A method for selective debromination of hydrogen to prepare o-chlorobenzoic acid

Abstract

This invention belongs to the field of preparation of halogenated substituted benzoic acids, specifically relating to a method for selectively debrominating o-chlorobenzoic acid via hydrogenation. The invention uses hydrogen as a reducing agent, palladium as a catalyst, and methanol-water solution as a solvent, with 2-chloro-3-bromobenzoic acid, 2-chloro-5-bromobenzoic acid, or mixtures thereof as raw materials to prepare o-chlorobenzoic acid. This invention controls debromination through selective hydrogenation without dechlorination, suppressing the formation of the byproduct benzoic acid. This scheme is rationally designed, simple in process, and operates under mild reaction conditions, providing a new approach for the synthesis of o-chlorobenzoic acid.

Description

Technical Field

[0001] This invention belongs to the field of preparation of halogenated substituted benzoic acid, and specifically relates to a method for preparing o-chlorobenzoic acid by selective debromination via hydrogenation. Background Art

[0002] o-Chlorobenzoic acid is an important organic intermediate widely used in the synthesis of pharmaceuticals, pesticides, fragrances, and chemical materials. Traditional synthesis methods suffer from problems such as cumbersome steps, low yield, low purity, or environmental pollution.

[0003] Currently, methods for preparing o-chlorobenzoic acid include the o-methylaniline diazotization method, the o-chlorotoluene oxidation method, the o-chlorotoluene chlorination hydrolysis method, and the o-chlorobenzonitrile hydrolysis method. However, while the o-methylaniline diazotization method has relatively mild reaction conditions, it has a long process route, high cost, and generates a significant amount of waste. The o-chlorotoluene oxidation method has advantages such as a short process route, less waste gas and wastewater, and low cost, but it suffers from a long production cycle. The o-chlorotoluene chlorination hydrolysis method uses chlorine gas to chlorinate the methyl group before hydrolysis, which has the significant drawback of the highly toxic chlorine gas used as a raw material. The o-chlorobenzonitrile hydrolysis method suffers from high raw material prices and the generation of nitrogen-containing wastewater.

[0004] Therefore, it is of great significance to develop a novel method for preparing o-chlorobenzoic acid. Summary of the Invention

[0005] To address the existing technical problems, the present invention aims to provide a method for preparing o-chlorobenzoic acid using selective debromination via hydrogenation.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A method for preparing o-chlorobenzoic acid by selective debromination via hydrogenation uses hydrogen as a reducing agent, palladium catalyst as a catalyst, methanol aqueous solution as a solvent, and 2-chloro-3-bromobenzoic acid and / or 2-chloro-5-bromobenzoic acid as raw materials to prepare o-chlorobenzoic acid.

[0008] The reaction formula is as follows:

[0009] .

[0010] The purity of the prepared o-chlorobenzoic acid was 98.0-99.9%, and the yield was 95-99.5%.

[0011] The methanol-water solution contains 10-50% water by mass, preferably 30-40%. On one hand, by controlling the proportion of water added, the activity of the palladium catalyst is controlled, thereby achieving debromination without dechlorination. On the other hand, by adding water to the solvent, the formation of methyl 2-chlorobenzoate can be avoided, increasing the yield of o-chlorobenzoic acid.

[0012] The palladium catalyst is palladium on carbon; preferably, the palladium catalyst is 5% palladium on carbon.

[0013] The mass ratio of the catalyst to the raw material is 1:(10~100).

[0014] The mass ratio of the catalyst to the solvent is (0.1~5):100. When the mass concentration of the catalyst is too high, it will trigger side reactions that produce non-target products, or the reaction rate will be too fast, leading to runaway reaction. When the mass concentration of the catalyst is too low, the reaction rate is slow, the conversion rate is low, and the product yield is low.

[0015] Specifically, the above method includes: placing the raw materials, catalyst, and solvent in a reaction vessel, stirring and reacting under a hydrogen atmosphere, and obtaining o-chlorobenzoic acid after filtration, concentration, extraction, and separation.

[0016] The steps to achieve the hydrogen atmosphere are as follows: after purging the air with nitrogen, maintain the pressure, then purge with hydrogen and maintain the pressure.

[0017] The hydrogen pressure is 0.5-1.0 MPa.

[0018] The reaction temperature is 10-50℃. When the temperature is below 10℃, the reaction time is significantly prolonged, which leads to excessive hydrogenation of the product or the generation of side reactions, thereby reducing the product yield and purity. When the temperature is above 50℃, the generation of dechlorination impurities cannot be controlled.

[0019] Preferably, the reaction temperature is 30-40℃.

[0020] The reaction time is 3-5 hours.

[0021] The beneficial effects of this invention are:

[0022] 1. This invention is the first to prepare o-chlorobenzoic acid using 2-chloro-3-bromobenzoic acid, 2-chloro-5-bromobenzoic acid or a mixture thereof as raw materials. The preparation process is simple, the catalyst can be recycled and reused, and 2-chloro-3-bromobenzoic acid and 2-chloro-5-bromobenzoic acid in wastewater can be recovered and reused, thus achieving coordinated development of economic and environmental benefits.

[0023] 2. This invention achieves precise control of the palladium catalyst activity under acidic conditions by adjusting the amount of water added to the solvent and the reaction temperature, thereby achieving the effect of debromination without dechlorination and improving the purity and yield of o-chlorobenzoic acid. Attached Figure Description

[0024] Figure 1 This is the HPLC spectrum of the reaction solution prepared in Example 1;

[0025] Figure 2 This is the HPLC spectrum of the reaction solution prepared in Example 2;

[0026] Figure 3 This is the HPLC spectrum of the reaction solution prepared in Comparative Example 1;

[0027] Figure 4 This is the HPLC spectrum of the reaction solution after treatment with Comparative Example 2;

[0028] Figure 5 This is the HPLC spectrum of the reaction solution after treatment with Comparative Example 3;

[0029] Figure 6 This is the GC-MS spectrum of the reaction solution after treatment in Example 1;

[0030] Figure 7 The GC-MS spectrum of the reaction solution after treatment in Comparative Example 2 is shown.

[0031] Figure 8 This is the HPLC spectrum of the reaction solution prepared in Comparative Example 4;

[0032] Figure 9 This is the HPLC spectrum of the reaction solution prepared in Comparative Example 5. Detailed Implementation

[0033] The following are specific embodiments of the present invention, which further describe the technical solution of the present invention, but the present invention is not limited to these embodiments. Unless otherwise specified, all raw materials used in the specific embodiments of the present invention are commercially available products.

[0034] The technical solution of the present invention will now be described in detail with reference to the accompanying drawings.

[0035] The HPLC chromatograms were obtained using an Agilent 1260, and the GC-MS chromatograms were obtained using an Agilent 122-5563UI.

[0036] In this invention, 5% palladium on carbon refers to palladium on carbon with a palladium content of 5%.

[0037] The filtration in the following examples and comparative examples is vacuum filtration, which is performed using filter paper with a pore size of 0.45 micrometers; the concentration is achieved by rotary evaporation.

[0038] Example 1

[0039] Take 10g of 2-chloro-5-bromobenzoic acid, 0.5g of 5% palladium on carbon, 350g of methanol, and 150g of water, and put them into a 1L high-pressure reactor. After replacing the mixture with N2 three times, maintain the pressure at 0.5 MPa for 10 min, then replace it with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 30℃ for 4 h to obtain the reaction solution.

[0040] The reaction solution was analyzed by HPLC, and the raw material conversion rate was 100%. The HPLC chromatogram of the reaction solution is shown below. Figure 1 As shown, where t R =3.3 min is the peak of 2-chlorobenzoic acid (i.e., o-chlorobenzoic acid); t R =3.0 min is the peak of benzoic acid.

[0041] After filtration, concentration, extraction and separation, the reaction solution yielded 6.61 g of 2-chlorobenzoic acid, with a yield of 99.2% and a purity of 99.9%.

[0042] like Figure 6 The image shows the GC-MS spectrum of the treated reaction solution. The molecular ion peak and other fragment peaks indicate that it is the target product, 2-chlorobenzoic acid.

[0043] Example 2

[0044] Take 10g of a mixture of 2-chloro-3-bromobenzoic acid and 2-chloro-5-bromobenzoic acid in a mass ratio of 1:1, 0.5g of 5% palladium on carbon, 350g of methanol, and 150g of water, and place them in a 1L high-pressure reactor. After purging with N2 three times, maintain the pressure at 0.5 MPa for 10 min, then purge with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 20℃ for 4 h to obtain the reaction solution.

[0045] The reaction solution was analyzed by HPLC, and the raw material conversion rate was 100%. The HPLC chromatogram of the reaction solution is shown below. Figure 2 As shown, t R =3.3 min is the peak of 2-chlorobenzoic acid; t R =3.0 min is the peak of benzoic acid.

[0046] After filtration, concentration, extraction and separation, the reaction solution yielded 6.58 g of 2-chlorobenzoic acid, with a yield of 98.7% and a purity of 98.0%.

[0047] Comparative Example 1

[0048] Take 10g of 2-chloro-5-bromobenzoic acid, 0.5g of 5% palladium on carbon, 350g of methanol, and 150g of water, and put them into a 1L high-pressure reactor. After replacing the mixture with N2 three times, maintain the pressure at 0.5 MPa for 10 min, then replace it with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 60℃ for 4 h to obtain the reaction solution.

[0049] The reaction solution was analyzed by HPLC, and the raw material conversion rate was 100%. The HPLC chromatogram of the reaction solution is shown below. Figure 3 As shown, t R =3.3 min is the peak of 2-chlorobenzoic acid, t R =3.0 min is the peak of benzoic acid.

[0050] After filtration, concentration, extraction and separation, the reaction solution yielded 6.24 g of 2-chlorobenzoic acid, with a yield of 93.85% and a purity of 96.5%.

[0051] The difference between this comparative example and Example 1 is the reaction temperature. This comparative example uses a reaction temperature of 60°C, which results in higher palladium catalyst activity, leading to more dechlorination side reactions and thus a lower yield.

[0052] Comparative Example 2

[0053] Take 10g of a mixture of 2-chloro-3-bromobenzoic acid and 2-chloro-5-bromobenzoic acid in a mass ratio of 1:1, 0.5g of 5% palladium on carbon, and 500g of methanol, and place them in a 1L high-pressure reactor. After purging with N2 three times, maintain the pressure at 0.5 MPa for 10 min, then purge with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 20℃.

[0054] The reaction solution was analyzed by HPLC, and the raw material conversion rate was 100%.

[0055] After filtration, concentration, extraction, and separation, 7.18 g of methyl 2-chlorobenzoate was obtained from the reaction solution, with a yield of 99.1%. The HPLC chromatogram of the treated reaction solution is shown below. Figure 4 As shown, t R =7.5 min is the peak of methyl 2-chlorobenzoate.

[0056] Figure 7 The GC-MS spectrum of the treated reaction solution is inferred from the molecular ion peak and other fragment peaks to be the target product, methyl 2-chlorobenzoate.

[0057] The difference between this comparative example and Example 2 is that water was not added to the solvent, thus the debromination reaction generates hydrogen bromide, creating an acidic environment. When the solvent is entirely methanol, under anhydrous acidic conditions, benzoic acid readily reacts with methanol to form ester compounds.

[0058] Comparative Example 3

[0059] Take 10g of 2-chloro-5-bromobenzoic acid, 0.5g of Raney nickel, 350g of methanol, and 150g of water, and put them into a 1L high-pressure reactor. After replacing the nitrogen with N2 three times, maintain the pressure at 0.5MPa for 10min, then replace the nitrogen with H2 three times, and keep the pressure at 0.5MPa. Turn on the stirrer at 400rpm and react at 30℃.

[0060] The reaction solution was analyzed by HPLC, and the raw material conversion rate was 7%.

[0061] The reaction solution was filtered and concentrated, and 2-chloro-5-bromobenzoic acid was recovered after extraction and separation. The HPLC spectrum of the treated reaction solution is shown below. Figure 5 As shown, t R =4.48 min is the peak of 2-chloro-5-bromobenzoic acid.

[0062] The difference between this comparative example and Example 1 is that Raney nickel is used as a catalyst, which is not active enough, resulting in a low conversion rate in the hydrodebromination reaction.

[0063] Comparative Example 4

[0064] This comparative example is the same as Example 1, except that 350g of methanol is replaced with 350g of isopropanol.

[0065] The HPLC spectrum of the prepared reaction solution is as follows: Figure 8 As shown, the raw material conversion rate is 96.31%.

[0066] The reaction solution was filtered, concentrated, extracted, and separated to recover 4.65g, with a yield of 70% and a purity of 73.2%.

[0067] This comparative example uses isopropanol as a solvent to generate isopropyl 2-chlorobenzoate (t R =7.454 min), the low conversion rate of raw materials may be due to the poor solubility of isopropanol molecules in raw materials and products, resulting in a low yield.

[0068] Comparative Example 5

[0069] This comparative example is the same as Example 1, except that the solvent of 350g methanol and 150g water is replaced with 200g methanol and 300g water.

[0070] The HPLC spectrum of the prepared reaction solution is as follows: Figure 9 As shown, the raw material conversion rate is 99.64%. However, a large number of impurity peaks are generated at 1.7 min.

[0071] The reaction solution was filtered, concentrated, extracted, and separated to recover 3.37 g of o-chlorobenzoic acid, with a yield of 50.6% and a purity of 71.1%.

[0072] The yield of o-chlorobenzoic acid obtained in this comparative example was low because the increased water content affected the reaction activity of the catalyst, leading to a decrease in conversion rate.

Claims

1. A method for selectively debrominating o-chlorobenzoic acid via hydrogenation, characterized in that, o-Chlorobenzoic acid was prepared by using hydrogen as a reducing agent, palladium catalyst as a catalyst, methanol aqueous solution as a solvent, and 2-chloro-3-bromobenzoic acid and / or 2-chloro-5-bromobenzoic acid as raw materials. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation includes: placing raw materials, catalysts and solvents in a reaction vessel, stirring and reacting under a hydrogen atmosphere, and obtaining o-chlorobenzoic acid by filtration, concentration and extraction. The mass percentage of water in the methanol-water solution is 10-50%. The palladium catalyst is palladium on carbon; The reaction temperature is 10-50℃.

2. The method for preparing o-chlorobenzoic acid by selective debromination via hydrogenation according to claim 1, characterized in that, The water content in the methanol-water solution is 30-40% by mass.

3. The method for preparing o-chlorobenzoic acid by selective debromination via hydrogenation according to claim 1, characterized in that, The mass ratio of the catalyst to the raw material is 1:(10~100).

4. The method for preparing o-chlorobenzoic acid by selective debromination via hydrogenation according to claim 1, characterized in that, The mass ratio of the catalyst to the solvent is (0.1~5):

100.

5. The method for preparing o-chlorobenzoic acid by selective debromination of hydrogenation according to claim 1, characterized in that, The reaction temperature is 30-40℃.

6. The method for preparing o-chlorobenzoic acid by selective debromination of hydrogenation according to claim 1, characterized in that, The reaction time is 3-5 hours.

Images