A preparation method of 2-(4-hydroxyphenoxy) quinoxaline

Abstract

The present invention relates to the field of chemical synthesis technology, and specifically relates to a preparation method of a clean 2-(4-hydroxyphenoxy) quinoxaline. The method comprises the following steps: (1) successively adding 2-hydroxyquinoxaline and cuprous iodide to an alkali solution at 60-70 °C to obtain an alkali solution of 2-hydroxyquinoxaline; (2) adding a palladium catalyst and a ligand to an aqueous solution of p-chlorophenol to obtain a p-chlorophenol system solution; (3) at 60-70 °C, dropping the p-chlorophenol system solution into the alkali solution of 2-hydroxyquinoxaline, heating to 90-100 °C for heat preservation after dropping, and then cooling and filtering to obtain 2-(4-hydroxyphenoxy) quinoxaline. The present invention uses 2-hydroxyquinoxaline and p-chlorophenol as raw materials, and under the action of a catalyst, synthesizes 2-(4-hydroxyphenoxy) quinoxaline, successfully replaces hydroquinone with p-chlorophenol, shortens the reaction steps, reduces the content of phenolic compounds in the generated wastewater, and improves the environmental protection benefit.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and particularly relates to a method for preparing a clean 2-(4-hydroxyphenoxy) quinoxaline. Background Art

[0002] 4-(6-chloroquinoxalin-2-yloxy)phenol is an important intermediate for preparing herbicides such as quizalofop-p-ethyl, clodinafop-propargyl, and quinoxyphen. 2-(4-hydroxyphenoxy) quinoxaline is a common impurity in 4-(6-chloroquinoxalin-2-yloxy)phenol. It is a dechlorinated impurity of 4-(6-chloroquinoxalin-2-yloxy)phenol and will always exist in the product during the subsequent process of preparing herbicides such as quizalofop-p-ethyl, clodinafop-propargyl, and quinoxyphen. In order to control the product quality, it is necessary to strictly control it as an important impurity reference substance in the subsequent product preparation.

[0003] The reaction process of the preparation method of 2-(4-hydroxyphenoxy) quinoxaline is as follows:

[0004] 。

[0005] Ether compounds can be prepared by dehydrating two hydroxyl groups under strong acidic and high-temperature conditions. However, 2-hydroxyquinoxaline will decompose and ring-open under high temperature and acidic conditions. Therefore, 2-hydroxyquinoxaline and hydroquinone cannot be directly dehydrated to form an ether bond. The above reaction process uses the reaction of the phenoxy anion of hydroquinone to replace the chlorine of quinoxaline under strong alkaline conditions. Since hydroquinone will be oxidized to benzoquinone under strong alkaline conditions, in order to alleviate the oxidation of hydroquinone under strong alkaline conditions, the existing process uses the method of dropping alkali solution to maintain the pH of the system at 9-10. In the production process, in order to reduce the residue of the intermediate 2-chloroquinoxaline, the amount of hydroquinone is usually increased. Therefore, a large amount of phenolic wastewater will be generated after the reaction. The phenolic wastewater has a high chromaticity. It is difficult to remove the color of the sewage by simple sewage treatment methods, and the phenomenon of color reversion will occur when the pH changes, becoming an environmental protection problem.

[0006] Therefore, it is necessary to find a preparation method to replace the above route. Summary of the Invention

[0007] Aiming at the environmental protection defect that the existing technology generates a large amount of phenolic wastewater and is not easy to treat, the present invention provides a method for preparing a clean 2-(4-hydroxyphenoxy) quinoxaline. The present invention uses 2-hydroxyquinoxaline and p-chlorophenol as raw materials, and under the action of a catalyst, synthesizes 2-(4-hydroxyphenoxy) quinoxaline. Successfully, p-chlorophenol is used to replace hydroquinone, shortening the reaction steps, reducing the content of phenolic compounds in the generated wastewater, and improving the environmental protection benefits.

[0008] The technical solution of the present invention is as follows:

[0009] A preparation method of a cleaning type 2-(4-hydroxyphenoxy) quinoxaline, and the reaction formula is as follows:

[0010]

[0011] It includes the following steps:

[0012] (1) Add 2-hydroxyquinoxaline and cuprous iodide to an alkali solution at 60-70 °C in sequence to obtain an alkali solution of 2-hydroxyquinoxaline;

[0013] (2) Add a palladium catalyst and a ligand to an aqueous solution of p-chlorophenol to obtain a solution of the p-chlorophenol system;

[0014] (3) At 60-70 °C, drop the solution of the p-chlorophenol system into the alkali solution of 2-hydroxyquinoxaline. After dropping, raise the temperature to 90-100 °C for heat preservation, and then cool down and filter to obtain 2-(4-hydroxyphenoxy) quinoxaline.

[0015] Further, the palladium catalyst is at least one of palladium acetate or palladium chloride.

[0016] Further, the dosage of cuprous iodide is 4wt%-5wt% of 2-hydroxyquinoxaline.

[0017] Further, in the solution of the p-chlorophenol system, the mass ratio of p-chlorophenol to 2-hydroxyquinoxaline is 3-4:1.

[0018] Further, the dosage of the palladium catalyst is 0.08wt%-0.1wt% of 2-hydroxyquinoxaline.

[0019] Further, the ligand is dppp (1,3-bis(diphenylphosphino)propane), dppe (1,2-bis(diphenylphosphino)ethane) or dppf (1,1'-bis(diphenylphosphino)ferrocene), and the mass ratio of the ligand to the palladium catalyst is 2-4:1.

[0020] Further, step (1) is specifically:

[0021] Prepare a sodium hydroxide solution with a concentration of 8%-12%, raise the temperature to 60-70 °C, add 2-hydroxyquinoxaline, stir to dissolve, add cuprous iodide, stir to dissolve, and displace with nitrogen for several times to obtain an alkali solution of 2-hydroxyquinoxaline.

[0022] Further, in step (1), the amount of substance of 2-hydroxyquinoxaline is the same as that of sodium hydroxide.

[0023] Further, step (2) is specifically:

[0024] Weigh p-chlorophenol that is 3 to 4 times the mass of 2-hydroxyquinoxaline and 0.5 to 1.5 times the amount of water. Stir and heat until all of the p-chlorophenol is melted. After purging with nitrogen several times, add the catalyst and ligand, and then purge with nitrogen several more times to obtain a solution of the p-chlorophenol system.

[0025] Further, step (3) is specifically as follows:

[0026] At 60 to 70 °C, slowly add the solution of the p-chlorophenol system dropwise to the alkaline solution of 2-hydroxyquinoxaline over a period of 4 to 6 hours. After the addition is complete, raise the temperature to 90 to 100 °C and hold for 4 to 6 hours. Check that the residual amount of 2-hydroxyquinoxaline is less than 0.5%, then cool to 70 to 80 °C and filter.

[0027] Further, it also includes step (4), where the filtrate is allowed to stand and separate at 70 to 80 °C, the aqueous phase is separated, and the washed organic phase is recycled to the next batch.

[0028] The beneficial effects of the present invention are as follows:

[0029] (1) The present invention uses cuprous iodide and a palladium-based catalyst in combination. The palladium catalyst has the characteristic of being able to insert between the benzene ring and chlorine, but it cannot completely remove the chlorine. In this application, cuprous iodide is added to promote the removal of chlorine; the addition of palladium reduces the difficulty of the catalytic coupling reaction of cuprous iodide, lowers the reaction activation energy, and reduces the reaction temperature required.

[0030] The prior art mainly uses a copper catalyst to replace the palladium catalyst for the coupling reaction. The present invention uses cuprous iodide as the main catalyst and a palladium catalyst, solving the technical problem that the reaction substrate has too low activity and is not easy to react. On the other hand, since p-chlorophenol has both chlorine and a hydroxyl group, if the two catalysts are placed in one system, it will cause an increase in self-coupling impurities. This application uses a heterogeneous reaction, adding cuprous iodide to the alkaline solution of 2-hydroxyquinoxaline and adding the palladium catalyst to the p-chlorophenol system, and alleviating the generation of coupling impurities through a two-phase reaction.

[0031] (2) By the method of dropping p-chlorophenol and controlling the reaction temperature, the reaction selectivity is improved, effectively avoiding the self-coupling reaction of p-chlorophenol.

[0032] (3) Through the protection of the ligand and nitrogen, the oxidation of palladium is slowed down, effectively extending the service life of the palladium catalyst; at the same time, cuprous iodide itself is also reducing, and can also alleviate the oxidation of palladium.

[0033] (4) The present invention uses p-chlorophenol instead of hydroquinone. p-Chlorophenol is extremely insoluble in water, so there are only extremely small amounts of phenolic compounds in the production wastewater of the present invention, solving the environmental protection problems of high cost and complex processes for treating phenolic wastewater. Secondly, p-chlorophenol also has an obvious cost advantage compared to hydroquinone.

[0034] (5) 4-Chlorophenol serves as both a reaction solvent and a reaction substrate, and is easily separated from the reaction system and can be recycled.

[0035] (6) The production step of preparing 2-chloroquinoxaline from 2-hydroxyquinoxaline in the present invention is omitted, simplifying the production process and avoiding the use of highly polluting and high-risk chlorination processes. Specific Embodiments

[0036] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0037] Example 1

[0038] A method for preparing clean 2-(4-hydroxyphenoxy)quinoxaline, the specific steps are as follows:

[0039] (1) Prepare 200 g of a 10% sodium hydroxide solution, heat it to 60 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, add 3.1 g of cuprous iodide, stir to dissolve, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0040] (2) Weigh 307.4 g of 4-chlorophenol and 76.8 g of water, stir and heat to 60 °C. After the system is displaced with nitrogen three times, add 0.061 g of palladium chloride and 0.18 g of dppe, and displace with nitrogen three times again to obtain a 4-chlorophenol system solution;

[0041] (3) At 60 °C, drop the 4-chlorophenol system solution into the alkaline solution of 2-hydroxyquinoxaline. The dropping time is 5 h. After dropping, heat up to 90 °C and keep warm for 4 h. Detect that the residue of 2-hydroxyquinoxaline is 0.4%. Cool down to 75 °C and filter. Wash the filter cake with 200 g of water. The mass of the dried filter cake is 115 g. The content detected by HPLC is 96.3%, and the yield is 93.1%;

[0042] (4) Let the filtrate stand and separate at 70 °C, separate the aqueous phase, and recycle 249 g of the washed organic phase to the next batch.

[0043] Example 2

[0044] A method for preparing clean 2-(4-hydroxyphenoxy)quinoxaline, the specific steps are as follows:

[0045] (1) Prepare 200 g of 10% sodium hydroxide solution, heat it up to 65 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, add 3.8 g of cuprous iodide, stir to dissolve, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0046] (2) Weigh 60 g of p-chlorophenol and 76.8 g of water, add 249 g of the recovered filtrate from Example 1, stir and heat to 65 °C. After displacing the system with nitrogen three times, add 0.077 g of palladium chloride and 0.23 g of dppp, and displace with nitrogen three times again to obtain a p-chlorophenol system solution;

[0047] (3) At 65 °C, dropwise add the p-chlorophenol system solution to the alkaline solution of 2-hydroxyquinoxaline. The dropping time is 5 h. After dropping, heat up to 95 °C and keep warm for 5 h. Detect that the residue of 2-hydroxyquinoxaline is 0.4%. Cool down to 75 °C and filter. Wash the filter cake with 200 g of water. The mass of the dried filter cake is 117 g. The content detected by HPLC is 96.0%, and the yield is 94.4%;

[0048] (4) Let the filtrate stand for liquid separation at 70 °C, separate the aqueous phase, and recycle 240 g of the washed organic phase to the next batch.

[0049] Example 3

[0050] A preparation method of clean 2-(4-hydroxyphenoxy)quinoxaline is as follows:

[0051] (1) Prepare 200 g of 10% sodium hydroxide solution, heat it up to 65 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, add 3.1 g of cuprous iodide, stir to dissolve, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0052] (2) Weigh 60 g of p-chlorophenol and 76.8 g of water, add 240 g of the recovered filtrate from Example 2, stir and heat to 65 °C. After displacing the system with nitrogen three times, add 0.077 g of palladium acetate and 0.23 g of dppe, and displace with nitrogen three times again to obtain a p-chlorophenol system solution;

[0053] (3) At 65 °C, dropwise add the p-chlorophenol system solution to the alkaline solution of 2-hydroxyquinoxaline. The dropping time is 5 h. After dropping, heat up to 95 °C and keep warm for 5 h. Detect that the residue of 2-hydroxyquinoxaline is 0.3%. Cool down to 75 °C and filter. Wash the filter cake with 200 g of water. The mass of the dried filter cake is 117 g. The content detected by HPLC is 97.2%, and the yield is 95.6%;

[0054] (4) Let the filtrate stand for liquid separation at 70 °C, separate the aqueous phase, and recycle 245 g of the washed organic phase to the next batch.

[0055] (5) During the machine washing process of filtering 2-(4-hydroxyphenoxy)quinoxaline, 420 g of wastewater was generated, and the detected COD was 14,300.

[0056] Example 4

[0057] A preparation method of a clean 2-(4-hydroxyphenoxy)quinoxaline is as follows:

[0058] (1) Prepare 250 g of an 8% sodium hydroxide solution, heat it to 65 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, add 3.1 g of cuprous iodide, stir to dissolve, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0059] (2) Weigh 76.8 g of water, add 245 g of the recovered filtrate from Example 3, stir and heat until all p-chlorophenol is melted. After the system is displaced with nitrogen three times, add 0.077 g of palladium acetate and 0.23 g of dppf, and displace with nitrogen three times again to obtain a p-chlorophenol system solution;

[0060] (3) At 65 °C, add the p-chlorophenol system solution dropwise to the alkaline solution of 2-hydroxyquinoxaline. The dropping time is 5 h. After the dropping is completed, heat up to 95 °C and keep warm for 5 h. Detect that the residue of 2-hydroxyquinoxaline is 0.5%. Cool down to 75 °C and filter. The mass of the filter cake after drying is 108 g. The content detected by HPLC is 95.4%, and the yield is 86.6%;

[0061] (4) Let the filtrate stand for liquid separation at 70 °C, separate the aqueous phase, and the organic phase after washing with water is 180 g.

[0062] Comparative Example 1

[0063] Weigh 84.5 g of 2-chloroquinoxaline and 73 g of hydroquinone, add 153.6 g of water, heat to 90 °C, dropwise add 200 g of a 10% sodium hydroxide solution. During the dropping process, control the system pH at 9-10, heat up to 98-100 °C and keep warm for reaction for 12 h; sample and detect that the residue of 2-chloroquinoxaline is 0.5%; cool down to 80 °C, filter by suction, and use 900 g of water at 70-80 °C to wash the filter cake in three batches until the filtrate is colorless. The mass of the filter cake after drying is 112 g. The content detected by HPLC is 95.1%, and the yield is 89.5%. After detection, the content of p-phenylenedioxyquinoxalin-2-yl ether in the product is 1.25%, and 1150 g of black phenolic wastewater is generated, with a COD of 121,000.

[0064] Description of Comparative Example 1: 2-(4-Hydroxyphenoxy)quinoxaline was synthesized using 2-chloroquinoxaline and hydroquinone as raw materials, and its content was slightly low. The impurity was the ether formed by the reaction of two molecules of 2-chloroquinoxaline and one molecule of hydroquinone. Due to the deep color of the wastewater, more water was needed to wash the product, resulting in a large amount of wastewater. At the same time, due to the dissolution of excessive hydroquinone and its oxides in water, the wastewater was deeply colored and had a high COD.

[0065] Comparative Example 2

[0066] (1) Prepare 200 g of 10% sodium hydroxide solution, heat it to 60 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, add 3.1 g of cuprous iodide, stir to dissolve, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0067] (2) Weigh 307.4 g of p-chlorophenol and 76.8 g of water, stir and heat to 60 °C, and displace with nitrogen three times to obtain a p-chlorophenol system solution;

[0068] (3) At 60 °C, drop the p-chlorophenol system solution into the alkaline solution of 2-hydroxyquinoxaline. The dropping time is 5 h. After dropping, heat it to 90 °C and keep it warm for 4 h. Detect that the residual amount of 2-hydroxyquinoxaline is 88.3%. After continuing to keep it warm for 4 h, detect the reaction and find that the raw materials no longer react; terminate the reaction.

[0069] Description of Comparative Example 2: Only cuprous iodide was used for catalysis, and the reaction conversion rate was low.

[0070] Comparative Example 3

[0071] (1) Prepare 200 g of 10% sodium hydroxide solution, heat it to 60 °C, add 76.8 g of 2-hydroxyquinoxaline, stir until dissolved, and displace with nitrogen three times to obtain an alkaline solution of 2-hydroxyquinoxaline;

[0072] (2) Weigh 307.4 g of p-chlorophenol and 76.8 g of water, stir and heat to 60 °C. After displacing the system with nitrogen three times, add 0.061 g of palladium chloride and 0.18 g of dppe, and displace with nitrogen three times again to obtain a p-chlorophenol system solution;

[0073] (3) At 60 °C, the p-chlorophenol system solution was added dropwise to the alkaline solution of 2-hydroxyquinoxaline over a period of 5 h. After the addition was complete, the temperature was raised to 90 °C and maintained for 4 h. The residual amount of 2-hydroxyquinoxaline was detected to be 28.6%. 0.061 g of palladium chloride and 0.18 g of dppe were added. It was maintained at 90 °C for 4 h, and the residual amount of 2-hydroxyquinoxaline was detected to be 15.8%. 0.12 g of palladium chloride and 0.36 g of dppe were added. It was maintained at 90 °C for 4 h, and the residual amount of 2-hydroxyquinoxaline was detected to be 3.5%. Another 0.12 g of palladium chloride and 0.36 g of dppe were added. After maintaining at 90 °C for 4 h, the reaction was detected and it was found that the raw materials no longer reacted; the reaction was terminated.

[0074] Comparative Example 3 description: Only palladium chloride was used as the catalyst. The reaction was relatively fast in the early stage and slow in the later stage. It was necessary to continuously add new palladium chloride. When the residual amount of the raw materials was small, the reaction could not continue. The cost was high and the conversion rate was low.

[0075] Comparative Example 4

[0076] (1) 200 g of 10% sodium hydroxide solution was prepared and heated to 60 °C. 76.8 g of 2-hydroxyquinoxaline was added and stirred until dissolved to obtain the alkaline solution of 2-hydroxyquinoxaline.

[0077] (2) 307.4 g of p-chlorophenol and 76.8 g of water were weighed, stirred and heated to 60 °C. After the system was purged with nitrogen three times, 3.1 g of copper iodide was added and stirred until dissolved. 0.061 g of palladium chloride and 0.18 g of dppe were added. It was purged with nitrogen three times again to obtain the p-chlorophenol system solution.

[0078] (3) At 60 °C, the p-chlorophenol system solution was added dropwise to the alkaline solution of 2-hydroxyquinoxaline over a period of 5 h. After the addition was complete, the temperature was raised to 90 °C and maintained for 4 h. The residual amount of 2-hydroxyquinoxaline was detected to be 0.4%. The temperature was lowered to 75 °C and filtered. The mass of the dried filter cake was 115 g. The content detected by HPLC was 86.3% and the yield was 83.4%.

[0079] Comparative Example 4 description: When copper iodide and palladium chloride were placed in one system, the content and yield of the obtained product were both low. The large coupling impurities of p-chlorophenol led to a low yield of the product, and the conversion rate of the raw material 2-hydroxyquinoxaline was low due to unknown impurities resulting in a low yield.

[0080] Although the present invention has been described in detail by way of preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, those of ordinary skill in the art can make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions should all be within the scope of the present invention. / Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention.

Claims

1. A preparation method of a cleaning type 2-(4-hydroxyphenoxy) quinoxaline, characterized in that, The reaction formula is as follows: ； It includes the following steps: (1) Add 2-hydroxyquinoxaline and cuprous iodide to an alkali solution at 60-70 °C in sequence to obtain an alkali solution of 2-hydroxyquinoxaline; (2) Add a palladium catalyst and a ligand to an aqueous solution of p-chlorophenol to obtain a p-chlorophenol system solution; Among them, the palladium catalyst is at least one of palladium acetate or palladium chloride, and the ligand is 1,3-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)ethane or 1,1'-bis(diphenylphosphino)ferrocene; (3) At 60-70 °C, dropwise add the p-chlorophenol system solution to the alkali solution of 2-hydroxyquinoxaline. After the addition is completed, raise the temperature to 90-100 °C for heat preservation, and then cool down and filter to obtain 2-(4-hydroxyphenoxy)quinoxaline.

2. The preparation method according to claim 1, characterized in that, The dosage of cuprous iodide is 4wt%-5wt% of 2-hydroxyquinoxaline.

3. The preparation method according to claim 1, characterized in that, In the p-chlorophenol system solution, the mass ratio of p-chlorophenol to 2-hydroxyquinoxaline is 3-4:

1.

4. The preparation method according to claim 1, characterized in that, The dosage of the palladium catalyst is 0.08wt%-0.1wt% of 2-hydroxyquinoxaline.

5. The preparation method according to claim 1, characterized in that, The mass ratio of the ligand to the palladium catalyst is 2-4:

1.

6. The preparation method according to claim 1, characterized in that, Step (1) is specifically as follows: Prepare a sodium hydroxide solution with a concentration of 8%-12%, raise the temperature to 60-70 °C, add 2-hydroxyquinoxaline, stir to dissolve, add cuprous iodide, stir to dissolve, and displace with nitrogen for several times to obtain an alkali solution of 2-hydroxyquinoxaline.

7. The preparation method according to claim 1, characterized in that, Step (2) is specifically as follows: Weigh p-chlorophenol 3-4 times the mass of 2-hydroxyquinoxaline and 0.5-1.5 times the mass of water, stir and heat until p-chlorophenol is completely melted. After displacing with nitrogen for several times, add the palladium catalyst and the ligand, and displace with nitrogen several times again to obtain a p-chlorophenol system solution.

8. The preparation method according to claim 1, characterized in that, Step (3) is specifically as follows: At 60-70 °C, dropwise add the p-chlorophenol system solution to the alkali solution of 2-hydroxyquinoxaline. The dropping time is 4-6 h. After the addition is completed, raise the temperature to 90-100 °C for heat preservation for 4-6 h. Detect that the residue of 2-hydroxyquinoxaline is less than 0.5%, and cool down to 70-80 °C for filtration.

9. The preparation method according to claim 1, characterized in that, It also includes step (4), let the filtrate stand and separate at 70-80 °C, separate the aqueous phase, and recycle the washed organic phase to the next batch.

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