CN114213202A - Preparation method of 2, 4-substituted benzoic acid - Google Patents
Preparation method of 2, 4-substituted benzoic acid Download PDFInfo
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Abstract
The invention discloses a preparation method of 2, 4-substituted benzoic acid, which takes 2, 4-substituted toluene as a raw material, sulfuric acid as a solvent, nitric acid as an oxidant, ozone as a catalyst at a proper flow rate, and synthesis reaction is carried out at a reaction temperature of 100-180 ℃. After the reaction is finished, diluting the reaction system by using distilled water, fully separating out the product, filtering, and pumping to dry to obtain the target product. The reacting step is carried out in a high shear mixing device. The method has the advantages of simple synthesis process, easy product separation, no solid waste generation, no transition metal residue, simple subsequent treatment and the like, and has excellent yield.
Description
Technical Field
The invention belongs to the field of fine chemical engineering, and particularly relates to a preparation method of a 2, 4-substituted benzoic acid compound.
Background
Based on the requirement of sustainable development strategy, the development of low-toxicity, high-efficiency and biodegradable herbicides is a necessary way to comply with the development of modern agriculture. Since the eight ninety years of the last century, a few new bionic herbicides for C3 and C4 plants were developed in succession, and the market value was huge. 2, 4-substituted benzoic acids are important intermediates of the novel herbicides, and therefore are receiving wide attention from researchers in fine chemistry. Such as 4-methylsulfonyl-2-nitrobenzoic acid for the production of mesotrione, 2-chloro-4-fluorobenzoic acid for the production of saflufenacil, etc., as shown in figure 1.
In view of the problems of low yield and complex treatment process of the method for preparing the 2, 4-substituted benzoic acid compound in the prior art, the invention provides the preparation method of the 2, 4-substituted benzoic acid compound based on the green chemical technology, and has huge application market prospect for developing the novel green herbicide.
As one of 2, 4-substituted benzoic acids, there are various methods for synthesizing 2-nitro-4-methylsulfonylbenzoic acid, and chinese patent application No. CN201510133705 and the like disclose that oxidation is achieved by using nitric acid as an oxidizing agent and using vanadium pentoxide as a catalyst. The method is also a main method adopted by the current industrial production, and has the advantages that nitric acid is cheap and easy to obtain, but a large amount of waste acid is generated, and the catalyst as a transition metal oxide has the problem of residue, so that the environmental protection pressure is high; CN201110001352 reports that hydrogen peroxide is used as an oxidant, and the hydrogen peroxide is green and environment-friendly, but the dosage of the hydrogen peroxide is large, and the yield is low; patent US5591890 reports cobalt acetate as catalyst and air as oxidant; CN201110288563 uses metalloporphyrin as a catalyst to prepare 2-nitro-4-methylsulfonylbenzoic acid, but the method has the problems of low oxidation capacity, poor oxidation effect and the like.
Based on the defects of the prior art, the invention of a novel preparation method of 2, 4-substituted benzoic acid is needed.
Disclosure of Invention
1. Problems to be solved
The invention aims to provide a preparation method of a 2, 4-substituted benzoic acid compound, which has the advantages of no solid waste, no metal residue, high yield and simple subsequent treatment.
2. Technical scheme
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the invention provides a preparation method of 2, 4-substituted benzoic acid, which comprises a 2, 4-substituted toluene dissolving step and a reaction step; in the dissolving step, concentrated sulfuric acid is used as a solvent; in the reaction step, ozone is used as a catalyst, nitric acid is used as an oxidant, and the general formula of the 2, 4-substituted benzoic acid is as follows:
in the general chemical structure of the 2, 4-substituted benzoic acid compound, X is one of nitro, methylsulfonyl, fluorine, chlorine or bromine; y is one of nitro and chloro.
The applicant finds that nitric acid is used as an oxidant, vanadium pentoxide is used as a catalyst, although the yield can be ensured, after the synthesis is finished, alkali fusion and acid precipitation sections are required to be continuously treated, and the problem of residual transition metal exists, solid waste still needs to be cleaned, so that the industrial application is inconvenient.
The chemical reaction formula of the preparation method of the 2, 4-substituted benzoic acid compound is shown in figure 1.
As a further improvement of the present invention, the reaction step is performed in a high shear mixing device, under the conditions of the reaction system of the present invention, if the reaction is performed in a high shear mixing device, the high shear mixing device can be effectively utilized for process intensification, and the applicant has unexpectedly found that the process intensification by using ozone as a catalyst in combination with the high shear mixing device can significantly improve the yield, and the reaction yield can be greatly improved compared with vanadium pentoxide as a catalyst.
As a further improvement of the method, the reaction temperature is 100-180 ℃.
As a further improvement of the invention, the preparation method comprises the following steps:
1) dissolving 2, 4-substituted toluene in concentrated sulfuric acid, stirring, heating to 100-180 ℃, dropwise adding nitric acid into the solution, and introducing ozone into the system;
2) starting a high-shear mixing device, controlling the temperature to be 100-180 ℃, and reacting for 2-12 h;
3) after the reaction is finished, the obtained reaction mixed solution is naturally cooled to room temperature, a proper amount of distilled water is added into the system, and after the solid is fully separated out, the 2, 4-substituted benzoic acid is obtained by filtering and pumping.
As a further improvement of the present invention, in the step 2), the high shear rate is adjusted to 5000-.
As a further improvement of the invention, the 2, 4-substituted benzoic acid compound is any one of the following compounds: 4-methylsulfonyl-2-nitrobenzoic acid, 2-chloro-4-methylsulfonylbenzoic acid, 2-chloro-4-nitrobenzoic acid, 4-fluoro-2-nitrobenzoic acid, 4-chloro-2-nitrobenzoic acid, 4-bromo-2-nitrobenzoic acid, 2-chloro-4-fluorobenzoic acid.
According to a further improvement of the invention, the mass ratio of the 2, 4-substituted toluene to the concentrated sulfuric acid is 1: 2-10, and the mass concentration of the concentrated sulfuric acid is 50-90%.
As a further improvement of the invention, the reaction process is followed by TLC.
In a further improvement of the invention, in the step 1), the mass concentration of the nitric acid is 50-70%, and the input proportion of the nitric acid is 2-15 equiv.
As a further improvement of the invention, in the step 1), ozone is introduced in an amount of 20g per hour.
As a further improvement, the method comprises the following specific steps: dissolving corresponding 2, 4-substituted toluene in concentrated sulfuric acid with proper volume, stirring, heating to 100-180 ℃, dropwise adding nitric acid with proper concentration into the solution, introducing ozone with proper flow into the system, starting a high-shear mixing device (Shanghai Frouk company, model FA-25), adjusting the high-shear speed to 5000-.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) the preparation method of the 2, 4-substituted benzoic acid compound has the advantages that concentrated sulfuric acid is used as a solvent in a reaction system, nitric acid is used as an oxidant, and ozone is used as a catalyst; the reaction system replaces vanadium catalysts with ozone, so that high yield can be guaranteed, products after reaction are easy to separate, solid wastes and transition metal residues are avoided, and the waste acid recovery process is simple.
(2) The preparation method of the 2, 4-substituted benzoic acid compound takes concentrated sulfuric acid as a solvent, nitric acid as an oxidant and ozone as a catalyst, and is matched with a high-shear mixing device (FA-25 of Shanghai Frank company) to strengthen the reaction process, so that the reaction time is greatly shortened, the efficiency is improved, and the reaction yield can be greatly improved.
(3) The preparation method of the 2, 4-substituted benzoic acid compound has simpler synthesis process and post-treatment process, and in the post-treatment process, appropriate amount of distilled water is added after the reaction is finished, and the corresponding product can be obtained after the solid is fully separated out, filtered and dried.
Drawings
Figure 1 is a structure of mesotrione and saflufenacil;
FIG. 2 is a general formula for preparing 2, 4-substituted benzoic acid compounds;
FIG. 3 is a chemical formula of the products prepared in examples 1-7.
Detailed Description
The present invention will be described in further detail with reference to the following examples and the accompanying drawings. The following description is only exemplary of the present invention, and is not intended to limit the present invention in any way, and those skilled in the art can modify the present invention by the following claims and their equivalents. Any simple modifications or equivalent changes made to the following examples according to the technical essence of the present invention, without departing from the technical spirit of the present invention, fall within the scope of the present invention.
Example 1
The preparation method of the 4-methylsulfonyl-2-nitrobenzoic acid compound adopts the following reaction formula:
the specific operation steps are as follows:
dissolving 0.05mol of 2-nitro-4-methylsulfonyl toluene in a proper volume of concentrated sulfuric acid (with the mass concentration of 50-90%), wherein the mass ratio of the 2-nitro-4-methylsulfonyl toluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (with the mass concentration of 50-70%) (2-15 equiv.) into the solution, introducing ozone (with the amount of 20g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25, Shanghai Fruke Co., Ltd.), adjusting the high-shear speed to 5000-20000 revolutions, controlling the temperature to be maintained at 100-180 ℃, reacting for 2-12h, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, fully separating out solids, filtering, and pumping to dry to obtain corresponding 2-nitro-4-methylsulfonylbenzoic acid, a light yellow solid and a melting point: 211 ℃ and 212 ℃ with a yield of 90 percent.
1H NMR(400MHz,DMSO)δ14.25(s,1H,-COOH),8.53(d,1H,J＝1.6Hz,phenyl-H3),8.33(dd,1H,J＝8.0Hz,1.6Hz,phenyl-H5),8.12(d,1H,J＝8.0Hz,phenyl-H6),3.39(s,3H,-CH3).13C NMR(100MHz,DMSO)δ165.7,148.4,144.2,132.4,132.3,131.7,123.5,43.5。
Comparative example 1
The reaction system of this comparative example was the same as in example 1, except that no high shear mixing device was used in the reaction, and the preparation method of the 4-methylsulfonyl-2-nitrobenzoic acid compound employed the following reaction formula:
the specific operation steps are as follows: dissolving 0.05mol of 2-nitro-4-methylsulfonyl toluene in a proper volume of concentrated sulfuric acid (with the mass concentration of 50-90%), wherein the mass ratio of the 2-nitro-4-methylsulfonyl toluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (50-70%) (2-15 equiv.) with proper concentration into the solution, introducing ozone (20 g per hour) with proper flow into the system, mechanically stirring (by using a conventional mixing device), controlling the temperature to be maintained at 100-180 ℃, reacting for 2-12h, tracking and detecting by TLC (thin-layer chromatography), naturally cooling reaction mixed liquid to room temperature after the reaction is finished, adding proper amount of distilled water into the system, fully separating out solids, filtering, and draining to obtain corresponding 2-nitro-4-methylsulfonylbenzoic acid, a light yellow solid, a melting point: 211 ℃ and 212 ℃ with a yield of 80 percent.
1H NMR(400MHz,DMSO)δ14.25(s,1H,-COOH),8.53(d,1H,J＝1.6Hz,phenyl-H3),8.33(dd,1H,J＝8.0Hz,1.6Hz,phenyl-H5),8.12(d,1H,J＝8.0Hz,phenyl-H6),3.39(s,3H,-CH3).13C NMR(100MHz,DMSO)δ165.7,148.4,144.2,132.4,132.3,131.7,123.5,43.5。
The reaction system of this comparative example was the same, but no high shear mixing device was used in the reaction procedure, yielding 80% product.
Comparative example 2
In the reaction system of the comparative example, vanadium pentoxide solid was used as a catalyst, and other conditions were the same as in example 1, and the preparation method of the 4-methylsulfonyl-2-nitrobenzoic acid compound employed the following reaction formula:
the specific operation steps are as follows: dissolving 0.05mol of 2-nitro-4-methylsulfonyl toluene in a proper volume of concentrated sulfuric acid (with the mass concentration of 50-90%), wherein the mass ratio of the 2-nitro-4-methylsulfonyl toluene to the concentrated sulfuric acid is 1: 2-10; adding vanadium pentoxide solid powder (0.5-30 mol%), stirring, heating to 100-180 ℃, dropwise adding nitric acid (with the mass concentration of 50-70%) (2-15 equiv.) with a proper concentration into the solution, introducing air (with the amount of 20g per hour) into the system at the same time, starting a high-shear mixing device (FA-25 of Shanghai Frank company), adjusting the high-shear speed to 5000 and 20000 turns, controlling the temperature to be 100-180 ℃, reacting for 2-12h, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, fully separating out solids, filtering, and drying to obtain corresponding 2-nitro-4-methylsulfonylbenzoic acid, a light yellow solid and a melting point: 211 ℃ and 212 ℃ and the yield is 85 percent.
1H NMR(400MHz,DMSO)δ14.25(s,1H,-COOH),8.53(d,1H,J＝1.6Hz,phenyl-H3),8.33(dd,1H,J＝8.0Hz,1.6Hz,phenyl-H5),8.12(d,1H,J＝8.0Hz,phenyl-H6),3.39(s,3H,-CH3).13C NMR(100MHz,DMSO)δ165.7,148.4,144.2,132.4,132.3,131.7,123.5,43.5。
The reaction process of this comparative example was carried out in a high shear mixing device, effectively promoting the yield improvement, but still relatively low compared to ozone as catalyst, the yield of this comparative example was only 85%.
Example 2
The preparation method of the 2-chloro-4-methylsulfonylbenzoic acid compound adopts the following reaction formula:
the specific operation steps are as follows: dissolving 2-chloro-4-methylsulfonyl toluene (0.05mol) in concentrated sulfuric acid (50-90% by mass) with a proper volume, wherein the mass ratio of the 2-chloro-4-methylsulfonyl toluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (the mass concentration is 50-70%) (2-15 equiv.) into the solution, introducing ozone (20 g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Fruke company), adjusting the high-shear speed to 5000-20000 revolutions, controlling the temperature to be maintained at 100-180 ℃, reacting for 2-12 hours, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, and after the solid is fully separated out, filtering and draining to obtain the corresponding 2-chloro-4-methylsulfonylbenzoic acid.
2-chloro-4-methylsulfonylbenzoic acid, colorless crystals, melting point: 192 ℃ and 194 ℃ with a yield of 86 percent.
1H NMR(400MHz,DMSO)δ13.96(s,1H,-COOH),8.08(d,1H,J＝1.2Hz,phenyl-H3),8.00(d,1H,J＝8.0Hz,phenyl-H6),7.97(dd,1H,J＝8.0Hz,1.6Hz,phenyl-H5),3.33(s,3H,-CH3).13C NMR(100MHz,DMSO)δ165.7,148.4,144.2,132.4,132.2,131.7,123.5,43.5。
Example 3
The preparation method of the 2-chloro-4-nitrobenzoic acid compound adopts the following reaction formula:
the specific operation steps are as follows: dissolving 2-chloro-4-nitrotoluene (0.05mol) in a proper volume of concentrated sulfuric acid (mass concentration is 50-90%), wherein the mass ratio of the 2-chloro-4-nitrotoluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (the mass concentration is 50-70%) (2-15 equiv.) into the solution, introducing ozone (20 g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Fruke company), adjusting the high-shear speed to 5000-20000 revolutions, controlling the temperature to be maintained at 100-180 ℃, reacting for 2-12 hours, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, and after the solid is fully separated out, filtering and draining to obtain the corresponding 2-chloro-4-nitrobenzoic acid.
2-chloro-4-nitrobenzoic acid, bright yellow solid, melting point: 137 ℃ and 138 ℃, and the yield is 88 percent.1H NMR(400MHz,DMSO)δ14.02(s,1H,-COOH),8.32(s,1H,phenyl-H3),8.23(d,1H,J＝8.0Hz,phenyl-H5),7.99(d,1H,J＝8.4Hz,phenyl-H6).13C NMR(100MHz,DMSO)δ166.2,149.4,138.1,132.6,132.0,125.8,122.8。
Example 4
The preparation method of the 4-fluoro-2-nitrobenzoic acid compound adopts the following reaction formula:
dissolving 4-fluoro-2-nitrotoluene (0.05mol) in a proper volume of concentrated sulfuric acid (mass concentration is 50-90%), wherein the mass ratio of the 4-fluoro-2-nitrotoluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (the mass concentration is 50-70%) (2-15 equiv.) into the solution, introducing ozone (20 g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Fruke company), adjusting the high-shear speed to 5000 and 20000 turns, controlling the temperature to be 100-180 ℃, reacting for 2-12 hours, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, and after the solid is fully separated out, filtering and drying to obtain the corresponding 4-fluoro-2-nitrobenzoic acid.
4-fluoro-2-nitrobenzoic acid, yellow solid, melting point: 142 ℃ and 143 ℃ with a yield of 87 percent.
1H NMR(400MHz,DMSO)δ13.97(s,1H,-COOH),8.01-7.96(m,2H,phenyl-H3 and phenyl-H5),7.68-7.63(m,1H,phenyl-H6).13C NMR(100MHz,DMSO)δ165.16,163.5(d,JC-F＝252.1Hz),150.5(d,JC-F＝9.6Hz),133.3(d,JC-F＝9.3Hz),123.3(d,JC-F＝3.8Hz),120.2(d,JC-F＝21.5Hz),112.3(d,JC-F＝27.7Hz).19F NMR(376MHz,DMSO)δ-104.71。
Example 5
The preparation method of the 2-chloro-4-fluorobenzoic acid compound adopts the following reaction formula:
dissolving 2-chloro-4-fluorotoluene (0.05mol) in a proper volume of concentrated sulfuric acid (mass concentration is 50-90%), wherein the mass ratio of the 2-chloro-4-fluorotoluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (with the mass concentration of 50-70%) (2-15 equiv.) into the solution, introducing ozone (with the amount of 20g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Fruke company), adjusting the high-shear speed to 5000 plus 20000 turns, controlling the temperature to be maintained at 100-180 ℃, reacting for 2-12h, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, and after the solid is fully separated out, filtering and drying to obtain the corresponding 2-chloro-4-fluorobenzoic acid.
2-chloro-4-fluorobenzoic acid, white solid, melting point: 181 ℃ and 183 ℃, and the yield is 89 percent.1H NMR(400MHz,DMSO)δ13.4(s,1H,-COOH),7.90(dd,J＝8.4,6.4Hz,1H，phenyl-H3),7.53(dd,J＝8.8,2.4Hz,1H，phenyl-H5),7.31(td,J＝8.4,2.4Hz,1H，phenyl-H6).13C NMR(100MHz,DMSO)δ166.2,163.6(d,JC-F＝251.1Hz),134.2(d,JC-F＝11.0Hz),133.8(d,JC-F＝9.7Hz),128.2(d,JC-F＝3.5Hz),118.6(d,JC-F＝25.1Hz),115.1(d,JC-F＝21.2Hz).19F NMR(376MHz,DMSO)δ-106.8。
Example 6
The preparation method of the 4-chloro-2-nitrobenzoic acid compound adopts the following reaction formula:
dissolving 4-chloro-2-nitrotoluene (0.05mol) in concentrated sulfuric acid (with the mass concentration of 50-90%) with a proper volume, wherein the mass ratio of the 4-chloro-2-nitrotoluene to the concentrated sulfuric acid is 1: 2-10, stirring, heating to 100-180 ℃, dropwise adding nitric acid (with the mass concentration of 50-70%) (2-15 equiv.) into the solution, introducing ozone (with the amount of 20g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Franke company), adjusting the high-shear speed to 5000-20000 rotation, controlling the temperature to be maintained between 100-180 ℃, reacting for 2-12h, performing TLC tracking detection, naturally cooling the reaction mixed solution to room temperature after the reaction is finished, adding a proper amount of distilled water into the system, and fully separating out solids, filtering and pumping to obtain the corresponding 4-chloro-2-nitrobenzoic acid.
4-chloro-2-nitrobenzoic acid, colorless solid, melting point: 141 ℃ and 142 ℃ with a yield of 90 percent.1H NMR(400MHz,DMSO)δ14.05(s,1H,-COOH),8.15(d,1H,J＝2.0Hz,phenyl-H3),7.90(d,1H,J＝8.0Hz,phenyl-H6),7.85(dd,1H,J＝8.0Hz,2.0Hz,phenyl-H5).13C NMR(100MHz,DMSO)δ165.3,149.9,137.3,133.2,132.3,125.7,124.2。
Example 7
The preparation method of the 4-bromo-2-nitrobenzoic acid compound adopts the following reaction formula:
dissolving 4-bromo-2-nitrotoluene (0.05mol) in a proper volume of concentrated sulfuric acid (mass concentration is 50-90%), wherein the mass ratio of the 4-bromo-2-nitrotoluene to the concentrated sulfuric acid is 1: 2-10; stirring, heating to 100-180 ℃, dropwise adding nitric acid (the mass concentration is 50-70%) (2-15 equiv.) into the solution, introducing ozone (20 g per hour) into the system at a proper flow rate, starting a high-shear mixing device (FA-25 of Shanghai Fruke company), adjusting the high-shear speed to 5000 and 20000 turns, controlling the temperature to be 100-180 ℃, reacting for 2-12 hours, performing TLC tracking detection, after the reaction is finished, naturally cooling the reaction mixed solution to room temperature, adding a proper amount of distilled water into the system, and after the solid is fully separated out, filtering and drying to obtain the corresponding 4-bromo-2-nitrobenzoic acid.
4-bromo-2-nitrobenzoic acid, light cyan solid, mp 166-.1H NMR(400MHz,DMSO)δ14.07(s,1H,-COOH),8.26(d,1H,J＝1.6Hz,phenyl-H3),7.99(dd,1H,J＝8.2Hz,1.8Hz,phenyl-H5),7.81(d,1H,J＝8.4Hz,phenyl-H6).13C NMR(100MHz,DMSO)δ165.4,149.8,136.2,132.4,126.9,126.0,125.7。
TABLE 1 yields of examples and comparative examples
| Examples | Yield of |
| Example 1 | 90％ |
| Comparative example 1 | 80％ |
| Comparative example 2 | 85％ |
| Example 2 | 86％ |
| Example 3 | 88％ |
| Example 4 | 87％ |
| Example 5 | 89％ |
| Example 6 | 90％ |
| Example 7 | 88％ |
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and any simple modification, equivalent change and modification made to the above embodiments according to the technical spirit of the present invention are within the scope of the technical solution of the present invention.
Claims (10)
1. A preparation method of 2, 4-substituted benzoic acid is characterized by comprising a 2, 4-substituted toluene dissolving step and a reaction step; in the dissolving step, concentrated sulfuric acid is used as a solvent; in the reaction step, ozone is used as a catalyst, nitric acid is used as an oxidant, and the general formula of the 2, 4-substituted benzoic acid is as follows:
in the general chemical structure of the 2, 4-substituted benzoic acid compound, X is one of nitro, methylsulfonyl, fluorine, chlorine or bromine; y is one of nitro and chloro.
2. The method of claim 1, wherein the reacting step is performed in a high shear mixing device.
3. The method for producing a 2, 4-substituted benzoic acid according to claim 1 or 2, wherein the reaction temperature is 100 to 180 ℃.
4. The method for producing a 2, 4-substituted benzoic acid according to claim 3, comprising the steps of:
1) dissolving 2, 4-substituted toluene in concentrated sulfuric acid, stirring, heating to 100-180 ℃, dropwise adding nitric acid into the solution, and introducing ozone into the system;
2) starting a high-shear mixing device, controlling the temperature to be 100-180 ℃, and reacting for 2-12 h;
3) after the reaction is finished, the obtained reaction mixed solution is naturally cooled to room temperature, a proper amount of distilled water is added into the system, and after the solid is fully separated out, the 2, 4-substituted benzoic acid is obtained by filtering and pumping.
5. The method of claim 4, wherein the high shear rate in step 2) is adjusted to 5000-.
6. The process for producing a 2, 4-substituted benzoic acid according to claim 5, wherein the 2, 4-substituted benzoic acid compound is any one of the following compounds: 4-methylsulfonyl-2-nitrobenzoic acid, 2-chloro-4-methylsulfonylbenzoic acid, 2-chloro-4-nitrobenzoic acid, 4-fluoro-2-nitrobenzoic acid, 4-chloro-2-nitrobenzoic acid, 4-bromo-2-nitrobenzoic acid, 2-chloro-4-fluorobenzoic acid.
7. The process for producing 2, 4-substituted benzoic acid according to claim 6, wherein the mass ratio of 2, 4-substituted toluene to concentrated sulfuric acid is 1: 2 to 10, and the concentration of concentrated sulfuric acid is 50 to 90%.
8. The method for preparing 2, 4-substituted benzoic acid according to claim 3, wherein said reaction process is followed by TLC.
9. The method for producing a 2, 4-substituted benzoic acid according to claim 3, wherein in step 1), the mass concentration of nitric acid is 50 to 70% and the charging ratio of nitric acid is 2 to 15equiv.
10. The method of claim 3, wherein the ozone is introduced in an amount of 20 g/hr in the step 1).
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| CN106631761A (en) * | 2016-09-12 | 2017-05-10 | 华东理工大学 | Method for preparing benzoic acid by oxidizing methylbenzene at atmospheric pressure and low temperature |
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| GB798619A (en) * | 1956-03-27 | 1958-07-23 | Gen Electric | Oxidation of aralkyl compounds to aromatic carboxylic acids |
| CN101177369A (en) * | 2007-12-14 | 2008-05-14 | 嘉兴学院 | Method for oxidation of benzene ring side chain containing electron-attracting groups by combination of ozone and nitric acid |
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