CN119080600A - A kind of preparation method of o-trifluoromethylbenzoic acid - Google Patents

Abstract

The invention discloses a method for preparing o-trifluoromethylbenzoic acid. Specifically, the invention provides a method for preparing a compound as shown in formula I, comprising the following steps: in the presence of an acid and nitrosylsulfuric acid, a compound as shown in formula II undergoes a hydrolysis reaction to generate a compound as shown in formula I. The preparation method can prepare the target compound with high yield and high purity, is simple to operate, does not produce inorganic salt byproducts, is environmentally friendly, has low production cost, and is suitable for industrial production.

Description

Preparation method of o-trifluoromethyl benzoic acid

Technical Field

The technical scheme relates to the field of organic chemical synthesis, and mainly relates to a preparation method of o-trifluoromethyl benzoic acid.

Background

O-trifluoromethyl benzoic acid is an important organic intermediate and is widely applied to the fields of pesticides, medicines, dyes and the like. The current report of preparing o-trifluoromethyl benzoic acid has industrial production feasibility, wherein o-chlorotrifluorotoluene is taken as a raw material, a Grignard reagent of o-trifluoromethyl chlorobenzene is prepared through Grignard reaction, then the Grignard reagent is added with methyl chloroformate to synthesize o-trifluoromethyl benzoic acid methyl ester, and finally the o-trifluoromethyl benzoic acid as a target intermediate is synthesized through hydrolysis under a sodium hydroxide/water methanol system.

And o-trifluoromethyl benzaldehyde is used as a raw material, and o-trifluoromethyl benzoic acid is prepared by further oxidation.

In addition, o-trifluoromethyl toluene is taken as a raw material, is substituted by chlorine, is hydrolyzed into an intermediate o-trifluoromethyl benzaldehyde, and is oxidized into o-trifluoromethyl benzoic acid.

The existing preparation method of the o-trifluoromethyl benzoic acid has a plurality of problems, such as harsh reaction conditions, serious environmental pollution, low selectivity, more byproducts, complex post-treatment, high cost and the like. Therefore, the development of a novel, environment-friendly, efficient and low-cost preparation method of the o-trifluoromethyl benzoic acid has important theoretical and practical significance.

Disclosure of Invention

The invention aims to solve the technical problems of harsh reaction conditions, serious environmental pollution, low selectivity, more byproducts, complex post-treatment, high cost and the like of the traditional preparation method of the o-trifluoromethyl benzoic acid. The preparation method can prepare the target compound with high yield and high purity, is simple and convenient to operate, does not produce inorganic salt byproducts, is environment-friendly, has low production cost, and is suitable for industrial production.

The invention provides a preparation method of o-trifluoromethyl benzoic acid, which comprises the following steps of carrying out hydrolysis reaction on a compound shown in a formula II in the presence of acid and nitrosylsulfuric acid to generate a compound shown in a formula I;

in one embodiment of the invention, the acid is sulfuric acid.

In one embodiment of the invention, the concentration of the acid is 10% -90%, preferably 30% -90%, for example 30%, 50% or 70%.

In one embodiment of the present invention, the molar ratio of the compound represented by formula II to the acid is 1 (1-8), preferably 1 (1-5), for example 1:1.74, 1:2.9 or 1:4.

In one embodiment of the present invention, the nitrosylsulfuric acid is used in the form of a sulfuric acid solution of nitrosylsulfuric acid, and the concentration of the sulfuric acid solution of nitrosylsulfuric acid is 40%.

In one embodiment of the present invention, the molar ratio of the compound shown in formula II to the nitrosylsulfuric acid is 1 (1-1.4), for example, 1:1.2.

In one embodiment of the present invention, the hydrolysis reaction comprises the following steps:

Step 1, mixing the compound shown in the formula I with the acid to obtain a mixed solution:

Step 2, adding the nitrosylsulfuric acid into the mixed solution in the step 1;

the adding is preferably dropwise adding, and preferably, the speed of dropwise adding is controlled to be 80-110 ℃ in the temperature of the mixed solution.

In one embodiment of the present invention, the hydrolysis reaction is performed at a temperature of 70 to 120 ℃, preferably 80 to 110 ℃, for example 80 ℃, 90 ℃ or 110 ℃.

The progress of the hydrolysis reaction is monitored by methods conventional in the art (e.g., TLC, HPLC or NMR), typically by taking the end point of the reaction when the compound of formula II disappears or no longer reacts or the compound of formula I does not increase. The hydrolysis reaction time is 2-10 h.

In a certain scheme of the invention, after the hydrolysis reaction is finished, the post-treatment further comprises the steps of cooling the reaction liquid to 0-40 ℃, filtering, washing and drying to obtain the compound shown in the formula I, and preferably cooling the reaction liquid to 25 ℃.

In one embodiment of the present invention, the raw material for the hydrolysis reaction is composed of the sulfuric acid, the compound represented by formula II, and the nitrosylsulfuric acid.

In one scheme of the invention, the hydrolysis reaction is carried out by reacting sulfuric acid, the compound shown in the formula II and sulfuric acid solution of nitrosylsulfuric acid at a reaction temperature of 80-110 ℃,

The concentration of the sulfuric acid is 30%, 50% or 70%;

the molar ratio of the compound shown as the formula II to the sulfuric acid is 1:1.74, 1:2.9 or 1:4;

the concentration of the sulfuric acid solution of the nitrosylsulfuric acid is 40%;

The molar ratio of the compound shown in the formula II to the nitrosylsulfuric acid is 1:1.2.

The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.

The reagents and materials used in the present invention are commercially available.

The invention has the positive progress effects that:

(1) The o-trifluoromethyl benzoic acid is prepared by adopting the diazotization hydrolysis method of nitrosylsulfuric acid, so that the use of a metal catalyst is avoided, the reaction performance is better under the condition of low-concentration sulfuric acid, the environmental pollution is reduced, and the environmental protection of the reaction is improved;

(2) The reaction condition is mild, high temperature and high pressure are not needed, the energy consumption and the equipment loss are reduced, and the production cost is saved;

(3) The reaction selectivity is high, byproducts such as inorganic salt and the like are not generated, the post-treatment process is simplified, and the purity and the yield of the product are improved;

(4) The reaction filtrate can be directly used, so that the waste emission is reduced, and the resource utilization rate is improved;

(5) The operation steps are simple, the implementation is easy, and the method is suitable for large-scale industrial production.

Detailed Description

The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.

Example 1:

A500 ml four-necked flask was prepared, and equipped with a stirrer, a thermometer and a reflux condenser. To the flask was added 150g of a 70% strength sulfuric acid solution, starting material o-trifluoromethylbenzamide (50 g,0.264 mol). The flask was placed in an oil bath, the stirrer was turned on, and the temperature was slowly raised to 80 ℃ to keep the system clear. The addition of the nitrosylsulfuric acid/sulfuric acid solution (concentration: 40%,100.9 g) was started, during which the system temperature was monitored by a thermometer, keeping the temperature between 80 and 90 ℃ (addition time 5 h). After the nitrosylsulfuric acid/sulfuric acid solution is added dropwise, keeping the system at 80-90 ℃ for 2 hours, and confirming the completion of the raw material reaction through central control. Stopping heating, cooling to about 5 ℃, filtering, and collecting a filter cake. The filter cake is washed three times by using 50g of water, and then the filter cake is put into an oven to be dried for 12 hours at 60 ℃ to obtain 49.4g of o-trifluoromethyl benzoic acid which is a target product, the purity is 99.3%, and the yield is 98.5%. Product ¹ H NMR (400 MHz, DMSO-d 6) 8.19 (d, J=7.8 Hz, 1H), 8.13 (s, 1H), 7.96 (d, J=7.7 Hz, 1H), 7.72 (t, J=7.8 Hz, 1H). The filtrate was recovered and used for the next reaction.

The following examples prepare the synthesis with reference to example 1.

Example 2:

Sulfuric acid aqueous solution (50%, 150 g) and o-trifluoromethyl benzamide (50 g,0.264 mol) are added into a reaction bottle, the temperature is raised to 80-90 ℃, nitrosyl sulfuric acid/sulfuric acid solution (100.9 g, 40%) is added dropwise, the reaction bottle is subjected to dropwise addition for 4.5h, the dropwise addition is kept for 2h, the reaction of raw materials is confirmed through central control, stirring and cooling are carried out to room temperature, filtration is carried out, a filter cake is washed three times by water (the water consumption is 50g each time and 150g is all), the product is obtained through drying, the purity is 49.4g, the purity is 99.5%, and the yield is 98.5%.

Example 3

Sulfuric acid aqueous solution (30%, 150 g) and o-trifluoromethyl benzamide (50 g,0.264 mol) are added into a reaction bottle, the temperature is raised to 90 ℃, nitrosyl sulfuric acid/sulfuric acid solution (100.9 g, 40%) is added dropwise, the dropwise addition is carried out for 4 hours, the dropwise addition is completed, the heat preservation is carried out for 2 hours, the reaction of raw materials is confirmed through central control, the raw materials are stirred and cooled to room temperature, the filtration is carried out, a filter cake is washed three times by water (the water consumption is 50g each time and 150g total), the product is obtained by drying, the purity is 99.7%, and the yield is 97.9%.

Example 4

Sulfuric acid aqueous solution (70%, 150 g) and o-trifluoromethyl benzamide (50 g,0.264 mol) are added into a reaction bottle, the temperature is raised to 90 ℃, nitrosyl sulfuric acid/sulfuric acid solution (100.9 g, 40%) is added dropwise, the temperature is kept for 6 hours after the dropwise addition, the reaction of raw materials is confirmed by central control, stirring and cooling are carried out to room temperature, filtration is carried out, a filter cake is washed three times by water (the water consumption is 50g each time and 150g total), the product is obtained by drying, the purity is 99.2%, and the yield is 98.3%.

Example 5

Sulfuric acid aqueous solution (30%, 150 g) and o-trifluoromethyl benzamide (50 g,0.264 mol) are added into a reaction bottle, the temperature is raised to 110 ℃, nitrosyl sulfuric acid/sulfuric acid solution (100.9 g, 40%) is added dropwise, the temperature is kept for 5 hours, the dropwise addition is completed, the reaction of the raw materials is confirmed through central control, stirring and cooling are carried out to room temperature, filtration is carried out, a filter cake is washed three times by water (the water consumption is 50g each time and 150g is taken together), the product is obtained by drying, the purity is 49.0g and is more than 99.4%, and the yield is 97.7%.

The reaction center control method comprises the following steps:

GC analysis, analytical method parameters:

the o-trifluoromethylbenzamide chromatography retention time was 14.4min and the o-trifluoromethylbenzoic acid chromatography retention time was 12min.

Claims (10)

1. A preparation method of o-trifluoromethyl benzoic acid comprises the following steps of carrying out hydrolysis reaction on a compound shown in a formula II in the presence of acid and nitrosylsulfuric acid to generate a compound shown in a formula I;

2. the method of claim 1, wherein one or more of the following conditions are satisfied:

(1) The acid is sulfuric acid;

(2) The concentration of the acid is 10% -90%;

(3) The molar ratio of the compound shown in the formula II to the acid is 1 (1-8);

(4) The nitrosylsulfuric acid is used in the form of a sulfuric acid solution of nitrosylsulfuric acid;

(5) The molar ratio of the compound shown in the formula II to the nitrosylsulfuric acid is 1 (1-1.4).

3. The preparation method according to claim 2, characterized in that it satisfies one or more of the following conditions:

(1) The concentration of the acid is 30% -90%;

(2) The molar ratio of the compound shown in the formula II to the acid is 1 (1-5);

(3) The concentration of the sulfuric acid solution of the nitrosylsulfuric acid is 40%;

(4) The molar ratio of the compound shown in the formula II to the nitrosylsulfuric acid is 1:1.2.

4. A method of preparation as claimed in claim 3, characterised in that it satisfies one or both of the following conditions:

(1) The concentration of the acid is 30%, 50% or 70%;

(2) The molar ratio of the compound shown as the formula II to the acid is 1:1.74, 1:2.9 or 1:4.

5. The method of claim 1, wherein the hydrolysis reaction is performed by:

Step 1, mixing the compound shown in the formula I with the acid to obtain a mixed solution:

and 2, adding the nitrosylsulfuric acid into the mixed solution in the step 1.

6. The method of claim 5, wherein one or more of the following conditions are satisfied:

(1) The adding is dripping;

(2) The temperature of the hydrolysis reaction is 70-120 ℃;

(3) The method comprises the steps of cooling reaction liquid to 0-40 ℃, filtering, washing and drying to obtain the compound shown in the formula I.

7. The method of claim 6, wherein one or more of the following conditions are satisfied:

(1) The dropping speed is controlled to be 80-110 ℃ when the temperature of the mixed solution is controlled;

(2) The temperature of the hydrolysis reaction is 80-110 ℃;

(3) The reaction solution was cooled to 25 ℃.

8. The method of claim 7, wherein the hydrolysis reaction is at a temperature of 80 ℃, 90 ℃, or 110 ℃.

9. The process according to claim 2, wherein the starting material for the hydrolysis reaction consists of the sulfuric acid, the compound of formula II and the nitrosylsulfuric acid.

10. The process for producing a nitrosylsulfuric acid according to claim 2, wherein the hydrolysis reaction is carried out by reacting the sulfuric acid, the compound represented by the formula II and a sulfuric acid solution of nitrosylsulfuric acid at a reaction temperature of 80 to 110 ℃,

The concentration of the sulfuric acid is 30%, 50% or 70%;

the molar ratio of the compound shown as the formula II to the sulfuric acid is 1:1.74, 1:2.9 or 1:4;

the concentration of the sulfuric acid solution of the nitrosylsulfuric acid is 40%;

The molar ratio of the compound shown in the formula II to the nitrosylsulfuric acid is 1:1.2.