JP2006249036A - Method for producing 2, 3, 5-trimethylhydroquinone - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing 2,3,5-trimethylhydroquinone of high purity, useful as a raw material for vitamin E, by using 2,6-dimethylphenol that can inexpensively and industrially be mass-produced by dialkylation of phenol with methanol. <P>SOLUTION: 2,6-Dimethylphenol is oxygen-oxidized to prepare 2,6-dimethyl-p-benzoquinone and the 2,6-dimethyl-p-benzoquinone is hydrogenated to prepare 2,6-dimethyl-hydroquinone. Then, the resultant 2,6-dimethyl-hydroquinone is aminomethylated to form Mannich salt and the Mannich salt is subjected to hydrogenolysis to produce 2,3,5-trimethylhydroquinone. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing 2,3,5-trimethylhydroquinone useful as a raw material for vitamin E with high yield and high purity.

2,3,5-trimethylhydroquinone useful as a raw material for vitamin E is generally produced industrially from 2,3,6-trimethylphenol. However, this raw material 2,3,6-trimethylphenol has conventionally used m-cresol as a starting material industrially, but m-cresol is the Cymen method (patent document: (1) Japanese Patent Publication No. 51-025011). (2) U.S. Pat. No. 2728797, etc.) m / p-cresol obtained by butylation, separation and debutylation (Patent Document: (3) U.S. Pat. No. 2,297,588) Has been. The demand for m-cresol has increased for vitamin E, and the balance of p-cresol or its derivatives inevitably co-produced has become a problem.
In addition, a method for producing 2,3,5-trimethylhydroquinone from hydroquinone or methylhydroquinone as a raw material is also known. That is, a method of producing a Mannich salt of these raw material compounds and formaldehyde and hydrocracking it (Patent Documents: (4) JP-A-50-123632, (5) JP-A-51-51 No. 0004973, (6) German Patent No. 2025579, (7) German Patent No. 2006525). However, these methods are not industrially implemented because the raw hydroquinones are expensive and the process is complicated.
Therefore, there has been a demand for a highly efficient method for producing trimethylhydroquinone that does not use m-cresol as a raw material, is industrially easily implemented, and is highly effective.

Japanese Patent Publication No.51-025011 U.S. Pat.No. 2728797 US Patent No. 2297588 JP 50-123632 A JP 51-004973 A German Patent No. 2025579 German Patent No. 2006525

  The present invention has been made to solve the above-mentioned problems in the production of 2,3,5-trimethylhydroquinone, and the object of the present invention is to obtain industrially easily without using m-cresol as a raw material. An object of the present invention is to provide a method for producing 2,3,5-trimethylhydroquinone with high yield and high purity by using a raw material that can be used and carrying out a reaction under industrially easy reaction conditions.

According to the present invention, 2,6-dimethylphenol is oxidized with oxygen to obtain 2,6-dimethyl-P-benzoquinone (first step),
A step of hydrogenating the obtained 2,6-dimethyl-P-benzoquinone to obtain 2,6-dimethyl-hydroquinone (second step);
Next, a step of aminomethylating the obtained 2,6-dimethyl-hydroquinone to obtain a Mannich salt (third step),
Further, the step of hydrogenolysis of the obtained Mannich salt to obtain 2,3,5-trimethylhydroquinone (step 4) is sequentially performed. A manufacturing method is provided.

(Chemical formula 1)

  According to the method for producing 2,3,5-trimethylhydroquinone of the present invention, 2,6-dimethylphenol is used as a starting material. 2,6-Dimethylphenol, which is a raw material of the present invention, can be easily produced by dialkylating phenol with methanol. Therefore, it is currently industrially produced in large quantities as an intermediate raw material for heat-resistant resins and the like. . In the method for producing 2,3,5-trimethylhydroquinone of the present invention, by using 2,6-dimethylphenol as a starting material and sequentially performing the above four steps, Trimethylhydroquinone can be obtained with high yield and high purity. Moreover, in each process, since the reaction product can be used as a raw material of a next process, without refine | purifying, it is industrially easy to implement.

  A method for producing 2,3,5-trimethylhydroquinone from 2,6-dimethylphenol as a raw material through four reaction steps in the present invention is illustrated by the following reaction formula.

  In the first step, 2,6-dimethylphenol is oxidized with oxygen to obtain 2,6-dimethyl-P-benzoquinone. The oxygen oxidation method of 2,6-dimethylphenol is not particularly limited. For example, a method using oxygen as an oxidizing agent and a cobalt complex as a catalyst in an organic solvent (Japanese Patent Publication No. 56-026647), halogenation A method using copper as a catalyst (JP-A-49-36641), a method of oxidizing with oxygen-containing gas such as oxygen or air in the presence of a copper-based catalyst (JP-A-48-000434 or JP-A-03) Conventionally known methods such as No. -081249) can be used. However, in the production method of the present invention, it is preferable to use as a raw material for the reaction in the second step without purification after removing the high-boiling by-products of the dimer or higher from the reaction product in the first step. Therefore, for example, as described in JP-A-03-081249, in the presence of a catalyst composed of a mixture of a copper compound and a hydroxylamine and an inorganic acid salt or an oxime and an inorganic acid salt in an organic solvent. A method of oxidizing oxygen is preferably used.

  In the reaction, for example, raw materials such as 2,6-dimethylphenol, toluene and isopropyl alcohol are charged into a reaction vessel, and a copper compound such as cuprous chloride and cupric chloride and hydroxylamine such as hydroxylamine sulfate. A mixed catalyst composed of a salt of an acid and an inorganic acid is added, and an oxidation reaction is performed while an oxygen-containing gas, for example, a gas-phase oxygen oxidant such as air is passed through. After completion of the oxidation reaction, the reaction mixture is neutralized by adding an aqueous alkali solution, the aqueous phase is separated, and the catalyst is filtered off to obtain a crude reaction mixture. The obtained crude reaction-terminated mixture contains 2,6-dimethyl-P-benzoquinone, the raw material 2,6-dimethylphenol, a by-product, and a solvent. This reaction mixture is subjected to fractional distillation to obtain a fraction (crude product) containing 2,6-dimethyl-P-benzoquinone. On the other hand, a high-boiling by-product containing a dimer such as tetramethylbiphenol that adversely affects the reaction and product purity after the next step can be separated as, for example, a distillation residue.

Specifically, the oxidation catalyst used for the reaction in the first step is preferably a copper compound such as cuprous sulfate, cupric sulfate, cuprous nitrate, cuprous chloride, and cupric chloride. Particularly preferred is cupric chloride. Further, together with these copper compounds, hydroxylamines such as hydroxylamine and N, N-dimethylhydroxylamine or inorganic acid salts such as sulfates and hydrochlorides thereof may be used. The amount of copper compound used is preferably 0.01 to 0.2 moles per mole of 2,6-dimethylphenol as a raw material. Moreover, hydroxylamines which may be used with a copper compound or those inorganic acid salts are 0.2-5 mol times with respect to 1 mol of copper compounds.
Furthermore, the reaction solvent is not particularly limited as long as it is inert to the reaction, but preferably, for example, aliphatic alcohols such as t-butanol, i-butanol and isopropanol, or aromatic carbonization such as toluene and the like. A mixed solvent with hydrogen is used. The reaction temperature is preferably in the range of room temperature to 80 ° C., and the reaction pressure of an oxygen-containing gas such as oxygen or air used for the oxidation reaction is preferably about normal pressure to about 10 kg / cm ² .

In the second step of the production method of the present invention, 2,6-dimethyl-P-benzoquinone obtained in the first step is hydrogenated to obtain 2,6-dimethyl-hydroquinone.
The method for the hydrogen reduction reaction of 2,6-dimethyl-P-benzoquinone is not particularly limited. For example, as described in JP-A-48-049732, palladium, platinum, nickel, rhodium in an organic solvent. A conventionally known method such as performing a hydrogenation reaction in the presence of a hydrogenation catalyst such as can be used. However, in the production method of the present invention, it is preferable to use the crude 2,6-dimethyl-P-benzoquinone obtained in the reaction of the first step as the raw material of the second step. The product is derived from the reaction product mixture by filtering the catalyst and distilling off the solvent, etc., then 2,6-dimethyl-hydroquinone, the starting material, 2,6-dimethylphenol, and the other first step It is a crude reaction product containing the by-product of the above, and it is preferable from the economical viewpoint that the equipment is simplified and the operation is simplified without using the crude reaction product as a raw material for the reaction in the third step.

  The reaction is performed, for example, by charging a raw material, a crude 2,6-dimethyl-P-benzoquinone obtained in the first step, an organic solvent such as butyl acetate, and a hydrogenation catalyst such as Raney nickel into hydrogen gas. The hydrogenation reaction is carried out under heating and pressure while aeration. After completion of the hydrogenation reaction, the catalyst is filtered off to obtain a reaction mixture. The obtained reaction-terminated mixed solution contains 2,6-dimethyl-hydroquinone as a target product, 2,6-dimethylphenol as a starting material, a by-product and a solvent. This reaction mixture is subjected to fractional distillation to recover the organic solvent, and 2,6-dimethylphenol is recovered as required, and a residual liquid (crude product) containing 2,6-dimethyl-hydroquinone is obtained.

As the hydrogenation catalyst used in the reaction in the second step, a nickel catalyst such as Raney nickel or a noble metal catalyst such as palladium is preferably used, and these noble metals may be supported on a carrier such as carbon. These catalysts are preferably used in the range of 5 to 15% by weight with respect to the raw material 2,6-dimethyl-P-benzoquinone.
The reaction solvent is not particularly limited as long as it does not inhibit the reaction, but alcohols such as 2-propanol, alkyl esters such as butyl acetate, and ethers such as diethyl ether are preferably used.
The reaction temperature is preferably in the range of 50 to 150 ° C., and the pressure of hydrogen gas is preferably about 1 to 5 kg / cm ² .

The third and fourth steps in the production method of the present invention were obtained by aminomethylating the 2,6-dimethyl-hydroquinone obtained in the second step to obtain a Mannich salt (third step), and then obtained. The Mannich salt is hydrocracked to obtain 2,3,5-trimethylhydroquinone which is the object of the present invention (fourth step).
The methods of aminomethylation reaction and hydrogenolysis reaction are not particularly limited, and conventionally known methods described in, for example, German Patent No. 2006525 and German Patent No. 2025579 can be used.

In the reaction in the third step, for example, the crude 2,6-dimethyl-hydroquinone obtained in the second step, an organic solvent such as toluene, and a secondary amine such as morpholine are charged in a reaction vessel, and formalin and paraffin are added thereto. Mannich salt is obtained by adding formaldehyde and reacting. As the Mannich salt, for example, 3-morpholinomethyl-2,6-dimethyl-hydroquinone is obtained from morpholine and formaldehyde. The resulting reaction product mixture is cooled to room temperature to precipitate 3-morpholinomethyl-2,6-dimethyl-hydroquinone. By filtering this, the crude 3-morpholinomethyl-2,6- Mannich salts that are dimethyl-hydroquinone can be obtained.
The purity of the raw material 2,6-dimethyl-hydroquinone used in the reaction in the third step does not need to be high, and includes, for example, the raw material 2,6-dimethylphenol and low-boiling by-products derived from the oxidation step. It may be used in the range of 40 to 95%, preferably 80 to 95%. Examples of secondary amines used for aminomethylation include dialkylamines such as dimethylamine, cyclohexylamines such as methylcyclohexylamine, and cyclic secondary amines such as piperidine, pipecoline, and morpholine. Secondary amines are preferred, and morpholine is particularly preferred. Examples of formaldehyde include formalin and paraformaldehyde.

The amount of secondary amine relative to 1 mol of 2,6-dimethyl-P-hydroquinone as a raw material is preferably in the range of 1.0 to 2.0 mol. Similarly, the amount of lower aldehyde is preferably in the range of 1.0 to 2.0 mol.
As a solvent used in the reaction, even if it contains a large amount of raw materials (2,6-dimethylphenol) and by-products derived from the oxidation process, these products remain dissolved after completion of the reaction, and the target product has high purity and high yield. In addition, toluene, benzene, ethylbenzene, and the like can be easily obtained by filtration, and the formation of the diaminomethylated product as a by-product can be suppressed by precipitation of the desired Mannich salt during the reaction. An aromatic hydrocarbon solvent such as xylene is preferred, and the amount of the solvent is usually preferably 2 to 4 times the amount of raw 2,6-dimethyl-hydroquinone.

  The reaction temperature is preferably in the range of 40 to 60 ° C. because the amount of 2-methyl adduct of aminomethyl increases when the reaction temperature is 65 ° C. or higher. In addition, when the Mannich salt formed and precipitated during the reaction is separated by filtration, in addition to the target aminomethyl 1-mol adduct (3-morpholinomethyl-2,6-dimethylhydroquinone), some aminomethyl 2 mol Since adduct (3,5-dimorpholinomethyl-2,6-dimethylhydroquinone) is formed, 1-5% by weight of lower aliphatic alcohol such as methanol is added to the raw material 2,6-dimethyl-hydroquinone. It is preferable to dissolve the desired Mannich salt after dissolving these 2-mol adducts.

  Next, in the fourth step in the production method of the present invention, the crude Mannich salt obtained in the third step, for example, 3-morpholinomethyl-2,6-dimethyl-hydroquinone is used as a raw material. Into a reaction vessel, an organic solvent such as methanol and a noble metal catalyst such as a palladium catalyst on carbon are added, and hydrogenolysis is performed under heating and pressure while ventilating hydrogen gas. After completion of the hydrogenation reaction, the catalyst is filtered off to obtain a reaction mixture. An organic solvent and a decomposition product such as morpholine are separated from the obtained reaction end mixture by a conventional post-treatment operation, for example, distillation or the like from the obtained reaction end mixture, and methyl isobutyl ketone is added to the residual solution. The solvent such as toluene is added and dissolved by heating. Then, a crystallization solvent such as toluene is added thereto, followed by cooling, crystallization, filtration, and drying, and the 2,3,5-trimethylhydroquinone that is the object of the present invention. Can be obtained as a high-purity product.

In the reaction of the fourth step, the hydrocracking reaction catalyst is preferably a noble metal catalyst such as palladium, rhodium or platinum, and these may be supported on a carrier such as carbon. Of these, a palladium carbon catalyst is particularly preferred. The solvent used in the reaction is not particularly limited as long as it is inert to the reaction, but lower aliphatic alcohols such as methanol and 2-propanol, alkyl esters such as butyl acetate, and ethers such as tetrahydrofuran and dioxane are preferably used. It is done.
The reaction temperature is preferably in the range of 50 to 150 ° C., and the hydrogen gas pressure is preferably about 5 to 15 kg / cm ² .

According to the method for producing 2,3,5-trimethylhydroquinone of the present invention, the desired 2,3,5-trimethylhydroquinone is obtained by sequentially performing four reaction steps using 2,6-dimethylphenol as a starting material. It can be obtained with high yield and high purity. Further, in each step, the reaction product can be used as a raw material for the next step as a crude product without being purified and isolated, so that it is easy to implement industrially.
By using 2,6-dimethylphenol as a starting material, the above four reaction steps are sequentially performed to obtain high-purity 2,3,5-trimethylhydroquinone through an industrially easy reaction operation. The overall yield of 2,6-dimethylphenol is about 25-35%. In the production method of the present invention, unreacted 2,6-dimethylphenol, the solvent used in the reaction, secondary amine, etc. can be recovered and reused in each step, which is economically advantageous. .

1) Synthesis of 2,6-dimethyl-P-benzoquinone (DMBQ) (first step)
Into a 1 L four-necked flask equipped with a reflux condenser and a stirrer is charged 61.1 g (0.5 mol) of 2,6-dimethylphenol, then 322.5 g of toluene and 97.5 g of isopropyl alcohol are added, and the temperature is about The mixture was dissolved with stirring at 20 ° C.
To this was added 10.1 g (62.5 mmol) of hydroxylamine sulfate and 10.6 g (62.5 mmol) of cupric chloride dihydrate, and the mixture was stirred at a temperature of 20 ° C. for 2 hours while flowing air at a flow rate of about 500 cc / min. Reacts down. Then, while supplying air, the temperature is raised to 40 ° C. and the reaction is continued for 2 hours with stirring. At that time, the conversion of 2,6-dimethylphenol (by gas chromatography analysis) was 66.7%, and the selectivity for DMBQ was 78.3%.
After completion of the reaction, the reaction mixture is neutralized to pH = 6-7 by adding 75% phosphoric acid 0.3g and 10% soda ash aqueous solution 92.0g, washed with water and filtered to remove catalyst and inorganic salts. Thus, a reddish brown transparent reaction completion liquid was obtained.
The obtained reaction completion liquid was distilled to recover toluene and isopropyl alcohol, and then further heated to 100 ° C. and distilled under the condition of 0.5 KPa (about 4 mmHg) to obtain 44.8 g of a fraction.
The composition of the obtained fraction was 2,6-dimethylphenol 33.30%, DMBQ 61.50%, other impurities 5.20% (according to gas chromatography analysis), and according to quantitative analysis by gas chromatography calibration curve, The content of 6-dimethylphenol was 41.07% and the target intermediate 2,6-dimethyl-P-benzoquinone (DMBQ) was 48.21%. Dimer tetramethylbiphenol was not included.

2) Synthesis of 2,6-dimethyl-hydroquinone (DMHQ) (second step)
A 500 mL SUS autoclave was charged with 40.7 g of the fraction obtained in the first step, 122.1 g of butyl acetate was added, and 1.0 g of Raney nickel was further added.
After completion of the addition, the temperature was raised to 120 ° C., hydrogen was supplied at a hydrogen pressure of 3.5 to 5 kg / cm ² , and the reaction was carried out for 4 hours with stirring. Thereafter, the reaction mixture was cooled to room temperature and filtered to remove the Raney nickel catalyst to obtain 160.5 g of the reaction mixture.
The obtained reaction completion liquid was distilled to distill off 2,6-dimethylphenol and butyl acetate to obtain 22.3 g of a residual liquid. The composition of the residual liquid was 2,6-dimethyl-hydroquinone (DMHQ) 89.10%, 2,6-dimethylphenol 2.94%, and other 7.96% (gas chromatography).

3) Synthesis of 3-morpholinomethyl-2,6-dimethyl-hydroquinone (third step)
In a 500 mL four-necked flask equipped with a reflux condenser and a stirrer, 13.8 g of the residual liquid obtained in the second step was charged in a nitrogen gas atmosphere, and 41.4 g of toluene and 10.4 g (0.12 mol) of morpholine were added thereto. Add and dissolve under stirring. The obtained dissolved solution is kept at 30 ° C., and 10.2 g (0.12 mol) of 35% formalin solution is dropped into this over about 30 minutes. After completion of the dropwise addition, the reaction solution is reacted with stirring for 18 hours while maintaining the reaction solution at 30 ° C. During the reaction, 3-morpholinomethyl-2,6-dimethylhydroquinone is precipitated. Then, after further reacting with stirring at a temperature of 55-60 ° C. for 6 hours, 0.3 g of methanol was added, and then the reaction mixture was cooled to room temperature and filtered to obtain a purity of 98.8% (high performance liquid chromatograph). As a result, 20.1 g of crude crystals of 3-morpholinomethyl-2,6-dimethyl-hydroquinone were obtained. The obtained crystal was confirmed to be 3-morpholinomethyl-2,6-dimethyl-hydroquinone by molecular weight confirmation by mass spectrometry and proton nuclear magnetic resonance analysis.

4) Synthesis of 2,3,5-trimethylhydroquinone (TMHQ) (4th step)
Into a 500 mL SUS autoclave is charged 17.8 g (0.075 mol) of the crystals obtained in the third step, and 109.8 g of methanol and 0.91 g of a carbon-supported palladium catalyst are added in terms of Dry.
After completion of the addition, the temperature was raised to 120 to 130 ° C., and the reaction was conducted for 9 hours with stirring while supplying hydrogen at a hydrogen pressure of 9 to 10 kg / cm ² . After completion of the reaction, the reaction mixture was cooled to room temperature and filtered to remove the carbon-supported palladium catalyst to obtain 119.1 g of a reaction mixture. The TMHQ concentration in the reaction finished solution was 98.20% (according to high performance liquid chromatography analysis).
This reaction-terminated liquid was distilled to distill off methanol and morpholine to obtain a distillation residue liquid. Add 11.4 g of methyl isobutyl ketone, and dissolve it by heating to a temperature of about 100 ° C. Thereafter, 17.1 g of toluene was added thereto, and the mixture was cooled. The precipitated crystals were filtered, dried, and white crystals of 2,3,5-trimethylhydroquinone (TMHQ) having a purity of 99.4% (according to high performance liquid chromatography) 7.1. g (Mettler melting point 171.5 ° C.) was obtained. Further, the obtained crystal was confirmed to be 2,3,5-trimethylhydroquinone by molecular weight confirmation by mass spectrometry and proton nuclear magnetic resonance analysis.

Claims (6)

A step of oxidizing 2,6-dimethylphenol with oxygen to obtain 2,6-dimethyl-P-benzoquinone (first step);
A step of hydrogenating the obtained 2,6-dimethyl-P-benzoquinone to obtain 2,6-dimethyl-hydroquinone (second step);
Next, a step of aminomethylating the obtained 2,6-dimethyl-hydroquinone to obtain a Mannich salt (third step),
Further, the step of hydrocracking the obtained Mannich salt to obtain 2,3,5-trimethylhydroquinone (step 4) is performed sequentially, and 2,3,5-trimethylhydroquinone represented by the following chemical formula 1 is characterized. Manufacturing method.

(Chemical formula 1)   The method for producing 2,3,5-trimethylhydroquinone according to claim 1, wherein the first step is oxidation with an oxygen-containing gas in the presence of a copper compound catalyst in an organic solvent.   2. The method for producing 2,3,5-trimethylhydroquinone according to claim 1, wherein the second step is a hydrogenation reaction under pressure in an organic solvent in the presence of a hydrogenation catalyst.   The 2,3-dimethyl-P-benzoquinone used in the second step is a crude product obtained by removing a high-boiling by-product containing a dimer from an oxidation reaction mixture. A method for producing 5-trimethylhydroquinone.   5. The method for producing 2,3,5-trimethylhydroquinone according to claim 1 or 4, wherein the third step is a reaction of a cyclic secondary amine and formaldehyde in an aromatic hydrocarbon solvent to obtain a Mannich salt. The method for producing 2,3,5-trimethylhydroquinone according to claim 1, wherein the fourth step is a hydrocracking reaction under pressure in an organic solvent in the presence of a hydrogenation catalyst.