3-hydroxy-2, 4-dichloroacetophenone prepared by one-pot method and preparation method thereof
Through Fries' photorearrangement method and corn bran extraction technology, 3-hydroxy-2,4-dichloroacetophenone was prepared, solving the problems of flammable acylating agents and complex processes in traditional processes, and achieving an efficient, safe and environmentally friendly preparation method.
Patent Information
- Application Number
- CN202510030169.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-08
- Publication Date
- 2025-03-28
AI Technical Summary
In the traditional process of preparing 2,4-dichloroacetophenone, flammable acylating agents have a risk of explosion, and the process is complex and there are many by-products, making it difficult to achieve efficient and safe preparation.
3-hydroxy-2,4-dichloroacetophenone was prepared under mild reaction conditions by Fries' photorearrangement method, and ethyl 3-hydroxy-2,4-dichlorobenzoate was extracted using corn bran, and high selectivity was achieved through one-pot reaction, reducing the generation of by-products.
The high selective formation of 3-hydroxy-2,4-dichloroacetophenone is achieved, which simplifies the separation and purification process, reduces production costs, and has environmentally friendly characteristics.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to 3-hydroxy-2,4-dichloroacetophenone prepared by a one-pot method and a preparation method thereof. Background Art
[0002] 2,4-Dichloroacetophenone is an important organic intermediate, which is widely used in the synthesis of medicines, pesticides and dyes. In the field of medicine, it can be used to prepare key intermediates for the synthesis of certain antibacterial drugs; in the field of pesticides, it can be used as an intermediate for the synthesis of certain effective pesticides; in the field of dyes, it can provide specific structural groups to give specific colors and properties to dyes. Therefore, the efficient preparation of 2,4-dichloroacetophenone has important economic and industrial significance. The traditional process for preparing 2,4-dichloroacetophenone usually uses m-dichlorobenzene and an acylating agent under catalysis to obtain a crude 2,4-dichloroacetophenone product, and then obtains a pure product through purification and other processes. However, some acylating agents such as acetyl chloride are flammable and there is a risk of explosion during the production process. Therefore, it is necessary to seek new process routes to achieve the preparation of 2,4-dichloroacetophenone. 3-Hydroxy-2,4-dichloroacetophenone can be used as an intermediate for the generation of 2,4-dichloroacetophenone, and 2,4-dichloroacetophenone can be prepared through multi-stage reactions. Summary of the invention
[0003] In view of the above-mentioned shortcomings, the present invention discloses a green, safe and highly selective synthetic route, which adopts the Fries photorearrangement method to prepare 3-hydroxy-2,4-dichloroacetophenone, can realize the generation of highly selective products under mild reaction conditions, reduce the generation of by-products, improve the yield and simplify the separation and purification process. In addition, the raw materials disclosed in the present invention include 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester prepared with corn bran as the main raw material, realize the high added value utilization of processing by-products, and have the characteristics of being environmentally friendly. The purpose of the present invention is to provide 3-hydroxy-2,4-dichloroacetophenone prepared by a one-pot method and a preparation method thereof, in particular, a method for preparing 3-hydroxy-2,4-dichloroacetophenone with corn bran rich in vanillic acid as the raw material.
[0004] The specific technical solutions are as follows: The one-pot method for preparing 3-hydroxy-2,4-dichloroacetophenone comprises the following raw materials, calculated by weight: 40-60 parts of ethyl 3-hydroxy-2,4-dichlorobenzoate, 50-120 parts of an organic solvent, 10-30 parts of a catalyst, and 10-30 parts of a photosensitizer. The preparation of ethyl 3-hydroxy-2,4-dichlorobenzoate comprises the following steps: S1: Select corn bran for pulverization, mix the pulverized corn bran with deionized water in a weight ratio of 1: (10-30), perform ultrasonic extraction at 45-70°C and an ultrasonic power of 400-800 W for 1-2 hours, and filter to obtain a corn bran extract; S2: Mix corn bran extract and 10% to 20% dilute hydrochloric acid in parts by weight 1: (1 to 5), keep stirring, react at 50 to 80°C for 1 to 3 hours, stop the reaction, and add sodium hydroxide solution to adjust the pH value to 6.7 to 7.3; S3: removing the solvent from the substance obtained in S2 by evaporation to obtain a crude vanillic acid extract, and then recrystallizing it with ethanol as solvent to obtain vanillic acid; S4: In ethanol, vanillic acid and thionyl chloride are mixed in a weight ratio of 1: (1-3), stirred continuously at 5-20°C for 1-2 hours, and then sodium hydroxide solution is added to adjust the pH value to 6.7-7.3, and 2,4-dichlorobenzoic acid-3-methyl ether is obtained by recrystallization; S5: Mix the 2,4-dichlorobenzoic acid-3-methyl ether obtained in S4 and ethanol in a weight ratio of 1: (0.2-0.5), and reflux at 78-85° C. for 3-6 hours under the catalysis of concentrated sulfuric acid; S6: adding sodium hydroxide solution to the reaction product of S5 to adjust the pH value to 6.7-7.3, using ethyl acetate as the organic phase for extraction, and then evaporating the solvent to obtain ethyl 3-hydroxy-2,4-dichlorobenzoate.
[0005] In some of the embodiments, the mass fraction of concentrated sulfuric acid in S5 is 98%, and the mass fraction of concentrated sulfuric acid added is 1% to 5% of the total mass of the reactants.
[0006] In some embodiments, the organic solvent is selected from one or more of methanol, chloroform, carbon tetrachloride, toluene, and dichloromethane.
[0007] In some embodiments, the catalyst is selected from one or more of FeCl3, AlCl3, BF3, and sulfuric acid.
[0008] In some embodiments, the photosensitizer is selected from one or more of benzophenone and 1-hydroxycyclohexyl benzophenone.
[0009] The present invention also provides a method for preparing 3-hydroxy-2,4-dichloroacetophenone prepared by the one-pot method, and the steps of the preparation method are as follows: S7: In a multifunctional reactor, add ethyl 3-hydroxy-2,4-dichlorobenzoate, an organic solvent, a catalyst, and a photosensitizer according to weight, continue stirring, maintain the temperature at 40-60° C., use a 254 nm ultraviolet light source to irradiate the reaction system, and the reaction time is 4-8 hours; S8: monitoring the progress of the reaction by thin layer chromatography, and stopping the reaction when no 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is detected; S9: The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, and recrystallized with ethanol as a solvent, and washed with deionized water for 2 to 3 times, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.
[0010] The present invention has the following advantages: (1) High-value utilization of by-products from corn processing, which is sustainable and has low production costs; (2) The Fries photorearrangement reaction is used to specifically generate acyl compounds on the aromatic ring without affecting other functional groups. It has the characteristics of simple operation and mild reaction conditions. (3) During the Fries photorearrangement reaction, a catalyst and a photosensitizer are added, and the two work together to increase the yield of 3-hydroxy-2,4-dichloroacetophenone. DETAILED DESCRIPTION
[0011] The following will combine the technical process steps, specific implementation conditions and materials in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Example 1
[0012] Corn bran was selected for pulverization, and the pulverized corn bran was mixed with deionized water in a weight ratio of 1:15, and ultrasonic extraction was performed at 55°C and an ultrasonic power of 800 W for 2 hours, and the corn bran extract was filtered. The corn bran extract and 10% dilute hydrochloric acid were mixed in a weight ratio of 1:2, and the mixture was stirred continuously. The mixture was reacted at 60°C for 3 hours, and the reaction was stopped. Sodium hydroxide solution was added to adjust the pH value to 7.1. The solvent was removed by evaporation to obtain a crude extract of vanillic acid, and then the vanillic acid was recrystallized using ethanol as a solvent. Example 2
[0013] Corn bran was selected for pulverization, and the pulverized corn bran was mixed with deionized water in a weight ratio of 1:15, and ultrasonic extraction was performed at 55°C and an ultrasonic power of 800 W for 2 hours, and the corn bran extract was filtered. The corn bran extract and 20% dilute hydrochloric acid were mixed in a weight ratio of 1:2, and the mixture was stirred continuously. The mixture was reacted at 60°C for 2 hours, and the reaction was stopped. Sodium hydroxide solution was added to adjust the pH value to 7.1. The solvent was removed by evaporation to obtain a crude extract of vanillic acid, and then the vanillic acid was recrystallized using ethanol as a solvent. Example 3
[0014] In ethanol, the vanillic acid obtained in Example 1 and thionyl chloride are mixed in a weight ratio of 1:1, stirred continuously at 5°C for 1 hour, and then sodium hydroxide solution is added to adjust the pH value to 7.0, and 2,4-dichlorobenzoic acid-3-methyl ether is obtained by recrystallization. 2,4-dichlorobenzoic acid-3-methyl ether, ethanol, and concentrated sulfuric acid are mixed in a weight ratio of 1:0.2:0.02, and the mass fraction of concentrated sulfuric acid is 98%. Under the catalysis of concentrated sulfuric acid, reflux is carried out at 80°C for 4 hours. Sodium hydroxide solution is added to the product, the pH value is adjusted to 7.2, ethyl acetate is used as the organic phase for extraction, and then the solvent is evaporated to obtain 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester. Example 4
[0015] In ethanol, the vanillic acid obtained in Example 2 was mixed with thionyl chloride in a weight ratio of 1:2, and stirred continuously at 5°C for 2 hours, and then sodium hydroxide solution was added to adjust the pH value to 7.0, and 2,4-dichlorobenzoic acid-3-methyl ether was obtained by recrystallization. 2,4-dichlorobenzoic acid-3-methyl ether, ethanol, and concentrated sulfuric acid were mixed in a weight ratio of 1:0.2:0.04, and the mass fraction of concentrated sulfuric acid was 98%. Under the catalysis of concentrated sulfuric acid, reflux was performed at 80°C for 4 hours. Sodium hydroxide solution was added to the product, the pH value was adjusted to 7.2, ethyl acetate was used as the organic phase for extraction, and the solvent was evaporated to obtain 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester. Example 5
[0016] In ethanol, the vanillic acid obtained in Example 2 was mixed with thionyl chloride in a weight ratio of 1:3, and stirred continuously at 5°C for 2 hours, and then sodium hydroxide solution was added to adjust the pH value to 7.0, and 2,4-dichlorobenzoic acid-3-methyl ether was obtained by recrystallization. 2,4-dichlorobenzoic acid-3-methyl ether, ethanol, and concentrated sulfuric acid were mixed in a weight ratio of 1:0.2:0.04, and the mass fraction of concentrated sulfuric acid was 98%. Under the catalysis of concentrated sulfuric acid, reflux was performed at 80°C for 3 hours. Sodium hydroxide solution was added to the product, the pH value was adjusted to 7.2, ethyl acetate was used as the organic phase for extraction, and the solvent was evaporated to obtain 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester. Example 6
[0017] In a multifunctional reactor, 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester, an organic solvent, a catalyst, and a photosensitizer are added by weight, and stirring is continued. The temperature is maintained at 50°C, and a 254 nm ultraviolet light source is used to irradiate the reaction system. The reaction time is 4 hours. The degree of reaction is monitored by thin layer chromatography. When 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is not detected, the reaction is stopped. The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, recrystallized with ethanol as a solvent, washed 3 times with deionized water, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.
[0018] Table 1 Raw material ratios for the synthesis of 3-hydroxy-2,4-dichloroacetophenone in Example 6
[0019] The ethyl 3-hydroxy-2,4-dichlorobenzoate in Table 1 is ethyl 3-hydroxy-2,4-dichlorobenzoate prepared by the method of Example 3.
[0020] The yield of 3-hydroxy-2,4-dichloroacetophenone in the reaction system was calculated as shown in formula (1). The calculation showed that the yield of 3-hydroxy-2,4-dichloroacetophenone was 67%.
[0021] Example 7
[0022] In a multifunctional reactor, 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester, an organic solvent, a catalyst, and a photosensitizer are added by weight, stirred continuously, the temperature is maintained at 50°C, and a 254 nm ultraviolet light source is used to irradiate the reaction system. The reaction time is 5 hours. The degree of reaction is monitored by thin layer chromatography. When 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is not detected, the reaction is stopped. The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, recrystallized with ethanol as a solvent, washed 3 times with deionized water, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.
[0023] Table 2 Raw material ratios for the synthesis of 3-hydroxy-2,4-dichloroacetophenone in Example 7
[0024] The ethyl 3-hydroxy-2,4-dichlorobenzoate in Table 2 is ethyl 3-hydroxy-2,4-dichlorobenzoate prepared by the method of Example 4.
[0025] The yield of 3-hydroxy-2,4-dichloroacetophenone in the reaction system was calculated as shown in formula (1). The calculation showed that the yield of 3-hydroxy-2,4-dichloroacetophenone was 72%. Example 8
[0026] In a multifunctional reactor, 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester, an organic solvent, a catalyst, and a photosensitizer are added by weight, stirred continuously, the temperature is maintained at 50°C, and a 254 nm ultraviolet light source is used to irradiate the reaction system. The reaction time is 7 hours. The degree of reaction is monitored by thin layer chromatography. When 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is not detected, the reaction is stopped. The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, recrystallized with ethanol as a solvent, washed 3 times with deionized water, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.
[0027] Table 3 Raw material ratios for the synthesis of 3-hydroxy-2,4-dichloroacetophenone in Example 8
[0028] The ethyl 3-hydroxy-2,4-dichlorobenzoate in Table 3 is ethyl 3-hydroxy-2,4-dichlorobenzoate prepared by the method of Example 5.
[0029] The yield of 3-hydroxy-2,4-dichloroacetophenone in the reaction system was calculated as shown in formula (1). The calculation showed that the yield of 3-hydroxy-2,4-dichloroacetophenone was 77%. Example 9
[0030] In a multifunctional reactor, 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester, an organic solvent, a catalyst, and a photosensitizer are added by weight, stirred continuously, the temperature is maintained at 50°C, and a 254 nm ultraviolet light source is used to irradiate the reaction system. The reaction time is 7 hours. The degree of reaction is monitored by thin layer chromatography. When 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is not detected, the reaction is stopped. The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, recrystallized with ethanol as a solvent, washed 3 times with deionized water, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.
[0031] Table 4 Raw material ratios for the synthesis of 3-hydroxy-2,4-dichloroacetophenone in Example 9
[0032] The ethyl 3-hydroxy-2,4-dichlorobenzoate in Table 4 is ethyl 3-hydroxy-2,4-dichlorobenzoate prepared by the method of Example 5.
[0033] The yield of 3-hydroxy-2,4-dichloroacetophenone in the reaction system was calculated as shown in formula (1). The calculation showed that the yield of 3-hydroxy-2,4-dichloroacetophenone was 74%.
[0034] Technical personnel should note that although the present invention has been described according to the above specific implementation methods, the inventive concept of the present invention is not limited to this invention, and any modification using the inventive concept will be included in the scope of protection of this patent.
Claims
1. 3-Hydroxy-2,4-dichloroacetophenone prepared by a one-pot process, characterized in that: The raw materials of the 3-hydroxy-2,4-dichloroacetophenone prepared by the one-pot method are: 40-60 parts of ethyl 3-hydroxy-2,4-dichlorobenzoate, 50-120 parts of an organic solvent, 10-30 parts of a catalyst, and 10-30 parts of a photosensitizer, and the preparation of ethyl 3-hydroxy-2,4-dichlorobenzoate comprises the following steps: S1: Select corn bran for pulverization, mix the pulverized corn bran with deionized water in a weight ratio of 1: (10-30), perform ultrasonic extraction at 45-70°C and an ultrasonic power of 400-800 W for 1-2 hours, and filter to obtain a corn bran extract; S2: Mix corn bran extract and 10% to 20% dilute hydrochloric acid in parts by weight 1: (1 to 5), keep stirring, react at 50 to 80°C for 1 to 3 hours, stop the reaction, and add sodium hydroxide solution to adjust the pH value to 6.7 to 7.3; S3: removing the solvent from the substance obtained in S2 by evaporation to obtain a crude vanillic acid extract, and then recrystallizing it with ethanol as solvent to obtain vanillic acid; S4: In ethanol, vanillic acid and thionyl chloride are mixed in a weight ratio of 1: (1-3), stirred continuously at 5-20°C for 1-2 hours, and then sodium hydroxide solution is added to adjust the pH value to 6.7-7.3, and 2,4-dichlorovanillic acid is obtained by recrystallization; S5: Mix the 2,4-dichlorobenzoic acid-3-methyl ether obtained in S4 and ethanol in a weight ratio of 1: (0.2-0.5), and reflux at 78-85° C. for 3-6 hours under the catalysis of concentrated sulfuric acid; S6: adding sodium hydroxide solution to the reaction product of S5 to adjust the pH value to 6.7-7.3, using ethyl acetate as the organic phase for extraction, and then evaporating the solvent to obtain ethyl 3-hydroxy-2,4-dichlorobenzoate.
2. The 3-hydroxy-2,4-dichloroacetophenone prepared by the one-pot method according to claim 1, characterized in that: The mass fraction of the concentrated sulfuric acid in S5 is 98%, and the mass fraction of the concentrated sulfuric acid added is 1% to 5% of the total mass of the reactants.
3. The 3-hydroxy-2,4-dichloroacetophenone prepared by the one-pot method according to claim 1, characterized in that: The organic solvent is selected from one or more of methanol, chloroform, carbon tetrachloride, toluene and dichloromethane.
4. 3-hydroxy-2,4-dichloroacetophenone prepared by a one-pot process as claimed in claim 1, characterized in that The catalyst is selected from one or more of FeCl3, AlCl3, BF3 and sulfuric acid.
5. 3-Hydroxy-2,4-dichloroacetophenone prepared by a one-pot process as claimed in claim 1, characterized in that The photosensitizer is selected from one or more of benzophenone and 1-hydroxycyclohexyl benzophenone.
6. The method for preparing 3-hydroxy-2,4-dichloroacetophenone prepared by a one-pot process according to any one of claims 1 to 5, characterized in that: The specific steps are as follows: S7: In a multifunctional reactor, add ethyl 3-hydroxy-2,4-dichlorobenzoate, an organic solvent, a catalyst, and a photosensitizer according to weight, continue stirring, maintain the temperature at 40-60° C., use a 254 nm ultraviolet light source to irradiate the reaction system, and the reaction time is 4-8 hours; S8: monitoring the progress of the reaction by thin layer chromatography, and stopping the reaction when no 3-hydroxy-2,4-dichlorobenzoic acid ethyl ester is detected; S9: The reaction system is transferred to a multiple-effect evaporator to remove the organic solvent, and recrystallized with ethanol as a solvent, and washed with deionized water for 2 to 3 times, and dried to obtain 3-hydroxy-2,4-dichloroacetophenone.