阅读说明：本技术 一种连续法合成水杨酰胺的方法 (Method for synthesizing salicylamide by continuous method ) 是由 范谦 吴锋 李炜 李强 于 2021-10-18 设计创作，主要内容包括：本发明公开了一种连续法合成水杨酰胺的方法,(1)：酰氯化试剂光气与水杨酸的溶液在连续反应器中进行酰氯化反应,得到水杨酰氯；(2)：水杨酰氯与甲醇在连续反应器中进行酯化反应,得到水杨酸甲酯；(3)：水杨酸甲酯与氨的甲醇溶液在连续反应器中进行氨化反应,得到水杨酰胺。本发明的有益效果：(1)该工艺提高了水杨酸甲酯的反应收率(98%以上),无废水、废酸排放；(2)该工艺提高了水杨酰胺的反应收率(98%以上),无含氨氮废水排放；(3)该工艺实现了水杨酰胺的连续化反应,节约了产品的提纯能耗和成本。(4)产品纯度高、操作简便。(The invention discloses a method for synthesizing salicylamide by a continuous method, which comprises the following steps: carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor to obtain salicyloyl chloride; (2): carrying out esterification reaction on salicyloyl chloride and methanol in a continuous reactor to obtain methyl salicylate; (3): carrying out ammoniation reaction on methyl salicylate and methanol solution of ammonia in a continuous reactor to obtain salicylamide. The invention has the beneficial effects that: (1) the process improves the reaction yield of the methyl salicylate (more than 98 percent), and no waste water or waste acid is discharged; (2) the process improves the reaction yield of the salicylamide (more than 98 percent), and no wastewater containing ammonia nitrogen is discharged; (3) the process realizes the continuous reaction of the salicylamide, and saves the energy consumption and the cost for purifying the product. (4) High product purity and simple operation.)

1. A method for synthesizing salicylamide by a continuous method is characterized in that: the method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor to obtain salicyloyl chloride;

step (2): carrying out esterification reaction on salicyloyl chloride and methanol in a continuous reactor to obtain methyl salicylate;

and (3): carrying out ammoniation reaction on methyl salicylate and methanol solution of ammonia in a continuous reactor to obtain salicylamide.

2. The continuous process for the synthesis of salicylamide according to claim 1, characterized in that: the method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor, and removing excessive phosgene and a solvent through continuous desolventizing equipment to obtain salicyloyl chloride;

step (2): carrying out esterification reaction on salicyloyl chloride and methanol in a continuous reactor, and removing hydrogen chloride and excessive methanol generated by the reaction through continuous desolventizing equipment to obtain methyl salicylate;

and (3): performing ammoniation reaction on methyl salicylate and a methanol solution of ammonia in a continuous reactor, and performing deamination and methanol removal by using continuous desolventizing equipment to obtain high-content salicylamide; the removed ammonia gas and methanol are recycled and then returned to the ammonification and esterification working section.

3. The continuous process for the synthesis of salicylamide according to claim 1, characterized in that: the continuous reactor may independently be a microchannel reactor, a tubular reactor, a tower reactor, a loop reactor, or a combination thereof.

4. The continuous process for the synthesis of salicylamide according to claim 2, characterized in that: the continuous desolventizing device can be independently a film evaporator, a short-path distillation device, a molecular distillation device, a hypergravity rectification device or a combination thereof.

5. The continuous process for the synthesis of salicylamide according to claim 1, characterized in that: in the salicylic acid solution, the solvent is benzene, toluene, xylene, trimethylbenzene, chlorobenzene, dichlorobenzene or the combination thereof.

6. The continuous process for the synthesis of salicylamide according to claim 1, characterized in that: the method comprises the following steps:

step (1): carrying out acyl chlorination reaction on phosgene as an acyl chlorination reagent and a solution of salicylic acid in a continuous reactor, wherein the acyl chlorination temperature is 40-70 ℃, and preferably 50-60 ℃;

step (2): carrying out esterification reaction on salicyl chloride and methanol in a continuous reactor, wherein the esterification temperature is 10-50 ℃, and preferably 20-30 ℃;

and (3): the methyl salicylate and the methanol solution of ammonia are subjected to ammoniation reaction in a continuous reactor, wherein the ammoniation temperature is 40-100 ℃, and preferably 45-55 ℃.

7. The continuous process for the synthesis of salicylamide according to claim 6, characterized in that: the method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor, wherein the molar ratio of the phosgene to the salicylic acid is (1-5): 1, preferably (1.1-2): 1;

step (2): the salicyl chloride and methanol are subjected to esterification reaction in a continuous reactor, and the molar ratio of the salicyl chloride to the methanol is preferably 1: (0.9-10), preferably 1: (0.95-1.5);

and (3): carrying out ammoniation reaction on methyl salicylate and a methanol solution of ammonia in a continuous reactor, wherein the molar ratio of the methyl salicylate to the ammonia is 1: (1-20), preferably 1: (2-7).

Technical Field

The invention relates to a method for synthesizing salicylamide.

Background

Salicylamide (Salicylamide) has the chemical name of o-hydroxybenzamide and is an important intermediate of chemical industry, medicines, pesticides, spices and liquid crystals with wide application. It is also a medicine itself, and is used for the treatment of fever headache, arthralgia, neuralgia, etc. In recent years, salicylamide has been increasingly demanded as an important intermediate for fine chemicals.

The prior industrial production process of salicylamide generally adopts salicylic acid as a starting material, and the salicylic acid is esterified with methanol under the catalysis of sulfuric acid to generate methyl salicylate (for example: CN110563581A), and then the methyl salicylate is ammonolyzed in ammonia water to obtain the salicylamide (CN106518704A), and the production process has obvious defects, mainly comprising the following steps:

(1) the consumption of sulfuric acid is large (accounting for 10 percent of the total mass), a large amount of waste water and waste acid are generated in the post-treatment process, the yield of methyl salicylate is not high (the yield does not exceed 85 percent) because the esterification reaction can not completely convert the reversible raw materials, and the methyl salicylate needs to be rectified and purified finally, so the energy consumption is high, and the production cost is high.

(2) The ammonolysis reaction is carried out under the condition of ammonia water, a large amount of ammonia-containing wastewater is generated after the reaction, and because the reaction system is carried out in water, methyl salicylate is easy to generate side reaction and hydrolyze to generate salicylic acid, so that the yield is not high (the yield is lower than 90%).

(3) The traditional kettle type intermittent process is adopted for both esterification and aminolysis, so that the efficiency is low, and the product quality has certain fluctuation.

(4) Although the literature reports that solid acid, super acid and strong acid resin are used to replace sulfuric acid for esterification reaction, the cost is high, and the large-scale industrialization is difficult.

Along with the national stricter supervision on the safety and environmental protection of chemical production, higher requirements are provided for chemical process control and continuous production; the control on the chemical process is strengthened, the discharge of three wastes is reduced, and the control on-line amount of dangerous chemicals is an urgent problem to be solved by production enterprises.

Disclosure of Invention

The invention aims to provide a method for synthesizing salicylamide by a continuous method, which has high yield, high purity and simple and convenient operation.

The technical solution of the invention is as follows:

a method for synthesizing salicylamide by a continuous method is characterized in that: the method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor to obtain salicyloyl chloride;

step (2): carrying out esterification reaction on salicyloyl chloride and methanol in a continuous reactor to obtain methyl salicylate;

and (3): carrying out ammoniation reaction on methyl salicylate and methanol solution of ammonia in a continuous reactor to obtain salicylamide.

The method for synthesizing salicylamide by the continuous method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor, and removing excessive phosgene and a solvent through continuous desolventizing equipment to obtain salicyloyl chloride;

step (2): carrying out esterification reaction on salicyloyl chloride and methanol in a continuous reactor, and removing hydrogen chloride and excessive methanol generated by the reaction through continuous desolventizing equipment to obtain methyl salicylate;

and (3): performing ammoniation reaction on methyl salicylate and a methanol solution of ammonia in a continuous reactor, and performing deamination and methanol removal by using continuous desolventizing equipment to obtain high-content salicylamide; the removed ammonia gas and methanol are recycled and then returned to the ammonification and esterification working section.

The continuous reactor may independently be a microchannel reactor, a tubular reactor, a tower reactor, a loop reactor, or a combination thereof.

The continuous desolventizing device can be independently a film evaporator, a short-path distillation device, a molecular distillation device, a hypergravity rectification device or a combination thereof.

In the salicylic acid solution, the solvent is benzene, toluene, xylene, trimethylbenzene, chlorobenzene, dichlorobenzene or the combination thereof.

The method for synthesizing salicylamide by the continuous method comprises the following steps:

step (1): carrying out acyl chlorination reaction on phosgene as an acyl chlorination reagent and a solution of salicylic acid in a continuous reactor, wherein the acyl chlorination temperature is 40-70 ℃, and preferably 50-60 ℃;

step (2): carrying out esterification reaction on salicyl chloride and methanol in a continuous reactor, wherein the esterification temperature is 10-50 ℃, and preferably 20-30 ℃;

and (3): the methyl salicylate and the methanol solution of ammonia are subjected to ammoniation reaction in a continuous reactor, wherein the ammoniation temperature is 40-100 ℃, and preferably 45-55 ℃.

The method for synthesizing salicylamide by the continuous method comprises the following steps:

step (1): carrying out acyl chlorination reaction on a solution of an acyl chlorination reagent phosgene and salicylic acid in a continuous reactor, wherein the molar ratio of the phosgene to the salicylic acid is (1-5): 1, preferably (1.1-2): 1;

step (2): the salicyl chloride and methanol are subjected to esterification reaction in a continuous reactor, and the molar ratio of the salicyl chloride to the methanol is preferably 1: (0.9-10), preferably 1: (0.95-1.5);

and (3): carrying out ammoniation reaction on methyl salicylate and a methanol solution of ammonia in a continuous reactor, wherein the molar ratio of the methyl salicylate to the ammonia is 1: (1-20), preferably 1: (2-7).

The invention has the beneficial effects that: (1) the process improves the reaction yield of the methyl salicylate (more than 98 percent), and no waste water or waste acid is discharged; (2) the process improves the reaction yield of the salicylamide (more than 98 percent), and no wastewater containing ammonia nitrogen is discharged; (3) the process realizes the continuous reaction of the salicylamide, and saves the energy consumption and the cost for purifying the product. (4) High product purity and simple operation.

Drawings

FIG. 1 is a schematic process flow diagram of examples 1-29.

Detailed Description

The invention is further illustrated by the following specific examples, which are not intended to limit the invention thereto.

The purity of the product in this example was determined by High Performance Liquid Chromatography (HPLC), and the yield of the product was calculated after HPLC measurement of external standard content of salicylamide in the solution.

Comparative example 1

Adding chlorobenzene salicylate solution into a reaction kettle, heating to 55 ℃, introducing 2 times of equivalent of phosgene for phosgenation reaction, introducing nitrogen to remove excessive phosgene and HCl generated by the reaction after the reaction is finished, removing chlorobenzene under negative pressure after the reaction is finished to obtain salicyloyl chloride, adding 1 time of equivalent of methanol into the reaction kettle, performing esterification reaction at 25 ℃, introducing nitrogen to remove HCl generated by the reaction after the reaction is finished, obtaining methyl salicylate after the reaction is finished, adding the obtained methyl salicylate into the reaction kettle, adding methanol, introducing 3 times of equivalent of ammonia gas, performing ammoniation reaction at 50 ℃, and performing pressure relief and desolventization after the reaction is finished to obtain salicylamide. The reaction parameters and results are given in the following table:

examples 1 to 29

The method comprises the steps of enabling a salicylic acid solution (1 time equivalent) and phosgene to continuously enter an acyl chlorination reactor according to a certain proportion to react to generate salicyloyl chloride, enabling the obtained salicyloyl chloride solution to enter continuous desolventizing equipment to remove excessive phosgene and solvent, enabling the obtained salicyloyl chloride solution and methanol to respectively enter an esterification reactor according to a certain proportion to continuously react to generate methyl salicylate, enabling the obtained methyl salicylate solution to enter continuous desolventizing equipment to remove hydrogen chloride gas and excessive methanol, enabling the obtained methyl salicylate solution and an ammonia methanol solution to enter a continuous ammoniation reactor to synthesize salicylamide, enabling the salicylamide solution to be subjected to continuous deamination and dealcoholization to obtain salicylamide, and enabling the removed ammonia gas and methanol to return to an ammoniation and esterification working section after being recovered.

The reaction parameters and results are as follows:

thus, the excellent technical effects of the present invention can be seen.