A preparation method and application of azoxystrobin intermediate

Abstract

The invention provides a method for preparing an azoxystrobin intermediate and an application thereof. The preparation method comprises the following steps: mixing 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionic acid methyl ester and a solid catalyst for reaction to obtain (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate methyl ester, that is, obtaining the azoxystrobin intermediate. The preparation method provided by the invention is simple to operate, has rapid reaction, high reaction yield, does not need to use anhydride, and the solid catalyst can be reused, with low cost.

Description

Technical Field

[0001] The invention belongs to the field of fungicides, and specifically relates to a method for preparing an azoxystrobin intermediate and an application thereof, and in particular to a method for preparing an azoxystrobin intermediate with low cost and an application thereof. Background Art

[0002] Azoxystrobin is a methoxyacrylate fungicide pesticide that is widely praised in the market for its broad fungicidal spectrum, ability to increase crop disease resistance, improve stress resistance, long-lasting effect, and high efficiency and safety.

[0003] Methyl (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is an important intermediate for the synthesis of azoxystrobin, and its structure is shown in (I). Although there are many methods for preparing methyl (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate, the most widely used method is to prepare it by demethanolation of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate, and its structure is shown in (II).

[0004]

[0005] CN102070538A discloses a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxy methyl acrylate. The method mixes 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionic acid methyl ester with anhydride, and uses dimethyl sulfate to catalyze the reaction at 90-130°C to prepare (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxy methyl acrylate, and then performs negative pressure distillation and desolventizing treatment on the reaction solution, and then obtains the product after adding a solvent, crystallizing and filtering. When preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxy methyl acrylate, the yield of the method is 88.93%, and the yield still needs to be improved; the post-treatment of the reaction solution produces additional waste liquid, which increases environmental pressure.

[0006] CN104230819B discloses a method for synthesizing azoxystrobin, including coupling reaction of 4,6-dichloropyrimidine and 2-hydroxybenzonitrile in a suitable solvent to obtain 4-chloro-6-(2-cyanophenoxy)pyrimidine reaction solution under alkaline conditions and in the presence of a catalyst; directly adding 2-(2-hydroxyphenyl)-3,3-dimethoxypropionic acid methyl ester and alkali to the reaction solution obtained in the previous step, filtering the reaction solution to remove inorganic salts, washing the inorganic salts with a solvent, combining the filtrate and the washings, and directly using them in the next step without any treatment; adding an acidic catalyst and acetic anhydride to the reaction solution in the previous step, removing a molecule of methanol, and post-processing to obtain azoxystrobin. Each step of the synthesis method of the invention is carried out under mild conditions, does not require high temperature and high vacuum, is simple to operate, has a high yield, and has good product quality. However, the reaction still needs to use other raw materials, resulting in increased costs.

[0007] Since azoxystrobin is a widely used pesticide, the current preparation methods have problems such as insufficient yield, high cost, and environmental pollution. Therefore, how to provide a method for synthesizing azoxystrobin intermediates with low cost and high yield has become an urgent problem to be solved. Summary of the invention

[0008] In view of the deficiencies of the prior art, the object of the present invention is to provide a method for preparing an azoxystrobin intermediate and its application, and in particular to provide a method for preparing an azoxystrobin intermediate with low cost and its application. The preparation method provided by the present invention is simple to operate, has rapid reaction, high reaction yield, does not require the use of anhydride, and the solid catalyst can be reused, and has low cost.

[0009] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0010] In one aspect, the present invention provides a method for preparing azoxystrobin intermediate, the preparation method comprising the following steps:

[0011] Methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate and a solid catalyst are mixed for reaction to obtain methyl (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate, that is, the azoxystrobin intermediate.

[0012] The preparation method directly uses 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionic acid methyl ester and a solid catalyst for reaction, and has simple operation and rapid reaction; the solid catalyst can be reused, which reduces the cost, and the subsequent treatment only requires filtering to remove the solid catalyst, and no additional solid waste and waste liquid will be generated; at the same time, the use of acid anhydrides with relatively high costs is avoided, further reducing the production cost.

[0013] The solid catalyst includes SO4 2- / Mx O y Type solid superacid and / or metal oxide composite solid superacid, preferably SO4 2- / M x O y Type solid superacid.

[0014] The specific solid catalyst can effectively catalyze the reaction without containing acid anhydride, thereby improving the reaction yield.

[0015] Preferably, the SO4 2- / M x O y Type solid superacids include SO4 2- / ZrO2-Fe2O3, SO4 2- / TiO2-La2O3 or SO4 2- / Any one or a combination of at least two of TiO2-SnO2, such as SO4 2- / ZrO2-Fe2O3 and SO4 2- / Combination of TiO2-La2O3, SO4 2- / TiO2-La2O3 and SO4 2- / Combination of TiO2-SnO2 or SO4 2- / ZrO2-Fe2O3 and SO4 2- / TiO2-SnO2 combinations, etc., but not limited to the combinations listed above, other combinations not listed within the above combination range are also applicable.

[0016] Preferably, the metal oxide composite solid superacid comprises WO3 / ZrO2 and / or MoO3 / ZrO2.

[0017] Preferably, the reaction is carried out in a solvent, and the solvent includes an aromatic solvent.

[0018] Preferably, the aromatic solvent includes any one of toluene, o-xylene, p-xylene, mesitylene, 1,2,4-trimethylbenzene, chlorobenzene or nitrobenzene, or a combination of at least two thereof, such as a combination of toluene and o-xylene, a combination of p-xylene and mesitylene, or a combination of toluene and chlorobenzene, but is not limited to the combinations listed above. Other combinations not listed within the above combination range are also applicable.

[0019] Preferably, the mass ratio of the methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate to the solid catalyst is 1:(0.1-0.2).

[0020] Preferably, the reaction temperature is 80-100°C.

[0021] Preferably, the reaction temperature is 90-100°C.

[0022] Preferably, the reaction time is 1-2 hours.

[0023] Wherein, the mass ratio of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate to the solid catalyst can be 1:0.1, 1:0.11, 1:0.12, 1:0.13, 1:0.14, 1:0.15, 1:0.16, 1:0.17, 1:0.18, 1:0.19 or 1:0.2, etc., the reaction temperature can be 80°C, 82°C, 84°C, 86°C, 88°C, 90°C, 92°C, 94°C, 96°C, 98°C or 100°C, etc., and the reaction time can be 1h, 1.1h, 1.2h, 1.3h, 1.4h, 1.5h, 1.6h, 1.7h, 1.8h, 1.9h or 2h, etc., but are not limited to the values ​​listed above, and other values ​​not listed within the above numerical range are equally applicable.

[0024] The selection of the above specific reaction parameters can further improve the reaction yield.

[0025] Preferably, the reaction further comprises the following steps: filtering the reaction solution, washing the solid catalyst with a solvent, and then desolventizing.

[0026] The above steps can remove the solid catalyst only by simple filtration, without generating additional solid waste and waste liquid; and the solid catalyst can be washed with a solvent to recover the remaining reaction liquid and to simply and conveniently clean the solid catalyst, and the obtained solid catalyst can be directly used for the next reaction, thereby reducing the complexity and production cost of the production process; and the obtained product can be redissolved in toluene and directly subjected to subsequent reactions, thereby simplifying the overall process flow.

[0027] On the other hand, the present invention also provides the use of the preparation method as described above in the preparation of azoxystrobin.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The invention provides a method for preparing an azoxystrobin intermediate. The azoxystrobin intermediate is obtained by directly reacting methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate with a solid catalyst. The method has simple operation and rapid reaction, avoids acid anhydride with high use cost, and reduces production cost. By selecting a specific solid catalyst, the method can effectively catalyze the reaction without acid anhydride, thereby improving the reaction yield. By selecting specific reaction parameters, the reaction yield can be further improved. In addition, the method can remove the solid catalyst only by simple filtration, without causing additional solid waste and waste liquid. The solid catalyst can be washed with a solvent, so that the remaining reaction liquid can be recovered and the solid catalyst can be simply and conveniently cleaned. The obtained solid catalyst can be directly used for the next reaction, thereby reducing the complexity and production cost of the production process. Moreover, the obtained product can be redissolved in toluene, and the subsequent reaction can be directly carried out, thereby simplifying the overall process flow. DETAILED DESCRIPTION

[0030] In order to further explain the technical means and effects adopted by the present invention, the technical solution of the present invention is further described below in conjunction with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.

[0031] In the following example, the product solution was tested by liquid chromatography: 0.1 g of the product solution was diluted into 100 mL of a mixture of acetonitrile and water in a volume ratio of 1:1, and then a sample was taken for testing (Shimadzu liquid chromatograph LC-20AT, 250 mm C18 column, column temperature 35°C, detection wavelength 254nm, mobile phase acetonitrile-water system, acetonitrile to water volume ratio of 48:52, flow rate 1.0mL / min); since the (Z)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate methyl ester obtained by the reaction and the target product (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate methyl ester have different elution positions, the external standard method is used to determine the peak of the product (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate methyl ester in the liquid chromatography results of the product solution, and calculate its concentration and mass fraction in the product solution, and further calculate the yield and yield. Since the reaction raw materials are of high purity and relatively clean, and no other soluble substances are added during the reaction process in Examples 1-10, the purity of the product is relatively good after desolventizing, and the effect on chromatographic detection is small; in addition, since the injection concentration is low during detection, even if impurities exist, the effect on chromatographic detection is also small. Therefore, the present invention uses a method of direct detection without purification to detect the results in the following examples, and it will not affect the test results.

[0032] Example 1

[0033] In this embodiment, (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate was prepared by the following method, which specifically includes the following steps:

[0034] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of toluene, stir and heat until the system temperature reaches 100°C, add 4.76 g of SO4 2- / TiO2-La2O3 (loading rate: 10%), after reacting for 1 hour, stop the reaction, cool to 50℃ and filter the reaction solution, wash SO4 with toluene 2- / TiO2-La2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 92.02 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 43.83%, and the calculated reaction yield was 93.15%.

[0035] The characterization data are as follows:

[0036] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.8 (1H, s), 7.5-7.0 (4H, m), 6.9 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0037] Example 2

[0038] In this embodiment, (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate was prepared by the following method, which specifically includes the following steps:

[0039] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of chlorobenzene, stir and heat until the system temperature reaches 90°C, add 7.14 g of SO4 2- / TiO2-SnO2 (loading rate: 10%), after reacting for 2h, stop the reaction, filter the reaction solution when the temperature drops to 50℃, and wash SO4 with chlorobenzene 2- / TiO2-SnO2 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 105.11 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 38.27%, and the calculated reaction yield was 92.90%.

[0040] The characterization data are as follows:

[0041] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.7 (1H, s), 7.4-7.0 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0042] Example 3

[0043] In this embodiment, (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate was prepared by the following method, which specifically includes the following steps:

[0044] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of p-xylene, stir and heat until the system temperature reaches 80°C, add 9.53 g of SO4 2- / ZrO2-Fe2O3 (loading rate: 10%), after reacting for 1.5h, stop the reaction, cool to 50℃ and filter the reaction solution, wash SO4 with p-xylene 2- / ZrO2-Fe2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 112.50 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 35.67%, and the calculated reaction yield was 92.68%.

[0045] The characterization data are as follows:

[0046] 1 H NMR (DMSO, 400MHz): δ 8.7 (1H, s), 7.9 (1H, s), 7.6-7.2 (4H, m), 6.9 (1H, s), 3.9 (3H, s), 3.8 (3H, s).

[0047] Example 4

[0048] In this embodiment, (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate was prepared by the following method, which specifically includes the following steps:

[0049] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of toluene, stir and heat until the system temperature reaches 95°C, add 7.14 g of SO4 recovered in the same manner as in Example 1 2- / TiO2-La2O3 (loading rate: 10%), after reacting for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50℃, and wash SO4 with toluene 2- / TiO2-La2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 99.31 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 41.06%, and the calculated reaction yield was 94.18%.

[0050] The characterization data are as follows:

[0051] 1 H NMR (DMSO, 400MHz): δ 8.7 (1H, s), 7.8-7.6 (2H, m), 7.5-7.1 (3H, m), 6.9 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0052] Example 5

[0053] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0054] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of toluene, stir and heat until the system temperature reaches 100°C, add 7.14 g of SO4 recovered in the same manner as in Example 1 2- / TiO2-La2O3 (loading rate: 10%), after reacting for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50℃, and wash SO4 with toluene 2- / TiO2-La2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 101.38 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 40.13%, and the calculated reaction yield was 93.96%.

[0055] The characterization data are as follows:

[0056] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.8 (1H, s), 7.5-7.1 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0057] Example 6

[0058] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0059] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of toluene, stir and heat until the system temperature reaches 90°C, add 7.14 g of SO4 recovered in the same manner as in Example 1 2- / TiO2-La2O3 (loading rate: 10%), after reacting for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50℃, and wash SO4 with toluene 2- / TiO2-La2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 103.25 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 39.36%, and the calculated reaction yield was 93.86%.

[0060] The characterization data are as follows:

[0061] 1 H NMR (DMSO, 400MHz): δ 8.5 (1H, s), 7.9 (1H, s), 7.5-7.1 (4H, m), 6.9 (1H, s), 3.7 (3H, s), 3.6 (3H, s).

[0062] Example 7

[0063] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0064] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), mix with 40.0 mL of toluene, stir and heat until the system temperature reaches 80°C, add 7.14 g of SO4 recovered in the same manner as in Example 1 2- / TiO2-La2O3 (loading rate: 10%), after reacting for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50℃, and wash SO4 with toluene 2- / TiO2-La2O3 and recovered, the obtained washing liquid was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 100.90 g of solution, which was analyzed by liquid chromatography. The mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 39.34%, and the calculated reaction yield was 91.68%.

[0065] The characterization data are as follows:

[0066] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.9 (1H, s), 7.5-7.0 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0067] Example 8

[0068] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0069] Weigh 50.00g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135mol), mix with 40.0mL of toluene, stir and heat until the system temperature reaches 95°C, add 7.14g WO3 / ZrO2 (loading rate: 10%), react for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50°C, wash WO3 / ZrO2 with toluene and recover it, mix the washing liquid with the reaction solution, distill under reduced pressure, and then dissolve it with toluene to obtain 105.83g of solution, perform liquid chromatography analysis, measure and calculate the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution to be 37.59%, and calculate the reaction yield to be 91.88%.

[0070] The characterization data are as follows:

[0071] 1 H NMR (DMSO, 400MHz): δ 8.5 (1H, s), 7.7 (1H, s), 7.4-6.9 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0072] Example 9

[0073] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0074] Weigh 50.00g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135mol), mix with 40.0mL of toluene, stir and heat until the system temperature reaches 95°C, add 7.14g MoO3 / ZrO2 (loading rate: 10%), react for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50°C, wash MoO3 / ZrO2 with toluene and recover it, mix the washing liquid with the reaction solution, distill under reduced pressure, and then redissolve with toluene to obtain 102.57g of solution, perform liquid chromatography analysis, measure and calculate the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution to be 38.71%, and calculate the reaction yield to be 91.70%.

[0075] The characterization data are as follows:

[0076] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.8 (1H, s), 7.5-6.9 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0077] Example 10

[0078] In this embodiment, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0079] Weigh 50.00g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135mol), mix with 40.0mL of toluene, stir and heat until the system temperature reaches 95°C, add 7.14g of Zr(SO4)2 / γ-Al2O3 (loading rate: 10%), react for 1.5h, stop the reaction, filter the reaction solution when the temperature drops to 50°C, wash Zr(SO4)2 / γ-Al2O3 with toluene and recover it, mix the washing liquid with the reaction solution, distill under reduced pressure, and then dissolve it with toluene to obtain 101.43g of solution, perform liquid chromatography analysis, measure and calculate the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution to be 32.14%, and calculate the reaction yield to be 75.29%.

[0080] The characterization data are as follows:

[0081] 1 H NMR (DMSO, 400MHz): δ 8.5 (1H, s), 7.7 (1H, s), 7.5-7.1 (4H, m), 7.0 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0082] Comparative Example 1

[0083] In this comparative example, (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate was prepared by the following method, which specifically includes the following steps:

[0084] Weigh 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol), 27.84 g of acetic anhydride (content 99%, 0.270 mol), stir and heat until the system temperature reaches 95°C, add 0.26 g of p-toluenesulfonic acid (content 99%, 0.0015 mol), react for 1.5 hours, stop the reaction, cool to 50°C, transfer the reaction solution and wash the container, mix the washing solution with the reaction solution, distill under reduced pressure, and then redissolve with toluene to obtain 86.71 g of solution, perform liquid chromatography analysis, measure and calculate the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution to be 42.41%, and calculate the reaction yield to be 84.93%.

[0085] The characterization data are as follows:

[0086] 1H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.8 (1H, s), 7.4-7.0 (4H, m), 6.9 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0087] Comparative Example 2

[0088] In this comparative example, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0089] 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol) was weighed and mixed with 40.0 mL of toluene. The mixture was stirred and heated to 95° C., 0.26 g of p-toluenesulfonic acid (content 99%, 0.0015 mol) was added, and the reaction was stopped after 1.5 h. When the temperature was lowered to 50° C., the reaction solution was transferred and the container was washed. The washing solution was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 91.14 g of the solution. The solution was analyzed by liquid chromatography, and the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 27.07%, and the reaction yield was calculated to be 56.98%.

[0090] The characterization data are as follows:

[0091] 1 H NMR (DMSO, 400MHz): δ 8.6 (1H, s), 7.8 (1H, s), 7.6-7.0 (4H, m), 6.8 (1H, s), 3.8 (3H, s), 3.7 (3H, s).

[0092] Comparative Example 3

[0093] In this comparative example, a method for preparing (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is provided, which specifically comprises the following steps:

[0094] 50.00 g of methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate (content 95.25%, 0.135 mol) was weighed and mixed with 40.0 mL of toluene. The mixture was stirred and heated to 95° C., 0.15 g of methanesulfonic acid (content 99%, 0.0015 mol) was added, and the reaction was stopped after 1.5 h. When the temperature was lowered to 50° C., the reaction solution was transferred and the container was washed. The washing solution was mixed with the reaction solution, distilled under reduced pressure, and then redissolved with toluene to obtain 93.21 g of the solution. The solution was analyzed by liquid chromatography, and the mass fraction of (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate in the solution was measured and calculated to be 23.63%, and the reaction yield was calculated to be 50.87%.

[0095] The characterization data are as follows:

[0096] 1 H NMR (DMSO, 400MHz): δ 8.5 (1H, s), 7.7 (1H, s), 7.4-6.9 (4H, m), 6.8 (1H, s), 3.7 (3H, s), 3.6 (3H, s).

[0097] The above results show that the preparation method provided by the present invention can effectively synthesize the azoxystrobin intermediate, i.e., (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate, by using a specific solid catalyst as a catalyst without using anhydride, saving a lot of costs; it can be found from Example 4 that the present invention can recover the solid catalyst after the reaction and continue to use it in the next reaction without any impact on the reaction, and can be repeatedly recycled, greatly reducing the cost; by comparing Examples 4-7, it can be found that the present invention improves the reaction yield by controlling the reaction temperature, and the reaction yield is further improved within the preferred temperature range; by comparing Examples 4, 8-10, it can be found that the present invention selects a specific solid catalyst as a catalyst, compared with other solid The catalyst significantly improves the yield of the reaction, and the yield is further improved within the preferred range; by comparing Example 4 and Comparative Example 1, it can be found that the method provided by the present invention has a higher product yield than the method in the prior art. Since the obtained myclobutanil intermediate needs to undergo the next step of reaction, it needs to undergo a desolventizing and re-dissolving process. During the desolventizing and re-dissolving process, the organic acid-acid anhydride system used in the prior art will cause the intermediate product to deteriorate, thereby reducing the yield. The preparation method of the present invention does not require the use of anhydride, thereby reducing costs and avoiding the occurrence of the above situation. The product has a high yield and is not easy to deteriorate, thereby providing help for subsequent reactions; by comparing Example 4 and Comparative Examples 2-3, it can be found that the present invention, by using a specific solid catalyst, can still achieve a high yield in the reaction without the presence of anhydride, compared with conventional catalysts.

[0098] The applicant declares that the present invention illustrates the preparation method and application of the azoxystrobin intermediate of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0099] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0100] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A method for preparing an azoxystrobin intermediate, characterized in that: The preparation method comprises the following steps: Mixing 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionic acid methyl ester and a solid catalyst for reaction to obtain (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate methyl ester, that is, obtaining the azoxystrobin intermediate; The solid catalyst is SO4 2- / M x O y Type solid superacid and / or metal oxide composite solid superacid; The SO4 2- / M x O y Type solid superacid is SO4 2- / ZrO2-Fe2O3, SO4 2- / TiO2-La2O3 or SO4 2- / Any one or a combination of at least two of TiO2-SnO2; The metal oxide composite solid superacid is WO3 / ZrO2 and / or MoO3 / ZrO2.

2. The preparation method according to claim 1, characterized in that: The solid catalyst is SO4 2- / M x O y Type solid superacid.

3. The preparation method according to claim 1, characterized in that: The reaction is carried out in a solvent, and the solvent is an aromatic solvent.

4. The preparation method according to claim 3, characterized in that: The aromatic solvent is any one of toluene, o-xylene, p-xylene, mesitylene, 1,2,4-trimethylbenzene, chlorobenzene or nitrobenzene, or a combination of at least two of them.

5. The preparation method according to claim 1, characterized in that: The mass ratio of the methyl 2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3,3-dimethoxypropionate to the solid catalyst is 1:(0.1-0.2).

6. The preparation method according to claim 1, characterized in that: The reaction temperature is 80-100°C.

7. The preparation method according to claim 6, characterized in that: The reaction temperature is 90-100°C.

8. The preparation method according to claim 1, characterized in that: The reaction time is 1-2h.

9. The preparation method according to claim 1, characterized in that: After the reaction, the method further comprises the following steps: filtering the reaction solution, washing the solid catalyst with a solvent, and then desolventizing.

10. Use of the preparation method according to any one of claims 1 to 9 in the preparation of azoxystrobin.

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