A continuous flow synthesis method for hydroquinone

Abstract

This invention relates to a continuous flow synthesis method for hydroquinone, a chemical and pharmaceutical intermediate, belonging to the field of chemical intermediate synthesis. The method for preparing hydroquinone uses phenol as a starting material, which undergoes oxidation to obtain p-benzoquinone, followed by hydrogenation reduction to obtain hydroquinone. Both steps are performed in a microreactor system. The synthesis method includes the following steps: (1) Phenol, catalyst 1, and organic solvent are prepared as component A, and an oxidant is used as component B. A and B react in a microchannel reactor 1 to obtain intermediate I benzoquinone; (2) Intermediate I benzoquinone is mixed with an organic solvent and reacted with hydrogen in a microchannel reactor 2 under the action of catalyst 2 to obtain hydroquinone. This invention utilizes a microreactor system with excellent heat and mass transfer performance, significantly shortening the reaction time. Both steps are completed within 50 minutes, and the reaction efficiency is high, energy consumption is low, safety is high, automation is high, and the environment is environmentally friendly.

Description

Technical Field

[0001] This invention relates to a continuous flow synthesis method for hydroquinone, a chemical and pharmaceutical intermediate, belonging to the field of chemical intermediate synthesis. Background Technology

[0002] Hydroquinone is a white crystalline powder, mainly used in the production of black and white developing agents, anthraquinone dyes, azo dyes, rubber antioxidants, stabilizers, and antioxidants. Currently, there are three production processes for hydroquinone on the market: the p-diisopropylbenzene method, the aniline redox method, and the phenol hydrogen peroxide hydroxylation method.

[0003] The p-diisopropylbenzene process is mainly used in foreign production processes (Mitsui Chemicals, Japan; Eastman Chemical, USA). It involves an alkylation reaction of benzene and propylene to produce two isopropylbenzene isomers. p-Cumene and m-Cumene are then separated. p-Cumene is then oxidized to diisopropylbenzene oxide, which is subsequently decomposed into hydroquinone and acetone using an acidic catalyst. This process is difficult to separate the byproducts p- and m-isopropylbenzene, and propylene is a flammable and explosive gas with high storage costs and significant reaction hazards.

[0004] The aniline redox process is a traditional synthesis process with a history of 80 years. It was first invented by Eastman Chemical Company in the United States. Currently, this process has been phased out abroad, but it is still used by many factories in China. The manganese dioxide used in this process causes high pollution and consumes a lot of energy. The reduction of iron powder also causes high pollution and is considered an obsolete process. The industrialization of alternative reducing agents is not yet mature.

[0005] The hydrogen peroxide hydroxylation method for phenol primarily produces industrial-grade products. The hydrogen peroxide oxidation method is the lowest-cost and simplest process, currently used by companies such as Solvay, Yubu, and Sanjili. The reaction process involves reacting sulfuric acid with a certain amount of hydrogen peroxide and methyl isobutyl ketone to form peroxyketone, which acts as a catalyst to catalyze the oxidation of phenol to produce hydroquinone and catechol. These are then separated and purified to obtain the final product. However, this process is difficult to separate the byproduct catechol from the main product hydroquinone, making it challenging to produce high-purity hydroquinone. Furthermore, the hydrogen peroxide reaction in a batch reactor poses a high risk of flammability and explosion.

[0006] Existing methods for synthesizing hydroquinone all have various drawbacks. Therefore, there is a need to find a synthesis method that is simple to react, highly safe, highly automated, environmentally friendly, and has a high yield. Summary of the Invention

[0007] To overcome the shortcomings of existing hydroquinone synthesis methods, this invention provides a continuous flow method for preparing hydroquinone. This continuous flow synthesis method can reduce the safety risks of oxidation and hydrogenation reduction reactions, increase product yield, shorten the production cycle, improve production efficiency, reduce energy consumption and waste emissions, and is suitable for industrial production.

[0008] This invention is achieved through the following method:

[0009] The present invention describes a method for preparing hydroquinone based on a microreaction system, which uses phenol as a starting material, obtains p-benzoquinone through oxidation reaction, and then obtains hydroquinone through hydrogenation reduction.

[0010] Both reactions are prepared in a microreaction system, which includes a one-way valve, a micromixer, and a microchannel reactor connected in sequence.

[0011] The micro mixer is any one of the following: static mixer, T-type micro mixer, Y-type micro mixer, cross-shaped micro mixer, coaxial flow micro mixer, or flow focusing micro mixer.

[0012] The microchannel reactor is either a tubular reactor or a fixed-bed reactor.

[0013] The specific steps of the method are as follows:

[0014] The first step involves preparing component A with phenol, catalyst 1, and organic solvent, and using oxidant as component B. A and B react in microchannel reactor 1 to obtain intermediate I, p-benzoquinone.

[0015] In the second step, intermediate I, p-benzoquinone, is mixed with an organic solvent and reacted with hydrogen in a microchannel reactor 2 under the action of catalyst 2 to obtain hydroquinone.

[0016]

[0017] In the first step reaction:

[0018] Catalyst 1 is one or more of the following: copper sulfate, copper sulfate monohydrate, cuprous chloride, copper chloride, elemental copper, copper oxide, copper acetate, copper acetate monohydrate, copper nitrate, zinc oxide, manganese dioxide, elemental selenium, cobalt nitrate, and ferric chloride.

[0019] The organic solvent is one or more of methanol, ethanol, isopropanol, water, acetonitrile, ethyl acetate, dichloromethane, chloroform, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0020] The oxidant is oxygen or air;

[0021] The molar ratio of phenol to oxidant is 1:3-1:20, preferably 1:10-1:20;

[0022] The molar ratio of catalyst to phenol is 1:5-1:20, preferably 1:10-1:20;

[0023] The microchannel reactor 1 is a tubular reactor;

[0024] The tubular reactor has an inner diameter of 3-8 mm and a length of 7000-8000 mm.

[0025] The reaction time is 20-50 min, the reaction temperature is 60-120℃, preferably 60-100℃, and the system pressure is 5.0-10.0 MPa;

[0026] In the second step of the reaction:

[0027] The catalyst 2 is one or more of carbon, elemental palladium, platinum on carbon, palladium hydroxide, palladium acetylacetone, palladium acetate, Raney nickel, and reduced nickel;

[0028] The organic solvent is one or more of methanol, ethanol, isopropanol, water, acetonitrile, ethyl acetate, dichloromethane, chloroform, acetone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0029] The molar ratio of intermediate I p-benzoquinone to hydrogen is 1:1-1:10, preferably 1:2-1:10, and more preferably 1:2-1:3;

[0030] The microchannel reactor 2 is a fixed-bed plate reactor;

[0031] The plate reactor has an inner diameter of 20-30 mm and a length of 2000-3000 mm.

[0032] The reaction temperature is 30-90℃, preferably 70-90℃; the reaction time is 2-8 min, preferably 2-4 min; the reaction system pressure is 1.0-10.0 MPa, preferably 5-10 MPa.

[0033] Specifically, the reaction steps of the present invention are as follows:

[0034] The first step involves preparing phenol, catalyst 1, and organic solvent into component A, and oxygen as component B. Component A is pumped into a tubular reactor, and oxygen is simultaneously introduced into the tubular reactor for reaction. The gas and liquid flow rates are controlled to ensure that the materials are retained in the system for a certain period of time. After the reaction is completed, intermediate I is obtained by vacuum distillation.

[0035] In the second step, intermediate I is mixed with an organic solvent and hydrogen gas, which are then introduced into a microreactor pre-loaded with catalyst 2. The system pressure is kept stable, and the gas and liquid flow rates are controlled to ensure that the materials are retained in the system for a certain period of time. After the reaction is complete, an organic solution of hydroquinone is obtained, which is then concentrated, centrifuged, and dried to obtain hydroquinone.

[0036] Beneficial effects of the present invention

[0037] The present invention proposes a method for preparing hydroquinone based on a microreaction system, which has the following advantages compared with the traditional batch reactor synthesis method:

[0038] 1. The micro-reaction system has excellent heat and mass transfer performance, which greatly shortens the reaction time, and both steps of the reaction are completed within 50 minutes;

[0039] 2. The continuous flow microchannel reaction system enables continuous production, which greatly improves the degree of automation compared to the traditional batch reactor, has high space-time efficiency, significantly reduces the number of workers, and significantly reduces production costs;

[0040] 3. The microchannel continuous flow reaction technology has a low scale-up effect and can quickly achieve industrial production;

[0041] 4. This invention uses clean oxygen as an oxidant, which is environmentally friendly and produces less waste than traditional methods. The continuous flow reaction used in catalytic hydrogenation reduces the safety issues associated with traditional batch reactors.

[0042] 5. This invention uses phenol as the starting material and employs a microchannel continuous equipment for both the oxidation and reduction steps, thereby reducing the liquid-holding reaction volume and minimizing the reaction risk of hazardous processes.

[0043] 6. It has high reaction efficiency, low energy consumption, high safety, high degree of automation, and environmental friendliness, giving it a huge leading advantage. Attached Figure Description

[0044] Figure 1 This is a diagram of the continuous flow synthesis reaction of the present invention.

[0045] Figure 2 This is the 1H NMR spectrum of hydroquinone. Detailed Implementation

[0046] Process screening process

[0047] In the following reactions:

[0048] The tubular reactor in the first step of the reaction has an inner diameter of 3-8 mm and a length of 7000-8000 mm;

[0049] The following example uses a tubular reactor with an inner diameter of 5mm and a length of 7000mm.

[0050] The plate reactor in the second step of the reaction has an inner diameter of 20-30 mm and a length of 2000-3000 mm.

[0051] The following example uses a fixed-bed plate reactor with an inner diameter of 20mm and a length of 2000mm.

[0052] Condition screening for the first step reaction

[0053] 1: Selection of catalyst 1 in the first step reaction

[0054]

[0055] The results showed that the catalytic effects of copper chloride and cuprous chloride were significantly better than those of other catalysts.

[0056] 2: The selection of the molar ratio of catalyst to phenol in the first step reaction, using copper chloride as the catalyst.

[0057]

[0058] The results showed that the yield of p-benzoquinone could reach more than 50% when the molar ratio of copper chloride to phenol was 1:5-1:20, while the yield of p-benzoquinone could reach more than 60% when the molar ratio of copper chloride to phenol was 1:10-1:20.

[0059] 3: The selection of the molar ratio of phenol to oxygen in the first step reaction: using ketone chloride as a catalyst, and the molar ratio of copper chloride to phenol is 1:10.

[0060]

[0061] The results showed that when the molar ratio of phenol to oxygen was 1:3-1:20, the yield of p-benzoquinone could reach more than 50%, and when the molar ratio of phenol to oxygen was 1:10-1:20, the yield of p-benzoquinone could reach more than 75%.

[0062] Furthermore, this invention selects copper chloride as a catalyst, and examines the effects of microreaction conditions on the yield and purity of p-benzoquinone under the conditions of a copper chloride:phenol molar ratio of 1:10 and a phenol:oxygen molar ratio of 1:10: 4: Optimization of reaction temperature

[0063]

[0064] The results showed that by changing the reaction temperature, the yield of p-benzoquinone was above 50% when the reaction temperature was 60-120℃, above 85% when the reaction temperature was 60-100℃, and above 90% when the reaction temperature was 80-100℃, with a yield above 85%.

[0065] 5: Optimization of reaction time and pressure

[0066]

[0067] The results showed that when the reaction time was 20-50 min and the pressure was 5-10 MPa, the yield of p-benzoquinone was over 95%; when the reaction time was 30-50 min and the pressure was 5-10 MPa, the yield of p-benzoquinone was over 95% and the purity was over 98%; when the reaction time was 30 min and the pressure was 5-7 MPa, the yield of p-benzoquinone was over 97% and the purity was over 99%.

[0068] The first step of the reaction was carried out under the following reaction conditions to prepare p-benzoquinone, and the results are as follows:

[0069]

[0070] The results showed that when the reaction time was 20-50 min, the reaction temperature was 60-100℃, the molar ratio of phenol to oxygen was 1:5-1:20, the molar ratio of copper chloride to phenol was 1:5-1:20, and the reaction pressure was 5-10 MPa, the purity and yield of p-benzoquinone could both reach over 85%. Furthermore, when the reaction time was 20-30 min, the molar ratio of phenol to oxygen was 1:10-1:20, the reaction temperature was 80-100℃, and the reaction pressure was 5-10 MPa, the yield and purity of p-benzoquinone both reached over 90%.

[0071] The second step involves screening the reaction conditions.

[0072] 1: Selection of catalyst 2 in the second step reaction

[0073]

[0074] The results showed that the reaction was better when the catalysts were palladium on carbon, platinum on carbon, and Raney nickel. Therefore, palladium on carbon, a commonly used catalyst, was selected as the reduction catalyst.

[0075] 2: The molar ratio of p-benzoquinone to hydrogen in the second step reaction intermediate I was selected, with palladium on carbon as the catalyst.

[0076]

[0077] The results showed that when the molar ratio of benzoquinone to hydrogen was 1:1 to 1:10, the yield of hydroquinone could reach over 95%. When the molar ratio of benzoquinone to hydrogen was 1:2 to 1:10, the yield of hydroquinone reached over 98%, and the purity was higher than 98%.

[0078] Furthermore, this invention selects palladium on carbon as a catalyst, and the molar ratio of benzoquinone to hydrogen is 1:4. The effect of micro-reaction conditions on the yield and purity of benzoquinone is investigated: 3: Selection of reaction pressure in the second step.

[0079]

[0080] The results showed that the yield could reach over 95% when the reaction pressure was 1-10 MPa.

[0081] 4: The second step reaction temperature was selected, with palladium on carbon as the catalyst, the molar ratio of p-benzoquinone to hydrogen being 1:4, and the reaction pressure being 4 MPa.

[0082]

[0083]

[0084] The results showed that when the reaction temperature was 30-90℃, the yield of hydroquinone was over 70%, while when the temperature was 70-90℃, the yield could reach over 95%, and the purity was over 97%.

[0085] 5: The second step reaction time selection: palladium on carbon is used as the catalyst, the molar ratio of p-benzoquinone to hydrogen is 1:4, the reaction pressure is 4 MPa, and the reaction temperature is 70℃.

[0086]

[0087] The results showed that when the reaction time was 2-8 min, the yield of hydroquinone was over 95% and the purity was over 99%. When the reaction time was 2-4 min, the yield of hydroquinone was over 98% and the purity was over 99%.

[0088] The second step reaction was carried out under the following conditions, using palladium on carbon as a catalyst to prepare hydroquinone. The results are as follows:

[0089]

[0090] When the reaction time is 2-4 min, the reaction temperature is 70-90℃, the reaction pressure is 4-7 MPa, and the molar ratio of p-benzoquinone to hydrogen is 1:2-1:5, the purity and yield of hydroquinone can both reach over 95%. When the reaction time is 3-4 min, the reaction temperature is 80-90℃, the reaction pressure is 5-7 MPa, and the molar ratio of p-benzoquinone to hydrogen is 1:3-1:5, the yield of hydroquinone reaches over 98%, and the purity reaches over 99%.

[0091] Example 1

[0092] 10g of phenol was added to 220g of ethanol and stirred until dissolved. Then, 1.5g of cuprous chloride was added, and the mixture was stirred at room temperature for 0.5h. The insoluble matter was removed by filtration, and the system pressure was maintained at 7.0MPa. The above reaction solution was fed into a tubular reactor using a plunger pump. Oxygen was introduced into the reactor at a phenol to oxygen molar ratio of 1:10. The reaction time was 35min and the reaction temperature was 80℃. After the reaction was completed, an ethanol solution of p-benzoquinone was obtained. The clarified liquid obtained after filtration was concentrated, centrifuged, and dried to obtain intermediate I with a yield of 97% and a purity of 99.777%.

[0093] 10 g of intermediate I was added to 150 g of DMF and stirred until dissolved. A fixed-bed reactor filled with 5% palladium on carbon was used to maintain a system pressure of 4.0 MPa. The reaction solution was then pumped into the fixed-bed reactor using a plunger pump, while hydrogen was simultaneously introduced into the system. The reaction residence time was 3 min, the reaction temperature was 80 °C, and the equivalent ratio of intermediate I to hydrogen was 1:5. After the reaction was complete, a DMF solution of hydroquinone was obtained. This solution was concentrated, crystallized, filtered, and dried to obtain hydroquinone with a purity of 99.281% and a yield of 98%.

[0094] Example 2

[0095] 100g of phenol was added to 1500g of water and stirred until dissolved. Then, 10g of copper chloride was added and stirred until dissolved at room temperature. The solution was filtered to remove insoluble matter and set aside for later use. The system pressure was maintained at 3.0MPa using oxygen, and the reaction solution was pumped into a tubular reactor using a plunger pump. The phenol to oxygen equivalent ratio was 1:12, the residence time was 40min, and the reaction temperature was 70℃. After the reaction was completed, an aqueous solution of intermediate I was obtained. This solution was concentrated, crystallized, centrifuged, and dried to obtain intermediate I with a yield of 90% and a purity of 95.205%.

[0096] 50g of intermediate I was dissolved in 500g of acetone. A fixed-bed reactor was filled with 5% platinum-carbon, and the system pressure was maintained at 4.0MPa. The reaction solution was pumped into the fixed-bed reactor using a plunger pump, while hydrogen was simultaneously introduced into the reaction system. The reaction time was 3 min, the reaction temperature was 80℃, and the equivalent ratio of intermediate I to hydrogen was 1:4. After the reaction was completed, an acetone solution of hydroquinone was obtained. The solution was concentrated, crystallized, filtered, and dried to obtain crude hydroquinone with a purity of 99.248% and a yield of 98%.

[0097] Example 3

[0098] 100g of phenol was dissolved in 1500g of water by stirring. 15g of copper chloride was added and dissolved by stirring at room temperature. The solution was filtered to remove insoluble matter and set aside. The reaction mixture was then pumped into a tubular reactor using a plunger pump while maintaining a nitrogen pressure of 7.0MPa, and oxygen was simultaneously introduced into the reaction system. The reaction residence time was 30 min, the reaction temperature was 80℃, and the phenol to oxygen equivalent ratio was 1:10. After the reaction was complete, an aqueous solution of intermediate I was obtained. This solution was then subjected to vacuum distillation and centrifugation to obtain intermediate I, with a yield of 99% and a purity of 99.711%.

[0099] 100g of intermediate I was dissolved in 3000g of methanol. A fixed-bed reactor was filled with 5% palladium on carbon. The system pressure was maintained at 4.0MPa using hydrogen gas. A plunger pump was used to pump the reaction solution into the fixed-bed reactor, simultaneously introducing hydrogen gas into the system. The reaction time was 2 min, the reaction temperature was 80℃, and the equivalent ratio of intermediate I to hydrogen gas was 1:4. After the reaction was complete, a methanol solution of hydroquinone was obtained. This solution was concentrated, crystallized, filtered, and dried to obtain hydroquinone with a purity of 99.014% and a yield of 98%.

[0100] 1 H NMR (400MHz, DMSO-d6) δ8.60 (s, 2H), 6.56 (s, 4H).

Claims

1. A continuous flow synthesis method for hydroquinone, characterized in that, Starting with phenol, p-benzoquinone is obtained through oxidation, followed by hydrogenation reduction to obtain hydroquinone. The reaction is prepared in a microreactor system. The microreactor system includes a check valve, a micromixer, and a tubular reactor or a fixed-bed reactor connected in sequence. The micro mixer can be any one of the following: static mixer, T-type micro mixer, Y-type micro mixer, cross-shaped micro mixer, coaxial flow micro mixer, or flow focusing micro mixer; The synthesis method includes the following steps: The first step involves preparing component A with phenol, catalyst 1, and organic solvent, and using oxidant as component B. A and B are reacted in a tubular reactor to obtain intermediate I, p-benzoquinone. The catalyst 1 is cuprous chloride or cupric chloride; The organic solvent is one or more of methanol, ethanol, isopropanol, and water; The oxidant is oxygen or air; The molar ratio of phenol to oxidant is 1:10-1:20; The molar ratio of catalyst to phenol is 1:10-1:20; The reaction time is 20-30 min, the reaction temperature is 80-100℃, and the system pressure is 5.0-10.0 MPa; In the second step, intermediate I, p-benzoquinone, is mixed with an organic solvent and reacted with hydrogen in a fixed-bed plate reactor under the action of catalyst 2 to obtain hydroquinone. The catalyst 2 is one or more of palladium on carbon, platinum on carbon, and Raney nickel; The organic solvents mentioned are methanol, ethanol, isopropanol, water, acetonitrile, ethyl acetate, dichloromethane, chloroform, acetone, etc. N , N -Dimethylformamide, N , N One or more of dimethylacetamide; The molar ratio of intermediate I p-benzoquinone to hydrogen is 1:1 to 1:10; The reaction time is 2-4 min, the reaction temperature is 70-90℃, and the reaction pressure is 4-7 MPa; The tubular reactor has an inner diameter of 3-8 mm and a length of 7000-8000 mm; the plate reactor has an inner diameter of 20-30 mm and a length of 2000-3000 mm.

2. The application of the continuous flow synthesis method of hydroquinone according to claim 1 in the preparation of hydroquinone.

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