Synthesis method of azoxystrobin intermediate

Abstract

The invention relates to a synthesis method of an azoxystrobin intermediate, and belongs to the technical field of organic synthesis.The synthesis method comprises the steps that benzofuranone serves as a raw material and is directly condensed with formate under the action of alkali, then dimethyl sulfate is methylated, and 3-(alpha-methoxyl) methylene benzofuranone is obtained. The use of expensive trimethyl orthoformate is avoided, and the cheap and easily available formate is adopted, so that the raw material cost of the azoxystrobin intermediate is greatly reduced, and the method is simple in process route, high in yield and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing an azoxystrobin intermediate. Background Technology

[0002] Azoxystrobin is a methoxyacrylate fungicide developed by Syngenta. It is highly effective and broad-spectrum, exhibiting good activity against most fungal diseases such as powdery mildew, rust, downy mildew, and rice blast. It can be used for foliar spraying, seed treatment, and soil treatment; it is mainly used on grains, rice, peanuts, grapes, potatoes, fruits and vegetables, and lawns. The chemical structural formulas of azoxystrobin and its intermediates are as follows:

[0003] .

[0004] Currently, numerous patents and publications both domestically and internationally report methods for synthesizing the azoxystrobin intermediate 3-(α-methoxy)methylenebenzofuranone. As described in patents CN1096454, CN102241651, CN107353255, and CN109651263, this intermediate is obtained from benzofuranone as a raw material under the action of a large amount of acid anhydride and trimethyl orthoformate. The synthetic route is as follows:

[0005] .

[0006] The high cost of raw materials for this synthetic route is due to the high price of trimethyl orthoformate and the need for a large excess of it.

[0007] Therefore, the search for a clean, efficient, low-cost method for synthesizing 3-(α-methoxy)methylenebenzofuranone, an intermediate of pyraclostrobin, suitable for industrial-scale production, is a key focus of research in this field. Summary of the Invention

[0008] This invention provides a method for synthesizing azoxystrobin intermediate, which solves the problems mentioned in the background art. The raw materials used in this synthesis method are cheaper, the yield is high, the reaction is safe and reliable, the process is simple and the reaction conditions are mild, and it has high industrial application value.

[0009] The present invention provides the following solution to the above-mentioned technical problems: a method for synthesizing an azoxystrobin intermediate, the method comprising the following steps: Step 1, adding benzofuranone, alkali and solvent to the reaction system, adding formate dropwise under stirring, and after the addition is complete, keeping the reaction at 35-40℃ for 2-4 hours to obtain a condensation reaction solution;

[0010] Step 2: Add dimethyl sulfate dropwise to the condensation reaction solution obtained in Step 1. After the addition is complete, continue to keep the reaction at 35-40℃ for 3-5 hours.

[0011] Step 3: After the reaction is completed, the product is washed, separated, and concentrated to obtain the 3-(α-methoxy)methylenebenzofuranone.

[0012] The formate has the structural formula HCOOR, where R is methyl or ethyl;

[0013] The synthesis process route is as follows:

[0014] .

[0015] Based on the above technical solution, the present invention can be further improved as follows.

[0016] Furthermore, the alkali mentioned in step 1 is selected from sodium methoxide.

[0017] Furthermore, the molar ratio of benzofuranone to base is 1:1.0-1.2; the molar ratio of benzofuranone to formate is 1:1.0-1.2; and the molar ratio of benzofuranone to dimethyl sulfate is 1:1.0-1.2.

[0018] Furthermore, the solvent is toluene.

[0019] The beneficial effects of this invention are: This invention provides a method for synthesizing azoxystrobin intermediate, which has the following advantages:

[0020] 1. Effectively reduces costs. This invention uses inexpensive formate esters (such as methyl formate and ethyl formate) to completely replace expensive trimethyl orthoformate, and eliminates the need for acid anhydrides, resulting in a significant reduction in raw material costs and outstanding economic benefits.

[0021] 2. The process route is simple and efficient. This invention adopts a "one-pot" series reaction, that is, condensation and methylation are carried out continuously in the same reaction system without the need to separate intermediates, which simplifies the operation steps, shortens the production cycle, and reduces equipment investment and energy consumption.

[0022] 3. Mild reaction conditions and high yield: The reaction can proceed smoothly under normal pressure and moderate temperature, and the operation is safe. By optimizing the conditions, the product yield can be stabilized at over 96%, which is higher than or equivalent to the current technology level.

[0023] 4. It is easy to industrialize, as the selected raw materials are all bulk industrial products that are readily available; the process parameters are wide-ranging and highly controllable, making it very suitable for large-scale industrial production.

[0024] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Specific embodiments of the present invention are given in detail in the following examples. Detailed Implementation

[0025] The principles and features of the present invention are described below. The examples given are for illustrative purposes only and are not intended to limit the scope of the invention. The invention is described more specifically by way of example in the following paragraphs. The advantages and features of the invention will become clearer from the following description.

[0026] Example 1:

[0027] Step 1: Add 26.8g (0.2mol) benzofuranone, 11.9g sodium methoxide, and 100.0g toluene solvent to the reaction flask, add 13.2g methyl formate dropwise, control the temperature at 35-40℃, and keep the reaction at this temperature for 3h after the addition is complete.

[0028] Step 2: Keep the temperature constant and add 27.7g of dimethyl sulfate to the above materials dropwise. After the addition is complete, keep the temperature constant and react for 4 hours.

[0029] Step 3: After the reaction is complete, water is added as the phase, and the organic phase is concentrated to obtain 34.1 g of 3-(α-methoxy)methylenebenzofuranone, with a yield of 96.8%.

[0030] The structure of the product was confirmed by ¹H-NMR:

[0031] 1H-NMR(DMSO-d6, 400MHz) 4.2(s, 3H), 7.15-7.19(m, 2H), 7.26-7.28(m,1H), 7.53(d, J=8.0Hz, 1H), 7.95(s, 1H).

[0032] Example 2:

[0033] Step 1: Add 26.8g (0.2mol) benzofuranone, 11.9g sodium methoxide, and 100.0g toluene solvent to the reaction flask, add 16.3g ethyl formate dropwise, control the temperature at 35-40℃, and keep the reaction at this temperature for 3h after the addition is complete.

[0034] Step 2: Add 27.7g of dimethyl sulfate to the above materials dropwise, and keep the mixture warm for 4 hours after adding the sulfate.

[0035] Step 3: After the reaction is complete, water is added as the phase, and the organic phase is concentrated to obtain 33.9 g of 3-(α-methoxy)methylenebenzofuranone, with a yield of 96.3%.

[0036] The structure of the product was confirmed by 1H NMR spectroscopy:

[0037] 1H-NMR(DMSO-d6, 400MHz) 4.2(s, 3H), 7.15-7.19(m, 2H), 7.26-7.28(m,1H), 7.53(d, J=8.0Hz, 1H), 7.95(s, 1H).

[0038] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Those skilled in the art can readily implement the present invention as described above. However, any modifications, alterations, or variations made by those skilled in the art without departing from the scope of the present invention, based on the disclosed technical content, are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, or variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A method of synthesizing a myclobutanil intermediate, characterized by, The synthesis method comprises the following steps: step 1, benzofuranone, sodium methoxide and toluene are added into a reaction system, formate is added dropwise under stirring, after dropwise addition is completed, incubation reaction is carried out at 35-40 DEG C for 2-4 hours, and a condensation reaction liquid is obtained; Step 2, dimethyl sulfate is added dropwise into the condensation reaction liquid obtained in the first step, after dropwise addition is completed, incubation reaction is continuously carried out at 35-40 DEG C for 3-5 hours; Step 3, after reaction is completed, washing, liquid separation and concentration treatment are carried out, and the 3-(alpha-methoxy) methylene benzofuranone is obtained; The structural formula of the formate is HCOOR, wherein R is methyl or ethyl; The synthesis process route is as follows: 。 2. The method of claim 1, wherein the azoxystrobin intermediate is ###0002### 2 The molar ratio of the benzofuranone to the base is 1:1.0-1.2; the molar ratio of the benzofuranone to the formate is 1:1.0-1.2; and the molar ratio of the benzofuranone to the dimethyl sulfate is 1:1.0-1.2.

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