WO2021135443A1

WO2021135443A1 - 2,3,5-trimethylhydroquinone synthesis method and device

Info

Publication number: WO2021135443A1
Application number: PCT/CN2020/117529
Authority: WO
Inventors: 吕国锋; 刘祥洪; 王勇; 田金金; 毛晨东; 刘丽丽; 彭飞
Original assignee: 上虞新和成生物化工有限公司; 浙江新和成药业有限公司; 山东新和成维生素有限公司
Priority date: 2019-12-30
Filing date: 2020-09-24
Publication date: 2021-07-08
Also published as: CN111253218A

Abstract

Provided are a 2,3,5-trimethylhydroquinone synthesis method and device; 2,3,5-trimethylbenzoquinone (TMBQ) is mixed with an alcohol–aromatic hydrocarbon or alcohol–alkane mixed solvent system, then the reaction liquid is thoroughly mixed with hydrogen by way of a hydrogen absorber, then enters a fixed bed equipped with a precious-metal catalyst to carry out a hydrogenation reaction to obtain 2,3,5-trimethylhydroquinone (TMHQ). The technical solution improves the selectivity of the reaction, effectively suppresses side reactions, reducing the impurity content of the product, improving the purity of 2,3,5-trimethylhydroquinone (TMHQ), simplifying the production process, and reducing emission of wastewater, waste gas, and solid waste, and has good environmental protection benefits.

Description

A synthetic method and device for 2,3,5-trimethylhydroquinone

Technical field

The invention relates to the field of fine organic chemistry synthesis, in particular to a synthesis method and device of 2,3,5-trimethylhydroquinone.

Background technique

2,3,5-Trimethylhydroquinone (hereinafter referred to as TMHQ) is an important intermediate for the synthesis of vitamin E. There are two general synthesis methods: 1) 2,3,5-Trimethylbenzoquinone (hereinafter referred to as TMBQ) ) Synthesis by reduction reaction with zinc powder and sulfuric acid; 2) Synthesis by reduction reaction of TMBQ with hydrogen in the presence of a precious metal catalyst. The reduction process of zinc powder/sulfuric acid process will produce a large amount of waste salt by-products. Considering environmental protection, the most popular application is the catalytic hydrogenation of precious metals, and the direct hydrogenation of palladium carbon, platinum carbon and Raney nickel is preferred.

When noble metal catalysts, such as platinum, palladium, etc. are used as catalysts for the hydrogenation reaction, the conversion rate of the reaction can reach more than 99.0%. When platinum is used as a catalyst, the selectivity can reach 99.0%, and when palladium is used as a catalyst, the selectivity can reach more than 97.5%. Considering the price factor, palladium catalysts are more widely used in industry than platinum catalysts. The reaction equation of this reaction is as follows:

The mechanism of the catalytic hydrogenation reaction is that after the double bond on the TMBQ ring is hydrogenated, the enol rearrangement takes place to obtain the product TMHQ. The patent CN201511021779.6 also holds the same view, and the details are as follows:

When the hydrogenation solvent contains more free radicals, the side reaction of demethylation is likely to occur and impurity 1 is formed. Although the content of impurity 1 is not high, it is very close to the physicochemical properties of TMHQ and is not easy to separate. In the subsequent preparation of VE, difficult to separate VE impurities are formed. The main side reactions are as follows:

Hydrogenation solvent adopts low-carbon alcohol (C ₁ -C ₃ ), the product TMHQ is easily dehydrated with alcohol to form etherate, and impurity 2 will be formed. Impurity 2 will be carried into the subsequent preparation of VE. The final product is an open-ring VE impurity. VE is difficult to separate and affects the quality of VE. The specific reaction formula is as follows:

When the hydrogenation solvent is a solvent with a strong polarity, the product and the raw material are likely to form hydrogen bonds, and the quinhydroquinone impurity 3 is obtained, especially when there is water, the impurity 3 is more likely to be generated. Impurity 3 is reddish brown. If there is residue in the post-processing, the product is almost white or yellow. Impurity 3 is brought to the subsequent preparation of VE, which directly affects the purity and light transmittance of VE. The color of impurity product is reddish brown and difficult It is removed by rectification and decolorization. The reaction formula is as follows:

Patent CN201511021779.6 uses a method of passivating (poisoning) catalysts to control catalyst activity and increase reaction selectivity, thereby increasing the purity of the final product TMHQ. If the control is good, the maximum by-product content (impurities) can be controlled at about 0.5%. Although this technical solution has made great progress, the shortcomings are still obvious: 1. The highest impurity content is 0.5%, which may be amplified in the subsequent VE preparation. The results of the small-scale verification also have this trend, that is, the impurity of TMHQ The content can be magnified 3-5 times in the preparation of VE. 2. The newly introduced catalyst deactivator is a new impurity, which has a certain impact on the subsequent VE preparation. The introduced deactivator cannot be effectively removed during TMHQ purification.

Patent US3839468 studied hydrogenation solvent systems such as ethanol, isopropyl ether, toluene, ethyl acetate, tert-butanol, dipropyl ether, acetone, methyl tert-butyl ether, etc., preferably acetone and methyl tert-butyl ether solvent systems. Both acetone and methyl tert-butyl ether have the disadvantages of high odor, low boiling point, high recovery loss, and low flash point, flammable and explosive.

There have been many research results on the solvent system for preparing TMHQ by the catalytic hydrogenation of precious metals in China, and it has been applied in production, and it has also achieved good conversion rate (generally above 95%) and selectivity (above 95%), but it is suitable for different solvents. The hydrogenation reaction effect of the system has its own advantages and disadvantages. Common solvent systems for preparing TMHQ by catalytic hydrogenation of precious metals include water, low-carbon alcohols and their aqueous solutions, such as water, methanol, ethanol, isopropanol, isobutanol, etc. Advantages: raw materials are easily available and cheap, but the disadvantage is that the product purity is not high , The conversion rate is 98-99%, and there are 1-2% of the raw material residue; low-carbon esters, such as methyl acetate, ethyl acetate, isobutyl acetate, etc., have the advantages of higher conversion rate, high selectivity, and basic The above can reach 99%. The disadvantage is that the solvent recovery rate is low, the esters are easily hydrolyzed, and the solvent treatment is troublesome; alkanes, such as pentane, heptane, hexane, cyclohexane, etc., have the advantage of easy to obtain, cheap and stable raw materials. , The disadvantages are volatile, large recovery loss, low flash point and unsafe; aromatic hydrocarbons, such as benzene, toluene, xylene, trimethylbenzene, etc., have the advantages of reaction selectivity and high product purity, but the disadvantage is that the reaction conversion rate is not high; others , Such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, N,N-dimethylformamide, etc., the advantages are small polarity, low boiling point, not easy to produce quinhydroquinone (ie impurity 3), the disadvantage is the safety risk of solvent recovery Large, etherate is easy to produce peroxide, tetrahydrofuran and N,N-dimethylformamide smell very big.

In short, the current technical defects in the hydrogenation of TMBQ to prepare TMHQ are: the selectivity of the hydrogenation reaction needs to be further improved, the product has many impurities, and the impurity content is high. None of the currently adopted technical methods can effectively solve the problem.

Summary of the invention

The technical problem to be solved by the present invention is to overcome the above-mentioned defects in the prior art and provide a synthesis method and device of 2,3,5-trimethylhydroquinone (TMHQ), which can improve the hydrogenation of TMBQ The selectivity of the reaction reduces side reactions.

The technical scheme of the present invention is as follows:

A synthesis method of 2,3,5-trimethylhydroquinone, including:

(1) 2,3,5-Trimethylbenzoquinone is dissolved in a mixed solvent to form a 2,3,5-Trimethylbenzoquinone solution;

The mixed solvent is composed of alcohol and hydrocarbon solvent;

(2) The 2,3,5-trimethylbenzoquinone solution absorbs hydrogen to form a hydrogen-containing reaction liquid;

(3) The hydrogen-containing reaction liquid undergoes a hydrogenation reaction under the action of a catalyst, and after the reaction is completed, the 2,3,5-trimethylhydroquinone is obtained by post-processing.

The invention uses a solvent to absorb hydrogen, first mixes the hydrogen with the reaction liquid, and then performs the hydrogenation reaction under the action of the catalyst, which can effectively control the hydrogenation reaction speed, appropriately reduce the hydrogenation reaction activity, and improve the reaction selectivity. Studies have shown that the mechanism of conventional TMBQ noble metal catalytic hydrogenation is that the noble metal absorbs hydrogen and then hydrogenates with TMBQ to complete the hydrogenation reaction. The amount of hydrogen attached to the catalyst is large, the activity is strong, and side reactions are prone to occur, which reduces the selectivity of the hydrogenation reaction. When hydrogen, catalyst, and solvent are mixed at the same time, the local concentration of hydrogen may be high. In the present invention, hydrogen is mixed with the solvent and then enters the catalytic system. The hydrogen absorption capacity of the solvent determines that the hydrogenation reaction will proceed relatively mildly, and side reactions are not prone to occur. It can effectively control the impurities 1, impurities 2, and impurities in the catalytic hydrogenation of TMBQ precious metals. 3 content, experimental verification, the average content of total impurities is 0.11%.

Preferably, in step (1), the alcohol is a C ₁ -C ₆ alcohol;

The hydrocarbon solvent is one or more of aromatic hydrocarbons and alkanes.

The invention adopts the alcohol-aromatic or alcohol-alkane mixed solvent system for hydrogenation to effectively change the hydrogen absorption capacity of the solvent and the polarity of the solvent system, so as to improve the quality of the hydrogenation reaction, that is, increase the selectivity of the hydrogenation reaction and reduce reaction impurities. Aromatics and alkanes are used to replace water to adjust the polarity of the system solvent and the solubility of the product, to better separate the product from the solvent system, to achieve no waste water discharge in production, to reduce the cost of solvent recovery in the hydrogenation reaction, and to simplify the production process.

Preferably, the alcohol is one or more of methanol, ethanol, propanol and butanol;

The aromatic hydrocarbon is one or more of benzene, toluene, xylene and trimethylbenzene, preferably toluene or xylene;

The alkanes are C ₅ -C ₈ alkanes, preferably n-hexane or cyclohexane.

Preferably, the mass percentage of the alcohol in the mixed solvent is 10-90%, preferably 50-60%.

Preferably, in step (1), the mass percentage concentration of the 2,3,5-trimethylbenzoquinone solution is 5-50%, preferably 10-20%.

The TMBQ hydrogenation reaction system of the present invention has a slightly positive pressure, and the hydrogen pressure is below 0.1 MPa (gauge pressure).

Preferably, in step (3), the catalyst is a supported catalyst, the carrier is activated carbon, silica or resin, and the active ingredient is a precious metal, including palladium, platinum, nickel or gold; the catalyst is preferably palladium on carbon or Platinum-carbon catalyst, at this time, the catalytic hydrogenation conversion rate can reach more than 99%, and the selectivity is more than 99%.

Preferably, in step (3), the hydrogenation reaction temperature is 30-120°C, preferably 50-80°C.

In the present invention, the post-processing process is as follows:

The reaction liquid undergoes gas-liquid separation to recover excess hydrogen, the liquid material is cooled and crystallized, and then the product TMHQ is separated by centrifugation for recrystallization, and the mother liquor is returned to step (1) for dissolving 2,3,5-trimethylbenzoquinone.

The present invention also provides a device for synthesizing 2,3,5-trimethylhydroquinone, including:

A mixing kettle for mixing 2,3,5-trimethylbenzoquinone and a reaction solvent, a hydrogen absorber for contacting the 2,3,5-trimethylbenzoquinone solution with hydrogen, and hydrogenation The reaction device of the reaction.

Preferably, the reaction device is a fixed bed reactor, and the catalyst is packed in the fixed bed reactor, so that continuous production can be realized.

In the present invention, the hydrogen absorber is a self-made hydrogen absorber, specifically a venturi tube, the side port is provided with a hydrogen inlet, the reaction liquid is pumped into the venturi tube, the side port sucks in hydrogen, and the reaction liquid mist The chemical ejection and hydrogen are mixed uniformly, and then enter the fixed bed reactor for hydrogenation reaction, which innovatively changes the reaction process of the noble metal catalytic hydrogenation reaction mechanism where hydrogen is first adsorbed on the catalyst and then hydrogenated with the target raw material. Firstly, the uniformly distributed solvent of hydrogen is put in the target raw material, and then it is contacted with the catalyst, which effectively balances the speed of each step of the reaction, suppresses side reactions, and reduces the generation of impurities.

The device of the present invention also includes auxiliary equipment, and the auxiliary equipment includes a gas-liquid separator, a crystallization kettle, a hydrogen booster pump and a hydrogen buffer tank.

The gas-liquid separator is used for gas-liquid separation of the reaction liquid produced by the fixed bed reactor; the crystallization kettle is used for crystallization and separation of the liquid material produced by the gas-liquid separator; the hydrogen pressurization The pump pressurizes the hydrogen generated by the gas-liquid separator and delivers it to the hydrogen buffer tank; the hydrogen buffer tank is used to input hydrogen into the hydrogen absorber.

Compared with the prior art, the beneficial effects of the present invention are as follows:

(1) The hydrogen is first mixed with the target raw material TMBQ and solvent, and then enters the fixed bed reactor for reaction, which can effectively control the concentration of activated hydrogen in the reaction system, increase the reaction speed, and suppress the formation of by-products.

(2) The use of conventional precious metal hydrogenation catalysts can achieve the effect of improving the selectivity of the hydrogenation reaction and reducing the impurity content without major changes in the existing production process.

(3) Using alcohol-aromatics and alcohol-alkanes as the reaction solvent system, and appropriately adjusting the hydrogen absorption capacity, polarity and solubility of the product TMHQ, an anhydrous reaction system can be realized and waste water discharge can be reduced. Control the reaction process-the speed of the enol rearrangement reaction to avoid side reactions due to excessive concentration of intermediates.

Description of the drawings

Figure 1 is a process flow diagram of the present invention.

Detailed ways

Fig. 1 is a process flow diagram of the present invention. As can be seen from Fig. 1, the device includes a mixing kettle, a hydrogen absorber, a fixed bed reactor, a gas-liquid separator and a crystallization kettle which are connected in sequence. The upper part of the mixing kettle is provided with a material inlet, and the lower part is provided with a solution outlet. The solution from the solution outlet is input into the hydrogen absorber through a pump set on the pipeline. A hydrogen inlet is provided on the side wall of the hydrogen absorber, and the hydrogen inlet is connected with a hydrogen buffer tank, and hydrogen is stored in the hydrogen buffer tank. The gas-liquid separator is provided with a gas outlet and a liquid outlet. The liquid outlet is connected to the crystallization kettle, and the recovered hydrogen can be obtained from the gas outlet. The recovered hydrogen is passed into the hydrogen buffer tank through a booster pump. After the solution in the crystallization kettle is crystallized, the solid obtained is the product TMHQ, and the mother liquor can be returned to the mixing kettle for continuous application.

The specific workflow is as follows:

TMBQ is mixed with the solvent in a certain proportion in the mixing kettle to form a TMBQ solution. The temperature is raised to the specified temperature. After the solution is mixed with hydrogen by the hydrogen absorber, it enters the fixed bed reactor filled with the catalyst. The fixed bed reactor controls the temperature at the specified temperature. Temperature is required, and the hydrogenation reaction is completed in a fixed bed reactor. The excess hydrogen is returned to the hydrogen buffer tank via a booster pump through the gas-liquid separator, and the liquid material enters the cooling crystallization kettle. After the cold treatment, the product is separated by centrifugation. TMHQ can be recrystallized again. The mother liquor enters the TMBQ mixing kettle to prepare the TMBQ reaction liquid.

The technical solutions of the present invention will be described in detail below in conjunction with specific embodiments.

Example 1

Put methanol: benzene=1:1 (W: W) mixed solvent 1000g into the 2000mL reactor, TMBQ200g, stir, preheat to 50℃, pump into the hydrogen absorber, suck in hydrogen for mixing, and then enter the container with 20g content It is a 2% palladium-carbon catalyst fixed bed reactor (tubular reactor), and the temperature is maintained at 50°C. The residence time of the material in the fixed bed is 10min. After the reaction, it enters the crystallization kettle to cool and crystallize, and the product TMHQ: 202.70g is filtered by centrifugation. Follow-up detection, conversion rate: 99.95%, selectivity: 99.92%, yield: 99.87%, Purity: 99.87%, total impurities: 0.13%.

Example 2-20

The difference between Examples 2-20 and Example 1 lies in the selection of different solvents, different ratios and reaction temperatures. Other conditions are the same as those of Example 1. All experimental results are summarized in Table 1.

Example 21

Put 1000g of methanol, 200g of TMBQ into the 2000mL reactor, stir, preheat to 50℃, pump into the hydrogen absorber, suck in hydrogen for mixing, and then enter the fixed bed reactor (tubular type) with 20g of 2% palladium-carbon catalyst Reactor), the temperature is maintained at 65°C. The residence time of the material in the fixed bed is 10min. After the reaction, it enters the crystallization kettle to cool and crystallize. The product TMHQ: 201.70g is filtered by centrifugation. Follow-up detection, conversion rate: 99.50%, selectivity: 99.00%, yield: 98.51%, Purity: 99.00%, total impurities: 1.00%.

Example 22

Put 1000g of ethanol and 200g of TMBQ into the 2000mL reactor, stir, preheat to 50℃, pump into the hydrogen absorber, suck in hydrogen for mixing, and then enter the fixed bed reactor (tubular type) with 20g of 2% palladium-carbon catalyst Reactor), the temperature is maintained at 75°C. The residence time of the material in the fixed bed is 10min. After the reaction, it enters the crystallization kettle to cool and crystallize. The product TMHQ: 202.30g is filtered out by centrifugation. Follow-up detection, conversion rate: 99.50%, selectivity: 99.40%, yield: 98.90%, Purity: 99.10%, total impurities: 0.90%.

Example 23

Put 1000g of propanol and 200g of TMBQ into the 2000mL reactor, stir, preheat to 50℃, pump into the hydrogen absorber, suck in hydrogen for mixing, and then enter the fixed bed reactor (tube with 20g of 2% palladium-carbon catalyst) Type reactor), the temperature is maintained at 82°C. The residence time of the material in the fixed bed is 10min. After the reaction, it enters the crystallization kettle to cool and crystallize. The product TMHQ: 201.42g is filtered by centrifugation. Follow-up detection, conversion rate: 99.20%, selectivity: 99.30%, yield: 98.51%, Purity: 99.14%, total impurities: 0.86%.

The results of Examples 21 to 23 show that, compared with the hydrogen absorption of a mixed solvent, the use of a separate alcohol solvent hydrogen absorption means reduces the yield, and at the same time cannot effectively reduce the generation of impurities.

Example 24

Put methanol: benzene=1:1 (W:W) mixed solvent 1000g, TMBQ200g, 20g 2% palladium-carbon catalyst into the 2000mL autoclave, stir, preheat to 50℃, and pass hydrogen (pressure≤ 0.4MPa) to carry out the reaction while maintaining the temperature at 50-60°C. The reaction time is 2h. The indicator for the completion of the reaction is that the hydrogen pressure rises. After stopping the hydrogen, the pressure is maintained for more than 10 minutes, the material is cooled and crystallized, and the product TMHQ is filtered by centrifugation: 202.67g, tracking detection, conversion rate: 99.24%, selectivity: 99.75%, yield: 98.99%, purity: 99.01%, total impurities: 0.99%.

Example 25

Put methanol:toluene=1:1 (W:W) mixed solvent 1000g, TMBQ200g, 20g 2% palladium-carbon catalyst into the 2000mL autoclave, stir, preheat to 50℃, and pass hydrogen (pressure≤ 0.4MPa) to carry out the reaction while maintaining the temperature at 70-80°C. The reaction time is 2h. The judgement index for the completion of the reaction is that the hydrogen pressure rises. After stopping the hydrogen gas, the pressure is maintained for more than 10 minutes, the material is cooled and crystallized, and the product TMHQ is filtered by centrifugation: 201.69g, tracking detection, conversion rate: 99.17%, selectivity: 99.54%, yield: 98.71%, purity: 99.20%, total impurities: 0.80%.

The results of Examples 24 and 25 show that using alcohol-aromatic hydrocarbon solvents but not using solvent hydrogen absorption means, the yield decreases and the generation of impurities cannot be effectively suppressed.

The experimental results of Examples 21-25 are summarized in Table 2.

Claims

A method for synthesizing 2,3,5-trimethylhydroquinone, which is characterized in that it comprises:

(1) 2,3,5-Trimethylbenzoquinone is dissolved in a mixed solvent to form a 2,3,5-Trimethylbenzoquinone solution;

The mixed solvent is composed of alcohol and hydrocarbon solvent;

(2) The 2,3,5-trimethylbenzoquinone solution absorbs hydrogen to form a hydrogen-containing reaction liquid;

(3) The hydrogen-containing reaction liquid undergoes a hydrogenation reaction under the action of a catalyst, and after the reaction is completed, the 2,3,5-trimethylhydroquinone is obtained by post-processing.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 1, wherein in step (1), the alcohol is a C 1 -C 6 alcohol;

The hydrocarbon solvent is one or more of aromatic hydrocarbons and alkanes.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 2, wherein the alcohol is one or more of methanol, ethanol, propanol, and butanol;

The aromatic hydrocarbon is one or more of benzene, toluene, xylene, and trimethylbenzene;

The alkanes are C 5 -C 8 alkanes.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 3, wherein the alcohol is propanol or butanol;

The aromatic hydrocarbon is toluene or xylene;

The alkane is n-hexane or cyclohexane.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 2, wherein the mass percentage of the alcohol in the mixed solvent is 10-90%.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 5, wherein the mass percentage of the alcohol in the mixed solvent is 50-60%.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 1, wherein in step (1), the mass percentage of the 2,3,5-trimethylquinone solution The concentration is 5-50%.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 7, wherein the mass percentage concentration of the 2,3,5-trimethylhydroquinone solution is 10-20% .
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 1, wherein in step (3), the catalyst is a supported catalyst, and the carrier is activated carbon, silica or resin , The active ingredient is palladium, platinum, nickel or gold.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 9, wherein the catalyst is a palladium-carbon or platinum-carbon catalyst.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 1, wherein in step (3), the hydrogenation reaction temperature is 30-120°C.
The method for synthesizing 2,3,5-trimethylhydroquinone according to claim 11, wherein the temperature of the hydrogenation reaction is 50-80°C.
A device for synthesizing 2,3,5-trimethylhydroquinone, which is characterized in that it comprises:

A mixing kettle for mixing 2,3,5-trimethylbenzoquinone and mixed solvents, a hydrogen absorber for contacting 2,3,5-trimethylbenzoquinone solution with hydrogen, and hydrogenation The reaction device of the reaction.
The device according to claim 13, wherein the reaction device is a fixed bed reactor.
The device according to claim 13, further comprising a gas-liquid separator, a crystallization kettle, a hydrogen booster pump, and a hydrogen buffer tank;

The gas-liquid separator is used for gas-liquid separation of the reaction liquid produced by the fixed bed reactor; the crystallization kettle is used for crystallization and separation of the liquid materials produced by the gas-liquid separator; the hydrogen pressurization The pump pressurizes the hydrogen generated by the gas-liquid separator and delivers it to the hydrogen buffer tank; the hydrogen buffer tank is used to input hydrogen into the hydrogen absorber.