Method for preparing o-chlorobenzoic acid through hydrogenation selective debromination

Abstract

The invention belongs to the field of preparation of halogen-containing substituted benzoic acid, and particularly relates to a method for preparing o-chlorobenzoic acid through hydrogenation selective debromination. According to the invention, hydrogen is used as a reducing agent, a palladium catalyst is used as a catalyst, a methanol aqueous solution is used as a solvent, and 2-chloro-3-bromobenzoic acid, 2-chloro-5-bromobenzoic acid or a mixture thereof are used as raw materials to prepare o-chlorobenzoic acid. According to the method, debromination is controlled through selective hydrogenation instead of dechlorination, so that generation of a byproduct benzoic acid is inhibited. The scheme is reasonable in design, simple in process and mild in reaction condition, and a new thought is provided for the synthesis method of o-chlorobenzoic acid.

Description

Technical Field

[0001] The invention belongs to the field of preparation of halogen-substituted benzoic acid, and particularly relates to a method for preparing o-chlorobenzoic acid by hydrogenation and selective debromination. 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 complex procedures, low yield, low purity, and environmental pollution.

[0003] Currently, o-chlorobenzoic acid is prepared by methods such as o-methylaniline diazotization, o-chlorotoluene oxidation, o-chlorotoluene chlorination and hydrolysis, and o-chlorobenzonitrile hydrolysis. However, the o-methylaniline diazotization method has relatively mild reaction conditions, but the process is long, costly, and produces a large amount of three wastes. The o-chlorotoluene oxidation method has the advantages of a short process, low waste gas and wastewater, and low cost, but suffers from a long production cycle. The o-chlorotoluene chlorination and hydrolysis method uses chlorine to chlorinate the methyl group before hydrolysis, which has the significant disadvantage of the high toxicity of the raw chlorine gas. The o-chlorobenzonitrile hydrolysis method has the disadvantages of high raw material prices and the generation of nitrogen-containing wastewater.

[0004] Therefore, it is very meaningful to develop a novel method for synthesizing o-chlorobenzoic acid. Summary of the Invention

[0005] In view of the existing technical problems, the object of the present invention is to provide a method for preparing o-chlorobenzoic acid by using hydrogenation selective debromination.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions: A method for preparing o-chlorobenzoic acid by hydrogenation and selective debromination adopts hydrogen as a reducing agent, a palladium catalyst as a catalyst, a 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.

[0007] The reaction formula is as follows: .

[0008] The purity of the prepared o-chlorobenzoic acid is 98.0-99.9%, and the yield is 95-99.5%.

[0009] The weight percentage of water in the methanol aqueous solution is 10-50%, preferably 30-40%. On the one hand, by controlling the proportion of added water, the activity of the palladium catalyst is controlled, thereby achieving the effect of debromination without dechlorination; on the other hand, by adding water to the solvent, the production of methyl 2-chlorobenzoate can be avoided, thereby increasing the yield of o-chlorobenzoic acid.

[0010] The palladium catalyst is palladium carbon; preferably, the palladium catalyst is 5% palladium carbon.

[0011] The mass ratio of the catalyst to the raw material is 1:(10~100).

[0012] The mass ratio of the catalyst to the solvent is (0.1-5):100. When the catalyst concentration is too high, side reactions may occur, resulting in the production of undesired products, or the reaction rate may be too fast, leading to runaway reaction. When the catalyst concentration is too low, the reaction rate is slow, the conversion rate is low, and the product yield is low.

[0013] Specifically, the method comprises: placing raw materials, a catalyst, and a solvent in a reaction kettle, stirring and reacting under a hydrogen atmosphere, and obtaining o-chlorobenzoic acid after filtering, concentrating, and extracting and separating the liquids.

[0014] The steps for achieving the hydrogen atmosphere are: using nitrogen to replace the air and then maintaining the pressure, and then using hydrogen to replace the air and maintaining the pressure.

[0015] The hydrogen pressure is 0.5-1.0 MPa.

[0016] The reaction temperature is 10-50°C. When the temperature is lower than 10°C, the reaction time is significantly prolonged, resulting in excessive hydrogenation of the product or the generation of side reactions, thereby reducing the product yield and purity; when the temperature is higher than 50°C, the generation of dechlorination impurities cannot be controlled.

[0017] Preferably, the reaction temperature is 30-40°C.

[0018] The reaction time is 3-5h.

[0019] Beneficial effects of the present invention: 1. The present invention is the first to use 2-chloro-3-bromobenzoic acid, 2-chloro-5-bromobenzoic acid or a mixture thereof as raw materials to prepare o-chlorobenzoic acid. Not only is the preparation process simple and the catalyst recyclable, but 2-chloro-3-bromobenzoic acid and 2-chloro-5-bromobenzoic acid in wastewater can also be recycled and reused, thus achieving the coordinated development of economic and environmental benefits.

[0020] 2. The present invention controls the activity of the palladium catalyst under acidic conditions by regulating the amount of water added to the solvent, the reaction temperature, etc., accurately achieves the effect of debromination without dechlorination, and improves the purity and yield of o-chlorobenzoic acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is the HPLC spectrum of the reaction solution prepared in Example 1; Figure 2 is the HPLC spectrum of the reaction solution prepared in Example 2; Figure 3This is the HPLC spectrum of the reaction solution prepared in Comparative Example 1; Figure 4 This is the HPLC spectrum of the reaction solution after treatment in Comparative Example 2; Figure 5 This is the HPLC spectrum of the reaction solution after treatment in Comparative Example 3; Figure 6 is the GC-MS spectrum of the reaction solution after treatment in Example 1; Figure 7 This is the GC-MS spectrum of the reaction solution after treatment in Comparative Example 2; Figure 8 This is the HPLC spectrum of the reaction solution prepared in Comparative Example 4; Figure 9 This is the HPLC spectrum of the reaction solution prepared in Comparative Example 5. DETAILED DESCRIPTION

[0022] The following are specific examples of the present invention, which further describe the technical solutions of the present invention, but the present invention is not limited to these examples. Unless otherwise specified, the raw materials used in the specific embodiments of the present invention are commercially available products.

[0023] The technical solution of the present invention is described in detail below with reference to the accompanying drawings.

[0024] The HPLC spectrum was measured by Agilent 1260, and the GC-MS spectrum was measured by Agilent 122-5563UI.

[0025] The 5% palladium carbon described in the present invention refers to palladium carbon with a palladium content of 5%.

[0026] The filtration in the following examples and comparative examples is suction filtration, which is performed using filter paper with a pore size of 0.45 μm; and the concentration is rotary evaporation.

[0027] Example 1 Take 10 g of 2-chloro-5-bromobenzoic acid, 0.5 g of 5% palladium on carbon, 350 g of methanol, and 150 g of water, and put them into a 1 L high-pressure reactor. After displacing with N2 three times, maintain the pressure at 0.5 MPa for 10 min, and then displace with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 30 ° C for 4 h to obtain a reaction solution.

[0028] The reaction solution was tested by HPLC, and the raw material conversion rate was 100%. The HPLC spectrum of the reaction solution was as follows: Figure 1 As shown, where t R =3.3min is the peak of 2-chlorobenzoic acid (i.e. o-chlorobenzoic acid); t R =3.0 min is the peak of benzoic acid.

[0029] The reaction solution was filtered, concentrated, and extracted to obtain 6.61 g of 2-chlorobenzoic acid with a yield of 99.2% and a purity of 99.9%.

[0030] like Figure 6 The GC-MS spectrum of the reaction solution after treatment is shown. The target product 2-chlorobenzoic acid is inferred from the molecular ion peak and other fragment peaks.

[0031] Example 2 A mixture of 10 g of 2-chloro-3-bromobenzoic acid and 2-chloro-5-bromobenzoic acid in a mass ratio of 1:1, 0.5 g of 5% palladium on carbon, 350 g of methanol, and 150 g of water were placed in a 1 L autoclave. The pressure was replaced with N2 three times and maintained at 0.5 MPa for 10 min. The pressure was then replaced with H2 three times while maintaining the pressure at 0.5 MPa. The mixture was stirred at 400 rpm and reacted at 20 °C for 4 h to obtain a reaction solution.

[0032] The reaction solution was tested by HPLC, and the raw material conversion rate was 100%. The HPLC spectrum of the reaction solution was as follows: Figure 2 As shown, t R =3.3min is the peak of 2-chlorobenzoic acid; t R =3.0 min is the peak of benzoic acid.

[0033] The reaction solution was filtered, concentrated, and extracted to obtain 6.58 g of 2-chlorobenzoic acid with a yield of 98.7% and a purity of 98.0%.

[0034] Comparative Example 1 Take 10 g of 2-chloro-5-bromobenzoic acid, 0.5 g of 5% palladium on carbon, 350 g of methanol, and 150 g of water, and put them into a 1 L high-pressure reactor. After displacing with N2 three times, maintain the pressure at 0.5 MPa for 10 min, and then displace with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400 rpm and react at 60 ° C for 4 h to obtain a reaction solution.

[0035] The reaction solution was tested by HPLC, and the raw material conversion rate was 100%. The HPLC spectrum of the reaction solution was as follows: 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.

[0036] The reaction solution was filtered, concentrated, and extracted to obtain 6.24 g of 2-chlorobenzoic acid with a yield of 93.85% and a purity of 96.5%.

[0037] The difference between this comparative example and Example 1 is the reaction temperature. This comparative example adopts a reaction temperature of 60° C., and the palladium catalyst is more active, resulting in more dechlorination side reactions, thereby reducing the yield.

[0038] Comparative Example 2 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 carbon, and 500g of methanol, and load them into a 1L high-pressure reactor. After displacing with N2 three times, maintain the pressure at 0.5 MPa for 10 minutes, and then displace with H2 three times while maintaining the pressure at 0.5 MPa. Stir at 400rpm and react at 20°C.

[0039] The reaction solution was detected by HPLC, and the raw material conversion rate was 100%.

[0040] The reaction solution was filtered, concentrated, and extracted to obtain 7.18 g of methyl 2-chlorobenzoate with a yield of 99.1%. The HPLC spectrum of the reaction solution after treatment was as follows: Figure 4 As shown, t R =7.5min is the peak of methyl 2-chlorobenzoate.

[0041] Figure 7 Figure 3 is the GC-MS spectrum of the reaction solution after treatment. The target product, methyl 2-chlorobenzoate, was inferred from the molecular ion peak and other fragment peaks.

[0042] The difference between this comparative example and Example 2 is that no water is added to the solvent, so the debromination reaction will generate hydrogen bromide, forming an acidic environment. When the solvent is entirely methanol, under anhydrous acidic conditions, benzoic acid easily reacts with methanol to form ester compounds.

[0043] Comparative Example 3 Take 10g of 2-chloro-5-bromobenzoic acid, 0.5g of Raney nickel, 350g of methanol, and 150g of water, load them into a 1L high-pressure reactor, replace them with N2 three times, maintain the pressure at 0.5MPa for 10min, then replace them with H2 three times while maintaining the pressure at 0.5MPa, turn on the stirring at 400rpm, and react at 30℃.

[0044] The reaction solution was detected by HPLC, and the raw material conversion rate was 7%.

[0045] The reaction solution was filtered and concentrated, and 2-chloro-5-bromobenzoic acid was recovered after extraction and separation. The HPLC spectrum of the reaction solution after treatment was as follows: Figure 5 As shown, t R =4.48min is the peak of 2-chloro-5-bromobenzoic acid.

[0046] The difference between this comparative example and Example 1 is that Raney nickel is used as the catalyst, which is not active enough, so the conversion rate in the hydrodebromination reaction is low.

[0047] Comparative Example 4 This comparative example is the same as Example 1, except that 350 g of methanol is replaced by 350 g of isopropanol.

[0048] The HPLC spectrum of the reaction solution prepared is as follows Figure 8 As shown, the raw material conversion rate is 96.31%.

[0049] The reaction solution was filtered and concentrated, and 4.65 g was recovered after extraction and separation, with a yield of 70% and a purity of 73.2%.

[0050] This comparative example uses isopropyl alcohol as solvent to produce 2-chlorobenzoic acid isopropyl ester (t R =7.454min), the raw material conversion rate was low, which may be due to the poor solubility of isopropanol molecules on the raw materials and products, resulting in low yield.

[0051] Comparative Example 5 This comparative example is the same as Example 1, except that the solvent of 350 g methanol and 150 g water is replaced by 200 g methanol and 300 g water.

[0052] The HPLC spectrum of the reaction solution prepared is as follows Figure 9 As shown in the figure, the conversion rate of raw materials is 99.64%, but a large amount of impurity peaks are generated at 1.7 min.

[0053] The reaction solution was filtered and concentrated, and 3.37 g of o-chlorobenzoic acid was recovered after extraction and separation, with a yield of 50.6% and a purity of 71.1%.

[0054] The yield of o-chlorobenzoic acid obtained in this comparative example is low. This is because the increase in the amount of water affects the reaction activity of the catalyst, resulting in a decrease in the conversion rate.

Claims

1. A method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation, characterized in that: O-chlorobenzoic acid is prepared by using hydrogen as a reducing agent, a palladium catalyst as a catalyst, a methanol aqueous solution as a solvent, and 2-chloro-3-bromobenzoic acid and / or 2-chloro-5-bromobenzoic acid as raw materials.

2. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 1, wherein The mass percentage of water in the methanol aqueous solution is 10-50%.

3. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 2, wherein: The mass percentage of water in the methanol aqueous solution is 30-40%.

4. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 1, wherein The palladium catalyst is palladium carbon.

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

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

100.

7. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 1, characterized in that: The method for preparing o-chlorobenzoic acid by hydrogenation and selective debromination comprises: placing raw materials, a catalyst, and a solvent in a reaction kettle, stirring and reacting under a hydrogen atmosphere, and obtaining o-chlorobenzoic acid after filtering, concentrating, and extracting and separating the liquids.

8. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 7, characterized in that: The reaction temperature is 10-50°C.

9. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 8, characterized in that: The reaction temperature is 30-40°C.

10. The method for preparing o-chlorobenzoic acid by selective debromination by hydrogenation according to claim 7, characterized in that: The reaction time is 3-5h.

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