Synthesis method of 2-methyl-alpha-methoxyimino methyl phenylacetate

Abstract

The invention relates to a synthetic method of 2-methyl-alpha-methoxyimino methyl phenylacetate, and belongs to the technical field of organic synthesis, the process of the method comprises the following steps: Step 1: adding o-halotoluene, 2-(methoxyimino) methyl acetate and a solvent into a reaction flask, adding alkali and a catalyst, reacting for 1-2 hours at the temperature of 50-60 DEG C, and reacting for 1-2 hours to obtain 2-methyl-alpha-methoxyimino methyl phenylacetate; the alkali is sodium carbonate or potassium carbonate, and the catalyst is a Cu-TMEDA catalyst; 2, after the reaction is finished, water is added for washing, an organic phase is concentrated under reduced pressure, the solvent is recycled, and 2-methyl-alpha-methoxyimino methyl phenylacetate is obtained. The 2-methyl-alpha-methoxyimino methyl phenylacetate is obtained through catalytic synthesis by taking o-halogen toluene and 2-(methoxyimino) methyl acetate as raw materials, compared with a traditional synthesis process, flammable and explosive nitrite ester is not used, the reaction is safe and reliable, the raw materials are cheap and easy to obtain, the process is simple and smooth, the reaction conditions are mild, and the method is suitable for industrial production. The method is more suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate. Background Art

[0002] Trifloxystrobin and kresoxim-methyl are highly effective and safe methoxyacrylate fungicides with the characteristics of high efficiency, low toxicity and broad fungicide spectrum. They are effective against powdery mildew, leaf spot, rust, downy mildew, apple scab, etc. The chemical structures of trifloxystrobin, kresoxim-methyl and their key intermediates are as follows: .

[0003] 2-methyl-α-methoxyiminophenylacetic acid methyl ester is a key intermediate for the synthesis of trifloxystrobin and kresoxim-methyl. In the existing synthesis method, most of them are condensation reaction of o-methylbenzene acetonitrile and nitrite under alkaline conditions, separation and purification, and then reaction with a methylating agent, and then cyano hydrolysis and reesterification to obtain the target compound. This type of synthesis method requires the use of flammable and explosive nitrite, there is a great safety hazard, and the reaction operation steps are complicated, and the intermediate needs post-processing separation and purification. It is not suitable for industrial amplification, or it is made of o-methylbenzoyl cyanide as a raw material, but it needs to be prepared using a highly toxic reagent sodium cyanide, and the synthesis method reaction route is long, the raw material cost is high, and there are more three wastes.

[0004] The synthesis method reported in Chinese patent CN108863845 is to react o-methylbenzene acetonitrile and tert-butyl nitrite at 60°C under alkaline conditions, demethylate under reduced pressure, acidify with hydrochloric acid, extract with ethyl acetate, dry, desolventize and other post-processing, then dropwise add dimethyl sulfate under alkaline conditions below 10°C, filter after reaction, rotary evaporation, dissolve in ethyl acetate and other post-processing operations, and finally hydrolyze the cyano group into amide, and esterify with hydrochloric acid gas to obtain the target product. This synthesis method uses tert-butyl nitrite, which is flammable and explosive, and the operation steps are complicated.

[0005] Zhu Xiaomeng [Master's thesis of Shandong Normal University, 2013] condensed o-methylbenzene acetonitrile and ethyl nitrite under alkaline conditions. After post-treatment, the solvent DMF was replaced to react with dimethyl sulfate under alkaline conditions, and then cyanide was hydroesterified in a sulfuric acid methanol system to obtain the target product. This synthesis method also uses flammable and explosive nitrite compounds, and the operation steps are cumbersome.

[0006] Therefore, seeking a simple and smooth process, low cost, and suitable for industrial scale-up production of trifloxystrobin and kresoxim-methyl intermediate 2-methyl-α-methoxyiminophenylacetic acid methyl ester synthesis process is the focus of research in this field. Summary of the invention

[0007] The present invention provides a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, which solves the problems raised by the above-mentioned background technology. The raw materials of the synthesis process are cheap and easily available, and the use of flammable and explosive nitrites is avoided. The method is safe and reliable, the reaction conditions are mild, the process is simple and smooth, and the method is suitable for industrialized scale-up production.

[0008] The present invention solves the above-mentioned technical problem in the following way: a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, wherein the method comprises the following steps: Step 1: add o-halotoluene, methyl 2-(methoxyimino)acetate and a solvent into a reaction flask, wherein the molar ratio of methyl 2-(methoxyimino)acetate to o-halotoluene is 1:1.0-1.5, X in the o-halotoluene is chlorine, the solvent is toluene, add a base and a catalyst, wherein the base is sodium carbonate or potassium carbonate, the catalyst is a Cu-TMEDA catalyst, and the amount of the catalyst is 1-5% of the weight of methyl 2-(methoxyimino)acetate, and heat the reaction after the addition is completed, the heat preservation temperature is 50-60°C, and the heat preservation time is 3-4 hours; Step 2: After the reaction is completed, water is added for washing, and the organic phase is concentrated under reduced pressure to recover the solvent to obtain 2-methyl-α-methoxyiminophenylacetic acid methyl ester. The synthetic process route is as follows: .

[0009] Based on the above technical solution, the present invention can also be improved as follows.

[0010] Furthermore, X in the o-halotoluene may also be bromine.

[0011] Furthermore, the solvent may be a mixed solvent of one or more solvents selected from xylene, DMF, and NMP.

[0012] Furthermore, the alkali may include sodium hydroxide, potassium hydroxide and sodium methoxide.

[0013] The beneficial effect of the present invention is that the present invention provides a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, which has the following advantages: Using o-halotoluene and 2-(methoxyimino)acetic acid methyl ester as raw materials, 2-methyl-α-methoxyiminophenylacetic acid methyl ester is synthesized by catalysis. Compared with the traditional synthesis process, the use of flammable and explosive nitrite is avoided, the reaction is safe and reliable, and the raw material cost is low; Compared with the existing preparation method using o-methylbenzoyl cyanide as raw material and highly toxic reagent sodium cyanide, the synthesis process has a shorter reaction route, lower raw material cost, and less waste. The raw materials of the invention are cheap and readily available, the process is simple and smooth, the reaction conditions are mild, and the method is more suitable for industrialized scale-up production.

[0014] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail below. The specific implementation of the present invention is given in detail by the following embodiments. DETAILED DESCRIPTION

[0015] The principles and features of the present invention are described below, and the examples are only used to explain the present invention and are not used to limit the scope of the present invention. The present invention is described more specifically by way of example in the following paragraphs. According to the following description and claims, the advantages and features of the present invention will become clearer.

[0016] It should be noted that when a component is referred to as being "fixed to" another component, it may be directly on the other component or there may also be a component centered. When a component is considered to be "connected to" another component, it may be directly connected to the other component or there may also be a component centered. When a component is considered to be "set on" another component, it may be directly set on the other component or there may also be a component centered. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items. Embodiment 1:

[0018] Step 1: In a reaction bottle, add 15.2g o-chlorotoluene, 11.7g (0.1mol) methyl 2-(methoxyimino)acetate and 50g toluene solvent, add 6.4g sodium carbonate and 0.1g catalyst Cu-TMEDA, after addition, keep the temperature at 50-60℃ and react for 3 hours; Step 2: After the reaction was completed, water was added for washing, and the organic phase was concentrated under reduced pressure to recover the solvent to obtain 18.9 g of methyl 2-methyl-α-methoxyiminophenylacetate with a yield of 91.3%.

[0019] In the GC-MS analysis, a molecular ion peak of m / z 207 was detected. Embodiment 2:

[0020] Step 1: In a reaction bottle, add 15.2g o-chlorotoluene, 11.7g (0.1mol) methyl 2-(methoxyimino)acetate and 50g toluene solvent, add 8.3g potassium carbonate and 0.1g catalyst Cu-TMEDA, after addition, keep the temperature at 50-60℃ and react for 3 hours; Step 2: After the reaction was completed, water was added for washing, and the organic phase was concentrated under reduced pressure to recover the solvent to obtain 19.1 g of methyl 2-methyl-α-methoxyiminophenylacetate with a yield of 92.2%.

[0021] In the GC-MS analysis, a molecular ion peak of m / z 207 was detected.

[0022] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any ordinary technician in the industry can smoothly implement the present invention as described above. However, any equivalent changes, modifications and evolutions made by technicians familiar with the profession without departing from the scope of the technical solution of the present invention using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, characterized in that: Its synthesis method comprises the following steps: Step 1: add o-halotoluene, methyl 2-methoxyiminoacetate and a solvent into a reaction flask, wherein the molar ratio of methyl 2-methoxyiminoacetate to o-halotoluene is 1:1.0-1.5, X in the o-halotoluene is chlorine, the solvent is toluene, add a base and a catalyst, wherein the base is sodium carbonate or potassium carbonate, the catalyst is a Cu-TMEDA catalyst, and the amount of the catalyst is 1-5% of the weight of methyl 2-methoxyiminoacetate, and the reaction is carried out by heat preservation at a temperature of 50-60°C for 3-4 hours; Step 2: After the reaction is completed, water is added for washing, and the organic phase is concentrated under reduced pressure to recover the solvent to obtain 2-methyl-α-methoxyiminophenylacetic acid methyl ester. The synthetic process route is as follows: 。 2. The method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate according to claim 1, characterized in that: X in the o-halotoluene may also be bromine.

3. The method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate according to claim 1, characterized in that: The solvent may also be a mixed solvent of one or more solvents selected from xylene, DMF, and NMP.

4. The method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate according to claim 1, characterized in that: Sodium hydroxide, potassium hydroxide and sodium methoxide may also be used as the base.

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