An environmentally friendly method for synthesizing 6-chloro-2-hydroxyquinolin
By replacing traditional methods with electrolytic reduction technology, the problem of sulfur-containing wastewater pollution during the synthesis of quizalofop-P-ethyl intermediates has been solved, achieving environmentally friendly synthesis, reducing costs, and shortening reaction time.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- JINGBO AGROCHEM TECH CO LTD
- Filing Date
- 2023-07-04
- Publication Date
- 2026-08-04
AI Technical Summary
The synthesis of the intermediate 6-chloro-2-hydroxyquinoxaline, currently used for quizalofop-P-ethyl, generates a large amount of sulfur-containing wastewater, causing environmental pollution and incurring high costs.
Electrolytic reduction is used instead of traditional sulfur-containing reducing agents. This is achieved by adding p-chloro-o-nitroacetanilide to an alkaline solution to induce a ring-closing reaction. Electrolysis is carried out using a platinum/graphite or platinum/lead electrode system, followed by oxygenation and acidification treatment to reduce the discharge of sulfur-containing wastewater.
It effectively reduces the discharge of sulfur-containing wastewater, lowers synthesis costs, shortens the reaction cycle, and protects the environment.
Smart Images
Figure CN116732541B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, specifically to an environmentally friendly synthesis method for 6-chloro-2-hydroxyquinoxaline. Background Technology
[0002] Quizalofop-P-ethyl is a highly selective foliar herbicide for dryland fields, exhibiting high selectivity between gramineous weeds and dicotyledonous crops. Its target pests are similar to those of quizalofop-P-ethyl, and it provides good control of gramineous weeds in broadleaf crop fields. Quizalofop-P-ethyl is a low-toxicity herbicide, environmentally safe, and therefore has broad prospects for technical synthesis and formulation processing.
[0003] Currently, the main synthetic route for the intermediate 6-chloro-2-hydroxyquinoxaline, derived from quizalofop-P-ethyl, involves first cyclizing p-chloro-o-nitroacetoacetanilide under the action of a certain concentration of liquid alkali, then reducing it with a traditional sulfur-containing reducing agent (such as NaHS) to obtain the sodium salt, followed by acidification to obtain 6-chloro-2-hydroxyquinoxaline. The reaction route is shown below:
[0004]
[0005] This process generates a large amount of sulfur-containing wastewater, which severely pollutes the environment. Therefore, developing a new technology to reduce environmental pollution is an urgent problem to be solved in this field. Summary of the Invention
[0006] To address the problems existing in the prior art, this invention provides an environmentally friendly synthesis method for 6-chloro-2-hydroxyquinoxaline. Specifically, the method involves cyclically closing p-chloro-o-nitroacetoacetanilide under the action of a certain concentration of liquid alkali, using electrolytic reduction instead of traditional reducing agents to obtain the sodium salt, and then acidifying it to obtain the quizalofop-P-ethyl intermediate (6-chloro-2-hydroxyquinoxaline). This method significantly reduces the discharge of sulfur-containing wastewater, and the reaction conditions are mild with a short reaction cycle. It protects the environment while reducing the cost of synthesizing the quizalofop-P-ethyl intermediate (6-chloro-2-hydroxyquinoxaline).
[0007] An environmentally friendly synthetic method for 6-chloro-2-hydroxyquinoxaline, the specific steps of which are as follows:
[0008] (1) Add p-chloro-o-nitroacetylaniline to the alkaline solution with stirring, and keep the reaction at the temperature after the solid dissolves.
[0009] (2) After the reaction in step (1), slowly raise the temperature and continue to keep the temperature high. After the reaction is completed, add water and cool down to room temperature.
[0010] (3) Using a two-electrode system, the reaction solution obtained in step (2) is electrolyzed, and samples are taken and monitored until the raw material reaction is complete. The reaction solution is then subjected to high-temperature oxygenation, and samples are taken and monitored until all the reduced intermediates are converted into the target product. The product is then adjusted to acid and filtered to obtain the product. The product is dried in an oven to obtain the quizalofop-P-ethyl intermediate (6-chloro-2-hydroxyquinoxaline).
[0011] The concentration of the alkali solution in step (1) is 20-60 wt%, and the molar ratio of the alkali to p-chloro-o-nitroacetylaniline is 5.0-5.5. Preferably, the optimal concentration of the alkali solution is 30 wt%, as a higher concentration of alkali solution will increase the amount of dihydroxyl impurities in the reaction.
[0012] Preferably, the alkali in the alkaline solution in step (1) is selected from potassium hydroxide, sodium hydroxide, etc.
[0013] The temperature of the heat preservation reaction in step (1) is 10-40℃, and the heat preservation reaction time is 2-5h.
[0014] The temperature of the heat preservation reaction in step (2) is 40-80℃, and the heat preservation reaction time is 2-5h;
[0015] Preferably, the amount of water added in step (2) is 2-8 times the mass of the reaction solution;
[0016] In the two-electrode system described in step (3), the anode can be selected from any one of iron, copper, platinum, titanium, etc., and the cathode can be selected from any one of carbon rod, graphite, lead, iron, copper. However, in order to obtain better electrolysis results, research and experiments have shown that the two-electrode system (anode / cathode) is better when selected from platinum / graphite and platinum / lead, especially platinum / lead.
[0017] Preferably, in step (3), the electrolysis time is controlled at 4-8 hours and the current is controlled at 4-6A;
[0018] Preferably, in step (3), the oxygenation temperature is 40-80℃ and the oxygenation time is 1-4h;
[0019] Preferably, the acid used for acid adjustment in step (3) is selected from hydrochloric acid or sulfuric acid, the pH is adjusted to 3-5 during the acidification process, and the drying temperature is 80°C.
[0020] Compared with existing methods, the method provided by this invention has the advantage of using an environmentally friendly electrolytic synthesis route, which avoids the traditional route that uses sulfur-containing reducing agents for reduction, greatly reducing the discharge of sulfur-containing wastewater. In addition, the reaction temperature is mild and the reaction cycle is short, which protects the environment and reduces the cost of synthesizing the intermediate of quizalofop-P-ethyl (6-chloro-2-hydroxyquinoxaline). Attached Figure Description
[0021] Figure 1 This is a liquid phase tracking spectrum after electrolysis in Example 4;
[0022] Figure 2 This is the liquid phase tracking spectrum after oxygenation in Example 4;
[0023] Figure 3 This is the mass spectrum of the over-reduced solution produced by electrolysis in Example 4. Detailed Implementation
[0024] The following detailed embodiments further illustrate the above-described content of the present invention, but should not be construed as limiting the scope of the invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Unless otherwise specified, conventional techniques are used in the following embodiments.
[0025] Example 1
[0026] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it down to 0℃ to obtain the electrolyte. Use platinum as the anode and graphite as the cathode to electrolyze the reaction solution. Control the current at 6A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium nitrogen oxides. Then, purify the reaction solution with oxygen at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 68% and the yield is 52%.
[0027] Example 2
[0028] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and graphite as the cathode to electrolyze the reaction solution. Control the current at 4A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium nitride at 6.3%. Introduce oxygen into the reaction solution at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH to 3-5 with hydrochloric acid, filter to obtain the product, and wash with water until neutral. The product content is 72% and the yield is 56%.
[0029] Example 3
[0030] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and graphite as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample to track and detect that 4.5% of the sodium salt of nitrogen oxides remains. Introduce oxygen into the reaction solution at 70℃ for 4 hours to track and detect that all the over-reduction intermediates are converted into the target product. Adjust the pH with hydrochloric acid to 3-5. Filter to obtain the product and wash with water until neutral. The product content is 78% and the yield is 66%.
[0031] Example 4
[0032] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water at a mass of 3 times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium salt of nitrogen oxides. The reaction solution is then aerated at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 85% and the yield is 77%.
[0033] In the attached diagram Figure 1 , Figure 2 The images show the liquid phase spectra after electrolysis and after oxygenation, respectively. A comparison reveals that after oxygenation, all intermediate states following the product are converted into the main product. To determine the structure of these intermediate states, liquid chromatography-mass spectrometry (LC-MS) analysis was performed, as shown in the attached figures. Figure 3 As shown, the mass of the product analyzed by liquid chromatography-mass spectrometry is 181, and the molecular weight of the intermediate state is 183, which indicates that it is an over-reduced impurity.
[0034] Example 5
[0035] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 6A and the electrolysis time at 4 hours. Take a sample to monitor and detect that the sodium salt of nitrogen oxides remains at 0.25%. Introduce oxygen into the reaction solution at 70℃ for 4 hours to monitor and detect that all over-reduction intermediates are converted into the target product. Adjust the pH with hydrochloric acid to 3-5, filter to obtain the product, and wash with water until neutral. The product content is 80% and the yield is 70%.
[0036] Example 6
[0037] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 4A and the electrolysis time at 8 hours. Take a sample and monitor the residual sodium salt of nitrogen oxides. Then, purify the reaction solution with oxygen at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 74% and the yield is 64%.
[0038] Comparative Example 1
[0039] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water with a mass of 3 times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and a carbon rod as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium salt of nitrogen oxides. The reaction solution is then purged with oxygen at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 64% and the yield is 42%.
[0040] Comparative Example 2
[0041] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and copper as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium salt of nitrogen oxides. The reaction solution is then purged with oxygen at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 68% and the yield is 56%.
[0042] Comparative Example 3
[0043] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use titanium as the anode and graphite as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium nitrogen oxides. The sodium salts were 18.1%. The reaction solution was then aerated at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediates to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content was 60% and the yield was 38%.
[0044] Comparative Example 4
[0045] Weigh 8.14g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25℃ for 3 hours. Then, raise the temperature to 75℃ and keep it at that temperature for another 3 hours. Add water at a mass of 3 times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use titanium as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 5A and the electrolysis time at 4 hours. Take a sample and monitor the residual sodium nitrogen oxides. The sodium salts remain at 16.3%. Infuse the reaction solution with oxygen at 70℃ for 4 hours to monitor the complete conversion of the over-reduction intermediates into the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 62% and the yield is 40%.
[0046] Comparative Example 5
[0047] Weigh 8.14 g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10 g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25 °C for 3 h. Then, raise the temperature to 75 °C and keep it at that temperature for another 3 h. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 2 A and the electrolysis time at 4 h. Take a sample and monitor the residual sodium nitrogen oxides. The remaining sodium salt is 14.3%. The reaction solution is then aerated at 70 °C for 4 h to monitor the complete conversion of the over-reduction intermediate to the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 66% and the yield is 44%.
[0048] Comparative Example 6
[0049] Weigh 8.14 g of sodium hydroxide and prepare a 30% sodium hydroxide aqueous solution in a four-necked flask. Add 10 g of p-chloro-o-nitroacetanilide and, after the solid dissolves, keep the reaction at 25°C for 3 h. Then, raise the temperature to 75°C and keep it at that temperature for another 3 h. Add water three times the mass of the reaction solution and cool it to room temperature to obtain the electrolyte. Use platinum as the anode and lead as the cathode to electrolyze the reaction solution. Control the current at 5 A and the electrolysis time at 2 h. Take a sample and monitor the residual sodium nitrogen oxides. Detect the residual sodium salt at 8.4%. Purge the reaction solution with oxygen at 70°C for 4 h and monitor the conversion of all over-reduction intermediates into the target product. Adjust the pH with hydrochloric acid to 3-5. Filter the product and wash it with water until neutral. The product content is 70% and the yield is 48%.
[0050] Based on the above embodiments and comparative examples, the following data was obtained, as shown in the table below:
[0051] Example 1 Platinum / Graphite 6 4 4.12 68 52 Example 2 Platinum / Graphite 4 4 6.30 72 56 Example 3 Platinum / Graphite 5 4 4.50 78 66 Example 4 Platinum / Lead 5 4 0.29 85 77 Example 5 Platinum / Lead 6 4 0.25 80 70 Example 6 Platinum / Lead 4 8 1.81 74 64 Comparative Example 1 Platinum / carbon rod 5 4 15.2 64 42 Comparative Example 2 Platinum / Copper 5 4 12.4 68 46 Comparative Example 3 Titanium / Graphite 5 4 18.1 60 38 Comparative Example 4 Titanium / Lead 5 4 16.3 62 40 Comparative Example 5 Platinum / Lead 2 4 14.3 66 44 Comparative Example 6 Platinum / Lead 5 2 8.4 70 48
Claims
1. An environmentally friendly method for synthesizing 6-chloro-2-hydroxyquinoxaline, characterized in that, The specific steps are as follows: (1) Add p-chloro-o-nitroacetanilide to the alkaline solution with stirring, and keep the reaction at the temperature after the solid dissolves; (2) After the reaction in step (1), slowly raise the temperature and continue to keep the temperature high. After the reaction is completed, add water and cool down to room temperature. (3) Using a two-electrode system, the reaction solution obtained in step (2) is electrolyzed, and the sample is taken and monitored until the raw material reaction is complete. The reaction solution is then subjected to high temperature oxygenation, and the reduced intermediate state is completely converted into the target product. After the product is adjusted to acid and filtered, the product is obtained. The product is then dried in an oven to obtain 6-chloro-2-hydroxyquinoxaline. In step (3), the electrolysis time is controlled at 4-8h and the current is controlled at 4-6A.
2. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, The concentration of the alkali solution in step (1) is 20-60 wt%, and the molar ratio of the alkali to p-chloro-o-nitroacetylaniline is 5.0-5.
5.
3. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, The temperature of the heat preservation reaction in step (1) is 10-40℃ and the heat preservation reaction time is 2-5h; the temperature of the heat preservation reaction in step (2) is 40-80℃ and the heat preservation reaction time is 2-5h.
4. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, In step (2), the amount of water added is 2-8 times the mass of the reaction solution.
5. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, In the two-electrode system described in step (3), the anode is selected from platinum or titanium, and the cathode is selected from carbon rod, graphite, or lead.
6. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 5, characterized in that, The two-electrode system described in step (3) is selected from platinum / graphite or platinum / lead.
7. The environmentally friendly synthetic method for 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, In step (3), the oxygenation temperature is 40-80℃ and the oxygenation time is 1-4h.
8. The environmentally friendly synthesis method of 6-chloro-2-hydroxyquinoxaline according to claim 1, characterized in that, The acid used for acid adjustment in step (3) is selected from hydrochloric acid or sulfuric acid. The pH is adjusted to 3-5 during the acidification process, and the drying temperature is 80℃.