Method for synthesizing trifloxystrobin through one-pot method

Abstract

The invention relates to a method for synthesizing trifloxystrobin through a one-pot method, and belongs to the technical field of organic synthesis.The method comprises the following steps that 1, E-2-(2-halomethylphenyl)-2-methoxyiminoacetic acid methyl ester, m-trifluoromethyl acetophenone, hydroxylamine hydrochloride or hydroxylamine sulfate and a solvent are added into a reaction flask, then alkali is added, and after addition is completed, a heat preservation reaction is conducted; and Step 2, after the reaction is finished, filtering to remove salt, and concentrating filtrate under reduced pressure to obtain trifloxystrobin. Compared with a traditional synthesis method of the trifloxystrobin, the synthesis method of the trifloxystrobin has the advantages that the 3-trifluoromethyl acetophenone and the E-2-(2-halomethylphenyl)-2-methoxyiminoacetic acid methyl ester are used as raw materials, the trifloxystrobin is directly synthesized by a one-pot method, the reaction route is short, the raw material cost is low, and the synthesis method of the trifloxystrobin by the one-pot method has the advantages that the synthesis efficiency is high, and the synthesis cost is low. The preparation method has the advantages that the preparation of m-trifluoromethyl acetophenone oxime from m-trifluoromethyl acetophenone is not needed, the whole synthesis process is simpler and more efficient, the reaction conditions are mild, and the preparation method is suitable for industrial large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for synthesizing trifloxystrobin by a one-pot method. Background Art

[0002] Trifloxystrobin is a highly efficient and safe methoxyacrylate fungicide, which has the characteristics of high efficiency, low toxicity, broad bactericidal spectrum, etc., and is effective against powdery mildew, leaf spot, rust, downy mildew, apple scab, etc. The chemical structural formula of trifloxystrobin is as follows:

[0003]

[0004] At present, many patents and literatures at home and abroad have reported the synthesis methods and purification methods of trifloxystrobin. In the existing synthesis methods, as disclosed in Chinese patents CN201510570919, CN201310504599, CN201410017449, CN201680071842, CN201880069221, etc., 3-(trifluoromethyl)acetophenone oxime and methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate are used to synthesize trifloxystrobin in the presence of an excessive acid-binding agent or base. These synthesis methods all require the preparation of 3-(trifluoromethyl)acetophenone oxime from 3-(trifluoromethyl)acetophenone first, and then the synthesis of trifloxystrobin. The process is complex and the yield is not high, resulting in a high raw material cost of trifloxystrobin and no competitiveness in the market.

[0005] These existing synthesis methods do not meet the requirements of efficient and clean processes and are not conducive to large-scale production. Therefore, seeking a clean, efficient, low-cost trifloxystrobin synthesis process suitable for industrial scale-up production is the focus of research in this field. Summary of the Invention

[0006] The present invention provides a method for synthesizing trifloxystrobin by a one-pot method, which solves the problems raised in the above background art. The raw materials of the synthesis method are cheap and easily available, safe and reliable, the process is simple and the reaction conditions are mild, which is suitable for industrial scale-up production.

[0007] The solution of the present invention to the above technical problems is as follows: A method for synthesizing trifloxystrobin by a one-pot method, the synthesis method comprising the following steps:

[0008] Step1: Add methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, 3-(trifluoromethyl)acetophenone, hydroxylamine hydrochloride or hydroxylamine sulfate and a solvent into a reaction flask. In the methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, X is bromine, the solvent is acetone or acetonitrile, and then add a base, the base is sodium carbonate or potassium carbonate. After adding, keep the reaction at a constant temperature, the constant temperature is 70-80 °C, and the constant temperature time is 2-3 hours;

[0009] Step 2: After the reaction is completed, filter to remove salts, and concentrate the filtrate under reduced pressure to obtain trifloxystrobin. The synthetic process route is as follows:

[0010]

[0011] Based on the above technical solutions, the present invention can be further improved as follows.

[0012] Furthermore, the molar ratio of methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, 3-(trifluoromethyl)acetophenone, hydroxylamine hydrochloride or hydroxylamine sulfate is 1:1.0 - 1.1:1.0 - 1.1.

[0013] The beneficial effects of the present invention are as follows: The present invention provides a method for synthesizing trifloxystrobin by a one-pot method, which has the following advantages:

[0014] 1. Compared with the traditional method for synthesizing trifloxystrobin, the synthesis method of the present trifloxystrobin uses 3-(trifluoromethyl)acetophenone and methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate as raw materials, and directly synthesizes trifloxystrobin by a one-pot method. The reaction route is short and the raw material cost is low.

[0015] 2. By adopting the one-pot method for synthesizing trifloxystrobin, there is no need to first prepare 3-(trifluoromethyl)acetophenone oxime from 3-(trifluoromethyl)acetophenone. The overall synthesis process is simpler and more efficient, the reaction conditions are mild, and it is suitable for industrial scale-up production.

[0016] 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 in accordance with the content of the specification, the following provides a detailed description of the preferred embodiments of the present invention. The specific embodiments of the present invention are given in detail by the following examples. Detailed Embodiments

[0017] The principles and features of the present invention will be described below. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention. The present invention will be 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.

[0018] It should be noted that when a component is referred to as "fixed to" another component, it can be directly on the other component or there may 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.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs. The terms used in the description of the present invention herein are for the purpose of describing specific embodiments only 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.

[0020] Example 1:

[0021] Step1: In a reaction flask, add 150 g of acetone as the solvent, 28.6 g (0.1 mol) of methyl E-2-(2-bromomethylphenyl)-2-methoxyiminoacetate, 20.6 g of 3-(trifluoromethyl)acetophenone oxime, 7.6 g of hydroxylamine hydrochloride, and 15.2 g of potassium carbonate. Heat to 70 - 80 °C and keep the reaction for 2 - 3 h;

[0022] Step2: After the reaction is completed, filter to remove the salt, and concentrate the filtrate under reduced pressure to obtain 37.8 g of trifloxystrobin, with a yield of 92.6%.

[0023] LC-MS: (M + H)+ 409.

[0024] Example 2:

[0025] Step1: In a reaction flask, add 150 g of acetonitrile as the solvent, 28.6 g (0.1 mol) of methyl E-2-(2-bromomethylphenyl)-2-methoxyiminoacetate, 20.6 g of 3-(trifluoromethyl)acetophenone oxime, 7.6 g of hydroxylamine hydrochloride, and 15.2 g of potassium carbonate. Heat to 70 - 80 °C and keep the reaction for 2 - 3 h;

[0026] Step2: After the reaction is completed, filter to remove the salt, and concentrate the filtrate under reduced pressure to obtain 38.1 g of trifloxystrobin, with a yield of 93.3%.

[0027] LC-MS: (M + H)+ 409.

[0028] Example 3:

[0029] Step1: In a reaction flask, add 150 g of acetonitrile as the solvent, 28.6 g (0.1 mol) of methyl E-2-(2-bromomethylphenyl)-2-methoxyiminoacetate, 20.6 g of 3-(trifluoromethyl)acetophenone oxime, 7.6 g of hydroxylamine hydrochloride, and 11.7 g of sodium carbonate. Heat to 70 - 80 °C and keep the reaction for 2 - 3 h;

[0030] Step2: After the reaction is completed, filter to remove the salt, and concentrate the filtrate under reduced pressure to obtain 37.5 g of trifloxystrobin, with a yield of 91.9%.

[0031] LC-MS: (M + H)+ 409.

[0032] As described above, it is only the preferred embodiment of the present invention and does not impose any formal limitations on the present invention; any ordinary technician in the industry can smoothly implement the present invention according to the above description; however, any minor changes, modifications and equivalent variations made by those skilled in the art within the scope of the technical solution of the present invention by using the technical content disclosed above are equivalent embodiments of the present invention; at the same time, any equivalent changes, modifications and variations made to the above embodiments based on the substantial 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 trifloxystrobin by a one-pot method, and the synthesis method comprises the following steps: Step 1: Add methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, α,α,α-trifluoro-m-tolyl methyl ketone, hydroxylamine hydrochloride or hydroxylamine sulfate and a solvent into a reaction flask. In the methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, X is bromine, and the solvent is acetone or acetonitrile. Then add a base, and the base is sodium carbonate or potassium carbonate. After adding, carry out a heat preservation reaction, the heat preservation temperature is 70-80 °C, and the heat preservation time is 2-3 hours; Step 2: After the reaction is completed, filter to remove salts, and concentrate the filtrate under reduced pressure to obtain trifloxystrobin. The synthetic process route diagram is as follows:

2. The method for synthesizing trifloxystrobin by a one-pot method according to claim 1, characterized in that, The molar ratio of the methyl E-2-(2-halomethylphenyl)-2-methoxyiminoacetate, α,α,α-trifluoro-m-tolyl methyl ketone, hydroxylamine hydrochloride or hydroxylamine sulfate is 1:1.0-1.1:1.0-1.1.

Images