Imidazole carboxylic oxime ester compound and preparation method and application thereof

Abstract

The application discloses an imidazole carboxylic acid oxime ester compound and a preparation method and application thereof. The imidazole carboxylic acid oxime ester compound has a structural formula as shown in formula I. The preparation method of the compound is simple in operation and raw materials are easy to obtain. The compound has a broad-spectrum fungicidal activity, and has a significant inhibitory effect on tomato botrytis cinerea, oilseed rape sclerotinia sclerotiorum, apple tree armillaria mellea, rice rhizoctonia solani and wheat fusarium graminearum, and can be used as a fungicide for the prevention and treatment of the above plant diseases.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pathogenic bacteria control, and particularly relates to an imidazole carboxylic acid oxime ester compound, a preparation method and application. BACKGROUND

[0002] Oxime ester compounds have excellent biological activity, and their medical value has been widely reported. Agricultural activity also has a good research foundation. In 2017, Xia Li-juan et al. reported that the 1,4-pentadiene-3-ketone oxime ester compound containing a heterocycle has good inhibitory activity on wheat scab and apple tree rot fungi (Application Chemistry, 2017, 34, 316). Jiang Lin et al. synthesized a series of 3,3-dimethyl-1-(pyridine-3-yl)-butan-2-one oxime ester new molecules, which have good fungicidal activity on eggplant sclerotinia and tomato gray mold (Organic Chemistry, 2017, 37, 2767).

[0003] Imidazole is a five-membered heterocycle containing three carbon atoms and two nitrogen atoms. Imidazole derivatives have various excellent biological activities, such as anticancer, anti-inflammatory, bactericidal, herbicidal, insecticidal, etc. Chen et al. introduced an imidazole active group into a 3,4-dichloroisothiazole lead to design a series of derivatives with high inhibitory effect on rhizoctonia solani of cereal crops, and the results show that the introduction of the imidazole group greatly improves the fungicidal activity of the compounds (Journal of Agricultural and Food Chemistry, 2018, 66, 7319);

[0004] In order to discover new agricultural fungicides, the inventors introduced imidazole carboxylic acid into the oxime ester structure to obtain a new compound shown in formula I, and found that they have good effects on preventing and treating plant pathogenic fungi. The application discloses an imidazole carboxylic acid oxime ester compound with a novel structure and application thereof as an agricultural fungicide. SUMMARY

[0005] The purpose of the present application is to provide an imidazole carboxylic acid oxime ester compound, a preparation method and application.

[0006] In order to achieve the above-mentioned purpose, the technical scheme of the present application is as follows:

[0007] An imidazole carboxylic acid oxime ester compound is a compound shown in formula I

[0008]

[0009] wherein: R is selected from at least one of hydrogen, halogen, nitro, C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, phenoxy, benzyloxy and diethylamino;

[0010] R is mono-, di- or tri-substituted;

[0011] or a salt of the compound of formula I.

[0012] Optionally, an imidazole oxime formate compound of formula I is characterized by being a compound of formula II, III and IV, according to the different positions of imidazole substitution;

[0013]

[0014] wherein R is selected from at least one of hydrogen, fluorine, chlorine, bromine, nitro, methyl, isopropyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenoxy, benzyloxy and diethylamino;

[0015] R is mono-, di- or tri-substituted;

[0016] or a salt of the compound of formula II, III and IV.

[0017] An imidazole oxime formate compound is characterized by being a compound of formula II, III and IV;

[0018]

[0019] Specific substituents of the compound of formula II, III and IV are shown in the following table:

[0020]

[0021]

[0022]

[0023] or a salt of the compound of formula II, III and IV.

[0024] A preparation method of an imidazole oxime formate compound is characterized by comprising the following steps: adding a compound of formula VI or a compound of formula VII and a compound of formula V into an organic solvent to react, to obtain a compound of formula I;

[0025]

[0026] Optionally, a preparation method of an imidazole oxime formate compound is characterized by mixing an additive into the organic solvent, the additive being selected from one or more of triethylamine, pyridine, dicyclohexyl carbodiimide, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, 4-dimethylaminopyridine and bis(4-nitrophenyl) carbonate;

[0027] The organic solvent is at least one selected from dichloromethane, chloroform, toluene, ethyl acetate and tetrahydrofuran.

[0028] Optionally, the reaction temperature of the reaction is -25-60 DEG C, and the reaction time is 5 min-24 h.

[0029] The molar ratio of the compound of formula V to the compound of formula VI is 1:(1-1.2).

[0030] The molar ratio of the compound of formula V to the compound of formula VII is 1:(1-1.2).

[0031] The application of the imidazole carboxylic acid oxime ester compound in the preparation of a plant fungicide.

[0032] Optionally, the plant fungicide is used for preventing and treating plant gray mold, sclerotinia disease, rot disease, sheath blight and / or bunt caused by Botrytis cinerea, Sclerotinia sclerotiorum, Valsa mali, Rhizoctonia solani and / or Fusarium graminearum.

[0033] A plant fungicide, wherein the plant fungicide takes the imidazole carboxylic acid oxime ester compound in the application as an active component; the weight percentage of the active component in the composition is 0.1%-99%.

[0034] The application has the following advantages:

[0035] The imidazole carboxylic acid with excellent bioactive fragments is introduced into the oxime ester compound, the obtained compound has novel structure and wide-spectrum fungicidal activity, and has obvious inhibitory effect on tomato gray mold, rape sclerotinia disease, apple tree rot disease, rice sheath blight and / or wheat bunt. BRIEF DESCRIPTION OF DRAWINGS

[0036] The accompanying drawings are included to provide a further understanding of the present disclosure and constitute a part of the specification, which together with the specific embodiments described below, serve to explain the present disclosure but do not constitute a limitation thereof. In the drawings:

[0037] Figure 1 The hydrogen spectrum of the imidazole carboxylic acid oxime ester compound II-04 in the application;

[0038] Figure 2 The carbon spectrum of the imidazole carboxylic acid oxime ester compound II-04 in the application;

[0039] Figure 3The hydrogen spectrum of the imidazole carboxylic oxime ester compound III-25 of the present application is shown in the following figure:

[0040] Figure 4 The hydrogen spectrum of the imidazole carboxylic oxime ester compound IV-06 of the present application is shown in the following figure. DETAILED DESCRIPTION

[0041] The present application is further described in conjunction with the specific examples, but the present application is not limited to these examples. The methods, if not specified, are conventional methods. The materials, if not specified, can be obtained from the public commercial channels.

[0042] The imidazole carboxylic oxime ester compound disclosed in the present application refers to the compound having the structure shown in formula I:

[0043]

[0044] wherein R is selected from at least one of hydrogen, halogen, nitro, C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, phenoxy, benzyloxy and diethylamino;

[0045] The substitution mode of R is single substitution, double substitution or triple substitution; the single substitution herein refers to that R is substituted with one substituent; the double substitution refers to that R is substituted with two substituents, and the two substituents can be the same or different; the triple substitution refers to that R is substituted with three substituents, and the three substituents can be the same or different;

[0046] or the salt of the compound shown in formula I.

[0047] Alternatively, the imidazole carboxylic oxime ester compound shown in formula I is characterized in that it is the compound shown in formula II, formula III and formula IV according to the different substitution positions of imidazole;

[0048]

[0049] wherein R is selected from at least one of hydrogen, fluorine, chlorine, bromine, nitro, methyl, isopropyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenoxy, benzyloxy and diethylamino;

[0050] The substitution mode of R is single substitution, double substitution or triple substitution;

[0051] or the salt of the compound shown in formula II, formula III and formula IV.

[0052] The imidazole carboxylic oxime ester compound is characterized in that it is the compound shown in formula II, formula III and formula IV;

[0053]

[0054] More specifically, the substituents of the compounds of Formula II, Formula III and Formula IV are shown in Table 1:

[0055] Table 1

[0056]

[0057]

[0058] or a salt of the compound of Formula II, Formula III and Formula IV.

[0059] The compound of Formula I is prepared by the following method:

[0060] The preparation method of the imidazole carboxylic oxime ester compound comprises the following steps: adding the compound of Formula VI or the compound of Formula VII and the compound of Formula V into an organic solvent to react, so as to obtain the compound of Formula I.

[0061]

[0062] The organic solvent is selected from at least one of dichloromethane, chloroform, toluene, ethyl acetate and tetrahydrofuran.

[0063] The additive is also added into the organic solvent, and the additive is selected from at least one of triethylamine, pyridine, dicyclohexyl carbodiimide, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, 4-dimethylaminopyridine and bis(4-nitrophenyl) carbonate.

[0064] The reaction temperature is -25-60℃, and the reaction time is 5min-24h.

[0065] The molar ratio of the compound of Formula V to the compound of Formula VI is 1:(1-1.2).

[0066] The molar ratio of the compound of Formula V to the compound of Formula VII is 1:(1-1.2).

[0067] The imidazole carboxylic oxime ester compound of any one of the present application is used for preparing a plant fungicide. The plant fungicide is used for preventing and treating Botrytis cinerea, Sclerotinia sclerotiorum, Valsa mali, Pyricularia oryzae and / or Gibberella zeae.

[0068] A plant fungicide, wherein the plant fungicide takes the imidazole carboxylic oxime ester compound of any one of the present application as an active component; the weight percentage content of the active component in the composition is 0.1%-99%.

[0069] The scheme of the present application is specifically described in combination with specific examples.

[0070] Example 1: Preparation of compound 2-chloro-6-fluorobenzaldehyde-O-(1-methyl-1H- imidazole-4-carbonyl) oxime (II-17)

[0071]

[0072] In a 25 mL single necked flask was added 2-chloro-6-fluorobenzaldehyde oxime 0.868 g (5 mmol), triethylamine 0.506 g (5 mmol), 10 mL dichloromethane, to which was added dropwise a solution of 1-methyl-4-imidazolecarbonyl chloride 0.723 g (5 mmol) in 10 mL dichloromethane at room temperature. After the addition was complete, the reaction was allowed to proceed for 30 minutes. Purification by column chromatography (petroleum ether: ethyl acetate = 5:1) and drying gave a white solid. Yield 63%, m.p. 94.1-96.0 °C. 1 H NMR (400 MHz, CDC13) δ: 8.89 (s, 1H), 7.77 (d, J = 1.4 Hz, 1H), 7.54 (d, J = 1.3 Hz, 1H), 7.39-7.35 (m, 1H), 7.28 (dt, J = 8.1, 1.1 Hz, 1H), 7.12 (ddd, J = 9.6, 8.3, 1.2 Hz, 1H), 3.80 (s, 3H). 13 C NMR (101 MHz, CDC13) δ: 161.19 (d, J = 261.1 Hz), 159.73, 150.73 (d, J = 3.4 Hz), 139.00, 135.75 (d, J = 4.2 Hz), 132.43 (d, J = 9.9 Hz), 131.67, 127.65, 125.92 (d, J = 3.6 Hz), 117.51 (d, J = 14.4 Hz), 115.24 (d, J = 22.0 Hz), 33.99. HRMS: C 12 H9ClFN3O2[M+H] + Calculated 282.0440, found 282.0444.

[0073] Example 2: Preparation of compound 4-(tert-butyl)benzaldehyde-O-(1-methyl-1H- imidazole-5-carbonyl) oxime (III-25)

[0074]

[0075] To 4-tert-butylbenzaldehyde oxime 0.886 g (5 mmol), 1 -methyl-5-imidazolecarboxylic acid 0.631 g (5 mmol) and dicyclohexylcarbodiimide 1.032 g (5 mmol) in 20 mL of chloroform, stirred at room temperature for 24 h. After concentration on a rotary evaporator, purified by silica gel column chromatography with a mobile phase ratio of petroleum ether: ethyl acetate = 4: 1, concentrated by rotary evaporation to obtain white solid. Yield 84%, m.p. 130.9-131.4 °C. 1 H NMR (500 MHz, CDC13) δ: 8.48 (s, 1H), 7.84 (s, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.63 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H), 3.98 (s, 3H), 1.34 (s, 9H). 13 CNMR (126 MHz, CDC13) δ: 157.76, 155.31, 143.20, 137.88, 137.78, 129.55, 129.28, 128.49, 120.84, 57.97, 34.12, 18.39. HRMS: C 16 H 19 N3O2[M+H] + Calculated 286.1550, found 286.1562.

[0076] Example 3: Preparation of compound 4-(tert-butyl)benzaldehyde-O-(1 -methyl- 1H-imidazole-2-carbonyl)oxime (IV-11)

[0077]

[0078] To 3-bromobenzaldehyde oxime 1.000 g (5 mmol), 1 -methyl-2-imidazolecarboxylic acid 0.631 g (5 mmol) and dicyclohexylcarbodiimide 1.032 g (5 mmol) in 20 mL of tetrahydrofuran, stirred at 50 °C for 24 h. After concentration on a rotary evaporator, purified by silica gel column chromatography with a mobile phase ratio of petroleum ether: ethyl acetate = 3: 1, concentrated by rotary evaporation to obtain white solid. Yield 87%, m.p. 157.9-158.4 °C. 1 H NMR (500 MHz, DMSO-d6) δ: 8.91 (s, 1H), 8.01 (d, J = 1.8 Hz, 1H), 7.85 (dd, J = 7.7, 1.5 Hz, 1H), 7.79 (dd, J = 7.8, 1.9 Hz, 1H), 7.59 (q, J = 7.9, 7.1 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.17 (s, 1H), 3.99 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 157.47, 156.58, 147.70, 134.59, 132.70, 132.18, 130.57, 129.85, 129.65, 128.63, 125.94, 36.01. HRMS: C 12 H 10 BrN3O2[M+H] + Calcd 308.0029, Found 308.0019.

[0079] Other compounds of the present application can be prepared according to the above examples.

[0080] The appearance, melting point and structure identification data of some compounds are shown as follows:

[0081] Benzaldehyde-O-(1-methyl-1H-imidazole-4-carbonyl) oxime (II-01): white solid, m.p. 155.7-156.1 °C. 1 H NMR (500 MHz, CDCl3) δ 8.60 (s, 1H), 7.80-7.78 (m, 2H), 7.75 (d, J = 1.3 Hz, 1H), 7.52 (d, J = 1.3 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H), 7.44 (dd, J = 8.1, 6.4 Hz, 2H), 3.79 (s, 3H).

[0082] 2-Methylbenzaldehyde-O-(1-methyl-1H-imidazole-4-carbonyl) oxime (II-02): white solid, m.p. 153.9-154.2 °C. 1 H NMR (500 MHz, CDCl3) δ 8.48 (s, 1H), 7.77 (d, J = 1.3 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46-7.44 (m, 3H), 7.38 (d, J = 1.5 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 3H).

[0083] 3-Methylbenzaldehyde-O-(1-methyl-1H-imidazole-4-carbonyl) oxime (II-03): white solid, m.p. 155.6-156.0 °C. 1 H NMR (500 MHz, CDCl3) δ 8.55 (s, 1H), 7.74 (d, J = 1.4 Hz, 1H), 7.64 (s, 1H), 7.51 (d, J = 1.4 Hz, 1H), 7.44 (d, J = 1.4 Hz, 2H), 7.37 (d, J = 1.4 Hz, 1H), 3.77 (s, 3H), 2.38 (s, 3H).

[0084] 4-methylbenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-04): white solid, m.p. 158.4-159.0 °C. 1 H NMR (500 MHz, CDC13) δ 8.56 (s, 1H), 7.74 (d, J = 1.4 Hz, 1H), 7.68 (d, J = 8.1 Hz, 2H), 7.51 (d, J = 1.4 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H), 2.40 (s, 3H).

[0085] 3-fluorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-05): white solid, m.p. 160.1-160.7 °C. 1 H NMR (500 MHz, CDC13) δ 8.54 (s, 1H), 7.73 (d, J = 1.4 Hz, 1H), 7.54 - 7.48 (m, 3H), 7.39 (td, J = 8.0, 5.6 Hz, 1H), 7.15 (tdd, J = 8.3, 2.6, 1.0 Hz, 1H), 3.77 (s, 3H).

[0086] 4-fluorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-06): white solid, m.p. 154.2-154.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.59 (s, 1H), 7.81 (dd, J = 8.6, 5.5 Hz, 2H), 7.77 (d, J = 1.3 Hz, 1H), 7.53 (d, J = 1.3 Hz, 1H), 7.28 (s, 1H), 7.14 (t, J = 8.6 Hz, 2H), 3.80 (s, 3H).

[0087] 2-chlorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-07): white solid, m.p. 147.9-148.5 °C. 1 H NMR (500 MHz, CDC13) δ 9.05 (s, 1H), 8.17 (dd, J = 7.8, 1.5 Hz, 1H), 7.77 (d, J = 1.4 Hz, 1H), 7.54 (d, J = 1.4 Hz, 1H), 7.45 - 7.39 (m, 2H), 7.33 (ddd, J = 8.3, 6.6, 2.1 Hz, 1H), 3.80 (s, 1H).

[0088] 3-chlorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-08): white solid, m.p. 185.7-186.4 °C. 1H NMR (500 MHz, CDC13) δ 8.58 (s, 1H), 7.84 (s, 1H), 7.79 (d, J = 1.2 Hz, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.60 (s, 1H), 7.50 - 7.44 (m, 1H), 7.43 - 7.36 (m, 1H), 3.82 (s, 3H).

[0089] 4-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-09): white solid, m.p. 188.3-189.0 °C. 1 H NMR (500 MHz, CDC13) δ 8.58 (s, 1H), 7.84 (s, 1H), 7.79 (d, J = 1.2 Hz, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.60 (s, 1H), 7.50 - 7.44 (m, 1H), 7.43 - 7.36 (m, 1H), 3.82 (s, 3H).

[0090] 2-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-10): white solid, m.p. 147.7-147.9 °C. 1 H NMR (500 MHz, CDC13) δ 8.58 (s, 1H), 7.84 (s, 1H), 7.79 (d, J = 1.2 Hz, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.60 (s, 1H), 7.50 - 7.44 (m, 1H), 7.43 - 7.36 (m, 1H), 3.82 (s, 3H).

[0091] 3-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-11): white solid, m.p. 102.7-103.5 °C. 1 H NMR (500 MHz, CDC13) δ 8.58 (s, 1H), 7.84 (s, 1H), 7.79 (d, J = 1.2 Hz, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.60 (s, 1H), 7.50 - 7.44 (m, 1H), 7.43 - 7.36 (m, 1H), 3.82 (s, 3H).

[0092] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-12): white solid, m.p. 152.3-153.1 °C. 1H NMR (500 MHz, CDC13) δ 8.62 (s, 1H), 7.65 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.22 (s, 1H), 7.14 (s, 1H), 4.09 (s, 3H).

[0093] 4-Nitrobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-13): white solid, m.p. 155.9-156.4 °C. 1 H NMR (500 MHz, CDC13) δ 8.56 (s, 1H), 8.03 (s, 1H), 7.44 (dd, J = 7.5, 6.3 Hz, 1H), 7.26 (d, J = 1.0 Hz, 1H), 7.23 (dd, J = 8.1, 6.5 Hz, 2H), 7.18 (s, 1H), 4.12 (s, 3H).

[0094] 4-Methoxybenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-14): white solid, m.p. 143.2-143.7 °C. 1 H NMR (500 MHz, CDC13) δ 8.50 (s, 1H), 7.70 - 7.69 (m, 2H), 7.69 (s, 1H), 7.49 (d, J = 1.4 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 3.75 (s, 3H).

[0095] 4-(Trifluoromethyl)benzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-15): white solid, m.p. 152.2-152.7 °C. 1 H NMR (400 MHz, CDC13) δ 8.59 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 1.4 Hz, 1H), 7.52 (d, J = 1.4 Hz, 1H), 7.29 - 7.27 (m, 2H), 3.79 (s, 3H).

[0096] 4-(Trifluoromethoxy)benzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-16): white solid, m.p. 162.3-162.9 °C. 1 H NMR (500 MHz, CDC13) δ 8.66 (s, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.79 (d, J = 1.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.57 (s, 1H), 3.82 (s, 3H).

[0097] 3,4-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-18): white solid, m.p. 143.1-143.6 °C. 1 H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.76 (d, J = 1.4 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46 (d, J = 1.4 Hz, 2H), 7.38 (d, J = 1.4 Hz, 1H), 3.79 (s, 3H).

[0098] 3,5-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-19): white solid, m.p. 133.3-133.5 °C. 1 H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.76 (d, J = 1.4 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46 (d, J = 1.4 Hz, 2H), 7.38 (d, J = 1.4 Hz, 1H), 3.79 (s, 3H).

[0099] 3,5-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-19): white solid, m.p. 133.3-133.5 °C. 1 H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.76 (d, J = 1.4 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46 (d, J = 1.4 Hz, 2H), 7.38 (d, J = 1.4 Hz, 1H), 3.79 (s, 3H).

[0100] 3,5-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-19): white solid, m.p. 133.3-133.5 °C. 1 H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.76 (d, J = 1.4 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46 (d, J = 1.4 Hz, 2H), 7.38 (d, J = 1.4 Hz, 1H), 3.79 (s, 3H).

[0101] 4-(Diethylamino)benzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-22): white solid, m.p. 107.3-107.7 °C. 1H NMR (500 MHz, Chloroform-d) δ 8.34 (s, 1H), 7.78 (d, J = 0.9 Hz, 1H), 7.65 - 7.48 (m, 3H), 6.63 (d, J = 8.9 Hz, 1H), 3.95 (s, 3H), 3.39 (q, J = 7.1 Hz, 4H), 1.18 (t, J = 7.1 Hz, 6H).

[0102] 3-Phenoxybenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-23): white solid, m.p. 174.8-175.0 °C. 1 H NMR (400 MHz, CDC13) δ 8.54 (s, 1H), 7.72 (d, J = 1.4 Hz, 1H), 7.51 - 7.48 (m, 1H), 7.44 (s, 1H), 7.40 - 7.33 (m, 3H), 7.14 - 7.09 (m, 2H), 7.01 (d, J = 7.5 Hz, 2H), 3.75 (s, 3H).

[0103] 4-(Benzyl oxy)benzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-24): white solid, m.p. 175.7-175.9 °C. 1 H NMR (400 MHz, CDC13) δ 8.53 (s, 1H), 7.73 - 7.71 (m, 3H), 7.50 (d, J = 1.4 Hz, 1H), 7.45 - 7.34 (m, 5H), 7.01 (d, J = 8.8 Hz, 2H), 5.11 (s, 2H), 3.77 (s, 3H).

[0104] 4-(tert-Butyl)benzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-25): white solid, m.p. 188.3-189.0 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.51 (s, 1H), 7.70 (d, J = 1.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.50 - 7.49 (m, 1H), 7.41 - 7.40 (m, 2H), 3.74 (s, 3H), 1.28 (s, 9H).

[0105] 2-Fluorobenzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (II-26): white solid, m.p. 161.5-161.8 °C. 1H NMR (500 MHz, Chloroform-d) δ 8.49 (s, 1H), 7.84 (s, 1H), 7.64 (s, 1H), 7.55 - 7.51 (m, 2H), 7.43 (td, J = 8.0, 5.6 Hz, 1H), 7.19 (td, J = 8.4, 2.7 Hz, 1H), 3.98 (s, 3H).

[0106] 2-Nitrobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-27): white solid, m.p. 154.1-154-5 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.49 (s, 1H), 7.84 (s, 1H), 7.64 (s, 1H), 7.55 - 7.51 (m, 2H), 7.43 (td, J = 8.0, 5.6 Hz, 1H), 7.19 (td, J = 8.4, 2.7 Hz, 1H), 3.98 (s, 3H).

[0107] 2,4-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-4-carbonyl) oxime (II-28): white solid, m.p. 168.4-169.3 °C. 1H NMR (500 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.76 (d, J = 1.4 Hz, 1H), 7.53 (d, J = 1.4 Hz, 1H), 7.46 (d, J = 1.4 Hz, 1H), 6.97 (td, J = 8.4, 2.5 Hz, 1H), 6.88 (ddd, J = 10.8, 8.7, 2.5 Hz, 1H), 3.79 (s, 3H).

[0108] Benzaldehyde-O-(1 -methyl- 1 H-imidazole-5-carbonyl) oxime (III-01): white solid, m.p. 98.5-98.6 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.49 (s, 1H), 7.84 (s, 1H), 7.64 (s, 1H), 7.55 - 7.51 (m, 2H), 7.43 (td, J = 8.0, 5.6 Hz, 1H), 7.19 (td, J = 8.4, 2.7 Hz, 1H), 3.98 (s, 3H).

[0109] 2-Methylbenzaldehyde-O-(1 -methyl- 1 H-imidazole-5-carbonyl) oxime (III-02): white solid, m.p. 155.5-155.6 °C. 1H NMR (500 MHz, CDC13) δ 8.76 (s, 1H), 7.90 (dd, J = 7.7, 1.4 Hz, 1H), 7.86 (s, 1H), 7.64 (s, 1H), 7.38 (td, J = 7.5, 1.5 Hz, 1H), 7.28 - 7.25 (m, 2H), 3.99 (s, 3H), 2.53 (s, 3H).

[0110] 3-methylbenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-03): white solid, m.p. 153.4-153.9 °C. 1 H NMR (500 MHz, CDC13) δ 8.39 (s, 1H), 7.75 (s, 1H), 7.56 (s, 2H), 7.44 (d, J = 7.4 Hz, 1H), 7.23 (dt, J = 13.4, 7.6 Hz, 2H), 3.88 (s, 3H), 2.30 (s, 3H).

[0111] 4-methylbenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-04): white solid, m.p. 154.7-155.2 °C. 1 H NMR (500 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.02 (s, 1H), 7.80 (s, 1H), 7.70 (d, J = 7.9 Hz, 2H), 7.35 (d, J = 7.8 Hz, 2H), 3.90 (s, 3H), 2.38 (s, 3H).

[0112] 3-fluorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-05): white solid, m.p. 150.7-151.0 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.49 (s, 1H), 7.84 (s, 1H), 7.64 (s, 1H), 7.56 - 7.49 (m, 2H), 7.45 - 7.42 (m, 1H), 7.21 - 7.17 (m, 1H), 3.98 (s, 3H).

[0113] 4-fluorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-06): white solid, m.p. 185.3-185.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.65 (s, 1H), 7.80 (dd, J = 8.7, 5.5 Hz, 2H), 7.22 (s, 1H), 7.17 (s, 1H), 7.15 (d, J = 2.6 Hz, 2H), 4.10 (s, 3H).

[0114] 2-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-07): white solid, m.p. 180.2-181.0 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.44 (s, 1H), 7.79 (s, 1H), 7.64 - 7.61 (m, 3H), 7.56 (d, J = 8.5 Hz, 2H), 3.95 (s, 3H).

[0115] 3-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-08): white solid, m.p. 223.5-223.9 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.49 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.86 (s, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.51 - 7.49 (m, 1H), 7.43 (td, J = 7.9, 1.8 Hz, 2H), 4.02 (s, 3H).

[0116] 4-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-09): white solid, m.p. 154.9-155.7 °C. 1 H NMR (500 MHz, CDCl3) δ 8.47 (s, 1H), 7.83 (s, 1H), 7.72 (d, J = 8.5 Hz, 2H), 7.63 (s, 1H), 7.42 (d, J = 8.4 Hz, 2H), 3.97 (s, 3H).

[0117] 2-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-10): white solid, m.p. 155.7-156.4 °C. 1 H NMR (500 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.05 (s, 1H), 7.95 (d, J = 7.4 Hz, 1H), 7.90 (s, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 7.8 Hz, 2H), 3.91 (s, 3H).

[0118] 3-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-11): white solid, m.p. 174.0-174.5 °C. 1H NMR (500 MHz, CDC13) δ 8.43 (s, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.66 - 7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H).

[0119] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-12): white solid, m.p. 156.2-156.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.43 (s, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.66 - 7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H).

[0120] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-12): white solid, m.p. 156.2-156.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.43 (s, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.66 - 7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H).

[0121] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-12): white solid, m.p. 156.2-156.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.43 (s, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.66 - 7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H).

[0122] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-12): white solid, m.p. 156.2-156.8 °C. 1 H NMR (500 MHz, CDC13) δ 8.43 (s, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.66 - 7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H).

[0123] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-12): white solid, m.p. 156.2-156.8 °C. 1H NMR (500 MHz, CDC13) δ 8.98 (d, J = 1.0 Hz, 1H), 7.37 (td, J = 8.3, 5.6 Hz, 1H), 7.27 (dd, J = 8.1, 1.1 Hz, 1H), 7.22 (d, J = 0.9 Hz, 1H), 7.14 - 7.11 (m, 2H), 4.08 (s, 3H).

[0124] 2,4-Difluorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-17): white solid, m.p. 188.9-189.4 °C. 1 H NMR (500 MHz, CDC13) δ 8.83 (s, 1H), 8.14 (td, J = 8.5, 6.4 Hz, 1H), 7.77 (d, J = 1.4 Hz, 1H), 7.54 (d, J = 1.4 Hz, 1H), 7.28 (s, 1H), 6.98 (td, J = 8.0, 2.3 Hz, 1H), 6.90 (ddd, J = 10.8, 8.7, 2.5 Hz, 1H), 3.81 (s, 3H).

[0125] 3,4-Difluorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-18): white solid, m.p. 184.7-185.2 °C. 1 H NMR (500 MHz, CDC13) δ 8.68 (s, 1H), 8.05 (td, J = 8.4, 6.5 Hz, 1H), 7.82 (s, 1H), 7.63 (s, 1H), 6.95 (td, J = 8.3, 2.5 Hz, 1H), 6.88 (ddd, J = 10.7, 8.5, 2.5 Hz, 1H), 3.96 (s, 3H).

[0126] 3,4,5-Trifluorobenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-19): white solid, m.p. 173.2-173.6 °C. 1 H NMR (500 MHz, CDC13) δ 8.41 (s, 1H), 7.83 (s, 1H), 7.66 (s, 1H), 7.47 - 7.44 (m, 2H), 3.98 (s, 3H).

[0127] 3,5-Bis(trifluoromethyl)benzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-20): white solid, m.p. 71.7-72.2 °C. 1H NMR (500 MHz, CDC13) δ 8.78 (s, 1H), 8.49-8.48 (m, 1H), 8.23 (s, 1H), 8.02 (s, 1H), 7.33 (s, 1H), 7.21 (s, 1H), 4.15 (s, 3H).

[0128] 4-(Diethylamino)benzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-21): white solid, m.p. 149.9-150.1 °C. 1 H NMR (500 MHz, CDC13) δ 8.46 (s, 1H), 7.82 (dd, J = 3.9, 2.0 Hz, 2H), 7.64 (d, J = 1.8 Hz, 2H), 7.46 (dd, J = 2.2, 1.1 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 3.98 (s, 3H), 3.70 (q, J = 7.0 Hz, 4H), 1.23 (t, J = 7.0 Hz, 6H).

[0129] 3-Phenoxybenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-22): white solid, m.p. 163.5-164.1 °C. 1 H NMR (500 MHz, CDC13) δ 8.35 (s, 1H), 7.72 (s, 1H), 7.55 (s, 1H), 7.39 (dd, J = 7.7, 1.3 Hz, 1H), 7.31-7.22 (m, 4H), 7.04-7.00 (m, 2H), 6.91 (dd, J = 8.6, 1.2 Hz, 2H), 3.84 (s, 3H).

[0130] 4-Isopropylbenzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-23): white solid, m.p. 159.6-160.0 °C. 1 H NMR (500 MHz, CDC13) δ 8.38 (s, 1H), 7.72 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.53 (s, 1H), 7.20 (d, J = 8.0 Hz, 2H), 3.86 (s, 3H), 2.84 (p, J = 6.9 Hz, 1H), 1.16 (d, J = 7.0 Hz, 6H).

[0131] 4-(Benzyl oxy)benzaldehyde-O-(l-methyl-lH-imidazole-5-carbonyl) oxime (III-24): white solid, m.p. 178.9-179.6 °C. 1H NMR (500 MHz, CDC13) δ 8.45 (s, 1H), 7.84 (s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.63 (s, 1H), 7.45 - 7.39 (m, 4H), 7.36 (d, J = 7.2 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 5.12 (s, 2H), 3.98 (s, 3H).

[0132] 2-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-26): white solid, m.p. 96.8-97.7.

[0133] 2-Nitrobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-27): white solid, m.p. 159.0-160.0 °C.

[0134] 3-Nitrobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-28): white solid, m.p. 190.9-191.7 °C.

[0135] 3-Phenoxybenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-29): white solid, m.p. 150.5-150.7 °C.

[0136] Benzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-01): white solid, m.p. 178.7-2179.1 °C. 1 H NMR (500 MHz, CDC13) δ 8.45 (s, 1H), 7.84 (s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.63 (s, 1H), 7.45 - 7.39 (m, 4H), 7.36 (d, J = 7.2 Hz, 1H), 7.04 (d, J = 8.8 Hz, 2H), 5.12 (s, 2H), 3.98 (s, 3H).

[0137] 2-Methylbenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-02): white solid, m.p. 151.7-152.3 °C. 1 H NMR (500 MHz, DMSO-d6) δ 9.02 (s, 1H), 7.81 - 7.80 (m, 1H), 7.59 (s, 1H), 7.46 (td, J = 7.5, 1.4 Hz, 1H), 7.36 (d, J = 7.8 Hz, 2H), 7.16 (s, 1H), 4.00 (s, 3H), 2.51 (s, 3H).

[0138] 3-methylbenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-03): white solid, m.p. 189.1-191.4 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.88 (s, 1H), 7.95 (dd, J = 7.8, 1.4 Hz, 1H), 7.75 (d, J = 1.4 Hz, 1H), 7.51 (d, J = 1.4 Hz, 1H), 7.37 - 7.33 (m, 1H), 7.26 - 7.21 (m, 2H), 3.78 (s, 3H), 2.47 (s, 3H).

[0139] 4-methylbenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-04): white solid, m.p. 153.3-153.5 °C. 1 H NMR (500 MHz, CDCl3) δ 8.65 (s, 1H), 7.68 (d, J = 7.9 Hz, 2H), 7.26 (d, J = 7.9 Hz, 2H), 7.22 (s, 1H), 7.14 (s, 1H), 4.10 (s, 3H), 2.42 (s, 3H).

[0140] 2-fluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-05): white solid, m.p. 146.7-147.3 °C.1H NMR (500 MHz, Chloroform-d) δ 8.20 (dd, J = 8.1, 1.3 Hz, 1H), 7.90 (s, 1H), 7.76 (td, J = 7.6, 1.3 Hz, 1H), 7.70 (td, J = 7.8, 1.6 Hz, 1H), 7.51 (s, 1H), 7.45 (s, 1H), 4.00 (s, 1H), 3.82 (s, 3H).

[0141] 3-fluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-06): white solid, m.p. 157.7-158.0 °C. 1 H NMR (500 MHz, Chloroform-d) δ 8.66 (s, 1H), 8.15 (s, 1H), 7.54 (dd, J = 9.3, 2.2 Hz, 1H), 7.50 (dt, J = 7.6, 1.4 Hz, 1H), 7.25 (d, J = 0.9 Hz, 1H), 7.22 - 7.18 (m, 1H), 7.16 (s, 1H), 4.11 (s, 3H).

[0142] 4-Fluorobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-07): white solid, m.p. 146.7-147.9 °C. 1 H NMR (500 MHz, CDC13) δ 8.49 (s, 1H), 7.83 (s, 1H), 7.80 (dd, J = 8.7, 5.5 Hz, 2H), 7.64 (s, 1H), 7.15 (s, 2H), 3.98 (s, 3H).

[0143] 2-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-08): white solid, m.p. 179.3-180.0 °C. 1 H NMR (500 MHz, CDC13) δ 8.90 (s, 1H), 8.08 (dd, J = 7.6, 1.4 Hz, 1H), 7.84 (s, 1H), 7.62 (s, 1H), 7.39 (dd, J = 5.9, 1.8 Hz, 2H), 7.29 (ddd, J = 8.4, 6.3, 2.3 Hz, 1H), 3.95 (s, 3H).

[0144] 3-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-09): white solid, m.p. 178.5-179.6 °C. 1 H NMR (500 MHz, CDC13) δ 8.65 (s, 1H), 7.84 (s, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.49 (dd, J = 8.0, 2.2 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 7.25 (s, 1H), 7.16 (s, 1H), 4.12 (s, 3H).

[0145] 4-Chlorobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-10): white solid, m.p. 187.9-188.6 °C. 1 H NMR (500 MHz, CDC13) δ 8.65 (s, 1H), 7.66 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.27 (s, 1H), 7.16 (s, 1H), 4.11 (s, 3H).

[0146] 4-Bromobenzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-12): white solid, m.p. 181.2-181.5 °C. 1H NMR (500 MHz, DMSO-d6) δ 8.92 (s, 1H), 7.77 (s, 4H), 7.59 (s, 1H), 7.16 (s, 1H), 3.99 (s, 3H).

[0147] 4-Nitrobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-13): white solid, m.p. 150.2-150.5 °C. 1 H NMR (500 MHz, CDC13) δ 8.33 (d, J = 8.8 Hz, 1H), 8.26 - 8.22 (m, 1H), 7.88 (dd, J = 113.2, 8.8 Hz, 2H), 7.23 (d, J = 36.8 Hz, 1H), 6.98 (d, J = 43.9 Hz, 2H), 3.86 (s, 3H).

[0148] 4-Methoxybenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-14): white solid, m.p. 160.0-160.7 °C. 1 H NMR (500 MHz, CDC13) δ 8.61 (s, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.21 (s, 1H), 7.13 (s, 1H), 6.95 (d, J = 8.7 Hz, 2H), 4.09 (s, 3H), 3.86 (s, 3H).

[0149] 4-(Trifluoromethyl)benzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-15): white solid, m.p. 193.4-193.7 °C. 1 H NMR (500 MHz, CDC13) δ 8.73 (s, 1H), 8.20 (s, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 7.26 (s, 1H), 7.17 (s, 1H), 4.12 (s, 3H).

[0150] 4-(Trifluoromethoxy)benzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV-16): white solid, m.p. 193.5-194.2 °C. 1 H NMR (500 MHz, CDC13) δ 8.19 (s, 1H), 7.92 - 7.88 (m, 1H), 7.76 (d, J = 1.2 Hz, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.62 - 7.59 (m, 2H), 3.92 (s, 3H).

[0151] 2-Chloro-6-fluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV- 17): white solid, m.p. 170.3-171.2 °C. 1 H NMR (400 MHz, CDC13) δ 8.46 (s, 1H), 7.29 (d, J = 4.3 Hz, 1H), 7.25 (d, J = 2.2 Hz, 2H), 7.14 (d, J = 5.8 Hz, 1H), 7.07 (ddd, J = 9.9, 7.7, 1.8 Hz, 1H), 4.10 (s, 3H).

[0152] 2,4-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV- 18): white solid, m.p. 180.2-180.5 °C. 1 H NMR (500 MHz, CDC13) δ 8.84 (s, 1H), 8.15 (td, J = 8.5, 6.4 Hz, 1H), 7.90 - 7.65 (m, 1H), 7.54 (s, 1H), 7.07 - 6.94 (m, 1H), 6.90 (ddd, J = 10.8, 8.7, 2.5 Hz, 1H), 3.81 (s, 3H).

[0153] 3,4-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV- 19): white solid, m.p. 147.9-150.4 °C. 1 H NMR (500 MHz, CDC13) δ 8.89 (s, 1H), 8.08 (td, J = 8.4, 6.4 Hz, 1H), 7.22 (d, J = 1.0 Hz, 1H), 7.14 (s, 1H), 6.97 (td, J = 8.5, 2.4 Hz, 1H), 6.89 (ddd, J = 10.8, 8.6, 2.4 Hz, 1H), 4.09 (s, 3H).

[0154] 3,5-Difluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV- 20): white solid, m.p. 114.3-114.6 °C. 1 H NMR (500 MHz, CDC13) δ 8.55 (s, 1H), 7.79 (s, 1H), 7.54 (s, 1H), 7.35 (d, J = 5.5 Hz, 2H), 6.95 (td, J = 7.5, 6.4, 4.3 Hz, 1H), 3.81 (s, 3H).

[0155] 3,4,5-Trifluorobenzaldehyde-O-(1 -methyl- 1 H-imidazole-2-carbonyl) oxime (IV- 21): white solid, m.p. 160.1-160.7 °C. 1H NMR (500 MHz, CDC13) δ 8.49 (s, 1H), 7.78 (s, 1H), 7.54 (d, J = 1.4 Hz, 1H), 7.47 (t, J = 6.9 Hz, 2H), 3.81 (s, 3H).

[0156] 3,5-Bis(trifluoromethyl)benzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-22): white solid, m.p. 159.2-160.7 °C. 1 H NMR (500 MHz, CDC13) δ 8.63 (s, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.23 (s, 1H), 7.14 (s, 1H), 7.05 (d, J = 8.8 Hz, 1H), 4.11 (s, 3H).

[0157] 4-(Diethylamino)benzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-23): white solid, m.p. 180.1-181.1 °C. 1 H NMR (500 MHz, CDC13) δ 8.53 (s, 1H), 7.60 (d, J = 8.9 Hz, 2H), 7.19 (d, J = 0.9 Hz, 1H), 7.10 (s, 1H), 6.65 (d, J = 9.0 Hz, 2H), 4.08 (s, 3H), 3.40 (p, J = 6.8 Hz, 4H), 1.19 (t, J = 7.1 Hz, 6H).

[0158] 4-(Benzyl oxy)benzaldehyde-O-(l-methyl-lH-imidazole-2-carbonyl) oxime (IV-24): white solid, m.p. 109.4-110.1 °C. 1 H NMR (500 MHz, CDC13) δ 8.62 (s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.46 - 7.40 (m, 4H), 7.38 - 7.34 (m, 1H), 7.22 (s, 1H), 7.13 (s, 1H), 7.04 (d, J = 8.8 Hz, 2H), 5.13 (s, 2H), 4.09 (s, 3H).

[0159] 4-(tert-Butyl)benzaldehyde-O-(l-methyl-lH-imidazole-4-carbonyl) oxime (IV-25): white solid, m.p. 188.3-189.0 °C. 1H NMR (400 MHz, CDC13) δ 8.56 (s, 1H), 7.73 (d, J = 1.4 Hz, 2H), 7.70 (s, 1H), 7.51 (d, J = 1.3 Hz, 1H), 7.45 (d, J = 8.3 Hz, 2H), 3.77 (s, 3H), 1.33 (s, 9H).

[0160] Example 4: In vitro fungistatic activity of compounds of formula I against five plant pathogens

[0161] The fungicidal activity of compounds of formula I was determined by mycelial growth rate method. The test strains were Botrytis cinerea, Sclerotinia sclerotiorum, Valsa mali, Rhizoctonia solani and Fusarium graminearum.

[0162] The compounds of formula I were weighed and dissolved in dimethyl sulfoxide to prepare a stock solution with a concentration of 10,000 mg / L. The stock solution was diluted to 50 mg / L with sterilized and cooled PDA medium. The medium was poured into Petri dishes (9 cm in diameter) and 15 mL was added to each dish. Each compound was tested in quadruplicate. The PDA medium was allowed to cool and solidify. The PDA plates were inoculated with the test strains and incubated at 25°C in the dark. The colony diameters were measured after 72 hours of incubation.

[0163] The mycelial growth inhibition rate was calculated using the following formula:

[0164]

[0165] The in vitro fungicidal activity data of some compounds are shown in Table 2.

[0166] Table 2 In vitro fungicidal activity of some compounds of formula I (inhibition rate % / 50 mg / L)

[0167]

[0168]

[0169]

[0170] As can be seen from Table 2, the compounds of formula I provided by the present application have certain inhibitory activities against the five plant pathogenic fungi tested. Among them,

[0171] The inhibitory rates of compounds II-11, II-20, IV-09, IV-16, IV-21 and IV-22 against Rhizoctonia solani are greater than 80%, and the inhibitory rates of compounds II-10, III-10, III-24, IV-17 and IV-25 are greater than 90%;

[0172] The inhibitory rates of compounds II-24 and IV-16 against Valsa mali are 84.1% and 80.5% respectively, and the inhibitory rates of compounds III-24, IV-13, IV-22 and IV-24 are all 100%;

[0173] The inhibitory rates of compounds II-03, II-04, II-05, II-11, II-18, II-20, II-21, II-23, II-24, III-02, III-05, III-10, III-12, III-17, III-18, III-22, IV-05, IV-18, IV-19 and IV-23 against Sclerotinia sclerotiorum are greater than 80%, and the inhibitory rates of compounds II-01, II-10, II-12, II-15, III-06, III-09, III-16, IV-06, IV-07, IV-10, IV-15, IV-16 and IV-17 are greater than 90%;

[0174] The inhibitory rates of compounds III-15, IV-13, IV-15, IV-16, IV-24 and IV-25 against Botrytis cinerea are greater than 80%, and the inhibitory rates of compounds II-10, II-17, III-02, III-03, III-04, III-10, III-13, III-16, III-22, IV-01, IV-02, IV-04, IV-05, IV-06, IV-07, IV-08, IV-09, IV-10, IV-11, IV-12 and IV-17 are greater than 90%;

[0175] The inhibitory rates of compounds II-24 and IV-16 against Gibberella zeae are 88.9% and 80.9% respectively, and the inhibitory rates of compounds IV-22 and IV-24 are both 100%.

[0176] Example 5: In vivo fungicidal activity of some compounds of formula I

[0177] Phytoxicity test on apple tree. The test was carried out by using the method of scalding and inoculating. The 1-year-old branches were cut into segments, then immersed in 1% sodium hypochlorite solution for 5 min for sterilization, and then dried and smeared with paraffin on both ends to prevent water loss and bacterial infection. (1) Protective effect: punch a hole with a 5 mm diameter puncher on the surface of the apple branch, spray the required concentration of the liquid, and inoculate the pathogen 24 h after spraying; (2) Therapeutic effect: punch a hole with a 5 mm diameter puncher on the surface of the apple branch and inoculate the pathogen, and then spray the required concentration of the liquid 24 h after inoculation. Water was used as a blank control. After 5-7 days of culture, the control effect was investigated.

[0178] In vivo control effect on apple tree:

[0179] At a dose of 200 mg / L, the protective effect of compounds IV-13 and IV-15 on apple tree was 91% and 94%, respectively, and the therapeutic effect of compounds IV-13 and IV-15 on apple tree was 90% and 87%, respectively.

[0180] Phytoxicity test on tomato gray mold. The test was carried out by using the method of potting: select healthy tomato plants with consistent growth. (1) Protective effect: spray the required concentration of the liquid, dry naturally, and inoculate the pathogen on the leaves 24 h later; (2) Therapeutic effect: inoculate the pathogen on the leaves 24 h before spraying the required concentration of the liquid. Water was used as a blank control. After 7 days of culture in a humidifying box, the control effect was investigated.

[0181] In vivo (plant) control effect on tomato gray mold:

[0182] At a dose of 200 mg / L, the protective effect of compounds III-10, IV-08, IV-10 and IV-25 on tomato gray mold was 87%, 84%, 94% and 91%, respectively, and the therapeutic effect of compounds III-10, IV-08, IV-10 and IV-25 on tomato gray mold was 66%, 74%, 92% and 82%, respectively.

[0183] The effect of the compounds on the control of tomato gray mold on tomato fruits was determined by using the method of needle puncture. Select several tomato fruits of the same size, wash with sterile water and dry for standby use. (1) Protective effect: spray the required concentration of the liquid, and inoculate the pathogen on the tomato wound 24 h later; (2) Therapeutic effect: inoculate the pathogen on the tomato wound 24 h before spraying the required concentration of the liquid. Water was used as a blank control. After 7 days of culture in a humidifying box, the control effect was investigated.

[0184] In vivo control effect on tomato gray mold (fruit):

[0185] At a dose of 200 mg / L, the protective effects of compounds II-10, IV-08, IV-10 and IV-25 on tomato gray mold were 86%, 96%, 99% and 91%, respectively, and the treatment effects of compounds II-10, IV-08, IV-10 and IV-25 on tomato gray mold were 81%, 88%, 99% and 83%, respectively.

[0186] Pharmacodynamic determination on rice sheath blight. The pot method was used to determine: healthy rice plants growing to two true leaves were selected for the test. (1) Protective effect: first spray the required concentration of liquid, and inoculate rice sheath blight fungus 24 hours later. (2) Treatment effect: inoculate rice sheath blight fungus 24 hours before spraying the required concentration of liquid. Water was used as a blank control. After inoculation, the plants were moved to a humidity box for 7 days of culture, and then the control effect was investigated.

[0187] At a dose of 200 mg / L, the protective and treatment effects of compound II-10 and the like on rice sheath blight were 78% and 77%, respectively.

[0188] The results of the bioactivity determination show that the compounds of formula I have good inhibitory effect on tomato gray mold fungus, apple rot fungus, rapeseed sclerotinia fungus, rice sheath blight fungus and / or wheat scab fungus, and can be used as fungicides for the prevention and treatment of the above plant pathogens.

[0189] The above describes the preferred embodiments of the present disclosure, but the present disclosure is not limited to the specific details in the above embodiments. Within the technical concept range of the present disclosure, various simple modifications can be made to the technical solutions of the present disclosure, and these simple modifications all belong to the protection range of the present disclosure.

[0190] In addition, it should be noted that each specific technical feature described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present disclosure will not further describe various possible combination manners.

[0191] In addition, various different embodiments of the present disclosure can also be combined in any manner, as long as they do not deviate from the idea of the present disclosure, and they should also be considered as disclosed by the present disclosure.

Claims

1. An imidazole carboxylic acid oxime ester compound, characterized by, A compound of Formula I ； wherein: R is selected from at least one of hydrogen, halogen, nitro, C1-C4 alkyl, C1-C4 alkoxy, halo C1-C4 alkyl, halo C1-C4 alkoxy, phenoxy, benzyloxy and diethylamino; R is mono-, di- or tri-substituted; or a salt of the compound of Formula I.

2. The imidazole formic acid oxime ester compound according to claim 1, a compound represented by formula I, characterized by the different positions of imidazole substitution, ###0001### formula I A compound of Formula II, Formula III or Formula IV ； wherein: R is selected from at least one of hydrogen, fluorine, chlorine, bromine, nitro, methyl, isopropyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenoxy, benzyloxy and diethylamino; R is mono-, di- or tri-substituted; or a salt of the compound of Formula II, Formula III and Formula IV.

3. The imidazole formic acid oxime ester compound according to claim 1, characterized by, A compound of Formula II, Formula III or Formula IV ； Specific substituents of the compound of Formula II, Formula III and Formula IV are shown in the following table: ； or a salt of the compound of Formula II, Formula III or Formula IV.

4. A process for producing the imidazole formic acid oxime ester compound according to any one of claims 1 to 3, characterized by, comprising the following steps: reacting a compound of Formula VI or a compound of Formula VII with a compound of Formula V in an organic solvent to obtain a compound of Formula I; 。 5. The method of claim 4, wherein the imidazole formic acid oxime ester compound is prepared by the reaction of the imidazole formic acid with the oxime ester compound in the presence of the base. adding an additive to the organic solvent, the additive being selected from one or more of triethylamine, pyridine, dicyclohexyl carbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 4-dimethylaminopyridine and bis(4-nitrophenyl) carbonate; the organic solvent is selected from one of dichloromethane, toluene, ethyl acetate and tetrahydrofuran.

6. The method of claim 4, wherein the imidazole formic acid oxime ester compound is prepared by the reaction of the imidazole formic acid with the oxime ester compound in the presence of the base. the reaction temperature is -25-60°C, and the reaction time is 5 min-24 h; the molar ratio of the compound of Formula V to the compound of Formula VI is 1: (1-1.2); the molar ratio of the compound of Formula V to the compound of Formula VII is 1: (1-1.2).

7. Use of the imidazole oxime ester compound of any one of claims 1-3 in the preparation of a plant fungicide.

8. Use of the imidazole oxime ester compound prepared by the method of any one of claims 4-6 in the preparation of a plant fungicide.

9. Use according to claim 7 or 8, characterized in that, The plant fungicide is used for preventing and treating botrytis blight, sclerotinia blight, rot blight, sheath blight and / or bunt.

10. A plant fungicide, characterized by, The plant fungicide uses the imidazole oxime ester compound of any one of claims 1-3 as an active ingredient; The weight percentage of the active ingredient in the plant fungicide composition is 0.1%-99%.

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