Synthetic method of p-fluorobenzoic acid

Abstract

The invention discloses a synthesis method of p-fluorobenzoic acid, and relates to the technical field of chemical synthesis. According to the method, p-fluorobenzonitrile is adopted as a reaction raw material, p-fluorobenzoic acid is prepared through a fluorine-chlorine exchange and hydrolysis combined method, nitrobenzene and sulfolane are used as a mixed solvent in the fluorine-chlorine exchange process, it can be guaranteed that p-fluorobenzoic acid is synthesized within a short time, the yield of the synthesized p-fluorobenzoic acid is high, and the method is suitable for industrial production. The problems of serious environmental pollution, high raw material cost and low yield of p-fluorobenzoic acid synthesis in the prior art are solved.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing p-fluorobenzoic acid. Background Art

[0002] 4-Fluorobenzoic acid is an important organic intermediate, which is widely used in medicine, pesticide, dye and other industries. The products synthesized with 4-fluorobenzoic acid have excellent performance. The pesticide produced with 4-fluorobenzoic acid as raw material has the advantages of high physiological activity, high efficiency and low toxicity; the polymer produced with 4-fluorobenzoic acid has the characteristics of good heat resistance, good toughness and high strength.

[0003] The synthesis methods of p-fluorobenzoic acid include: (1) using p-aminotoluene as a raw material, generating p-fluorotoluene through a diazotization reaction, and generating p-fluorotoluene through an oxidation reaction to generate p-fluorobenzoic acid. This method is an industrial production method, and has the advantage of low raw material prices, but the yield is not high, and a large amount of waste gas and wastewater are generated, which poses environmental problems; (2) using p-methylfluorobenzene as a raw material, directly generating p-fluorobenzoic acid through an oxidation reaction. This method uses air or oxygen for the oxidation reaction, and the reaction selectivity is not high; (3) using fluorochlorobenzene as a raw material, and preparing p-fluorobenzoic acid by an electrochemical method. This method has high raw material prices, immature processes, and high energy consumption.

[0004] In the prior art, CN 1187321C discloses a method for preparing p-chlorobenzonitrile by fluorination of p-fluorobenzonitrile. Specifically, p-chlorobenzonitrile and alkali metal fluoride are used as raw materials, 1,3-dimethyl-2-imidazolidinone (DMI) is used as solvent, and the reaction is carried out for 2-4 hours at 260-285°C and 0.2-0.6MPa to obtain p-fluorobenzonitrile. However, 1,3-dimethyl-2-imidazolidinone is used as solvent to reduce the amount of reaction solvent used in the reaction process, and the reaction time is long and the reaction conditions are harsh. Patent CN1772724A discloses a preparation process of pentafluorobenzoic acid. Specifically, potassium chloride, pentafluorobenzonitrile, benzonitrile and auxiliary agent k-12 are heated and reacted for several hours under the protection of nitrogen to obtain pentachlorobenzonitrile; and then formic acid is hydrolyzed in pentachlorobenzonitrile. During the fluorine exchange process, the reaction temperature is 300°C, the reaction time is 15 hours, and the product yield is 65.3-82.3%. During the acidic hydrolysis process, the reaction temperature is 140°C, the reaction time is 10 hours, and the product yield is 28.9-71.9%. The above reaction conditions are high, the reaction time is long, and the yield is low.

[0005] Therefore, it is necessary to develop a synthesis process of p-chlorobenzoic acid with high yield and short reaction time. Summary of the invention

[0006] In view of the above-mentioned prior art, the purpose of the present invention is to provide a method for synthesizing p-fluorobenzoic acid. The present invention adopts p-fluorobenzonitrile as a reaction raw material, and prepares p-fluorobenzoic acid by a method combining fluorine-chlorine exchange and hydrolysis, and uses nitrobenzene and cyclopentane as a mixed solvent in the fluorine-chlorine exchange process, which can ensure that p-fluorobenzoic acid is synthesized in a short time and the yield of the synthesized p-fluorobenzoic acid is high, thereby solving the problems of large environmental pollution, high raw material cost and low yield in the synthesis of p-fluorobenzoic acid in the prior art.

[0007] To achieve the above object, the present invention adopts the following technical solution:

[0008] The present invention provides a method for synthesizing p-fluorobenzoic acid, comprising the following steps:

[0009] (1) p-chlorobenzonitrile is used as a reaction raw material, hydrogen fluoride or potassium fluoride is used as a fluorination agent, and a mixture of nitrobenzene and sulfolane is used as a reaction solvent. The reaction raw material and the fluorination agent are mixed and placed in the reaction solvent for a fluorination reaction to obtain p-fluorobenzonitrile;

[0010] (2) Add acid to p-fluorobenzonitrile and undergo hydrolysis to obtain p-fluorobenzoic acid.

[0011] Preferably, in step (1), the volume ratio of nitrobenzene to sulfolane in the reaction solvent is 1:(1-1.5).

[0012] Further preferably, the volume ratio of nitrobenzene to sulfolane is 1:1.2.

[0013] Preferably, in step (1), the molar ratio of the reaction raw material to the fluorination agent is 1:(2-10).

[0014] Preferably, in step (1), the total mass of the reaction raw materials and the fluorination agent to the mass of the reaction solvent is 1:(2-10).

[0015] Further preferably, the volume ratio of the total mass of the reaction raw materials and the fluorination reagent to the reaction solvent is 1:4.

[0016] Preferably, in step (1), the reaction temperature is 200-500° C., the reaction pressure is 0.1-3 MPa, and the reaction time is 10 min-10 h.

[0017] Preferably, in step (2), the acid is hydrochloric acid or sulfuric acid.

[0018] Further preferably, the mass fraction of the sulfuric acid is 98%, and the mass fraction of the hydrochloric acid is 30-37.5%.

[0019] Preferably, in step (2), the molar ratio of p-fluorobenzonitrile to acid is 1:(1.05-1.5).

[0020] Preferably, in step (2), the hydrolysis reaction temperature is 50-100° C. and the reaction time is 1-10 h.

[0021] Beneficial effects of the present invention:

[0022] The invention adopts p-chlorobenzonitrile as a reaction raw material, and prepares p-fluorobenzoic acid through a method combining fluorine-chlorine exchange and hydrolysis. In the process of fluorine-chlorine exchange reaction, nitrobenzene and cyclopentane sulfone are used as mixed solvents to achieve the purpose of shortening the reaction time and reducing the temperature and pressure parameters required for the reaction. At the same time, the invention adopts a method combining fluorine-chlorine exchange and hydrolysis, which can ensure that p-fluorobenzoic acid is synthesized in a short time and the yield of the synthesized p-fluorobenzoic acid is high, thereby solving the problems of large environmental pollution, high raw material cost and low yield in the prior art of p-fluorobenzoic acid synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 : Schematic diagram of the synthesis of p-fluorobenzoic acid. DETAILED DESCRIPTION

[0024] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0025] In order to enable those skilled in the art to more clearly understand the technical solution of the present application, the technical solution of the present application will be described in detail below in conjunction with specific embodiments.

[0026] As described in the background art, the synthesis method of p-fluorobenzoic acid is to use p-fluorotoluene as a raw material, cobalt acetate as a catalyst, add acetic acid, and react to obtain p-fluorobenzoic acid. Alternatively, p-fluorobenzaldehyde is used as a raw material, an acid is added, and p-fluorobenzoic acid is obtained by reaction. However, the above synthesis method has the problems of low yield and generation of a large amount of wastewater and waste gas, and the synthesis conditions required are relatively high.

[0027] Based on this, the present invention provides a preparation method of p-fluorobenzoic acid. The present invention adopts p-fluorobenzonitrile as a reaction raw material, first adopts fluorine-chlorine exchange to prepare p-chlorobenzonitrile, and in the fluorine-chlorine exchange process, adopts nitrobenzene and sulfolane as a mixed solvent. According to the molecular collision theory, the mixed solvent can shorten the reaction diffusion time, thereby shortening the reaction time. And by utilizing the unique properties of nitrobenzene and sulfolane, the two work together to better promote the dissolution and mixing of the reaction raw materials in the reaction process, thereby improving the reaction efficiency and product purity.

[0028] At the same time, the present invention adopts a method combining fluorine-chlorine exchange and hydrolysis, which can not only ensure the synthesis of p-fluorobenzoic acid in a short time, but also ensure the high yield of the synthesized p-fluorobenzoic acid, thereby solving the problems of great environmental pollution, high raw material cost and low yield in the synthesis of p-fluorobenzoic acid in the prior art.

[0029] The test materials used in the examples of the present invention are all conventional test materials in the art and can be purchased through commercial channels.

[0030] Example 1: Preparation of p-fluorobenzoic acid

[0031] (1) p-chlorobenzonitrile is used as a reaction raw material, anhydrous hydrogen fluoride is used as a fluorination agent, and nitrobenzene and sulfolane are mixed in a volume ratio of 1:1.2 as a reaction solvent. The reaction raw material and the fluorination agent are mixed in a molar ratio of 1:2, placed in the reaction solvent, and reacted at 300° C. and 0.1 MPa for 10 minutes to obtain p-chlorobenzonitrile, wherein the total mass ratio of the reaction raw material and the fluorination agent to the mass ratio of the reaction solvent is 1:2;

[0032] (2) Add 98% concentrated sulfuric acid to p-chlorobenzonitrile, wherein the molar ratio of p-chlorobenzonitrile to concentrated sulfuric acid is 1:1.2, and perform a hydrolysis reaction at 50° C. for 1 hour to obtain p-fluorobenzoic acid.

[0033] The yield of p-fluorobenzoic acid prepared in this example is 95%.

[0034] Example 2: Preparation of p-fluorobenzoic acid

[0035] (1) p-chlorobenzonitrile is used as a reaction raw material, anhydrous hydrogen fluoride is used as a fluorination agent, and nitrobenzene and cyclopentane are mixed in a volume ratio of 1:1 as a reaction solvent. The reaction raw material and the fluorination agent are mixed in a molar ratio of 1:6, placed in the reaction solvent, and reacted at 400° C. and 0.3 MPa for 30 minutes to obtain p-chlorobenzonitrile, wherein the total mass ratio of the reaction raw material and the fluorination agent to the mass ratio of the reaction solvent is 1:10;

[0036] (2) Add 98% concentrated sulfuric acid to p-chlorobenzonitrile, wherein the molar ratio of p-chlorobenzonitrile to concentrated sulfuric acid is 1:1.05, and perform a hydrolysis reaction at 90° C. for 1.5 hours to obtain p-fluorobenzoic acid.

[0037] The yield of p-fluorobenzoic acid obtained in this example is 96%.

[0038] Example 3: Preparation of p-fluorobenzoic acid

[0039] (1) p-chlorobenzonitrile is used as a reaction raw material, potassium chloride is used as a fluorination agent, and nitrobenzene and cyclopentane are mixed in a volume ratio of 1:1.5 as a reaction solvent. The reaction raw material and the fluorination agent are mixed in a molar ratio of 1:10, placed in the reaction solvent, and reacted at 200° C. and 0.1 MPa for 6 hours to obtain p-chlorobenzonitrile, wherein the total mass ratio of the reaction raw material and the fluorination agent to the mass ratio of the reaction solvent is 1:4;

[0040] (2) Add 98% concentrated sulfuric acid to p-chlorobenzonitrile, wherein the molar ratio of p-chlorobenzonitrile to concentrated sulfuric acid is 2:1, and perform a hydrolysis reaction at 90° C. for 1 hour to obtain p-fluorobenzoic acid.

[0041] The yield of p-fluorobenzoic acid prepared in this example is 98%.

[0042] Comparative Example 1:

[0043] The difference between this comparative example and Example 3 is that in step (1), the reaction solvent is only nitrobenzene, and the amount of the reaction solvent used is the same as that in Example 3.

[0044] The yield of p-fluorobenzoic acid prepared in this example is 57%.

[0045] Comparative Example 2:

[0046] The difference between this comparative example and Example 3 is that in step (1), the reaction solvent is only sulfolane, and the amount of the reaction solvent used is the same as that in Example 3.

[0047] The yield of p-fluorobenzoic acid prepared in this example is 62%.

[0048] Comparative Example 3:

[0049] The difference between this comparative example and Example 3 is that in step (1), the reaction solvent is 1,3-dimethyl-2-imidazolidinone (DMI), and the amount of the reaction solvent used is the same as that in Example 3.

[0050] The yield of p-fluorobenzoic acid prepared in this example is 51%.

[0051] Test Example 1:

[0052] In this test example, p-chlorobenzonitrile was used as a reaction raw material, and anhydrous hydrogen fluoride was used as a fluorination agent for fluorination reaction. During the reaction, the reaction temperature was 200°C and the reaction pressure was 0.1 MPa. The yield of p-chlorobenzonitrile in different reaction solvents at different reaction times (10 min, 30 min, 50 min and 60 min) was investigated. The results are shown in Table 1.

[0053] There are three treatment groups, as follows:

[0054] Treatment group 1: nitrobenzene was used as the reaction solvent;

[0055] Treatment group 2: sulfolane was used as the reaction solvent;

[0056] Treatment group 3: A mixed solvent of nitrobenzene and cyclopentane sulfone in a volume ratio of 1:1.2 was used as the reaction solvent.

[0057] Table 1 Yield of p-fluorobenzonitrile under different reaction solvents

[0058]

[0059] As can be seen from Table 1, the reaction solvent affects the yield of p-fluorobenzonitrile in the fluorination reaction. Specifically, treatment group 1 only uses nitrobenzene as a reaction solvent, and the yield of p-fluorobenzonitrile is 63% after 60min of reaction, and treatment group 2 only uses sulfolane as a reaction solvent. After 60min of reaction, the yield of p-fluorobenzonitrile is 67%, and treatment group 3 uses a mixed solvent composed of nitrobenzene and sulfolane as the same as the present application as a reaction solvent. After 60min of reaction, the yield of p-fluorobenzonitrile can reach 91%. It can be seen that the yield of the product can be significantly improved by using nitrobenzene and sulfolane. At the same time, when reacting for 10min, when only nitrobenzene is used as a reaction solvent, the yield is only 40%, and when only sulfolane is used as a reaction solvent, the reaction yield is only 44%, and the present invention uses nitrobenzene and sulfolane mixed as a reaction solvent, and the reaction yield is 68%, which shows that nitrobenzene and sulfolane can improve the reaction rate.

[0060] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for synthesizing p-fluorobenzoic acid, characterized in that: The following steps are involved: (1) p-chlorobenzonitrile is used as a reaction raw material, hydrogen fluoride or potassium fluoride is used as a fluorination agent, and a mixture of nitrobenzene and sulfolane is used as a reaction solvent. The reaction raw material and the fluorination agent are mixed and placed in the reaction solvent for a fluorination reaction to obtain p-fluorobenzonitrile; (2) Add acid to p-fluorobenzonitrile and undergo hydrolysis to obtain p-fluorobenzoic acid.

2. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: In the reaction solvent, the volume ratio of nitrobenzene to sulfolane is 1:(1-1.5).

3. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: The molar ratio of the reaction raw material to the fluorination agent is 1:(1-1.5).

4. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: The volume ratio of the total mass of the reaction raw materials and the fluorination reagent to the reaction solvent is 1:(2-10).

5. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: In step (1), the reaction temperature is 200-500° C., the reaction pressure is 0.1-3 MPa, and the reaction time is 10 min-10 h.

6. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: In step (2), the acid is hydrochloric acid or sulfuric acid, the mass fraction of the sulfuric acid is 98%, and the mass fraction of the hydrochloric acid is 30-37.5%.

7. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: In step (2), the molar ratio of p-fluorobenzonitrile to acid is 1:(1.05-1.5).

8. The method for synthesizing p-fluorobenzoic acid according to claim 1, characterized in that: In step (2), the hydrolysis reaction temperature is 50-100° C. and the reaction time is 1-10 h.

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