阅读说明：本技术 一种2,6-二氟苯甲酰胺的制备方法 (Preparation method of 2, 6-difluorobenzamide ) 是由 席亚男 张俊 于 2021-07-28 设计创作，主要内容包括：本发明公开了一种2,6-二氟苯甲酰胺的制备方法,通过微通道反应器高温水解2,6-二氟苯腈制的,包括以下步骤：S1：配置原料液：配置2,6-二氟苯腈水溶液备用；S2：搭建设备：设备由高压柱塞泵、不锈钢插片式反应器组成；S3：高温水解：将原料液经柱塞泵抽入不锈钢插片式反应器中进行反应,流出到后处理釜中进行后处理；S4：后处理：向处理釜中加入氯化钠溶液进行盐析,然后经过滤,水洗和干燥得到二氟苯甲酰胺。本发明在水解过程中不需加入任何催化剂,后处理无需酸碱中和,工艺简单,纯度好,收率高。本发明使用连续流工艺代替了传统的高压反应釜工艺,使反应过程更加可控、安全和高效。(The invention discloses a preparation method of 2, 6-difluorobenzamide, which is prepared by hydrolyzing 2, 6-difluorobenzonitrile at high temperature through a microchannel reactor and comprises the following steps: s1: preparing a raw material liquid: preparing 2, 6-difluorobenzonitrile aqueous solution for later use; s2: building equipment: the equipment consists of a high-pressure plunger pump and a stainless steel inserting piece type reactor; s3: high-temperature hydrolysis: pumping the raw material liquid into a stainless steel insert type reactor through a plunger pump for reaction, and flowing out of a post-treatment kettle for post-treatment; s4: and (3) post-treatment: adding sodium chloride solution into the treatment kettle for salting out, and then filtering, washing and drying to obtain the difluorobenzamide. The invention does not need to add any catalyst in the hydrolysis process, does not need acid-base neutralization in post-treatment, and has simple process, good purity and high yield. The invention uses continuous flow process to replace traditional high-pressure reaction kettle process, so that the reaction process is more controllable, safe and efficient.)

1. A preparation method of 2, 6-difluorobenzamide is characterized in that 2, 6-difluorobenzamide is prepared by hydrolyzing 2, 6-difluorobenzonitrile at a high temperature, wherein the reaction temperature is 220-300 ℃, the reaction pressure is 4-6Mpa, and the reaction time is 0.5-2 h.

2. The process according to claim 1, wherein the hydrolysis reaction is carried out in a microchannel reactor.

3. The process according to claim 2, wherein said reaction is carried out in the presence of a 2, 6-difluorobenzamide: the microchannel reactor is a stainless steel insert reactor, the reaction volume of the reactor is 300ml, the cooling volume of the reactor is 50ml, the temperature control range of the reactor is 50-300 ℃, and the pressure regulation range of the reactor is 0-6 Mpa.

4. The method for preparing 2, 6-difluorobenzamide according to claim 1-3, characterized by: the reaction operation steps are as follows:

s1: preparing a raw material liquid: sequentially adding a certain amount of deionized water and 2, 6-difluorobenzonitrile into a 20L reaction kettle, and stirring and dissolving the mixture clear for later use;

s2: building equipment: the equipment consists of a high-pressure plunger pump and a stainless steel inserting piece type reactor, wherein the high-pressure plunger pump is connected with the inlet end of the stainless steel inserting piece type reactor, then the equipment is started, the temperature and the pressure are set to a reaction required value, and the reaction time is set by the flow rate of the pump;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable in the step S2, pumping the raw material liquid in the step S1 into a reaction section in a stainless steel insert sheet type reactor through the plunger pump in the step S2 for reaction, cooling through a cooling end, and then flowing out of a post-treatment kettle;

s4: and (3) post-treatment: and (4) adding a sodium chloride solution into the post-treatment kettle in the step S3 for salting out, and then filtering, washing and drying to obtain the difluorobenzamide.

5. The process according to claim 4, wherein said reaction is carried out in the presence of a 2, 6-difluorobenzamide: in the step S1, the mass ratio of the deionized water to the 2, 6-difluorobenzonitrile is 2-4: 1.

6. The process according to claim 4, wherein said reaction is carried out in the presence of a 2, 6-difluorobenzamide: in the step S2, the reaction temperature is 240-260 ℃; the reaction pressure is 4-5 Mpa; the reaction time is 0.5-1.5 h.

7. The process according to claim 4, wherein said reaction is carried out in the presence of a 2, 6-difluorobenzamide: in the step S4, the weight ratio of the sodium chloride to the reaction liquid is 0.5-1: 10; the amount of water used in the water washing process is 10-30% of the weight of the solid; the drying temperature is 60-80 ℃; the drying time is 4-8 h.

Technical Field

The invention relates to the field of pesticide preparation, and particularly relates to a preparation method of 2, 6-difluorobenzamide.

Background

The 2, 6-difluorobenzamide is a key intermediate for synthesizing the benzoylurea insecticides, belongs to a chitin synthesis inhibitor, kills insects by inhibiting the biosynthesis of chitin in the bodies of the insects, and has the characteristics of high insecticidal activity, wide insecticidal spectrum, low residual quantity, strong selectivity, safety to people and livestock and the like. Therefore, the market at home and abroad has an increasing demand for high-quality 2, 6-difluorobenzamide.

The synthesis methods reported at present mainly fall into two categories: (1) aminolysis of difluorobenzoic acid and derivatives thereof; (2) and (3) hydrolyzing difluorobenzonitrile. Wherein the hydrolysis method of the difluorobenzonitrile comprises the following steps: (1) acid catalyzed hydrolysis; (2) strong bases catalyze the hydrolysis of hydrogen peroxide. Because one of the two methods uses strong acid and one uses strong base, the post-treatment needs to use a large amount of acid and base for neutralization, thereby not only wasting a large amount of acid and base, but also generating a large amount of waste salt to pollute the environment.

Microfluidics refers to the technology of manipulating complex fluids at microscopic dimensions. In recent years, microfluidics has revolutionized the fields of chemistry, medicine, and life sciences, which is advantageous in that it is safe, efficient, and low cost. The invention develops a method for preparing 2, 6-difluorobenzamide by hydrolyzing 2, 6-difluorobenzonitrile by a continuous flow method by utilizing the characteristics of high mixing mass transfer rate, uniform reaction, continuity and stability, accurate reaction control and the like of a microfluid technology.

Disclosure of Invention

Based on the technical problems in the background art, the invention provides a preparation method of 2, 6-difluorobenzamide.

A preparation method of 2, 6-difluorobenzamide comprises the step of preparing the 2, 6-difluorobenzamide by hydrolyzing 2, 6-difluorobenzonitrile at a high temperature of 220-.

Preferably, the pyrohydrolysis reaction is carried out in a microchannel reactor.

Preferably, the microchannel reactor is a stainless steel insert sheet reactor, the reaction volume of the reactor is 300ml, the cooling volume of the reactor is 50ml, the temperature control range of the reactor is 50-300 ℃, and the pressure regulation range of the reactor is 0-6 Mpa.

Preferably, the reaction operation steps are as follows:

s1: preparing a raw material liquid: sequentially adding a certain amount of deionized water and 2, 6-difluorobenzonitrile into a 20L reaction kettle, and stirring and dissolving the mixture clear for later use;

s2: building equipment: the equipment consists of a high-pressure plunger pump and a stainless steel inserting piece type reactor, wherein the high-pressure plunger pump is connected with the inlet end of the stainless steel inserting piece type reactor, then the equipment is started, the temperature and the pressure are set to a reaction required value, and the reaction time is set by the flow rate of the pump;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable in the step S2, pumping the raw material liquid in the step S1 into a reaction section in a stainless steel insert sheet type reactor through the plunger pump in the step S2 for reaction, cooling through a cooling end, and then flowing out of a post-treatment kettle;

s4: and (3) post-treatment: and (4) adding a sodium chloride solution into the post-treatment kettle in the step S3 for salting out, and then filtering, washing and drying to obtain the difluorobenzamide.

Preferably, the mass ratio of the deionized water to the 2, 6-difluorobenzonitrile is 2-4: 1.

Preferably, the reaction temperature is 240-260 ℃; the reaction pressure is 4-5 Mpa; the reaction time is 0.5-1.5 h.

Preferably, the weight ratio of the sodium chloride to the reaction liquid is 0.5-1: 10; the amount of water used in the water washing process is 10-30% of the weight of the solid; the drying temperature is 60-80 ℃; the drying time is 4-8 h.

Compared with the prior art, the invention has the beneficial effects that:

the method does not need to add any catalyst in the hydrolysis process, does not need acid-base neutralization in the post-treatment process, has simple process, good purity and high yield, and realizes green production. The invention uses the continuous flow process to replace the traditional high-pressure reaction kettle process, so that the reaction process is more controllable, safe and efficient, the production safety is improved, and the generation of byproducts is reduced.

The specific implementation mode is as follows:

the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1:

a preparation method of 2, 6-difluorobenzamide comprises the following operation steps in sequence:

s1: preparing a raw material liquid: respectively adding deionized water and 2, 6-difluorobenzonitrile into a reaction kettle, and uniformly stirring the deionized water and the 2, 6-difluorobenzonitrile according to the mass ratio of 2: 1 to prepare a solution for later use;

s2: building equipment: connecting a high-pressure plunger pump with a stainless steel inserting piece type reactor, setting the temperature of the reactor to be 240 ℃, setting the reaction pressure to be 4Mpa, and setting the flow rate of the plunger pump to be 2.5 ml/min;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable, pumping the raw material liquid into a stainless steel inserted disc tubular reactor by using a plunger pump for reaction, and then flowing out of a post-treatment kettle through a cooling section and a back pressure valve;

s4: and (3) post-treatment: adding sodium chloride solution into the treatment kettle for salting out, wherein the weight ratio of sodium chloride to the reaction solution is 0.5:10, then filtering, and washing the filter cake with water, wherein the volume of the filter cake is 15% of the solid weight; the drying temperature is 60 ℃; the drying time was 8 h.

As a result: the calculated yield of the product obtained by post-treatment is 85.2%, and the purity of the product is 98.8% by liquid phase detection.

Example 2:

a preparation method of 2, 6-difluorobenzamide comprises the following operation steps in sequence:

s1: preparing a raw material liquid: respectively adding deionized water and 2, 6-difluorobenzonitrile into a reaction kettle, and uniformly stirring the deionized water and the 2, 6-difluorobenzonitrile according to the mass ratio of 2: 1 to prepare a solution for later use;

s2: building equipment: connecting a high-pressure plunger pump with a stainless steel inserting piece type reactor, setting the temperature of the reactor to be 280 ℃, setting the reaction pressure to be 4Mpa, and setting the flow rate of the plunger pump to be 5 ml/min;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable, pumping the raw material liquid into a stainless steel inserted disc tubular reactor by using a plunger pump for reaction, and then flowing out of a post-treatment kettle through a cooling section and a back pressure valve;

s4: and (3) post-treatment: adding sodium chloride solution into the treatment kettle for salting out, wherein the weight ratio of sodium chloride to the reaction solution is 0.5:10, then filtering, and washing the filter cake with water, wherein the volume of the filter cake is 15% of the solid weight; the drying temperature is 60 ℃; the drying time was 8 h.

As a result: the calculated yield of the product obtained by post-treatment is 86.2%, and the purity of the product is 98.9% by liquid phase detection.

Example 3:

a preparation method of 2, 6-difluorobenzamide comprises the following operation steps in sequence:

s1: preparing a raw material liquid: respectively adding deionized water and 2, 6-difluorobenzonitrile into a reaction kettle, and uniformly stirring the deionized water and the 2, 6-difluorobenzonitrile according to the mass ratio of 3: 1 to prepare a solution for later use;

s2: building equipment: connecting a high-pressure plunger pump with a stainless steel inserting piece type reactor, setting the temperature of the reactor to be 240 ℃, setting the reaction pressure to be 4Mpa, and setting the flow rate of the plunger pump to be 2.5 ml/min;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable, pumping the raw material liquid into a stainless steel inserted disc tubular reactor by using a plunger pump for reaction, and then flowing out of a post-treatment kettle through a cooling section and a back pressure valve;

s4: salting out treatment: adding a sodium chloride solution into the post-treatment kettle in the step S3 for salting out, wherein the weight ratio of sodium chloride to the reaction solution is 0.5:10, then filtering, and washing the filter cake with water, wherein the volume is 15% of the solid weight; the drying temperature is 60 ℃; the drying time was 8 h.

As a result: the calculated yield of the product obtained by post-treatment is 86.1%, and the purity of the product is 99.0% by liquid phase detection.

Example 4:

a preparation method of 2, 6-difluorobenzamide comprises the following operation steps in sequence:

s1: preparing a raw material liquid: respectively adding deionized water and 2, 6-difluorobenzonitrile into a reaction kettle, and uniformly stirring the deionized water and the 2, 6-difluorobenzonitrile according to the mass ratio of 3: 1 to prepare a solution for later use;

s2: building equipment: connecting a high-pressure plunger pump with a stainless steel inserting piece type reactor, setting the temperature of the reactor to be 260 ℃, setting the reaction pressure to be 5Mpa, and setting the flow rate of the plunger pump to be 2.5 ml/min;

s3: high-temperature hydrolysis: after the temperature and the pressure are stable, pumping the raw material liquid into a stainless steel inserted disc tubular reactor by using a plunger pump for reaction, and then flowing out of a post-treatment kettle through a cooling section and a back pressure valve;

s4: and (3) post-treatment: adding sodium chloride solution into the treatment kettle for salting out, wherein the weight ratio of sodium chloride to the reaction solution is 0.5:10, then filtering, and washing the filter cake with water, wherein the volume of the filter cake is 15% of the solid weight; the drying temperature is 60 ℃; the drying time was 8 h.

As a result: the calculated yield of the product obtained by post-treatment is 86.3%, and the purity of the product is 99.0% by liquid phase detection.