Preparation method and application of carbonic acid oxime ester compound

Abstract

The present invention belongs to the field of pesticide technology, and in particular refers to a preparation method and application of a carbonate oxime ester compound, in order to solve the technical problems of high synthesis cost and greater environmental damage in the oxime ester synthesis process. By dissolving an aromatic ketone oxime compound, an azo compound and a metal salt in a solvent, a carbonate oxime ester compound is obtained after reacting at 90-110°C for 1-3h. The prepared carbonate oxime ester compound is a useful chemical and pharmaceutical intermediate, and also has very important applications in biological activity as an effective bactericide. The present invention realizes the esterification of aromatic ketone oxime compounds under mild and green reaction conditions, and provides a convenient and efficient method for the esterification of aromatic ketone oxime compounds. At the same time, a series of prepared carbonate oxime ester compounds are tested for their inhibitory activity against plant fungi, and novel and efficient compounds with spectral bactericidal effects are screened out, providing active compounds with novel structures for the development of new green pesticides.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and in particular relates to a preparation method and application of a carbonate oxime ester compound. Background Art

[0002] Fungal crop diseases have become one of the most concerning issues in global agriculture. Fungal diseases not only directly reduce crop yield and quality, but some pathogens can also produce a variety of toxins and metabolites harmful to humans and animals during their infection, posing a significant threat to agricultural product safety. According to incomplete statistics, fungal diseases have reduced the annual global yield of five major crops—corn, rice, wheat, potatoes, and soybeans—by 125 million tons. The damage to corn, wheat, and rice alone from these diseases results in $60 billion in annual economic losses to global agriculture. In an extreme scenario, if these five crops were to experience a simultaneous fungal pandemic in a given year, global grain production could decline by as much as 900 million tons, leading to hunger for 4.2 billion people and a global famine.

[0003] Rhizoctonia solani is a soil-borne pathogen that severely harms crops. It is characterized by strong infectivity, a short post-infection period, rapid spread, and destructive power. It has a wide host range, infecting at least 263 plant species, including rice, corn, soybeans, potatoes, and tobacco. Rhizoctonia solani primarily causes seed rot, seedling stunting, damping-off, and rice sheath blight. It primarily attacks the base of seedling stems or underground roots, initially appearing as oval or irregular dark brown lesions. Affected seedlings wilt during the day but recover at night, with the lesions gradually becoming sunken and shrinking, sometimes turning dark brown. As the lesions expand around the stem, they eventually dry up and die. Currently, the most effective control method for Rhizoctonia solani is chemical control. Traditional chemical fungicides such as carbendazim, metalaxyl, and tolclofos-methyl can significantly reduce the infection rate of Rhizoctonia solani in seedlings. However, traditional fungicides often have defects such as large dosage and serious environmental pollution. Therefore, it is of great significance to develop new green pesticides for the prevention and control of crop diseases and pests.

[0004] Oxime ester compounds have a wide range of applications, including insecticides, fungicides, pharmaceuticals, herbicides, and dyes. Many compounds also boast high efficacy, low toxicity, and low residue. Since the 1990s, oxime pesticides have developed rapidly, with the emergence of a large number of oxime ester compounds with herbicidal and germicidal activity. Acetophenone oximes are a class of benzo-heterocyclic compounds containing adjacent oxygen and nitrogen atoms. They possess high biological activity and pharmacological properties and are commonly used as insecticides. Acetophenone oxime derivatives exhibit excellent fungicidal activity and control against common diseases of vegetables, fruits, and melons, such as powdery mildew, anthracnose, and sclerotinia, with particular efficacy against powdery mildew. With their low dosage, high efficacy, and convenient preparation, they can reduce agricultural costs and improve environmental protection. Acetophenone oxime derivatives are expected to become a new and effective class of agricultural fungicides, replacing traditional agricultural fungicides currently on the market, which have developed significant resistance and require several times the original dosage.

[0005] There are currently two main methods for synthesizing oxime esters. The first method requires the reaction of ketone oxime and ethyl chloroformate under the conditions of pyridine and ether (Anilkumar, R., and S. Chandrasekhar et.al. Tetrahedron Letters (2000), 41 (28), 5427-5429). The second method is to obtain the target product by reacting acetophenone oxime and azodicarbonate compounds under the catalysis of metal Cu (Usman M, Ren ZH, Wang YY, et al. Organic & Biomolecular Chemistry, 2017, 15). The above conditions require the use of highly toxic chloroformate compounds on the one hand, and transition metal catalysis on the other hand, which is more harmful to the environment and has a high cost. Therefore, it is urgent to develop a low-toxic, low-cost, and green and environmentally friendly preparation method for oxime ester compounds. Summary of the Invention

[0006] To address the high costs and significant environmental hazards of existing oxime ester synthesis processes, the present invention provides a method for preparing carbonate oxime ester compounds and their applications. This method utilizes commercially available azo compounds as esterification reagents, eliminating the need for metal catalysts and highly toxic reagents. This method achieves the esterification of aromatic ketone oxime compounds under mild, environmentally friendly reaction conditions, providing a convenient and efficient method for the esterification of aromatic ketone oxime compounds.

[0007] To achieve the above object, the technical solution of the present invention is implemented as follows:

[0008] A method for preparing a carbonate oxime ester compound comprises dissolving an aromatic ketone oxime compound, an azo compound, and a metal salt in a solvent, reacting, and post-treating to obtain the carbonate oxime ester compound; the reaction formula is shown below:

[0009]

[0010] Wherein, Ar is a benzene ring substituted by H, CH3, Ph, Br, CF3, NH2, a 2-thiophene ring, and a 5-piperazine ring; R 1 is a CH3, Et group, R 2 For Et, i Pr, t-Bu group.

[0011] The aromatic ketone oxime compound is any one of acetophenone oxime, p-methylacetophenone oxime, p-bromoacetophenone oxime, 3',4'-(methylenedioxy)acetophenone oxime, 2-thiopheneacetonone oxime, o-aminoacetophenone oxime, phenylacetophenone oxime, 1-tetralone oxime, 2-naphthone oxime and p-phenylacetophenone oxime; the azo compound is any one of diisopropyl azodicarboxylate, diethyl azodicarboxylate and di-tert-butyl azodicarboxylate.

[0012] The metal salt is Na2CO3, KHCO3 or NaHCO3.

[0013] The molar ratio of the aromatic ketone oxime compound, the azo compound and the metal salt is 1:(2-5):(1-3).

[0014] The solvent is any one of dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, acetone, 1,2-dichloroethane, ethylene glycol dimethyl ether and toluene.

[0015] The concentration of the aromatic ketoxime compound in the solvent is 0.05-0.2 mol / L.

[0016] The reaction temperature is 90-110° C. and the reaction time is 1-3 hours.

[0017] The post-treatment steps include: after the reaction is completed, saturated ammonium chloride is added for quenching, the reaction solution is then transferred to a separatory funnel, extracted with ethyl acetate, the organic phase is washed twice with saturated ammonium chloride, the organic phase is collected, dried over anhydrous magnesium sulfate, and the solvent is removed under reduced pressure. The obtained residue is purified by 100-200 mesh silica gel column chromatography to obtain the target compound.

[0018] The carbonic acid oxime ester compound is prepared by the above preparation method.

[0019] The carbonic acid oxime ester compound is any one of the following compounds.

[0020]

[0021] The carbonic acid oxime ester compound is used as a fungicide in pesticides.

[0022] The reaction mechanism of the present invention is as follows: first, a metal salt (Na2CO3, KHCO3 or NaHCO3) removes the hydroxyl hydrogen of an aromatic ketone oxime compound to obtain an intermediate A, which then attacks the carbonyl group of an azo compound to obtain an intermediate B, and then electrons are transferred to the nitrogen anion of the intermediate B to finally obtain the target product I.

[0023]

[0024] The beneficial effects produced by the present invention are:

[0025] (1) The present invention proposes a method for preparing carbonate oxime ester compounds. By using commercial azo compounds as esterification reagents without the need for metal catalysts and highly toxic reagents, the esterification of aromatic ketone oxime compounds is achieved under mild and green reaction conditions, providing a convenient and efficient method for the esterification of aromatic ketone oxime compounds.

[0026] (2) The series of carbonate oxime ester compounds prepared by the preparation method proposed in the present invention have a good inhibitory effect on Rhizoctonia solani at a relatively low concentration (100 ppm). Among them, the inhibition rate of compound VII can reach 84%. This provides a new framework for the development of new green pesticides and an efficient approach for the development of new fungicides. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0028] Figure 1 is the NMR spectrum of compound I, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0029] Figure 2 This is the NMR spectrum of compound II, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0030] Figure 3 is the NMR spectrum of compound III, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0031] Figure 4 This is the NMR spectrum of compound IV, (a) NMR 1H spectrum, (b) NMR 13 C spectrum.

[0032] Figure 5 is the NMR spectrum of compound V, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0033] Figure 6 This is the NMR spectrum of compound VI, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0034] Figure 7 This is the NMR spectrum of compound VII, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0035] Figure 8 This is the NMR spectrum of compound VIII, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0036] Figure 9 This is the NMR spectrum of compound IX. (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0037] Figure 10 is the NMR spectrum of compound X, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0038] Figure 11 is the NMR spectrum of compound Ⅺ, (a) NMR 1 H spectrum, (b) NMR 13 C spectrum.

[0039] Figure 12 The NMR of compound Ⅻ 1 H spectrum.

[0040] Figure 13 The figure shows the inhibition of compound I prepared in Example 1 on five kinds of bacteria.

[0041] Figure 14 The inhibition of compounds I-X prepared in Examples 1-10 on Rhizoctonia solani is shown. DETAILED DESCRIPTION

[0042] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0043] Example 1

[0044] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0045] In a 25 mL pressure tube, 0.5 mmol of acetophenone oxime and 2 mmol of diisopropyl azodicarboxylate (DIAD) were added as reactants, 1 mmol of sodium carbonate was added as a base, and finally 10 mL of DMSO was added as a solvent. The reaction was allowed to proceed at 100°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound I (colorless liquid, yield 67%); the eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 1 . NMR data: 1 H NMR (400MHz, CDCl3) δ7.67 (d, J = 6.7Hz, 2H), 7.41-7.29 (m, 3H), 4.98 (dt, J = 12.5, 6.3Hz, 1H), 2.33 (s, 3H), 1.31 (d, J = 6.3Hz, 6H). 13 C NMR (100MHz, CDCl3) δ162.48, 153.91, 134.67, 130.59, 128.59, 127.02, 64.72, 14.36, 14.32.

[0046]

[0047] Example 2

[0048] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0049] In a 25 mL pressure tube, 0.5 mmol of p-methylacetophenone oxime and 1 mmol of DIAD were added as reactants, followed by 1 mmol of sodium carbonate as a base, and finally 20 mL of DMSO as a solvent, and the reaction was carried out at 100°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching, and the reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound II (white solid, yield 50%); the eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 2 . NMR data: 1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.2Hz,2H),7.20(d,J=8.1Hz,2H),5.04(dt,J=12.5,6.3Hz,1H),2.37(s,6H),1.37(d,J=6.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ162.19,153.53,140.85,131.80,129.27,126.92,72.85,21.81,21.40,14.26.

[0050]

[0051] Example 3

[0052] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0053] In a 25 mL pressure tube, 0.5 mmol of p-bromoacetophenone oxime and 2.5 mmol of DIAD were added as reactants, 1 mmol of sodium carbonate was added as a base, and finally 10 mL of DMSO was added as a solvent. The reaction was allowed to proceed at 100°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound III (colorless liquid, yield 51%). The eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 3 . NMR data: 1H NMR (400MHz, CDCl3) δ7.62(d,J=8.6Hz,2H),7.53(d,J=8.6Hz,2H),5.04(dt,J=12.5,6.3Hz,1H),2.37(s,3H),1.38(d,J=6.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ161.16,153.30,133.60,131.79,128.50,125.11,77.24,73.08,21.77,14.10.

[0054]

[0055] Example 4

[0056] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0057] In a 25 mL pressure tube, 0.5 mmol of 3',4'-(methylenedioxy)acetophenone oxime and 2 mmol of DIAD were added as reactants, followed by 1 mmol of sodium carbonate as a base, and finally 10 mL of DMSO as a solvent. The reaction was allowed to proceed at 90°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound IV (white solid, yield 43%). The eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 4 . NMR data: 1 H NMR (400MHz, CDCl3) δ7.31(s,1H),7.22(d,J=8.2Hz,1H),6.82(d,J=8.2Hz,1H),6. 00(s,2H),5.04(dt,J=12.5,6.2Hz,1H),2.47-2.24(m,3H),1.38(d,J=6.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ161.54,153.45,149.73,148.02,128.69,121.75,108.09,107.07,101.55,77.35,77.24,77.04,76.72,72.86,21.79,14.24.

[0058]

[0059] Example 5

[0060] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0061] In a 25 mL pressure tube, 0.5 mmol of 2-thiophene acetonide oxime and 2 mmol of DIAD were added as reactants, 1 mmol of sodium carbonate was added as a base, and finally 20 mL of DMSO was added as a solvent. The reaction was allowed to proceed at 100°C for 3 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound V (yellow liquid, yield 48%). The eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 5 . NMR data: 1 H NMR (400MHz, CDCl3) δ7.42(t,J=4.5Hz,2H),7.09-7.04(m,1H),5.03(dt,J=12.5,6.3Hz,1H),2.41(s,3H),1.37(d,J=6.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ157.64,153.10,137.72,129.24,129.05,127.23,73.08,21.79,14.42.

[0062]

[0063] Example 6

[0064] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0065] In a 25 mL pressure tube, 0.5 mmol of o-aminoacetophenone oxime and 2 mmol of DIAD were added as reactants, followed by 1 mmol of sodium carbonate as a base, and finally 10 mL of DMSO as a solvent. The mixture was reacted at 110°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound VI (yellow solid, yield 62%). The eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 6 . NMR data:1 H NMR (400MHz, CDCl3) δ8.17(d,J=8.3Hz,1H),7.66(d,J=7.9Hz,1H),7.54(t,J=7. 8Hz,1H),7.33(t,J=7.5Hz,1H),5.38(m,1H),2.62(s,3H),1.52(d,J=6.3Hz,6H). 13 CNMR (101MHz, CDCl3) δ150.43,149.10,140.39,129.05,126.04,123.48,120.34,114.70,72.17,21.98,12.34.

[0066]

[0067] Example 7

[0068] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0069] In a 25 mL pressure tube, 0.5 mmol of phenylacetone oxime and 2 mmol of DIAD were added as reactants, followed by 1 mmol of sodium carbonate as a base, and finally 10 mL of DMF as a solvent, and the reaction was carried out at 90°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching, and the reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound VII (colorless liquid, yield 50%); the eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 7 . NMR data: 1 HNMR (400MHz, CDCl3) δ7.72 (d, J = 7.7Hz, 2H), 7.48-7.36 (m, 3H), 5.12-4.98 (m, 1H), 2.95-2.80 (m, 2H), 1.38 (d, J = 6.3Hz, 6H), 1.19 (t, J = 8.5Hz, 3H). 13 C NMR (100MHz, CDCl3) δ167.18,153.63,133.71,130.46,128.63,127.26,72.87,21.82,21.62,11.35.

[0070]

[0071] Example 8

[0072] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0073] In a 25 mL pressure tube, 0.5 mmol of 1-tetralone oxime and 1.5 mmol of DIAD were added as reactants, followed by 1.5 mmol of sodium carbonate as a base, and finally 10 mL of DMSO as a solvent. The reaction was allowed to proceed at 100°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, collected, dried over anhydrous magnesium sulfate, and the solvent removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound VIII (yellow liquid, yield 40%); the eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 8 . NMR data: 1 H NMR (400MHz, CDCl3) δ8.16(dd,J=7.9,0.7Hz,1H),7.34(td,J=7.5,1.3Hz,1H),7.23(ddd,J=7.9,1.2,0.6Hz,1H),7.17(d,J=7.6Hz ,1H),5.05(dt,J=12.5,6.3Hz,1H),2.89(t,J=6.6Hz,2H),2.82-2.75(m,2H),1.89(dt,J=12.6,6.5Hz,2H),1.38(d,J=6.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ160.08,152.50,139.78,129.64,127.75,127.63,125.53,124.61,71.80,28.48,24.44,20.77,20.19.

[0074]

[0075] Example 9

[0076] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0077] In a 25 mL pressure tube, 0.5 mmol of 2-naphthone oxime and 2 mmol of DIAD were added as reactants, followed by 1.5 mmol of sodium carbonate as a base, and finally 10 mL of DMSO as a solvent. The reaction was allowed to proceed at 100°C for 2 h. After the reaction was completed, saturated ammonium chloride was added for quenching. The reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride. The organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound IX (yellow liquid, yield 40%). The eluent used for column chromatography was a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below, and the nuclear magnetic resonance spectrum is shown below. Figure 9 . NMR data: 1 H NMR (400MHz, CDCl3) δ8.16 (s, 1H), 7.97 (dd, J = 8.7, 1.5Hz, 1H), 7.91-7.81 (m, 3H), 7 .58-7.47(m,2H),5.08(dt,J=12.5,6.3Hz,1H),2.51(s,3H),1.40(d,J=6.3Hz,6H). 13 CNMR (100MHz, CDCl3) δ162.29,153.78,134.57,133.13,132.30,129.00,128.59,127.99,127.68,127.58,126.85,124.02,73.28,22.10,14.47.

[0078]

[0079] Example 10

[0080] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0081] In a 25 mL pressure tube, 0.5 mmol of p-phenylacetophenone oxime and 2 mmol of DIAD were added as reactants, 0.5 mmol of sodium carbonate was added as a base, and finally 10 mL of DMSO was added as a solvent, and the reaction was carried out at 100 ° C for 3 hours. After the reaction was completed, saturated ammonium chloride was added for quenching, and then the reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, the organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound X (white solid, yield 39%). The eluent used for column chromatography is a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown in the following formula, and the nuclear magnetic spectrum is shown in Figure 10 . 1HNMR (400MHz, CDCl3) δ7.84 (d, J=8.6Hz, 2H), 7.63 (dd, J=9.2, 7.9Hz, 4H), 7.46 (t, J=7.5Hz, 2H),7.38(t,J=7.3Hz,1H),5.06(dt,J=12.5,6.3Hz,1H),2.43(s,3H),1.39(d,J=6.3Hz,6H). 13 C NMR (101MHz, CDCl3) δ161.87,153.48,143.32,140.15,133.51,128.90,127.87,127.46,127.22,127.14,72.96,21.82,14.26.

[0082]

[0083] Example 11

[0084] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0085] In a 25mL pressure-resistant tube, 0.5mmol of acetophenone oxime and 2mmol of diethyl azodicarboxylate (DEAD) were added as reactants, followed by 1mmol of potassium bicarbonate as a base, and finally 10mL of DMSO as a solvent, and the reaction was carried out at 100°C for 1h. After the reaction was completed, saturated ammonium chloride was added for quenching, and the reaction solution was then transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, the organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound Ⅺ (colorless liquid, yield 51%). The eluent used for column chromatography is a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below. The nuclear magnetic spectrum is shown in Figure 11 . 1 H NMR (400MHz, CDCl3) δ7.74 (d, J = 6.7Hz, 2H), 7.49-7.37 (m, 3H), 4.36 (q, J = 7.1Hz, 2H), 2.40 (s, 3H), 1.39 (t, J = 7.1Hz, 3H). 13 C NMR (101MHz, CDCl3) δ = 162.48, 153.91, 134.67, 130.59, 128.59, 127.02, 64.72, 14.36, 14.32.

[0086]

[0087] Example 12

[0088] The preparation method of a carbonate oxime ester compound of this embodiment comprises the following steps:

[0089] In a 25mL pressure-resistant tube, 0.5mmol of acetophenone oxime and 2mmol of di-tert-butyl azodicarboxylate (DBAD) were added as reactants, and then 1mmol of sodium bicarbonate was added as a base. Finally, 10mL of DMSO was added as a solvent, and the reaction was carried out at 100°C for 2h. After the reaction was completed, saturated ammonium chloride was added for quenching, and then the reaction solution was transferred to a separatory funnel and extracted with ethyl acetate. The organic phase was washed twice with saturated ammonium chloride, the organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by 100-200 mesh silica gel column chromatography to obtain the target compound XII (colorless liquid, yield 43%). The eluent used for column chromatography is a mixture of petroleum ether and ethyl acetate in a certain proportion. The chemical structure of the obtained compound is shown below. The nuclear magnetic spectrum is shown in Figure 12 . 1 H NMR (400MHz, CDCl3) δ7.83-7.71 (m, 2H), 7.43 (td, J = 7.9, 4.0Hz, 3H), 2.41 (s, 3H), 1.60 (s, 9H).

[0090]

[0091] Biological activity detection

[0092] The present invention carries out bactericidal activity determination on 5 common pathogens in agricultural production, namely Fusarium graminearum (from wheat), Sclerotium rolfsii, Rhizoctonia solani (from tobacco), Fusarium moniliforme and Fusarium oxysporum.

[0093] Dissolve 3.3 mg of the synthesized drug in 0.66 mL of DMSO, then add an aqueous solution containing 1% Tween 80 to a 5 mg / mL stock solution. Aseptically pipette an appropriate amount of each test drug into a conical flask, shake thoroughly, and then pour equal amounts into three 9 cm diameter Petri dishes to create 100 μg / mL drug-containing plates. A blank control was used for the experiment, and each treatment was repeated three times. Aseptically, a 5 mm diameter punch was used to cut a bacterial cake from the edge of the colony. This cake was inoculated with an inoculator, mycelium side up, onto the center of the drug-containing plate. The plate was covered and incubated in a 26°C incubator. When the control colony expanded to a diameter exceeding 6 cm, the colony diameter was measured using the cross-hatch method and the average value was calculated. At the end of the incubation period, the inhibition rate was calculated.

[0094] The calculation formula is: Inhibition rate I = (D0-D t ) / D0×100%

[0095] Among them, D0 is the average diameter of the control mycelium, D t is the average diameter of mycelium in the sample disk.

[0096] First, the bactericidal activity of compound I against five pathogens was tested at a concentration of 100 ppm. Figure 13 As shown in the figure, it can be seen that compound I has a good inhibitory effect on Rhizoctonia solani, with an inhibition rate of 70%.

[0097] Secondly, the inhibition of the synthesized compound Ⅰ-X on Rhizoctonia solani was investigated. Figure 14 As shown. Newly prepared carbonate oxime ester compounds I-X were found to have a strong inhibitory effect on the growth of Rhizoctonia solani, with compound VII achieving an inhibition rate of 84%. Through experiments, novel, highly effective compounds with broad-spectrum fungicidal activity were screened, providing a novel framework for the development of new green pesticides. Furthermore, the prepared carbonate oxime ester compounds are also important chemical raw materials and key intermediates in the synthesis of pesticides and pharmaceuticals.

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a carbonate oxime ester compound, characterized in that: Dissolving an aromatic ketone oxime compound, an azo compound and a metal salt in a solvent, reacting and post-treating to obtain a carbonate oxime ester compound; wherein the metal salt is Na2CO3, KHCO3 or NaHCO3; The reaction formula is as follows: ； Wherein, Ar is a benzene ring substituted with H, CH3, Ph, Br, CF3, NH2, a 2-thiophene ring, and a 5-piperazine ring; R 1 is a CH3, Et group, R 2 For Et, i Pr, t -Bu group.

2. The method for preparing a carbonate oxime ester compound according to claim 1, wherein The aromatic ketone oxime compound is any one of acetophenone oxime, p-methylacetophenone oxime, p-bromoacetophenone oxime, 3',4'-(methylenedioxy)acetophenone oxime, 2-thiopheneacetonone oxime, o-aminoacetophenone oxime, phenylacetophenone oxime, 1-tetralone oxime, 2-naphthone oxime and p-phenylacetophenone oxime; the azo compound is any one of diisopropyl azodicarboxylate, diethyl azodicarboxylate and di-tert-butyl azodicarboxylate.

3. The method for preparing a carbonic acid oxime ester compound according to claim 1 or 2, wherein: The molar ratio of the aromatic ketone oxime compound, the azo compound and the metal salt is 1:(2-5):(1-3).

4. The method for preparing a carbonate oxime ester compound according to claim 3, wherein The solvent is dimethyl sulfoxide, N,N - Any one of dimethylformamide, 1,4-dioxane, acetone, 1,2-dichloroethane, ethylene glycol dimethyl ether and toluene.

5. The method for preparing a carbonate oxime ester compound according to claim 4, wherein The concentration of the aromatic ketone oxime compound in the solvent is 0.05-0.2 mol / L; the reaction temperature is 90-110° C., and the reaction time is 1-3 h.

6. The method for preparing a carbonate oxime ester compound according to claim 5, wherein: The post-processing steps include extraction, washing, collecting the organic phase, removing the solvent, and purification after the reaction is completed.

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