Synthetic method and application of picoxystrobin intermediate

Abstract

The invention discloses a synthesis method and application of a picoxystrobin intermediate, and the synthesis method of the picoxystrobin intermediate comprises the following steps: adding 200g of acetone, 45-55g of (E)-4-hydroxymethylene-3-isochromone and 15g of sodium hydroxide into a reaction flask, uniformly mixing, then dropwise adding 37-43g of dimethyl sulfate, stirring, reacting, filtering, washing, and drying to obtain the picoxystrobin intermediate. And after the dimethyl sulfate is dropwise added, heating the reaction flask to 20-30 DEG C, carrying out a stirring reaction, filtering the sodium methyl sulfate after the reaction is finished to obtain a filtrate, concentrating the filtrate, adding methanol into the filtrate, crystallizing, filtering and drying. According to the invention, acetone is used as a reaction system, dimethyl sulfate is used for methylation reaction, the reaction period is short, the energy consumption is low, the reaction process is safe, the operation is simple, the production cost is low, and the obtained main by-product and the solvent are almost in an insoluble state and are convenient to separate; the method takes acetone as a solvent, is simple to recover, low in energy consumption, safe to operate, good in environmental protection property and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of preparation of picoxystrobin intermediates, in particular to a synthesis method and application of a picoxystrobin intermediate. Background Art

[0002] In order to meet the needs of agricultural production, agricultural producers will use some fungicides to spray on crops, and strobilurin fungicides are one of them. Picoxystrobin is a commonly used strobilurin fungicide, which can effectively prevent and control foliar diseases on a variety of crops, such as leaf blight, leaf rust, glumes blight, brown spot, powdery mildew, etc. Its main function is to inhibit the respiration of the pathogen's mitochondria, thereby preventing the growth and reproduction of the pathogen.

[0003] Many raw materials are used in the synthesis of picoxystrobin. 4-methoxymethylene-3-isochromanone is the key intermediate for the synthesis of picoxystrobin. However, in the existing methods for synthesizing 4-methoxymethylene-3-isochromanone, the by-products are not easy to separate from 4-methoxymethylene-3-isochromanone, the reaction speed is slow and the reaction is not complete, resulting in a low yield of 4-methoxymethylene-3-isochromanone and a large amount of wastewater generated during the preparation process. People are in urgent need of improving the synthesis method of 4-methoxymethylene-3-isochromanone. Summary of the invention

[0004] The object of the present invention is to provide a method for synthesizing a picoxystrobin intermediate to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 45-55g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 37-43g of dimethyl sulfate, heating the reaction bottle to 20-30 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring for reaction, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone, wherein the 4-methoxymethylene-3-isochromanone is the target product.

[0007] As a further solution of the present invention: the stirring reaction time is 50-70 minutes, which can ensure that the reactants can react completely.

[0008] As a further solution of the present invention: when dimethyl sulfate is added dropwise, the temperature of the reaction bottle is 10-20 degrees Celsius, which can ensure that the reactants are only mixed but not reacted.

[0009] As a further solution of the present invention: the mass of added methanol is 18-23 g, which can ensure the separation of 4-methoxymethylene-3-isochromanone and by-products.

[0010] The present invention is also used to protect the use of the picoxystrobin intermediate obtained by the above synthesis method in the synthesis of picoxystrobin.

[0011] Compared with the prior art, the invention has the following beneficial effects: compared with the existing DMSO (dimethyl sulfoxide) reaction system, the invention uses acetone as the reaction system, adopts cheap and easily purchased dimethyl sulfate to carry out the methylation reaction, has a short reaction period and low energy consumption, a safe reaction process and is green and environmentally friendly, is simple to operate and has low production cost, has a high degree of reaction and high yield, and the main by-product obtained is almost insoluble in the solvent, which is convenient for separating the by-product and 4-methoxymethylene-3-isochromanone; the invention uses acetone as the solvent, has simple recovery and low energy consumption, improves the solvent recovery rate and reduces the reaction cost, is safe to operate and does not have the problem of generating a large amount of waste water in the DMSO reaction system, has good environmental protection, and is suitable for industrial production. DETAILED DESCRIPTION

[0012] The technical solution of this patent is further described in detail below in conjunction with specific implementation methods.

[0013] The present invention uses (E)-4-hydroxymethylene-3-isochromanone as a starting material, acetone as a solvent, and then reacts with dimethyl sulfate to obtain the target product 4-methoxymethylene-3-isochromanone. The main byproduct is insoluble in the solvent acetone, so that the main byproduct and the target product 4-methoxymethylene-3-isochromanone are easy to separate; acetone is used as the reaction solvent, and the recovery is simple and the recovery energy consumption is low, thereby improving the recovery rate of acetone and reducing the production cost. The synthesis method of the present invention has a short reaction cycle and low energy consumption, and after the reaction, there is no problem that the DMSO reaction system has a large amount of wastewater and is difficult to recover. It has good green environmental protection and is particularly suitable for industrial production.

[0014] Example 1

[0015] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 45g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 37g of dimethyl sulfate at 10 degrees Celsius, heating the reaction bottle to 20 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring and reacting for 50 minutes, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding 18g of methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone with a purity of 97.5% and a yield of 93%.

[0016] Example 2

[0017] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 48g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 38g of dimethyl sulfate at 12 degrees Celsius, heating the reaction bottle to 23 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring and reacting for 54 minutes, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding 19g of methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone with a purity of 98% and a yield of 92.1%.

[0018] Example 3

[0019] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 20g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 40g of dimethyl sulfate at 16 degrees Celsius, heating the reaction bottle to 26 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring and reacting for 60 minutes, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding 20g of methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone with a purity of 98.5% and a yield of 95%.

[0020] Example 4

[0021] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 52g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 41g of dimethyl sulfate at 28 degrees Celsius, heating the reaction bottle to 29 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring and reacting for 63 minutes, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding 21g of methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone with a purity of 96.4% and a yield of 94%.

[0022] Example 5

[0023] A picoxystrobin intermediate synthesis method comprises the following specific steps: adding 200g of acetone, 55g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mixing them evenly, then dripping 43g of dimethyl sulfate at 20 degrees Celsius, heating the reaction bottle to 30 degrees Celsius after the dripping of dimethyl sulfate is completed, stirring and reacting for 70 minutes, filtering sodium methyl sulfate after the reaction is completed to obtain a filtrate, concentrating the filtrate and adding 23g of methanol thereto, crystallizing, filtering and drying to obtain 4-methoxymethylene-3-isochromanone with a purity of 97.6% and a yield of 92.8%.

[0024] It can be seen from the above examples that the 4-methoxymethylene-3-isochromanone obtained by the preparation method of the present invention has a minimum purity of 96.4% and a minimum yield of 92.1%, both of which are higher than the existing DMSO (dimethyl sulfoxide) reaction system, and has broad application prospects.

[0025] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0026] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for synthesizing a picoxystrobin intermediate, characterized in that: The specific steps are as follows: add 200g of acetone, 45-55g of (E)-4-hydroxymethylene-3-isochromanone and 15g of sodium hydroxide into a reaction bottle and mix them evenly, then add 37-43g of dimethyl sulfate dropwise, after the addition of dimethyl sulfate is completed, heat the reaction bottle to 20-30 degrees Celsius and stir to react, after the reaction is completed, filter the sodium methyl sulfate to obtain a filtrate, concentrate the filtrate and add methanol thereto, crystallize, filter and dry.

2. The method for synthesizing a picoxystrobin intermediate according to claim 1, characterized in that: The stirring reaction time is 50-70 minutes.

3. The method for synthesizing a picoxystrobin intermediate according to claim 1 or 2, characterized in that: The temperature of the reaction bottle is 10-20 degrees Celsius when dimethyl sulfate is added dropwise.

4. The method for synthesizing a picoxystrobin intermediate according to claim 1, characterized in that: The mass of the added methanol is 18-23g.

5. The method for synthesizing a picoxystrobin intermediate according to claim 4, characterized in that: The mass of the added methanol is 20 g.

6. The method for synthesizing a picoxystrobin intermediate according to claim 2, characterized in that: The stirring reaction time is 60 minutes.

7. Use of a picoxystrobin intermediate obtained by the method for synthesizing a picoxystrobin intermediate according to any one of claims 1 to 6 in the synthesis of picoxystrobin.