Preparation process of 2-chloro-5-aminophenol based on modified chlorination reagent
Through the reaction of modified chlorination reagents and m-aminophenol, the environmental pollution, safety threats and low yields in traditional 2-chloro-5-aminophenol synthesis are solved, and a high-purity and high-efficiency preparation process is achieved, which simplifies the The operation process was completed.
Patent Information
- Application Number
- CN202411274538.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-12
- Publication Date
- 2024-12-10
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Traditional 2-chloro-5-aminophenol synthesis methods have problems such as environmental pollution, safety threats, waste of raw materials and low yields.
Using a preparation process based on modified chlorinated reagent, high purity is obtained by adding ethyl acetate to the reactor, cooling and mixing with m-aminophenol, dropping the modified chlorinated reagent, and then distilling and filtration under reduced pressure to obtain high purity. 2-Chloro-5-Aminophenol.
It improves reaction selectivity and yield, reduces by-product generation and chemical waste emissions, reduces operational hazards, simplifies process flow, and improves product purity and reaction efficiency.
Smart Images
Figure CN119100937A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of chemical preparation, in particular to a preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent. Background Art
[0002] 2-Chloro-5-aminophenol plays a vital role in the field of veterinary insecticides. As a key intermediate of imidacloprid, it not only affects the synthesis of imidacloprid, but is also an indispensable link in the entire veterinary insecticide industry chain. The research on its new synthesis method has important practical significance. While addressing a series of problems brought about by traditional synthesis methods, it provides the veterinary insecticide industry with a better quality and more environmentally friendly synthesis route, thus contributing to the sustainable development of the veterinary insecticide industry.
[0003] However, the traditional method for synthesizing 2-chloro-5-aminophenol has a series of obvious defects;
[0004] First, this method will produce a large amount of harmful waste during the production process, causing serious pollution to the environment. Secondly, the high temperature, high pressure and other conditions involved in the operation make the synthesis process full of dangers and pose a threat to the personal safety of the workers. In addition, the traditional synthesis method also has problems such as waste of raw materials and low yield. Summary of the invention
[0005] 1. Technical issues to be solved
[0006] In view of the above-mentioned shortcomings of the prior art, the present invention provides a preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent, which can effectively solve the problems of the prior art.
[0007] (II) Technical solution
[0008] To achieve the above objectives, the present invention is implemented through the following technical solutions:
[0009] The invention discloses a preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent, comprising the following steps:
[0010] Step 1: Add ethyl acetate to the reaction kettle, cool to -20°C, and keep stirring at a constant speed;
[0011] Step 2: pump m-aminophenol into the reaction kettle and stir until completely dissolved to form a joint suspension;
[0012] Step 3: Control the temperature at -20°C to -15°C, add 18% to 25.6% by weight of a modified chlorination reagent to the combined suspension, stir at a uniform speed after the addition is complete, and keep the mixture at the same temperature for 2 to 3 hours to obtain a mixed reactant;
[0013] Step 4: distill a certain amount of ethyl acetate from the mixed reaction product obtained in step 3 under reduced pressure, cool the residue to room temperature, slowly add deionized water under stirring, and a large amount of precipitation is immediately generated. Continue stirring for 1 hour to obtain a stirred product;
[0014] Step 5: Filter, rinse and dry the mixture obtained in step 4 to obtain 2-chloro-5-aminophenol.
[0015] Furthermore, after stopping the reaction in step 3, the chromatogram showed that the main product was 90.6%, chloro-5-aminophenol was 7.5%, and other by-products were 1.9%.
[0016] Furthermore, the modified chlorination reagent in step 3 is ethyl acetate containing dichlorohydantoin, and the mass concentration is 0.2 g / ml.
[0017] Furthermore, the preparation process of the modified dichlorohydantoin is as follows:
[0018] Dissolve dichlorohydantoin in dichloromethane, add in a mass ratio of 1:1.2, cool in an ice-water bath at 0°C, react for 2 hours, wash with water and saturated brine after the reaction, dry the organic phase with anhydrous magnesium sulfate to remove moisture, filter out the desiccant, and distill under reduced pressure to obtain protected dichlorohydantoin;
[0019] The protected dichlorohydantoin was dissolved in anhydrous acetonitrile, added in a mass ratio of 1:3, then 0.2% triphenylphosphine was added, and 1% iodomethane was slowly added. The reaction was carried out for 24 hours. After the reaction was completed, washing, drying, filtering out the desiccant and vacuum distillation were repeated to obtain modified dichlorohydantoin with a yield of 95% and a purity of 96%.
[0020] Furthermore, during the isothermal reaction in step 3, the reaction progress is monitored by HPLC, and the reaction is stopped when the content of m-aminophenol is lower than 0.2%.
[0021] Furthermore, in step 5, the stirred product is filtered, rinsed, and dried:
[0022] The stirred product is filtered to separate the solid product and the liquid, and filtered using a Buchner funnel to obtain a solid product;
[0023] The solid product was rinsed twice with ethyl acetate;
[0024] The solid product after filtering and rinsing was placed in a desiccator and vacuum dried for 12 h.
[0025] Furthermore, the volume ratio of the solid product to ethyl acetate is 1:2.
[0026] Furthermore, during the vacuum drying process, the temperature is 60°C and the vacuum degree is 9.310Pa.
[0027] Furthermore, the 2-chloro-5-aminophenol 115g obtained in step 5 has a yield of 88% and a purity of 99.5%
[0028] (III) Beneficial effects
[0029] Compared with the known prior art, the technical solution provided by the present invention has the following beneficial effects:
[0030] 1. The modified chlorination reagent can react with specific functional groups, which improves the selectivity of the reaction and thus obtains the target product with a higher yield.
[0031] 2. Due to the selectivity of the modified chlorination reagent, the generation of unnecessary by-products can be reduced or avoided, the discharge of chemical waste can be reduced, and the preparation process can be made more environmentally friendly. In the preparation process of the modified chlorination reagent, the selectivity of the target product is fully considered, which can reduce the generation of by-products and improve the purity of the product.
[0032] 3. The reaction conditions of the modified chlorination reagent are relatively mild, which can improve the controllability of the reaction and complete the reaction in a shorter time, thereby improving the efficiency of the reaction. The operation is relatively simple and the feasibility of the experimental operation is improved. BRIEF DESCRIPTION OF THE DRAWINGS
[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.
[0034] Figure 1 It is a schematic diagram of the process of the present invention. DETAILED DESCRIPTION
[0035] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are 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.
[0036] The present invention will be further described below in conjunction with the embodiments.
[0037] Example 1
[0038] A preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent in this embodiment, such as Figure 1 As shown, the following steps are included:
[0039] In a 2000ml four-necked flask, 1000ml of ethyl acetate and 100g of m-aminophenol were added, stirred and dissolved, cooled to -20°C, and the ethyl acetate solution of modified dichlorohydantoin (100g of modified dichlorohydantoin was dissolved in 500ml of ethyl acetate) was added dropwise at a temperature of -20°C to -15°C. After the addition was complete, the reaction was carried out at the same temperature for 2-3h. The reaction process was monitored by HPLC. When the m-aminophenol content was lower than 0.2%, the reaction was stopped (the chromatogram showed that the main product was 90.6%, chloro-5-aminophenol was 7.5%, and other by-products were 1.9%). Quantitative ethyl acetate was distilled off under reduced pressure. The residue was cooled to room temperature, and 300ml of water was slowly added under stirring. A large amount of precipitation was immediately generated. The mixture was stirred for 1h, filtered, rinsed, and dried to obtain 115g of 2-chloro-5-aminophenol with a yield of 88% and a purity of 99.5%.
[0040] The preparation process of modified dichlorohydantoin is as follows:
[0041] Dissolve dichlorohydantoin in dichloromethane, add in a mass ratio of 1:1.2, cool in an ice-water bath at 0°C, react for 2 hours, wash with water and saturated brine after the reaction, dry the organic phase with anhydrous magnesium sulfate to remove moisture, filter out the desiccant, and distill under reduced pressure to obtain protected dichlorohydantoin;
[0042] The protected dichlorohydantoin was dissolved in anhydrous acetonitrile, added in a mass ratio of 1:3, then 0.2% triphenylphosphine was added, and 1% iodomethane was slowly added. The reaction was carried out for 24 hours. After the reaction was completed, washing, drying, filtering out the desiccant and vacuum distillation were repeated to obtain modified dichlorohydantoin with a yield of 95% and a purity of 96%.
[0043] Example 2
[0044] A preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent of the present embodiment comprises the following steps:
[0045] In a 2000ml four-necked flask, add 1000ml of ethyl acetate and 100g of m-aminophenol, stir and dissolve, cool to -15℃, control the temperature at -15℃~-10℃ and add dropwise a solution of modified dichlorohydantoin in ethyl acetate (100g of modified dichlorohydantoin is dissolved in 500ml of ethyl acetate), after the addition is complete, keep the reaction at the same temperature for 2-3h, monitor the reaction progress by HPLC, stop the reaction when the m-aminophenol content is lower than 0.2% (at this time, the chromatogram shows that the main product is 89.8%, the impurity p-chloro-5-aminophenol is 8.0%, and the others are 2.2%), evaporate a certain amount of ethyl acetate under reduced pressure, cool the residue to room temperature, slowly add 300ml of water under stirring, and a large amount of precipitate is immediately generated, continue stirring for 1h, filter, rinse, and dry to obtain 114g of 2-chloro-5-aminophenol with a yield of 87% and a purity of 99.3%.
[0046] Example 3
[0047] A preparation process of 2-chloro-5-aminophenol based on a modified chlorination reagent of the present embodiment comprises the following steps:
[0048] In a 2000ml four-necked flask, add 1000ml of ethyl acetate and 100g of m-aminophenol, stir and dissolve, cool to -10℃, control the temperature at -10℃~0℃ and add dropwise a solution of modified dichlorohydantoin in ethyl acetate (100g of modified dichlorohydantoin is dissolved in 500ml of ethyl acetate), after the addition is complete, keep the reaction at the same temperature for 2-3h, monitor the reaction progress by HPLC, stop the reaction when the content of m-aminophenol is lower than 0.2% (at this time, the chromatogram shows that the main product is 88.3%, the impurity p-chloro-5-aminophenol is 8.8%, and the others are 2.9%), evaporate a certain amount of ethyl acetate under reduced pressure, cool the residue to room temperature, slowly add 300ml of water under stirring, and a large amount of precipitate is immediately generated, continue stirring for 1h, filter, rinse, and dry to obtain 111g of 2-chloro-5-aminophenol with a yield of 85% and a purity of 99.2%.
[0049] Performance Testing
[0050] The final products obtained in Examples 1-3 were used as Comparative Examples 1-3 to prepare a control group, as Comparative Example 4. The preparation process of Comparative Example 4 included the following steps:
[0051] Add 100 parts of 30% dilute hydrochloric acid and 23.7 parts of triphosphate into a flask, stir, then raise to reflux temperature, react for 8 hours, after the reaction is completed, separate the water layer at above 60°C, then cool to room temperature to obtain 2,4-dichloro-5-nitrophenol;
[0052] The following indicators are tested for comparison examples 1-4:
[0053]
[0054] In summary, the performance of Comparative Examples 1-3 in product purity, final product yield, solubility and crystallization characteristics are better than that of Comparative Example 4 prepared by conventional technology. Therefore, it can be seen that the modified chlorination reagent can react with specific functional groups, thereby improving the selectivity of the reaction and obtaining a higher yield of the target product. Thanks to the high selectivity of the modified chlorination reagent, the production of non-target products can be effectively reduced or eliminated during the preparation process, thereby reducing the emission of chemical waste and making the preparation process more environmentally friendly. Through careful design, the modified chlorination reagent has a higher selectivity for the target product during the preparation process, which helps to reduce the formation of by-products and improve the purity of the product.
[0055] In addition, the reaction conditions of the modified chlorination reagent are relatively mild, which helps to improve the controllability of the reaction process. Completing the reaction in a shorter time not only improves the reaction efficiency, but also simplifies the operation process, thereby enhancing the feasibility of industrial continuous production;
[0056] The high selectivity of the modified chlorination reagent in the preparation process not only helps to improve the purity of the product, but also reduces the generation of by-products. This is because during the reaction process, the modified chlorination reagent can react specifically with the target product and will not react with non-target substances. In this way, the content of the target substance in the reaction product will increase, thereby improving the purity of the product;
[0057] In addition, the reaction conditions of the modified chlorination reagent are relatively mild, which means that during the reaction, the reagent has less impact on the environment. At the same time, such mild reaction conditions also help to improve the controllability of the reaction process and complete the reaction in a shorter time, which not only improves the reaction efficiency but also simplifies the operation process. In this way, the feasibility of the experimental operation is enhanced.
[0058] In short, the application of modified chlorination reagents in the chemical preparation process can not only improve the selectivity and yield of the reaction, but also help reduce waste emissions and achieve green preparation. At the same time, it can also simplify the operation process and improve experimental efficiency. Therefore, modified chlorination reagents have broad application prospects in the field of chemical preparation.
[0059] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent, characterized in that: The following steps are involved: Step 1: Add ethyl acetate to the reaction kettle, cool to -20°C, and keep stirring at a constant speed; Step 2: pump m-aminophenol into the reaction kettle and stir until completely dissolved to form a joint suspension; Step 3: Control the temperature at -20°C to -15°C, add 18% to 25.6% by weight of a modified chlorination reagent to the combined suspension, stir at a uniform speed after the addition is complete, and keep the mixture at the same temperature for 2 to 3 hours to obtain a mixed reactant; Step 4: distill a certain amount of ethyl acetate from the mixed reaction product obtained in step 3 under reduced pressure, cool the residue to room temperature, slowly add deionized water under stirring, and a large amount of precipitation is immediately generated. Continue stirring for 1 hour to obtain a stirred product; Step 5: Filter, rinse and dry the stirred product obtained in step 4 to obtain 2-chloro-5-aminophenol.
2. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 1, characterized in that: After stopping the reaction in step 3, the chromatogram showed that the main product was 90.6%, chloro-5-aminophenol was 7.5%, and other by-products were 1.9%.
3. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 1, characterized in that: The modified chlorination reagent in step 3 is ethyl acetate containing dichlorohydantoin, and the mass concentration is 0.2 g / ml.
4. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 3, characterized in that: The preparation process of the modified dichlorohydantoin is: Dissolve dichlorohydantoin in dichloromethane, add in a mass ratio of 1:1.2, cool in an ice-water bath at 0°C, react for 2 hours, wash with water and saturated brine after the reaction, dry the organic phase with anhydrous magnesium sulfate to remove moisture, filter out the desiccant, and distill under reduced pressure to obtain protected dichlorohydantoin; The protected dichlorohydantoin was dissolved in anhydrous acetonitrile, added in a mass ratio of 1:3, then 0.2% triphenylphosphine was added, and 1% iodomethane was slowly added. The reaction was carried out for 24 hours. After the reaction was completed, washing, drying, filtering out the desiccant and vacuum distillation were repeated to obtain modified dichlorohydantoin with a yield of 95% and a purity of 96%.
5. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 1, characterized in that: During the isothermal reaction in step 3, the reaction progress is monitored by HPLC, and the reaction is stopped when the content of m-aminophenol is lower than 0.2%.
6. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 1, characterized in that: In step 5, the stirred product is filtered, rinsed, and dried: The stirred product is filtered to separate the solid product and the liquid, and filtered using a Buchner funnel to obtain a solid product; The solid product was rinsed twice with ethyl acetate; The solid product after filtering and rinsing was placed in a desiccator and vacuum dried for 12 h.
7. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 6, characterized in that: The volume ratio of the solid product to ethyl acetate is 1:
2.
8. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 6, characterized in that: During the vacuum drying process, the temperature was 60° C. and the vacuum degree was 9.310 Pa.
9. A process for preparing 2-chloro-5-aminophenol based on a modified chlorination reagent according to claim 1, characterized in that: 115 g of 2-chloro-5-aminophenol was obtained in step 5, with a yield of 88% and a purity of 99.5%.