JPH09249605A - Production of 2,3,5-trimethylhydroquinone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound easily in a high yield, useful as a raw material for synthetic vitamin E. SOLUTION: This 2,3,5-trimethylhydroquinone is obtained by oxidizing 2,3,6- trimethylphenol with a ketone peroxide in the presence of a lewis acid (e.g. at least one kind of compound selected from boron trifluoride, a complex thereof and a hydrogen fluoride adduct thereof). The ketone peroxide used in the reaction is synthesized by reacting a ketone with hydrogen peroxide or by an autoxidation of secondary alcohols, and preferably contains at least one structure expressed by formula I, II (X is an integer of 1-4), etc.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing 2,3,5-trimethylhydroquinone useful as a raw material for synthetic vitamin E.

[0002]

2. Description of the Prior Art As a method for producing 2,3,5-trimethylhydroquinone, (1) 2,3,6-trimethylphenol is sulfonated and further oxidized to give 2,3,5-trimethylbenzoquinone. Hydrogen reduction of 2,
Method for obtaining 3,5-trimethylhydroquinone (West German Patent Nos. 1932362 and 2225543), (2) 2,3,6-trimethylbenzoquinone is obtained by oxidizing 2,3,6-trimethylphenol. After doing
A method of reducing this with hydrogen to obtain 2,3,5-trimethylhydroquinone (JP-A-61-27936),
(3) 2,3,6-trimethylphenol is oxidized by hydrogen peroxide in the presence of ketone in the presence of sulfuric acid or a salt thereof or sulfonic acid or a salt thereof as a catalyst, if necessary. Method for obtaining 5-trimethylhydroquinone (Japanese Patent Publication No. 55-30693), (4) 2,
A known method is to obtain 2,3,5-trimethylhydroquinone by oxidizing 3,6-trimethylphenol with ketone peroxide in the presence of sulfuric acid or its salt or sulfonic acid or its salt (Japanese Patent Publication No. 55-31763). Has been.

However, the methods (1) and (2) have a problem that they are industrially undesirable because they produce industrial wastes as by-products and are multistage reactions. Further, the methods (3) and (4) have a problem that the yield of 2,3,5-trimethylhydroquinone is low and it is not industrially satisfactory.

[0004]

The present invention is based on 2, 3, 6
An object of the present invention is to provide a method for producing 2,3,5-trimethylhydroquinone from trimethylphenol with high yield and easily (in one step).

[0005]

[Means for Solving the Problems] The present inventors
As a result of earnest research on a method for producing 2,3,5-trimethylhydroquinone from -trimethylphenol, surprisingly, a Lewis acid was allowed to be present to oxidize 2,3,6-trimethylphenol with a ketone peroxide. 2,3,5 with significantly higher yield than the method
The present invention has been completed by discovering that trimethylhydroquinone can be produced.

That is, the object of the present invention is achieved by a method for producing 2,3,5-trimethylhydroquinone, which comprises oxidizing 2,3,6-trimethylphenol with ketone peroxide in the presence of a Lewis acid. It

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The ketone peroxide used in the present invention can be sufficiently used as a commercial product,
A compound synthesized by a reaction between a ketone and hydrogen peroxide according to a conventional method or by autoxidation of secondary alcohols, which contains at least one or more of the structures shown below in the molecule. Good.

[0008]

Embedded image (In the formula, x represents an integer of 1 to 4. Further, in the above structure, two bonds derived from a ketone may be bonded together to form a 5- or 6-membered ring.)

The ketone used for synthesizing the ketone peroxide is not particularly limited, but examples thereof include the following. (1) A ketone having 3 to 20 carbon atoms represented by the following general formula (I):

Embedded image (In the formula, R ¹ and R ² represent a linear or branched alkyl group having 1 to 18 carbon atoms or a phenyl group, which may be the same or different from each other. The hydrogen atom may be substituted with a halogen atom, a hydroxyl group, an amino group or a phenyl group, and these alkyl groups may have an unsaturated bond.)

(2) C3-20 diketone represented by the following general formula (II):

Embedded image (In the formula, n ¹ represents an integer of 0 to 16, and R ¹ and R ² have the same meaning as described above.)

(3) Cycloketone represented by the following general formula (III):

Embedded image (In the formula, n ² represents an integer of 4 to 11, and m ¹ + m ² is 3
Represents an integer of 10 to 10. R ¹ has the same meaning as described above. )

Of the ketones represented by the general formula (I), R
Examples of the linear or branched alkyl group in which ¹ and R ² have 1 to 18 carbon atoms (and do not have an unsaturated bond) include the following: methyl, ethyl, propyl, 1-methyl. Ethyl, butyl, 1-methylpropyl,
1,1-dimethylethyl, 2-methylpropyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, octyl, decyl, undecyl, 2-dodecyl, Tridecyl, tetradecyl, pentadecyl, octadecyl, etc.

Representative examples of the above-mentioned ketone having an alkyl group include the following: acetone, methyl ethyl ketone, 2-pentanone, 3-pentanone, 3-methyl-2-butanone, 2-hexanone, 3-hexanone. , 3-methyl-2-pentanone, 4-methyl-2-pentanone, 3,3-dimethyl-2-butanone, 2-heptanone, 3-heptanone, 4-heptanone, 2,4-dimethyl-3-pentanone, 2 -Octanone, 6-methyl-2-heptanone, 2-nonanone, 2,6-dimethyl-
4-heptanone, 2,2,4,4-tetramethyl-3-
Heptanone, 3-decanone, 6-undecanone, 2-tridecanone, 7-tridecanone, 2-tetradecanone,
2-pentadecanone, 2-hexadecanone, 2-heptadecane, 3-octadecanone, 4-nonadecanone, 5
-Icosanone, etc.

Of the ketones represented by the general formula (I), R
Representative examples of ketones in which ¹ and R ² are linear or branched alkyl groups having 1 to 18 carbon atoms and have an unsaturated bond include the following (provided that the unsaturated bond is May be a double bond or a triple bond, but a double bond is preferable): 3-buten-2-one, 3-penten-2-one, 5-hexen-2-one, 4-methyl-
3-Penten-2-one, 6-methyl-5-heptene-
2-one, 5-octen-2-one, 7-nonadecene-
2-on etc.

Of the ketones represented by the general formula (I), R
¹ and R ² are linear or branched alkyl groups having 1 to 18 carbon atoms, and their hydrogen atoms are substituted with halogen atoms (especially chlorine atom, bromine atom), hydroxyl group, amino group or phenyl group. Representative examples of such ketones include, for example, 1-chloro-2-propanone, 1-chloro-3-heptanone, 1-bromo-3-heptanone, 1-hydroxy-2-propanone, 3-hydroxy-2-butanone, 4-amino-4-methyl-2-
Pentanone, acetophenone, benzophenone, 1-phenyl-2-propanone, 1-phenyl-1-butanone, 1-phenyl-3-butanone, 1-phenyl-3-
Pentanone, 1,3-diphenyl-2-propanone, etc.

Typical examples of the diketone represented by the general formula (II) include the following: 2,3-butanedione, 2,4-pentanedione and 2,5-hexanedione.

Typical examples of the cycloketone represented by the general formula (III) include the following: cyclopentanone, cyclohexanone, 2-ethyl-1-cyclopentanone, 2-methyl-1-cyclohexanone. , Cyclododecanone, etc.

The ketone peroxide is, as described above,
It is easily synthesized by a known method by autoxidation of secondary alcohol. The secondary alcohol is not particularly limited, but for example, alcohols represented by the following (IV), (V) and (VI) corresponding to ketones (I), (II) and (III) are Each is listed.

(1) Secondary alcohol having 3 to 20 carbon atoms represented by the following general formula (IV):

Embedded image (In the formula, R ¹ and R ² have the same meanings as described above.)

(2) Di-secondary alcohol having 3 to 20 carbon atoms represented by the following general formula (V):

[Chemical 6] (In the formula, R ¹ , R ² and n ¹ have the same meanings as described above.)

(3) Cycloalcohol represented by the following general formula (VI):

Embedded image (In the formula, n ¹ , n ² , m ¹ , m ² and R ¹ have the same meanings as described above.)

Of the secondary alcohols represented by the general formula (IV), alcohols in which R ¹ and R ² are linear or branched (and have no unsaturated bond) having 1 to 18 carbon atoms Representative examples include, for example: 2-propanol, 2-butanol, 2-pentanol, 3-
Pentanol, 3-methyl-2-butanol, 2-hexanol, 3-hexanol, 3-methyl-2-pentanol, 3,3-dimethyl-2-butanol, 2-heptanol, 3-heptanol, 4-heptanol, Two
4-dimethyl-3-pentanol, 2-octanol,
6-methyl-2-heptanol, 2-nonanol, 2,
6-dimethyl-4-heptanol, 2,2,4,4-tetramethyl-3-pentanol, 3-decanol, 6-
Undecanol, 2-tridecanol, 7-tridecanol, 2-tetradecanol, 2-pentadecanol,
2-hexadecanol, 2-heptadecanol, 2-octadecanol, 3-octadecanol, 4-nonadecanol, 5-aicosadecanol and the like.

In the secondary alcohol represented by the general formula (IV), R ¹ and R ² are linear or branched alkyl groups having 1 to 18 carbon atoms and have an unsaturated bond. Typical examples of the alcohol include the following (however, the unsaturated bond may be a double bond or a triple bond, but a double bond is preferable): 3-butene-2-ol, 3- Penten-2-ol, 5-hexene-2-ol, 4-methyl-3-penten-2-ol, 6-methyl-5-hepten-2-ol, 5-octen-2-ol,
7-Nonadecen-2-ol and the like.

Among the secondary alcohols represented by the general formula (IV), R ¹ and R ² are linear or branched alkyl groups having 1 to 18 carbon atoms, and the hydrogen atom is Representative examples of alcohol substituted with a halogen atom (especially chlorine atom, bromine atom), hydroxyl group, amino group or phenyl group include, for example, the following: 1-chloro-2-butanol, 1-chloro- 3-heptanol, 1
-Bromo-3-heptanol, 1-hydroxy-2-propanol, 3-hydroxy-2-butanol, 4-amino-4-methyl-2-pentanol, diphenylmethanol, 1-phenylethanol, 1-phenyl-2-
Propanol, 1-phenyl-1-butanol, 1-phenyl-3-butanol, 1-phenyl-3-pentanol, 1,3-diphenyl-2-propanol and the like.

Representative examples of di-secondary alcohols of general formula (V) include, for example:
2,3-butanediol, 2,4-pentanediol,
2,5-hexanediol, etc.

Typical examples of the cycloalcohol represented by the general formula (VI) include the following: cyclopentanol, cyclohexanol, 2-ethyl-1.
-Cyclopentanol, 2-methyl-1-cyclohexanol and the like.

Particularly preferred among the above ketones are:
It is a C3-C15 saturated aliphatic monoketone having no substituents, a C5-C12 saturated alicyclic monoketone, or an aromatic monoketone. Further, among the above secondary alcohols, particularly preferable ones are those having 3 to 3 carbon atoms which do not have a substituent.
It is a saturated aliphatic monoalcohol having 15 carbon atoms, a saturated alicyclic monoalcohol having 5 to 12 carbon atoms, or an aromatic monoalcohol.

In the present invention, the oxidation of 2,3,6-trimethylphenol with ketone peroxide described in detail above is carried out under the following conditions. The amount of ketone peroxide used is not particularly limited, but the value of [amount of peroxide P / 2,3,6-trimethylphenol 1 mmol] is 0.005 to 1.0, particularly 0.01 to 0. It is preferably 5. However, the peroxide amount P is represented by the following formula:

[0029]

[Equation 1] (In the formula, a represents the amount of active oxygen (%), and b represents the weight of ketone peroxide (g))

The active oxygen in the present invention means one atom of oxygen of the peroxide bond (--O.O--), and peroxide is added to hydrochloric acid-potassium iodine or acetic acid-potassium iodine solution. It is oxygen that carries out the following reactions. The amount of active oxygen is the weight percentage of active oxygen contained in the peroxide of the sample, and the quantitative determination is carried out by reacting the peroxide with the following reaction (a) or (b) to release iodine. Is measured.

[0031]

Embedded image

The reaction is carried out at 0 to 250 ° C., preferably 45 to 2
It is carried out at a temperature of 00 ° C. The solvent may not be used, but when it is used, other solvents such as methyl acetate, ethyl acetate, ethylene diacetate, methyl benzoate, dimethyl phthalate, diethyl phthalate, benzene and the like can be used. , Acetone, methyl ethyl ketone, 2-pentanone, 3-pentanone, 3-methyl-2-butanone, 2
-Various ketones such as hexanone, 3-hexanone, 4-methyl-2-pentanone, 3,3-dimethyl-2-butanone, cyclopentanone and acetophenone are used.

The reaction time is not particularly limited, but depends on the reaction temperature and the amount of the catalyst (Lewis acid) described later. The reaction is usually carried out under atmospheric pressure, but it may be carried out under reduced pressure or increased pressure. The water content in the reaction system is 2, 3, 5-
It is preferable that the amount is as small as possible in order to improve the yield of trimethylhydroquinone.

The Lewis acid used in the present invention includes at least one compound selected from boron trifluoride, its complex and its hydrogen fluoride adduct. Examples of the complex of boron trifluoride include a carboxylic acid complex of boron trifluoride such as an acetic acid complex, an ether complex of boron trifluoride such as a dimethyl ether complex, a diethyl ether complex, a t-butylmethyl ether complex, and a dibutyl ether complex. ,
Amine complex of boron trifluoride such as ethylamine complex,
Examples thereof include alcohol complexes of boron trifluoride such as methanol complex, propanol complex and phenol complex, and sulfide complexes of boron trifluoride such as dimethyl sulfide complex. Examples of the hydrogen fluoride adduct of boron trifluoride include borofluoric acid (aqueous solution).

The Lewis acids may be used alone or in admixture and can be used either homogeneously or heterogeneously. When used in a heterogeneous system, it is used in various forms such as suspension or tablets. The amount of Lewis acid can be varied over a wide range, but in order to obtain a sufficient reaction rate, 2,3,6
-It is preferably 0.0005 mol% or more, more preferably 0.005 mol% or more, and particularly preferably 0.05 to 1 mol% with respect to trimethylphenol.

Although the case where the reaction of the present invention is carried out in a batch system has been described above, it is of course possible to carry out the reaction in a continuous system. That is, it can be carried out by a method of continuously feeding the raw material mixed solution into the catalyst packed bed to cause a reaction, or a method of dissolving or suspending the catalyst in the raw material mixed solution and passing it through the reaction zone. In the latter case, the required amount of catalyst is determined according to a batch system.

After the reaction, 2,3,5-trimethylhydroquinone can be easily separated according to a known method, because the reaction solution does not contain any substance that interferes with the separation of the target substance. For example, 2,3,5-trimethylhydroquinone can be obtained by cooling the reaction solution, and often removing the catalyst, and then subjecting the reaction solution to distillation. That is, water, which is a by-product, a ketone formed from ketone peroxide, 2,3,6-trimethylphenol as a raw material, and 2,3,5-trimethylhydroquinone as a target may be appropriately distilled and separated. The separated ketone and 2,3,6-trimethylphenol can be circulated and used for the next reaction.

[0038]

Next, the present invention will be described specifically with reference to examples and comparative examples. However, the ketone peroxides used in the following examples are the same as or synthesized by the same method as the following reference examples.

Reference Example 1 [Methylethylketone peroxide] (Permek N: manufactured by NOF CORPORATION) 55 wt% methylethylketone peroxide solution (active oxygen amount: 10.32) dissolved in dimethyl phthalate.
%).

Reference Example 2 [4-Methyl-2-pentanone peroxide] (synthetic product) 60.2 g (0.62 mo) of 35 wt% hydrogen peroxide solution
l) and 85% by weight of phosphoric acid (1.0 g) were mixed and stirred, and 60.2 g (0.60 mol) of 4-methyl-2-pentanone was added thereto at 15 to 20 ° C. to carry out a reaction for 20 minutes It was After the reaction is completed, 10 g of sodium sulfate is added to the reaction solution.
Was added to separate the organic layer, which was neutralized with sodium carbonate. The amount of active oxygen in the 4-methyl-2-pentanone peroxide solution obtained by filtration and separation was 5.04%.

Example 1 A glass three-necked flask with an internal volume of 100 ml equipped with a reflux condenser having a water separator, a thermometer and a stirrer was charged with 2.
13.62 g of 3,6-trimethylphenol (100 m
mol) and methyl ethyl ketone peroxide 0.75
After charging 52 g (P = 5.0) and replacing the inside of the reactor with nitrogen, the reactor was immersed in an oil bath at 70 ° C. When the temperature of the reaction solution reached 70 ° C., 0.0355 g (0.25 mmol) of diethyl ether complex of boron trifluoride was added, and the reaction solution was reacted for 1 hour while stirring. During this time, the produced water was continuously collected in the water separator. After completion of the reaction, the reaction solution was analyzed by gas chromatography to find that it was 2,3,5-trimethylhydroquinone 3.0.
5 g (2.00 mmol) had formed. The yield was 40.1% based on peroxide based on the definition below.

[0042]

[Equation 2]

Example 2 As a catalyst, 0.0523 borofluoric acid (42% aqueous solution) was used instead of the diethyl ether complex of boron trifluoride.
The reaction and analysis were performed in the same manner as in Example 1 except that g (0.25 mmol) was used. As a result, the yield of 2,3,5-trimethylhydroquinone was 38.6%.

Comparative Example 1 The reaction and analysis were conducted in the same manner as in Example 1 except that 0.030 g (0.22% by weight) of sulfuric acid was used as the catalyst instead of the diethyl ether complex of boron trifluoride. As a result, the yield of 2,3,5-trimethylhydroquinone was 2
2.4%.

Example 3 As an oxidizing agent, 4-methyl-2-pentanone peroxide 1.5 instead of methyl ethyl ketone peroxide was used.
The reaction and analysis were performed in the same manner as in Example 1 except that 873 g (P = 5.0) was used. As a result, the yield of 2,3,5-trimethylhydroquinone was 43.8%.
Table 1 shows the results of Examples and Comparative Examples.

[0046]

[Table 1]

[0047]

According to the present invention, the yield of 2,3,5-trimethylhydroquinone from 2,3,6-trimethylphenol in a one-step reaction is about twice as high as that of the known method using sulfuric acid as a catalyst. Can be manufactured in. Since the reaction of the present invention is one step and very easy, the present invention can provide an industrially suitable method for producing 2,3,5-trimethylhydroquinone.

Claims (2)

[Claims] 1. A method for producing 2,3,5-trimethylhydroquinone, which comprises oxidizing 2,3,6-trimethylphenol with ketone peroxide in the presence of a Lewis acid. 2. The Lewis acid is at least one compound selected from boron trifluoride, a complex thereof and a hydrogen fluoride adduct thereof, 2, 3,
A method for producing 5-trimethylhydroquinone.