Synthesis method of a fluxapyroxad intermediate, trifluoronitro-biphenyl

Abstract

The present invention relates to a method for synthesizing the fluxapyroxad intermediate trifluoronitro - biphenyl, belonging to the technical field of organic synthesis. The method process includes the following: Step1: Under nitrogen protection, add 3,4,5 - trifluorobromobenzene, o - nitrophenylboronic acid, a catalyst, a cocatalyst, a base and a solvent into a reaction flask. After addition, carry out a heat - preservation reaction; Step2: After the reaction is completed, through phase separation, the organic phase is concentrated to obtain 3’,4’,5’ - trifluoro - 2 - nitrobiphenyl. In the present invention, compared with the traditional method for synthesizing trifluoronitro - biphenyl, the method for synthesizing trifluoronitro - biphenyl directly uses 3,4,5 - trifluorobromobenzene and o - nitrophenylboronic acid as raw materials, avoiding the production steps of preparing 3,4,5 - trifluorobenzeneboronic acid from 3,4,5 - trifluorobromobenzene through multiple steps. Moreover, it can effectively improve the yield, has a high raw material utilization rate, and the preparation method of o - nitrophenylboronic acid is simple, which can effectively reduce the reaction cost. The reaction route is shorter, simpler and more efficient, the reaction conditions are mild, and it has high industrial application value.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly to a method for synthesizing the fluxapyroxad intermediate 3',4',5'-trifluoro-2-nitrobiphenyl. Background Art

[0002] Fluxapyroxad is a succinate dehydrogenase inhibitor (SDHI) fungicide developed by BASF. It is a highly efficient and low-toxic fungicide that inhibits the succinate dehydrogenase in complex II of the mitochondrial respiratory chain, thereby inhibiting the spore germination, germ tube, and hyphal growth of target fungi. It has a broad-spectrum bactericidal effect and is widely used in crops such as cereals, soybeans, cotton, fruits, and vegetables. Its application crops are continuously expanding, and the market development prospect is good. The chemical structural formulas of fluxapyroxad and its intermediate are as follows.

[0003]

[0004] Currently, many patents and literatures at home and abroad have reported methods for synthesizing the fluxapyroxad intermediate 3',4',5'-trifluoro-2-nitrobiphenyl. In the existing synthesis methods, as described in World Patents WO2018035685, WO2022243099, and Chinese Patents CN109942433, CN117088777, etc., 3,4,5-trifluorophenylboronic acid and o-chloronitrobenzene are used as raw materials and coupled under various catalyst conditions to obtain 3',4',5'-trifluoro-2-nitrobiphenyl. The synthesis route is shown in the following figure.

[0005]

[0006] In these synthesis methods, 3,4,5-trifluorophenylboronic acid is usually prepared from 3,4,5-trifluorobromobenzene through a Grignard reaction, boric acid ester addition, and hydrolysis. Its preparation yield is very low, and there are many three wastes. Due to the high price of the raw material 3,4,5-trifluorobromobenzene, the raw material cost of 3,4,5-trifluorophenylboronic acid is high, resulting in a high raw material cost of the intermediate 3',4',5'-trifluoro-2-nitrobiphenyl.

[0007] Therefore, seeking a clean, efficient, low-cost, and suitable industrial scale-up production process for the synthesis of the fluxapyroxad intermediate 3',4',5'-trifluoro-2-nitrobiphenyl is the focus of research in this field. Summary of the Invention

[0008] The present invention provides a method for synthesizing the fluxapyroxad intermediate trifluoro-nitrobiphenyl, which solves the problems raised in the above background art. The raw material cost is lower, the reaction is safe and reliable, the process is simple, the reaction conditions are mild, and it has high industrial application value.

[0009] The solution of the present invention to the above technical problems is as follows:

[0010] A method for synthesizing the fluxapyroxad intermediate 3',4',5'-trifluoro-2-nitrobiphenyl, the synthesis method comprising the following steps:

[0011] Step1, under nitrogen protection, add 3,4,5-trifluorobromobenzene, o-nitrophenylboronic acid, a catalyst, a cocatalyst, a base, and a solvent to a reaction flask. The molar ratio of 3,4,5-trifluorobromobenzene to o-nitrophenylboronic acid is 1:1.0 - 1.1. The catalyst is palladium on carbon, the cocatalyst is tetrabutylphosphonium bromide or tetraphenylphosphonium bromide, the solvent is a mixed solvent composed of toluene and water, and the base is sodium carbonate or potassium carbonate. After addition, keep the temperature for reaction, the heat preservation temperature is 60 - 70 °C, and the heat preservation time is 7 - 8 hours;

[0012] Step2, after the reaction is completed, after phase separation, the obtained organic phase is concentrated under reduced pressure to obtain 3',4',5'-trifluoro-2-nitrobiphenyl. The synthetic process route is as follows.

[0013]

[0014] On the basis of the above technical solution, the present invention can also be improved as follows.

[0015] Further, the dosage of the catalyst palladium on carbon is 0.1% - 5% of the mass of 3,4,5-trifluorobromobenzene.

[0016] Further, the dosage of the cocatalyst is 0.1% - 5% of the mass of 3,4,5-trifluorobromobenzene.

[0017] The beneficial effects of the present invention are: The present invention provides a method for synthesizing the fluxapyroxad intermediate 3',4',5'-trifluoro-2-nitrobiphenyl, having the following advantages:

[0018] 1. Compared with the traditional method for synthesizing 3',4',5'-trifluoro-2-nitrobiphenyl, the present synthesis method of 3',4',5'-trifluoro-2-nitrobiphenyl directly uses 3,4,5-trifluorobromobenzene and o-nitrophenylboronic acid as raw materials, avoiding the production steps of preparing 3,4,5-trifluorophenylboronic acid from 3,4,5-trifluorobromobenzene through multiple steps in the traditional production process, and can effectively improve the yield, with high raw material utilization rate. Moreover, the preparation method of o-nitrophenylboronic acid is simple, which can effectively reduce the reaction cost.

[0019] 2. Compared with the traditional synthesis method, such a synthesis method of 3',4',5'-trifluoro-2-nitrobiphenyl has a shorter reaction route, is simpler and more efficient, has mild reaction conditions, and has high industrial application value.

[0020] The above description is only an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and implement it according to the content of the specification, the following describes the preferred embodiments of the present invention in detail. The specific implementation manners of the present invention are given in detail by the following embodiments. Specific Embodiments

[0021] 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.

[0022] 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 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 for illustrative purposes only.

[0023] 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.

[0024] Example 1:

[0025] Step1: Under nitrogen protection, add 21.1 g (0.1 mol) of 3,4,5-trifluorobromobenzene, 18.3 g of o-nitrophenylboronic acid, 21 mg of catalyst palladium carbon, 30 mg of cocatalyst tetrabutylphosphonium bromide, 13.8 g of potassium carbonate and 60 g of solvent toluene / water into the reaction flask. The ratio of toluene to water is 2:1. Heat to 60 - 70 °C and keep the reaction for 7 - 8 h;

[0026] Step2: After the reaction is completed, after phase separation, the obtained organic phase is concentrated under reduced pressure to obtain 24.3 g of 3’,4’,5’-trifluoro-2-nitrobiphenyl, with a yield of 96.0%.

[0027] In the LC-MS detection in the negative ion mode, an ion (m / z 252) after the molecule loses a proton was detected.

[0028] Example 2:

[0029] Step 1: Under nitrogen protection, add 21.1 g (0.1 mol) of 3,4,5-trifluorobromobenzene, 18.3 g of o-nitrophenylboronic acid, 21 mg of palladium-carbon as a catalyst, 30 mg of tetrabutylphosphonium bromide as a cocatalyst, 13.8 g of potassium carbonate, and 60 g of toluene / water as a solvent into the reaction flask. The ratio of toluene to water is 2:1. Heat to 60 - 70 °C and keep the reaction for 7 - 8 h;

[0030] Step 2: After the reaction is completed, after phase separation, the obtained organic phase is concentrated under reduced pressure to obtain 23.9 g of 3’,4’,5’-trifluoro-2-nitrobiphenyl, with a yield of 94.4%.

[0031] In the LC-MS detection in the negative ion mode, an ion (m / z 252) after the molecule loses a proton was detected.

[0032] Example 3:

[0033] Step 1: Under nitrogen protection, add 21.1 g (0.1 mol) of 3,4,5-trifluorobromobenzene, 18.3 g of o-nitrophenylboronic acid, 21 mg of palladium-carbon as a catalyst, 30 mg of tetrabutylphosphonium bromide as a cocatalyst, 10.6 g of sodium carbonate, and 60 g of toluene / water as a solvent into the reaction flask. The ratio of toluene to water is 2:1. Heat to 60 - 70 °C and keep the reaction for 7 - 8 h;

[0034] Step 2: After the reaction is completed, after phase separation, the obtained organic phase is concentrated under reduced pressure to obtain 24.5 g of 3’,4’,5’-trifluoro-2-nitrobiphenyl, with a yield of 96.8%.

[0035] In the LC-MS detection in the negative ion mode, an ion (m / z 252) after the molecule loses a proton was detected.

[0036] As described above, it is only the preferred embodiment of the present invention, and it does not impose any form of limitation on the present invention; any ordinary technician in this industry can smoothly implement the present invention according to the above description; however, any slight changes, modifications, and equivalent variations made by those skilled in this professional field without departing from the technical solution of the present invention and 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 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 the fluxapyroxad intermediate trifluoronitro - biphenyl, characterized in that, The synthesis method comprises the following steps: Step 1, under nitrogen protection, add 3,4,5-trifluorobromobenzene, o-nitrophenylboronic acid, a catalyst, a cocatalyst, a base and a solvent into a reaction flask. The molar ratio of 3,4,5-trifluorobromobenzene to o-nitrophenylboronic acid is 1:1.0 - 1.

1. The catalyst is palladium on carbon, the cocatalyst is tetrabutylphosphonium bromide or tetraphenylphosphonium bromide, the solvent is a mixed solvent composed of toluene and water, and the base is sodium carbonate or potassium carbonate. After adding, keep the reaction at a certain temperature. The heat preservation temperature is 60 - 70 °C, and the heat preservation time is 7 - 8 hours; Step 2, after the reaction is completed, after phase separation, the obtained organic phase is concentrated under reduced pressure to obtain 3',4',5'-trifluoro-2-nitrobiphenyl. The synthetic process route is as follows.

2. The synthesis method of the fluxapyroxad intermediate trifluoronitro-biphenyl according to claim 1, characterized in that, The dosage of the catalyst palladium on carbon is 0.1% - 5% of the mass of 3,4,5-trifluorobromobenzene.

3. The synthesis method of the fluxapyroxad intermediate trifluoronitro-biphenyl according to claim 1, characterized in that, The dosage of the cocatalyst is 0.1% - 5% of the mass of 3,4,5-trifluorobromobenzene.

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