A method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate

Abstract

The present invention relates to a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, belonging to the technical field of organic synthesis. The method process includes the following steps: Step1: Add o-halotoluene, methyl 2-(methoxyimino)acetate and a solvent into a reaction flask. X in the o-halotoluene is chlorine, and the solvent is toluene. Add a base and a catalyst. The base is sodium carbonate or potassium carbonate, and the catalyst is a Cu-TMEDA catalyst. After adding, keep the reaction at a certain temperature; Step2: After the reaction is completed, add water for washing, and concentrate the organic phase under reduced pressure to recover the solvent to obtain methyl 2-methyl-α-methoxyiminophenylacetate. The present invention uses o-halotoluene and methyl 2-(methoxyimino)acetate as raw materials to catalytically synthesize methyl 2-methyl-α-methoxyiminophenylacetate. Compared with the traditional synthesis process, it avoids the use of flammable and explosive nitrites, the reaction is safe and reliable, the raw materials are cheap and easily available, the process is simple and smooth, the reaction conditions are mild, and it is more suitable for industrial scale-up production.

Description

Technical Field

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

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

[0003]

[0004] Methyl 2-methyl-α-methoxyiminophenylacetate is a key intermediate for synthesizing trifloxystrobin and kresoxim-methyl. In existing synthesis methods, most of them are to carry out a condensation reaction between o-methylphenylacetonitrile and nitrite under alkaline conditions, and then react with a methylation reagent after separation and purification, and then hydrolyze the cyano group and esterify it to obtain the target compound. Such synthesis methods need to use flammable and explosive nitrites, which pose great safety hazards, and the reaction operation steps are complex, and the intermediate needs to be post-treated for separation and purification. It is not suitable for industrial scale-up production, or uses o-methylbenzoyl cyanide as a raw material, but it needs to use highly toxic reagent sodium cyanide for preparation, and the synthesis method has a long reaction route, high raw material cost and more three wastes.

[0005] The synthesis method reported in Chinese Patent CN108863845 is to react o-methylphenylacetonitrile and tert-butyl nitrite at 60 °C under alkaline conditions, remove methanol under reduced pressure, acidify with hydrochloric acid, extract with ethyl acetate, dry, desolvate and other post-treatments, and then under alkaline conditions, below 10 °C, dropwise add dimethyl sulfate, filter after the reaction ends, rotary evaporate, dissolve with ethyl acetate and other post-treatment operations, and finally hydrolyze the cyano group into an amide and esterify it with hydrochloric acid gas to obtain the target product. This synthesis method uses flammable and explosive tert-butyl nitrite and has cumbersome operation steps.

[0006] Zhu Xiaomeng [Master's thesis of Shandong Normal University, 2013] condensed o-methylphenylacetonitrile and ethyl nitrite under alkaline conditions, and after post-treatment, changed the solvent to DMF and reacted with dimethyl sulfate under alkaline conditions, and then hydrolyzed and esterified the cyano group in a sulfuric acid-methanol system to obtain the target product. This synthesis method also uses flammable and explosive nitrite compounds and has cumbersome operation steps.

[0007] Therefore, seeking a synthesis process for methyl 2-methyl-α-methoxyiminophenylacetate, an intermediate of trifloxystrobin and kresoxim-methyl, which is simple and smooth in process, low in cost and suitable for industrial scale-up production, is the focus of research in this field. Summary of the Invention

[0008] The present invention provides a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, which solves the problems raised in the above-mentioned background art. The raw materials of the synthesis process are cheap and easily available, avoiding the use of flammable and explosive nitrites, being safe and reliable, with mild reaction conditions, a simple and smooth process, and being suitable for industrial scale-up production.

[0009] The solution of the present invention to the above technical problems is as follows: A method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, and the synthesis method includes the following:

[0010] Step1: Add o-halotoluene, methyl 2-(methoxyimino)acetate and a solvent into a reaction flask. 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. The base is sodium carbonate or potassium carbonate. The catalyst is a Cu-TMEDA catalyst. The dosage of the catalyst is 1 - 5% of the weight of methyl 2-(methoxyimino)acetate. After adding, keep the reaction at a constant temperature. The constant temperature is 50 - 60 °C, and the constant temperature time is 3 - 4 hours;

[0011] Step2: After the reaction is completed, add water for washing. The organic phase is concentrated under reduced pressure to recover the solvent to obtain methyl 2-methyl-α-methoxyiminophenylacetate. The synthesis process route is as follows:

[0012]

[0013] On the basis of the above technical solution, the present invention can also be improved as follows.

[0014] Further, X in the o-halotoluene can also be bromine.

[0015] Further, the solvent can also be selected from one or a mixture of solvents such as xylene, DMF, and NMP.

[0016] Further, the base can also be sodium hydroxide, potassium hydroxide, and sodium methoxide.

[0017] The beneficial effects of the present invention are as follows: The present invention provides a method for synthesizing methyl 2-methyl-α-methoxyiminophenylacetate, having the following advantages:

[0018] 1. Using o-halotoluene and methyl 2-(methoxyimino)acetate as raw materials, catalytically synthesizing methyl 2-methyl-α-methoxyiminophenylacetate. Compared with the traditional synthesis process, it avoids the use of flammable and explosive nitrites, the reaction is safe and reliable, and the raw material cost is low;

[0019] 2. Compared with the existing preparation method using highly toxic sodium cyanide with o-methylbenzoyl cyanide as the raw material, the reaction route of this synthesis process is shorter, the raw material cost is lower, and less three wastes are generated.

[0020] 3. The raw materials of the present invention are cheap and easily available, the process is simple and smooth, and the reaction conditions are mild, which is more suitable for industrial scale-up production.

[0021] The above description is only an overview of the technical solution of the present invention. In order to understand the technical means of the present invention more clearly and implement it according to the content of the specification, the following provides a detailed description of the preferred embodiments of the present invention. The specific implementation manners of the present invention are given in detail by the following embodiments. Specific Embodiment

[0022] The principles and features of the present invention are described below. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention. The present invention is described more specifically by way of example in the following paragraphs. The advantages and features of the present invention will be clearer according to the following description and claims.

[0023] It should be noted that when a component is referred to as being "fixed to" another component, it can be directly on the other component or there can also be an intermediate component. When a component is considered to be "connected" to another component, it can be directly connected to the other component or there may be an intermediate component at the same time. When a component is considered to be "disposed on" another component, it can be directly disposed on the other component or there may be an intermediate component at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are only for the purpose of illustration.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the specification of the present invention herein 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.

[0025] Example 1:

[0026] Step1: In a reaction flask, add 15.2 g of o-chlorotoluene, 11.7 g (0.1 mol) of methyl 2-(methoxyimino)acetate and 50 g of solvent toluene, add 6.4 g of sodium carbonate and 0.1 g of catalyst Cu-TMEDA. After adding, keep the temperature at 50 - 60 °C and carry out the reaction for 3 hours.

[0027] Step2: After the reaction is completed, add water for washing. The organic phase is 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%.

[0028] In the GC-MS analysis, a molecular ion peak at m / z 207 was detected.

[0029] Example 2:

[0030] Step1: In a reaction flask, add 15.2 g of o-chlorotoluene, 11.7 g (0.1 mol) of methyl 2-(methoxyimino)acetate, and 50 g of solvent toluene. Then add 8.3 g of potassium carbonate and 0.1 g of catalyst Cu-TMEDA. After addition, keep the temperature at 50 - 60 °C and carry out the reaction for 3 hours.

[0031] Step2: After the reaction is completed, add water for washing. The organic phase is concentrated under reduced pressure to recover the solvent, obtaining 19.1 g of methyl 2-methyl-α-methoxyiminophenylacetate with a yield of 92.2%.

[0032] In the GC-MS analysis, a molecular ion peak at m / z 207 was detected.

[0033] As mentioned above, it is only the preferred embodiment of the present invention, and there is no any form of restriction on the present invention; any ordinary technician in this industry can smoothly implement the present invention according to the above; however, any equivalent changes such as slight modifications, evolutions made by those familiar with the technology in the technical scope of the present invention without departing from the technical solution of the present invention using the technical content disclosed above are 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 still fall 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, The synthesis method comprises the following steps: Step 1: Add o-halotoluene, methyl 2-methoxyiminoacetate and a solvent into a reaction flask. 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. The base is sodium carbonate or potassium carbonate. The catalyst is a Cu-TMEDA catalyst. The dosage of the catalyst is 1 - 5% of the weight of methyl 2-methoxyiminoacetate. After adding, carry out a heat preservation reaction. The heat preservation temperature is 50 - 60 °C and the heat preservation time is 3 - 4 hours. Step 2: After the reaction is completed, add water for washing. The organic phase is concentrated under reduced pressure to recover the solvent to obtain methyl 2-methyl-α-methoxyiminophenylacetate. The synthetic process route is as follows:

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