the structure shown in Formula 4 to iodine is preferably 2:1.

[0093] The present invention does not have special requirements on the amount of the third organic solvent, as long as the cyclization-substitution reaction proceeds smoothly.

[0094] In this invention, the third mixture is preferably a mixture of the compound with the structure shown in Formula 4, the compound with the structure shown in Formula 5, and iodine solvent in a third organic solvent.

[0095] In this invention, the preferred temperature for the cyclization-substitution reaction is 100°C.

[0096] In this invention, the cyclization-substitution reaction is preferably detected by TLC. Preferably, after the cyclization-substitution reaction, the reaction solution is successively diluted with water, extracted with ethyl acetate, washed with the organic extract phase, and dried. The dried organic extract phase is then purified by column chromatography to obtain the pure compound with the structure described in Formula 2. In this invention, the washing is preferably done with sodium thiosulfate, and the drying reagent is preferably anhydrous sodium sulfate. The eluent used for column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate preferably (7–50):1, specifically preferably 7:1, 10:1, 40:1, 50:1, 30:1, 15:1, or 20:1.

[0097] In this invention, the organic acid alkali metal salt is preferably sodium acetate.

[0098] In this invention, the first organic solvent is preferably ethanol or methanol.

[0099] In this invention, the molar ratio of the compound with the structure shown in Formula 2 to hydroxylamine hydrochloride is preferably 0.5:1.5.

[0100] In this invention, the molar ratio of the compound with the structure shown in Formula 2 and the organic acid alkali metal salt is preferably 0.5:0.75.

[0101] In this invention, the first mixing is preferably performed by dissolving the compound with the structure shown in Formula 2, hydroxylamine hydrochloride, and an organic acid alkali metal salt in a first organic solvent. In this invention, the oxime oxidization reaction is preferably carried out at a temperature of 75°C.

[0102] In the present application, the oximation reaction is preferably detected by TLC. The present application preferably removes solvent from the reaction liquid obtained after the oximation reaction, extracts with ethyl acetate, washes the organic extract phase, and then dries to obtain a pure product of the heterocyclic oxime compound of formula 1 by column chromatography purification. In the present application, the specific embodiment of removing solvent is preferably reduced pressure distillation. The washing is preferably water washing, and the drying reagent used is preferably anhydrous sodium sulfate. The eluent used in the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably (3-40): 1, and more preferably 3:1, 10:1, 15:1, 40:1 or 20:1.

[0103] The present application uses cheap and readily available benzothiazole or aminophenyl mercaptan as a starting material for synthesis, and the experimental operation involved is simple and the steps are short.

[0104] The present application provides the application of the heterocyclic oxime compound in the prevention and treatment of plant pathogenic fungi.

[0105] In the present application, the plant pathogenic fungi preferably include one or more of Rhizoctonia solani, Rhizoctonia cerealis, Sclerotinia scleotiorum, Fusarium graminearum, Gaeumanomyce graminis, Botrytis cinerea, Phytophthora infestans, Phytophthora capsici, Alternaria solani, Fusarium fujikuroi, Fusarium sulphureum, Colletotrichum lagenarium, Phyricularia cerealis and the like.

[0106] The heterocyclic diaromatic oxime compound of the present application has good bacteriostatic activity and a wide fungicidal spectrum.

[0107] The present application provides a composition comprising a bacteriostatic active component and a pesticide-acceptable adjuvant; the bacteriostatic active component is the heterocyclic oxime compound or its pesticide-acceptable salt as described in the above technical solution or the heterocyclic oxime compound prepared by the preparation method as described in the above technical solution or its pesticide-acceptable salt.

[0108] The adjuvant described in the present application can be any known to those skilled in the art, including but not limited to solvents, diluents, fillers and / or carriers, dispersants, emulsifiers, wetting agents, penetrants, spreading agents, controlled release agents, dust control agents, antifoaming agents, foaming agents, warning pigments, stabilizers, thixotropic agents and thickening agents, etc. The composition described in the present application can be different types of dosage forms, including but not limited to powders, wettable powders, emulsions, emulsifiable concentrates, creams, pastes, gels, fumigants, smokes, aerosols, granules, microparticles and oils.

[0109] In order to further illustrate the present application, the technical solutions provided by the present application are described in detail below in combination with examples, but they should not be understood as limiting the scope of protection of the present application.

[0110] The following examples are prepared according to the flowchart shown in Figure 1 or Figure 2 .

[0111] Example 1: Synthesis of HXD-47.

[0112] According to the synthesis flow shown in Figure 3 , the following is prepared:

[0113] Step 1: Dissolve benzothiazole (405 mg, 3 mmol), 2'-methylacetophenone (267 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3:1) (6 mL:2 mL) solution, heat the mixture to 100℃, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40:1), to obtain the intermediate heterocyclic diketone compound HXD-35, yellow solid, yield 21%.

[0114] Step 2: Intermediate heterocyclic diketone compound HXD-35 (126 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), white solid HXD-47 was obtained, yield 65%.

[0115] 1 H NMR (500 MHz, CDC13) δ: 8.14-8.10 (m, 1H), 7.92-7.90 (m, 1H), 7.57-7.54 (m, 1H), 7.50-7.47 (m, 1H), 7.40-7.39 (m, 1H), 7.32-7.29 (m, 3H), 2.27 (s, 3H).

[0116] 13 C NMR (126 MHz, CDC13) δ: 160.79, 151.53, 148.07, 137.91, 134.44, 133.97, 130.81, 130.20, 130.10, 127.38, 127.12, 126.13, 123.88, 121.81, 19.90.

[0117] Example 2: Synthesis of HXD-46.

[0118] Step 1: Benzothiazole (405 mg, 3 mmol), 2'-chloroacetophenone (305 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) were dissolved in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), intermediate heterocyclic diketone compound HXD-31 was obtained, yellow solid, yield 29%.

[0119] Step 2: Intermediate heterocyclic diketone compound HXD-31 (136 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), white solid HXD-46 was obtained, yield 35%.

[0120] 1 H NMR (500 MHz, Methanol-d4) δ: 7.97-7.95 (m, 1H), 7.88-7.86 (m, 1H), 7.54 (dd, J = 7.8, 1.5 Hz, 1H), 7.49-7.42 (m, 4H), 7.35 (dd, J = 7.4, 1.9 Hz, 1H).

[0121] 13 C NMR (126 MHz, Methanol-d4) δ: 167.27, 154.30, 152.32, 135.69, 133.86, 132.51, 131.75, 131.67, 130.54, 127.91, 127.40 (2C), 124.10, 122.79.

[0122] Example 3: Synthesis of HXD-109a.

[0123] Step 1: Benzothiazole (405 mg, 3 mmol), 2'-fluoroacetophenone (276 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) were dissolved in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), intermediate heterocyclic diketone compound HXD-109 was obtained, yellow solid, yield 21%.

[0124] Step 2: Intermediate heterocyclic diketone compound HXD-109 (128 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), yellow solid HXD-109a was obtained, yield 50%.

[0125] 1 HNMR (400 MHz, DMSO) δ: 10.73 (br, 1H), 6.13-6.08 (m, 1H), 5.96-5.90 (m, 1H), 5.58-5.52 (m, 1H), 5.50-5.44 (m, 3H), 5.37-5.32 (m, 2H).

[0126] Example 4: Synthesis of HXD-144a.

[0127] According to the synthetic procedure shown in the following scheme: Figure 4

[0128] Step 1: 2'-methylacetophenone (268 mg, 2 mmol), 2-amino-4-chlorothiophenol (381 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 50: 1), intermediate heterocyclic diketone compound HXD-144 was obtained, yellow solid, yield 45%.

[0129] Step 2: Intermediate HXD-144 (143 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), yellow solid HXD-144a was obtained, yield 83%.

[0130] 1 ​H NMR (400 MHz, CDC13) δ: 8.12 (d, J = 1.9 Hz, 1H), 7.83 (d, J = 8.6 Hz, 1H), 7.48 (dd, J = 8.6, 2.0 Hz, 1H), 7.45-7.41 (m, 2H), 7.34-7.30 (m, 2H), 2.29 (s, 3H).

[0131] 13 C NMR (101 MHz, CDC13) δ: 166.69, 155.13, 154.41, 136.59, 133.25, 132.35, 130.44, 130.27, 129.98, 128.46, 126.85, 125.94, 124.01, 122.37, 19.96.

[0132] Example 5: Synthesis of HXD-88.

[0133] According to the synthetic procedure shown in the following scheme: Figure 5

[0134] Step 1: Dissolve benzothiazole (405 mg, 3 mmol), 2-bromoacetophenone (398 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 30: 1) to obtain the intermediate heterocyclic diketone compound HXD-69, yellow solid, yield 29%.

[0135] Step 2: Dissolve the intermediate heterocyclic diketone compound HXD-69 (159 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, monitor by TLC, after the reaction is completed, evaporate the solvent under reduced pressure, extract the resulting mixture with ethyl acetate. Wash the organic layer with water and dry over anhydrous sodium sulfate. Purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1) to obtain HXD-88, white solid, yield 53%.

[0136] 1 ​H NMR (400 MHz, CDC13) δ: 8.12-8.10 (m, 1H), 7.91-7.89 (m, 1H), 7.69 (dd, J = 8.0, 1.3 Hz, 1H), 7.59-7.55 (m, 2H), 7.51-7.48 (m, 1H), 7.47 7.44 (m, 1H), 7.40-7.37 (m, 1H).

[0137] 13 C NMR (126 MHz, CDC13) δ: 159.40, 151.31, 148.37, 135.44, 134.61, 133.31, 131.92, 131.49, 127.82, 127.31, 127.12, 124.29, 123.97, 121.81.

[0138] Example 6: Synthesis of HXD-114a.

[0139] Step 1: Dissolve benzothiazole (405 mg, 3 mmol), 3-bromoacetophenone (398 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 30: 1) to obtain the intermediate heterocyclic diketone compound HXD-114, yellow solid, yield 32%.

[0140] Step 2: Dissolve the intermediate heterocyclic diketone compound HXD-114 (159 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, monitor by TLC, after the reaction is completed, evaporate the solvent under reduced pressure, extract the resulting mixture with ethyl acetate. Wash the organic layer with water and dry over anhydrous sodium sulfate. Purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1) to obtain white solid HXD-114a, yield 84%.

[0141] 1 H NMR (400 MHz, CDC13) δ: 8.15 (d, J = 8.1 Hz, 1H), 8.00-7.95 (m, 1H), 7.90-7.86 (m, 1H), 7.66-7.57 (m, 3H), 7.39-7.30 (m, 2H).

[0142] Example 7: Synthesis of HXD-218a.

[0143] Step 1: Dissolve benzothiazole (405 mg, 3 mmol), 4-bromoacetophenone (398 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, TLC track monitoring, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 30: 1), to obtain the intermediate heterocyclic diketone compound HXD-218, yellow solid, yield 32%.

[0144] Step 2: Dissolve the intermediate heterocyclic diketone compound HXD-218 (159 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, TLC track monitoring, after the reaction is completed, evaporate the solvent under reduced pressure, extract the mixture obtained with ethyl acetate. The organic layer is washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), to obtain white solid HXD-218a, yield 84%.

[0145] 1 H NMR (400 MHz, CDCI3) δ: 8.59 (br, 1H), 8.16-8.14 (m, 1H), 8.00-7.97 (m, 1H), 7.67-7.60 (m, 6H).

[0146] 13 C NMR (101 MHz, CDCI3) δ: 164.95, 153.37, 151.18, 134.62, 133.57, 131.90, 130.78, 127.34, 126.56, 124.56, 124.21, 121.76.

[0147] Example 8: Synthesis of HXD-233a.

[0148] Step 1 : Dissolve benzothiazole (405 mg, 3 mmol), 2-iodoacetophenone (492 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL:2 mL) solution, heat the mixture to 100 °C, TLC track monitoring, after the reaction is complete, respectively, dilution with water, ethyl acetate extraction, extraction with sodium thiosulfate washing, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), to get intermediate heterocyclic diketone compound HXD-233, yellow solid, yield 18%.

[0149] Step 2: Dissolve intermediate heterocyclic diketone compound HXD-233 (182 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, TLC track monitoring, after the reaction is complete, the solvent is removed under reduced pressure, the mixture is extracted with ethyl acetate. The organic layer is washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), to get white solid HXD-233a, yield 53%.

[0150] 1 H NMR (500 MHz, CDC13) δ: 8.06 (d, J = 8.3 Hz, 1H), 7.91-7.88 (m, 1H), 7.86-7.83 (m, 1H), 7.54-7.51 (m, 1H), 7.49-7.41 (m, 3H), 7.17-7.13 (m, 1H).

[0151] Example 9: Synthesis of HXD-227c.

[0152] Step 1 : Dissolve benzothiazole (405 mg, 3 mmol), 2-hydroxyacetophenone (272 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL:2 mL) solution, heat the mixture to 100 °C, TLC track monitoring, after the reaction is complete, respectively, dilution with water, ethyl acetate extraction, extraction with sodium thiosulfate washing, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 30: 1), to get intermediate heterocyclic diketone compound HXD-227, yellow solid, yield 32%.

[0153] Step 2: Intermediate Heterocyclic Diketones HXD-227 (128 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1), white solid HXD-227c was obtained, yield 90%.

[0154] 1 H NMR (500 MHz, CDC13) δ: 8.12-8.10 (m, 1H), 7.94-7.92 (m, 1H), 7.55-7.52 (m, 1H), 7.48-7.46 (m, 1H), 7.26-7.24 (m, 2H), 7.00-6.98 (m, 1H), 6.82-6.79 (m, 1H).

[0155] 13 C NMR (126 MHz, CDC13) δ: 157.9, 156.9, 151.409, 151.0, 137.6, 135.1, 131.8, 129.8, 127.2, 127.0, 124.0, 121.8, 119.7, 117.8.

[0156] Example 10: Synthesis of HXD-90a.

[0157] According to the synthetic procedure shown in the following scheme: Figure 6

[0158] Step 1: CuI (95 mg, 0.5 mmol) Cs2C03(3250 mg, 10 mmol), N,N-dimethylglycine (206 mg, 2 mmol), phenol (564 mg, 6 mmol) were added to a dry Schlenk tube containing a magnetic stir bar, N2was bubbled through the mixture for 3 times, then 2-bromoacetophenone (647 μL, 5 mmol) and degassed dioxane (25 mL) were added. The vessel was sealed and then heated to 100 °C in a reaction block for 24 h. After the reaction mixture was cooled to room temperature, the solution was washed with water and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1) to give intermediate heterocyclic diketones HXD-A as a yellow liquid in 45% yield.

[0159] ​Step 2: Dissolve benzothiazole (405 mg, 3 mmol), HXD-A (424 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, TLC track monitoring, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15: 1), to get the intermediate heterocyclic diketone compound HXD-90, yellow solid, yield 29%.

[0160] Step 3: Dissolve the intermediate heterocyclic diketone compound HXD-90 (167 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, TLC track monitoring, after the reaction is completed, remove the solvent under reduced pressure, extract the mixture obtained with ethyl acetate. The organic layer is washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 3: 1), to get white solid HXD-90a, yield 66%.

[0161] 1 H NMR (500 MHz, CDC13) δ: 13.48 (br, 1H), 8.07-8.05 (m, 1H), 7.91-7.89 (m, 1H), 7.59 (dd, J = 7.6, 1.7 Hz, 1H), 7.54-7.51 (m, 1H), 7.47-7.44 (m, 1H), 7.43-7.40 (m, 1H), 7.25-7.19 (m, 3H), 7.05-7.01 (m, 1H), 7.00-6.97 (m, 2H), 6.94 (dd, J = 8.3, 1.1 Hz, 1H).

[0162] 13 C NMR (126 MHz, CDC13) δ: 159.59, 156.48, 157.37, 151.11, 146.87, 134.76, 131.83, 131.45, 129.73, 126.99, 126.77, 125.85, 123.87, 123.84, 123.33, 121.69, 119.67, 118.11.

[0163] Example 11: Synthesis of HXD-76

[0164] According to the synthetic procedure shown in the following scheme: Figure 7

[0165] ​Step 1: Dissolve benzothiazole (405 mg, 3 mmol), 2-chloroacetophenone (309 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1) to obtain the intermediate heterocyclic diketone compound HXD-31, yellow solid, yield 29%.

[0166] Step 2: Add K3PO4(254 mg, 1.2 mmol) Pd(OAc)2(11 mg), XPhos (48 mg), phenylboronic acid (134 mg, 1.1 mmol) and HXD-31 (135 mg, 0.5 mmol) in a dry Schlenk tube containing a magnetic stir bar, then add degassed nBuOH / H2O 4: 1 mixture (4.0 mL) under a stream of nitrogen. Seal the vessel and heat at 120 °C for 24 h. After cooling the reaction mixture to room temperature, wash the solution with water, extract the aqueous layer with ethyl acetate. Dry the organic layer over anhydrous sodium sulfate to obtain a crude mixture, purify with petroleum ether / ethyl acetate (v / v, 40: 1) as eluent to obtain HXD-60 (99 mg, yield 63%, yellow solid).

[0167] Step 3: Dissolve the intermediate heterocyclic diketone compound HXD-60 (158 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, monitor by TLC, after the reaction is completed, evaporate the solvent under reduced pressure, extract the mixture with ethyl acetate. Wash the organic layer with water, and dry over anhydrous sodium sulfate. Purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1) to obtain HXD-76, white solid, yield 48%.

[0168] 1 H NMR (500 MHz, CDC13) δ: 13.88 (br, 1H), 7.99-7.97 (m, 1H), 7.80-7.77 (m, 1H), 7.64-7.58 (m, 2H), 7.52-7.48 (m, 3H), 7.43-7.38 (m, 3H), 7.23-7.18 (m, 2H), 7.13-7.10 (m, 1H).

[0169] 13C NMR (126 MHz, CDCI3) d: 160.50, 150.97, 148.73, 142.23, 140.38, 134.26, 133.13, 131.17, 130.65, 130.38, 129.43, 128.27, 127.73, 127.33, 127.06, 126.83, 123.67, 121.64.

[0170] Example 12: Synthesis of HXD-123a

[0171] According to the synthetic procedure shown in the following scheme: Figure 8

[0172] Step 1 : Dissolve benzothiazole (405 mg, 3 mmol), 3'-methylacetophenone (267 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL: 2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by column chromatography on silica gel (eluent: V petroleum ether / V ethyl acetate = 40: 1) to give the intermediate heterocyclic diketone compound HXD-123, yellow solid, yield 40%.

[0173] Step 2: Dissolve the intermediate heterocyclic diketone compound HXD-123 (126 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, monitor by TLC, after the reaction is completed, evaporate the solvent under reduced pressure, extract the resulting mixture with ethyl acetate. Wash the organic layer with water and dry over anhydrous sodium sulfate. Purify by column chromatography on silica gel (eluent: V petroleum ether / V ethyl acetate = 20: 1) to give HXD-123a as a white solid, yield 40%.

[0174] 1 H NMR (500 MHz, CDCI3) d: 8.16-8.14 (m, 1H), 7.93-7.91 (m, 1H), 7.56-7.51 (m, 1H), 7.59-7.46 (m, 3H), 7.28-7.22 (m, 2H), 2.37 (s, 3H).

[0175] Example 13: Synthesis of HXD-110a

[0176] According to the synthetic procedure shown in the following scheme: Figure 9

[0177] ​​Step 1 : Dissolve benzothiazole (405 mg, 3 mmol), 2'-trifluoromethylacetophenone (408 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL:2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1) to obtain the intermediate heterocyclic diketone compound HXD-110, yellow solid, yield 19%.

[0178] Step 2: Dissolve the intermediate heterocyclic diketone compound HXD-110 (153 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) in ethanol solution, heat the mixture to 75 °C, monitor by TLC, after the reaction is completed, evaporate the solvent under reduced pressure, extract the resulting mixture with ethyl acetate. Wash the organic layer with water and dry over anhydrous sodium sulfate. Purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1) to obtain yellow solid HXD-110a, yield 80%.

[0179] 1 H NMR (400 MHz, CDC13) δ: 7.85-7.80 (m, 2H), 7.75-7.71 (m, 1H), 7.63-7.53 (m, 2H), 7.26 (dd, J = 8.4, 2.0 Hz, 1H), 6.66-6.57 (m, 2H).

[0180] Example 14: Synthesis of HXD-111a

[0181] According to the synthetic procedure shown in Figure 10

[0182] Step 1 : Dissolve benzothiazole (405 mg, 3 mmol), 2'-trifluoromethylacetophenone (408 mg, 2 mmol), potassium hydroxide (112 mg, 2 mmol) and iodine (760 mg, 3 mmol) in dimethyl sulfoxide: water (3: 1) (6 mL:2 mL) solution, heat the mixture to 100 °C, monitor by TLC, after the reaction is completed, dilute with water, extract with ethyl acetate, wash the extract with sodium thiosulfate, dry over anhydrous sodium sulfate, and purify by silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 40: 1) to obtain the intermediate heterocyclic diketone compound HXD-110, yellow solid, yield 19%.

[0183] ​Step 2: Intermediate heterocyclic diketone compound HXD-111 (134 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), white solid HXD-111a was obtained, yield 80%.

[0184] 1 HNMR (400 MHz, CDC13) δ: 8.08 (d, J = 8.2 Hz, 1H), 7.90-7.86 (m, 1H), 7.55-7.50 (m, 1H), 7.48-7.43 (m, 3H), 7.10-7.04 (m, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 3.70 (s, 3H).

[0185] 13 C NMR (101 MHz, CDC13) δ: 160.39, 158.14, 151.14, 146.87, 134.65, 131.52, 131.39, 126.91, 126.69, 123.75, 123.71, 121.63, 120.88, 111.53, 55.66.

[0186] Example 15: Synthesis of HXD-43a

[0187] According to the synthetic procedure shown in the following scheme: Figure 11

[0188] Step 1: 2-Acetylfuran (220 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15: 1), intermediate heterocyclic diketone compound HXD-43 was obtained, yellow solid, yield 25%.

[0189] ​Step 2: Intermediate HXD-43 (114 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by evaporation under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15:1) to give yellow solid HXD-43a, yield 20%.

[0190] 1 H NMR (500 MHz, CDC13) δ: 8.17-8.15 (m, 1H), 7.93-7.91 (m, 1H), 7.68 (dd, J = 1.8, 0.8 Hz, 1H), 7.63 (dd, J = 3.6, 0.8 Hz, 1H), 7.53-7.50 (m, 1H), 7.47-7.44 (m, 1H), 6.65-6.43 (m, 1H).

[0191] Example 16: Synthesis of HXD-55a

[0192] According to the synthetic procedure shown in the following scheme: Figure 12

[0193] Step 1: 2-Acetylthiophene (252 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15:1) to give intermediate heterocyclic diketone compound HXD-55, yellow solid, yield 20%.

[0194] Step 2: Intermediate HXD-55 (120 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by evaporation under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15:1) to give yellow solid HXD-55a, yield 23%.

[0195] 1 ​H NMR (500 MHz, CDCI3) δ: 8.50 (dd, J = 3.9, 1.2 Hz, 1 H), 8.16-8.14 (m, 1 H), 7.93-7.91 (m, 1 H), 7.68 (dd, J = 5.1, 1.2 Hz, 1 H), 7.54-7.51 (m, 1 H), 7.48-7.46 (m, 1 H), 7.22 (dd, J = 5.1, 3.9 Hz, 1 H).

[0196] 13 C NMR (126 MHz, CDCI3) δ: 164.63, 153.40, 146.29, 144.68, 134.89, 134.19, 131.60, 126.53, 126.38, 126.37, 124.10, 121.60.

[0197] Example 17: Synthesis of HXD-108a

[0198] According to the synthetic procedure shown in the following scheme: Figure 13

[0199] Step 1 : 2-Acetylthiazole (254 mg, 2 mmol), 2-aminothiophenol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, ethyl acetate extraction, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to obtain the intermediate heterocyclic diketone compound HXD-108, yellow solid, yield 25%.

[0200] Step 2: The intermediate HXD-108 (120 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15:1), to obtain yellow solid HXD-108a, yield 40%.

[0201] 1 H NMR (500 MHz, CDCI3) δ: 8.11-8.09 (m, 1 H), 8.05 (d, J = 3.2 Hz, 1 H), 7.93-7.91 (m, 1 H), 7.71 (d, J = 3.4 Hz, 1 H), 7.53-7.50 (m, 1 H), 7.47-7.44 (m, 1 H). ​

[0202] 13 C NMR (126 MHz, CDC13) δ: 163.68, 156.63, 152.88, 141.56, 140.45, 135.03, 126.46, 126.39, 124.20, 123.63, 121.90.

[0203] Example 18: Synthesis of HXD-70.

[0204] According to the synthetic procedure shown in the following scheme: Figure 14

[0205] Step 1: 2-Acetylpyridine (242 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1), to get intermediate heterocyclic diketone compound HXD-40, yellow solid, yield 20%.

[0206] Step 2: Intermediate HXD-40 (120 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to get white solid HXD-70, yield 23%.

[0207] 1 H NMR (500 MHz, CDC13) δ: 8.63-8.62 (m, 1H), 8.15-8.13 (m, 1H), 8.04-8.02 (m, 1H), 7.96-7.94 (m, 1H), 7.77-7.73 (m, 1H), 7.54-7.50 (m, 1H), 7.48-7.45 (m, 1H), 7.33-7.30 (m, 1H).

[0208] 13 C NMR (126 MHz, CDC13) δ: 158.35, 152.35, 148.97, 147.27, 144.00, 137.15, 135.67, 127.11, 127.06, 124.12, 122.90, 121.66, 120.96. ​

[0209] Example 19: Synthesis of HXD-288a.

[0210] according to Figure 15 The synthesis process shown is as follows:

[0211] Step 1: 2-Acetylpyrazine (244 mg, 2 mmol), 2-aminobenzylthiophenol (324 mg, 2.4 mmol), and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution. The mixture was heated to 100 °C and monitored by TLC. After the reaction was complete, the mixture was diluted with water and extracted with ethyl acetate. The extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1) to give the intermediate heterocyclic diaryl ketone compound HXD-288 as a yellow solid with a yield of 13%.

[0212] Step 2: Dissolve intermediate HXD-288 (120 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), and sodium acetate (61 mg, 0.75 mmol) in ethanol. Heat the mixture to 75 °C and monitor the reaction by TLC. After the reaction is complete, remove the solvent under reduced pressure and extract the mixture with ethyl acetate. Wash the organic layer with water and dry it on anhydrous sodium sulfate. Perform silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1) to give a white solid HXD-288a in 50% yield.

[0213] 1 H NMR (500MHz, CDCl3) δ: 9.46 (br, 1H), 8.64 (dd, J = 7.3, 2.4Hz, 2H), 8.11 (d, J = 8.2Hz, 1H), 8.02 (d, J = 8.0Hz, 1H), 7.61 (t, J = 7.7Hz, 1H), 7.58-7.53 (m, 1H).

[0214] Example 20: Synthesis of HXD-150a.

[0215] according to Figure 16 The synthesis process shown is as follows:

[0216] Step 1: 2-Acetylpyridine (242 mg, 2 mmol), 2-amino-4-chlorothiophenol (381 mg, 2.4 mmol), and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution. The mixture was heated to 100 °C and monitored by TLC. After the reaction was complete, the mixture was diluted with water and extracted with ethyl acetate. The extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, and subjected to silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1) to give the intermediate heterocyclic diaryl ketone compound HXD-150 as a brown solid with a yield of 15%.

[0217] Step 2: Intermediate HXD-150 (137 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 15:1) to give white solid HXD-150a, yield 43%.

[0218] 1 H NMR (500 MHz, CDC13) δ: 9.11-9.09 (m, 1H), 8.63-8.61 (m, 1H), 8.11-8.09 (m, 1H), 8.07-8.06 (m, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.60-7.58 (m, 1H), 7.42 (dd, J = 8.5, 2.0 Hz, 1H).

[0219] 13 C NMR (126 MHz, CDC13) δ: 167.91, 154.22, 149.71, 145.07, 144.65, 138.82, 137.16, 131.99, 126.51, 125.79, 124.92, 123.25, 122.24.

[0220] Example 21: Synthesis of HXD-162a.

[0221] According to the synthetic procedure shown in Figure 17

[0222] Step 1: 2-acetylbenzothiazole (354 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20:1) to give intermediate heterocyclic diketone compound HXD-162, yellow solid, yield 37%.

[0223] ​Step 2: Intermediate HXD-162 (120 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by evaporation under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), white solid HXD-162a was obtained with a yield of 61%.

[0224] 1 H NMR (400 MHz, CDC13) δ: 8.16-8.12 (m, 2H), 8.10-8.0 (m, 1H), 7.95-7.93 (m, 1H), 7.65-7.45 (m, 4H).

[0225] 13 C NMR (101 MHz, CDC13) δ: 163.66, 157.36, 152.95, 149.23, 142.09, 135.46, 135.09, 127.50, 127.48, 126.56, 126.48, 123.71, 123.09, 121.92.

[0226] Example 22: Synthesis of HXD-183a.

[0227] According to the synthetic procedure shown in the following scheme: Figure 18

[0228] Step 1: 2-Acetylbenzofuran (320 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, dried over anhydrous sodium sulfate, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), intermediate heterocyclic diketone compound HXD-183 was obtained as a yellow solid with a yield of 26%.

[0229] Step 2: Intermediate HXD-183 (140 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed by evaporation under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 20: 1), yellow solid HXD-183a was obtained with a yield of 48%.​

[0230] 1 H NMR (400 MHz, DMSO-d6) δ: 8.34-8.28 (m, 2H), 7.98 (d, J = 1.0 Hz, 1H), 7.87-7.83 (m, 1H), 7.76-7.69 (m, 3H), 7.62-7.57 (m, 1H), 7.50-7.45 (m, 1H).

[0231] Example 23: Synthesis of HXD-282a.

[0232] According to the synthetic procedure shown in the following scheme: Figure 19

[0233] Step 1: 2-Acetyl-6-bromopyridine (400 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, ethyl acetate extraction, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1), to get intermediate heterocyclic diketone compound HXD-282, yellow solid, yield 14%.

[0234] Step 2: Intermediate HXD-282 (160 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to get white solid HXD-282a, yield 56%.

[0235] 1 H NMR (500 MHz, CDCl3) δ: 8.07 (dd, J = 7.9, 0.9 Hz, 1H), 8.00-7.98 (m, 1H), 7.96-7.94 (m, 1H), 7.58 (t, J = 7.9 Hz, 1H), 7.51-7.48 (m, 1H), 7.46-7.43 (m, 2H).

[0236] Example 24: Synthesis of HXD-269a.

[0237] According to the synthetic procedure shown in the following scheme: Figure 20

[0238] ​​Step 1: 2-Acetyl-6-methoxypyridine (400 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1), to obtain the intermediate heterocyclic diketone compound HXD-269, yellow solid, yield 11%.

[0239] Step 2: The intermediate HXD-269 (135 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to obtain white solid HXD-269a, yield 35%.

[0240] 1 H NMR (500 MHz, CDC13) δ: 8.11 (d, J = 8.9 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.53-7.49 (m, 1H), 7.47-7.43 (m, 2H), 7.32-7.27 (m, 1H), 3.88 (s, 3H). Z / E ratio 3 / 2

[0241] 13 C NMR (126 MHz, CDC13) δ: 166.3, 156.7, 153.5, 149.1, 144.8, 134.8, 133.0, 127.1, 127.0, 126.1, 123.5, 122.4, 121.6, 56.1.

[0242] Example 25: Synthesis of HXD-169a.

[0243] According to the synthetic procedure shown in Figure 21 :

[0244] Step 1: 2-Acetyl-6-methylpyridine (270 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1), to obtain the intermediate heterocyclic diketone compound HXD-169 yellow solid, yield 11%.

[0245] Step 2: The intermediate HXD-169 (127 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to obtain white solid HXD-169a, yield 35%.

[0246] 1 H NMR (500 MHz, Chloroform-d) δ: 8.10-8.08 (m, 1H), 8.04-7.99 (m, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.60-7.56 (m, 1H), 7.54-7.51 (m, 1H), 7.21 (d, J = 7.7 Hz, 1H), 2.71 (s, 3H).

[0247] 13 C NMR (126 MHz, Chloroform-d) δ: 158.48, 156.55, 151.42, 148.88, 143.99, 137.37, 135.80, 126.98, 126.93, 123.53, 122.83, 121.59, 117.77, 23.64.

[0248] Example 26: Synthesis of HXD-281b.

[0249] According to the synthetic procedure shown in Figure 22

[0250] ​Step 1: 2-Acetyl-6-methoxypyridine (400 mg, 2 mmol), 2-aminobenzenethiol (324 mg, 2.4 mmol) and iodine (253 mg, 1.0 mmol) were dissolved in dimethyl sulfoxide solution, the mixture was heated to 100 °C, TLC tracking monitoring, after the reaction was completed, respectively, diluted with water, extracted with ethyl acetate, the extract was washed with sodium thiosulfate, anhydrous sodium sulfate drying, silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 7:1), to obtain the intermediate heterocyclic diketone compound HXD-281a, yellow solid, yield 11%.

[0251] Step 2: The intermediate HXD-281a (135 mg, 0.5 mmol), hydroxylamine hydrochloride (104 mg, 1.5 mmol), sodium acetate (61 mg, 0.75 mmol) were dissolved in ethanol solution, the mixture was heated to 75 °C, TLC tracking monitoring, after the reaction was completed, the solvent was removed under reduced pressure, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. Silica gel column chromatography (eluent: V petroleum ether / V ethyl acetate = 10:1), to obtain white solid HXD-281b, yield 35%.

[0252] 1 H NMR (500 MHz, CDCI3) δ: 8.04-8.02 (m, 1 H), 7.96-7.94 (m, 1 H), 7.69 (d, J = 7.5 Hz, 1 H), 7.63 (t, J = 7.8 Hz, 1 H), 7.54-7.51 (m, 1 H), 7.48-7.45 (m, 1 H), 6.77 (dd, J = 8.1, 0.8 Hz, 1 H), 4.09 (s, 3 H).

[0253] Test Example

[0254] Determination of the antibacterial activity of the heterocyclic diaryl oxime compounds prepared in Examples 1-26

[0255] The determination method is: the mycelial growth rate inhibition method is used for in vitro antibacterial activity evaluation, and the test strains are selected on PDA plates for activation, including Rhizoctonia solani, Rhizoctonia cerealis, Sclerotinia scleotiorum, Fusarium graminearum, Gaeumanomyce graminis, Botrytis cinerea, Phytophthora infestans, Phytophthora capsici, Alternaria solani, Fusarium fujikuroi, Fusarium sulphureum, Colletotrichum lagenarium, and Phyricularia cerealis. The compounds are configured into a series of gradient concentrations of PDA drug-containing plates (100 μM, 50 μM, 25 μM, 12.5 μM, 6.25 μM, and 3.125 μM), the test strains are prepared into 5 mm diameter fungus cakes and placed in the center of the drug-containing culture dish, and the culture is incubated at 25°C. The blank control is set, and Fluoxastrobin is used as a positive control, and the test is repeated 3 times. When the test strains in the blank control dish grow to the edge of the culture dish, the colony diameters of each drug-containing plate are measured by cross method, the inhibition rate of the compound on the mycelial growth is calculated, and the calculation formula is shown as formula I:

[0256]

[0257] The statistical software SPSS 20.0 is used to calculate the concentration of the compound when the inhibition rate is 50%, that is, the EC 50 value.

[0258] Table 1 Inhibition concentration (EC 50 , μM) of heterocyclic oxime compounds on four kinds of agricultural fungi

[0259]

[0260]

[0261]

[0262] Table 1 shows that heterocyclic oxime compounds exhibit certain inhibitory effects against various plant pathogens. With decreasing electronegativity of the ortho-substituents on the benzene ring, the antibacterial activity against *Sclerotinia sclerotinia*, the causal agent of rapeseed rot, gradually increases. Among them, HXD-88(-Br) shows the highest EC500 against *Sclerotinia sclerotinia*. 50 The EC50 reached 9.77 μM. When the benzene ring has a strong electron-withdrawing group -CF3, the EC50 against rice blast fungus reached 15.94 μM. Against wheat scab, the meta-substituent on the benzene ring had a significant impact on its activity; when the meta-substituent was -Br, the EC50 was [missing value]. 50 The concentration reached 19.30 μM. When both the benzene ring and the benzothiazole ring have substituents, in the case of disubstituents, HXD-144 has a -Cl group on the benzothiazole ring and an electron-donating -CH3 group ortho-to the benzene ring. Compared to HXD-47, which only has a methyl group on the benzene ring, the introduction of -Cl improves biological activity and enhances the EC50 activity against *Sclerotinia sclerotiorum* causal agent of rapeseed. 50 It reached 5.17 μmol / L.

[0263] Based on the data in Table 1, when the benzene ring was replaced with a five-membered heterocycle, the biological activity was not significantly improved. However, when pyridine was used, the EC50 activity against Fusarium graminearum, the causal agent of wheat blight, was significantly increased. 50 Reaching 8.48 μM, EC50 against anthrax in peppers 50 The activity of the benzothiazole dioxime basic skeleton reached 14.33 μM, and when the benzene ring was replaced with a benzothiazole ring, the EC50 activity against Sclerotinia sclerotinia, the causal agent of rapeseed rot, was significantly improved. 50 The activity reached 5.91 μM; replacing it with benzofuran did not significantly improve the activity. With pyridine ring immobilization, the EC50 of benzothiazole against rice blast was significantly improved when the substituent on benzothiazole was -4Cl. 50 The activity reached 6.15 μM. Compared to HXD-70, the activity decreased sharply after introducing a methyl group onto the pyridine ring. Heterocyclic oxime compounds are expected to be a new class of fungicide candidates or can be used directly as fungicides, which will be of great significance to the development of new pesticides.

[0264] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. Other embodiments can be obtained based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A heterocyclic oxime compound, characterized by, having a structure represented by Formula 1: In Formula 1, the configuration of the oxime group is E or Z; R1 is H or Cl; Ar is: 2-methylphenyl, 3-methylphenyl, 2-CF3-phenyl, 2-Cl-phenyl, 2-F-phenyl, 2-I-phenyl, 2-Br-phenyl, 3-Br-phenyl, 2-phenyl-phenyl, 2. The heterocyclic oxime compound according to claim 1, characterized by having any one of the following structures:

3. The method of producing the heterocyclic oxime compound according to claim 1, characterized by, comprising the following steps: performing an oximation reaction on a compound represented by Formula 2, hydroxylamine hydrochloride, an organic acid alkali metal salt, and an organic solvent under heating to obtain a heterocyclic oxime compound represented by Formula 1; R1and Ar in formula 2 are the same as R1and Ar in formula 1 of claim 1.

4. The production method according to claim 3, characterized by, The preparation method of the compound represented by Formula 2 comprises the following steps: performing a nucleophilic substitution reaction on a compound represented by Formula 3, a compound represented by Formula 4, an inorganic strong base, iodine, an organic solvent, and water under heating to obtain the compound represented by Formula 2; or mixing a compound represented by Formula 4, a compound represented by Formula 5, iodine, and an organic solvent, and performing a ring formation-substitution reaction under heating to obtain the compound represented by Formula 2; R1in Formula 3 or Formula 5 is consistent with R1in Formula 2 in Claim 3, and Ar in Formula 4 is consistent with Ar in Formula 2 in Claim 3.

5. Use of the heterocyclic oxime compounds as claimed in claim 2 for controlling phytopathogenic fungi, characterized in that The compound HXD-47, the compound HXD-114a, the compound HXD-123a, and the compound HXD-282a are used for preventing and treating one or more of Sclerotinia sclerotiorum, Gibberella zeae, and Colletotrichum capsici. The compound HXD-46, the compound HXD-109a, the compound HXD-144a, the compound HXD-88, the compound HXD-90a, and the compound HXD-55a are used for preventing and treating one or more of Sclerotinia sclerotiorum and Gibberella zeae. The compound HXD-233a is used for preventing and treating Sclerotinia sclerotiorum. The compound HXD-76, the compound HXD-110a, and the compound HXD-183a are used for preventing and treating one or more of Sclerotinia sclerotiorum, Gibberella zeae, and Magnaporthe oryzae. The compound HXD-43a is used for preventing and treating Gibberella zeae. The compound HXD-108a, the compound HXD-70, and the compound HXD-150a are used for preventing and treating one or more of Sclerotinia sclerotiorum, Gibberella zeae, Colletotrichum capsici, and Magnaporthe oryzae. The compound HXD-269a is used for preventing and treating one or more of Gibberella zeae, Colletotrichum capsici, and Magnaporthe oryzae.

6. A composition characterized in that, comprising an antibacterial active ingredient and a pesticidally acceptable adjuvant; the antibacterial active ingredient is the heterocyclic oxime compound or a salt thereof as claimed in claim 1 or 2.

7. Use of HXD-288a or HXD-162a in preventing and treating plant pathogenic fungi; the chemical structural formula of HXD-288a is: The chemical structural formula of HXD-162a is: The plant pathogenic fungi are selected from one or more of Sclerotinia sclerotiorum, Gibberella zeae, Colletotrichum capsici, and Magnaporthe oryzae.

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