JPH09176082A - Production of p-benzoquinones - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the above compound important as an intermediate for producing chemicals in a high yield without producing by products by oxidizing specific phenols with an oxidizing agent in the presence of specific phenols. SOLUTION: (A) Phenols of formula I (X is H or hydroxyl; R<1> to R<4> are H or an alkyl, an alkoxy, an alkylsulfonyl, an arylaryloxy, etc., which may have a substituent group) are oxidized with (C) an oxidizing agent in the presence of (B) a metal porphyrin complex (the metal is a complex-forming metal, preferably either one of Fe, N, Cr and Mn) to provide the objective compound of formula H. Moreover, the component B is preferably either one of hematins, hemins, hemes, hemoglobins and methemoglobin and the component C is preferably hydrogen peroxide or a material capable of isolating the hydrogen peroxide.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing p-benzoquinones.

[0002]

2. Description of the Related Art Certain quinones are biochemically active, and some quinones are used as intermediates for the production of useful drugs. In particular, trimethyl-p-benzoquinone (TMQ) is important as a vitamin E production intermediate. Industrially, a method has been adopted in which the para-position of 2,3,6-trimethylphenol (TMP) is sulfonated, and then oxidized with manganese dioxide. However, each method has many steps and a large amount of auxiliaries. It has drawbacks such as requiring materials. On the other hand, recently, several methods have been proposed. For example, a method of oxidizing TMP with hydrogen peroxide using a heteropolyacid as a catalyst (M. Shimizu, et al.
al. , Tetrahedoron Lett. , 1
989 . 471), a method of oxidizing with oxygen in the presence of a combined catalyst of cupric chloride and an amine [M. Shimiz
u, et al. Bull. Chem. Soc. Jp
n. , 65 , 1522 (1992)], a method of oxidizing NPV ₆ No ₆ supported on activated carbon with oxygen as a catalyst (S. Fujibayashi, et al., Che.
m. Lett. , 1994 , 1345).

However, the yield of TMQ is not always satisfactory by these methods, and the selectivity of the reaction is low, and hydroxytrimethyl-p-benzoquinone, 4-
Chloro-2,3,6-trimethylphenol, 4,4 '
-By-products such as dihydroxy-2,2 ', 3,3', 5,5'-hexamethylbiphenyl are produced, which makes purification of TMQ difficult. Especially, since the boiling point of 4-chloro-2,3,6-trimethylphenol is very close to that of TMQ, it is practically possible to separate them by a distillation operation.
Impossible. (Both boiling points: ~ 53 ° C / 0.4 mmH
g)

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing p-benzoquinones which has a good reaction yield and is easy to purify.

[0005]

[Means for Solving the Problems] The following general formula (1)

Embedded image [In the formula, X represents hydrogen or a hydroxyl group,
R ¹ , R ² , R ³ and R ⁴ are hydrogen and an alkyl group which may have a substituent, an alkoxy group, an alkylsulfonyl group, an aryl group, an aryloxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and a halogen. Is a group independently selected from the group consisting of. ] The phenol represented by the following formula is oxidized with an oxidizing agent in the presence of a metalloporphyrin complex (the metal represents a complex salt-forming metal), and the following general formula (2)

Embedded image [In the formula, R ¹ , R ² , R ³ and R ⁴ are the same as defined above. ] It is related with the manufacturing method of p-benzoquinone shown by these.

When N, N'-tetramethyl-4,4'-diaminodiphenylmethane is oxidized with hydrogen peroxide using hemin as a catalyst, Michler hydrol (N, N'-tetramethyl-4,4'-diaminobenzhydride) is obtained. It is known that rolls are generated (Tetrahedron L
ett. 1989,957), the reaction is -CH ₂ - after a reaction for changing the, - a -CH (OH)
At this time, the catalytic activity of hemin was extremely low. Further, there is a method for producing diaminodiphenylmethanol by oxidizing diaminodiphenylmethane with hydrogen peroxide in the presence of an iron protoporphyrin complex.
-88545, but this reaction also-
It remains a reaction that changes CH ₂ — to —CH (OH) —. However, when this metalloporphyrin complex such as hemin is used as an oxidation catalyst for phenols, surprisingly, p-benzoquinones were produced in high yield without accompanying side reaction products.

The phenols as the raw material of the present invention are represented by the following general formula (1)

Embedded image [In the formula, X represents hydrogen or a hydroxyl group,
R ¹ , R ² , R ³ and R ⁴ are hydrogen and an alkyl group which may have a substituent, an alkoxy group, an alkylsulfonyl group, an aryl group, an aryloxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and a halogen. Is a group independently selected from the group consisting of. ] In particular, R ¹ , R ² , R
³ and R ⁴ are hydrogen and an alkyl group having 1 to 4 carbon atoms which may have a substituent, an alkoxy group having 1 to 4 carbon atoms, an alkylsulfonyl group having 1 to 4 carbon atoms, an aryl group, an aryloxy group, aryl It is preferably a group independently selected from the group consisting of a sulfonyl group, an aralkyl group, a hydroxyl group and halogen.

Examples of alkyl in the alkyl group or alkylsulfonyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, and the like, and examples of the alkoxy group include methoxy, ethoxy, propoxy, and iso. Propoxy, butoxy, isobutoxy and the like can be mentioned. Examples of the aryl group include a phenyl group and a substituted phenyl group,
Examples of the aryloxy group include phenoxy, substituted phenoxy and the like, examples of the aralkyl group include benzyl, phenethyl, trityl and the like, and examples of the alkylsulfonyl group include methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl and the like. Examples of the arylsulfonyl group include phenylsulfonyl. In addition, the alkyl group, the alkoxy group, and halogen as substituents are added to these groups as 1
~ 3 introduced, such as 2-, 3- or 4-methylphenoxy, 2-, 3- or 4-chlorophenoxy.

Typical examples of the phenols include trimethylphenols, triethylphenols, dimethylphenols, methylphenols and phenols.

The oxidizing agent used in the present invention may be selected from the group consisting of oxygen, hydrogen peroxide, a material that releases hydrogen peroxide, an organic hydroperoxide and a percarboxylic acid, but is not particularly limited. Compounds that liberate hydrogen oxide or hydrogen peroxide are preferred. Examples of materials that release hydrogen peroxide include compounds such as anthrahydroquinone, 2-ethylanthrahydroquinone, and 2-t-butylanthrahydroquinone, and metal peroxides such as sodium peroxide and barium peroxide, and acids such as acetic acid and formic acid. There is a combination with.

There are no particular restrictions on the hydrogen peroxide or the material that releases hydrogen peroxide used in the present invention, and commercially available industrial products can be used as they are. It is suitable to use a molar to 10-fold molar amount, especially an equimolar to 4-fold molar amount. Although depending on the reaction conditions, the yield of the desired product varies depending on the amount of hydrogen peroxide used relative to the phenols, as shown in FIG. 1, for example.

The metal porphyrin complex has the following formula (wherein M represents a complex salt-forming metal).

[Chemical 6] A heme represented by the following formula (wherein M represents a complex salt-forming metal)

Embedded image And the following formula (wherein M represents a complex salt-forming metal)

Embedded image The metal porphyrin complex such as hemins represented by or a compound in which these complexes are bound is used.

The metal is not particularly limited as long as it is a metal capable of forming a complex, and examples thereof include Fe, Ni, Cr and M.
n, Pt, Pd, Pb, Ti, V, Cu, Zr, Co,
Although Mo, Ag, W, Ir, Au, etc. can be mentioned, Fe, Mn, Cr, Ni, etc. are particularly preferable, and Fe is most preferable.

R ^{11 to} R ¹⁸ are hydrogen, an alkyl group (eg, methyl group, ethyl group, etc.), an alkyl group having a carboxyl group as a substituent (eg, carboxymethyl group, 2-carboxyethyl group, etc.), It may be a group independently selected from the group consisting of a hydroxyalkyl group (for example, 1-hydroxyethyl group and the like), a vinyl group, an aldehyde group.

As the iron porphyrin complex, iron (II
I) Although a synthetic product such as 2,3,7,8,12,13,17,18-octaethylporphyrin chloride may be used, the following formula, which is easily available in large amounts from bovine blood, etc.

Embedded image The hem expressed by

Embedded image Hematin and the following formula

Embedded image In addition to hemin, etc., Ethiohem, Mesohem,
Protohem, deuterohem, hemathem, coprohem, urohem, spirography graphics hem, cryptohem,
It is practical to use an iron porphyrin complex such as natural heme such as heme c and heme a, or a compound in which these complexes are bound such as hemoglobin and methemoglobin.

Hemin can be obtained as a precipitate by heat treatment of bovine blood in acetic acid containing a small amount of salt (H. Fi).
scher, Org. Syn. , Collect. vo
l. , 3 . 443), hematin is easily obtained by treating hemin with sodium hydroxide. Heme can also be obtained by reducing hematin. Methemoglobin is the Fe (II) in the heme by treating hemoglobin with an oxidizing agent such as potassium ferricyanide.
Is oxidized to Fe (III).

The amount of these catalysts used is 1/200 per mol of phenols as the amount of metalloporphyrin complex.
The amount is 1/10 mol, and particularly preferably 1/100 to 1/20 mol.

Although the reaction of the present invention can be carried out in a homogeneous system or a heterogeneous system, it is preferably carried out in a homogeneous system, and particularly preferably in acetic acid. In addition, lower fatty acids such as formic acid and propionic acid can be used. Also,
Acetic acid can be used as a mixture with water, but it is preferable to use acetic acid having an acetic acid concentration of 80 wt% or more.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION When carrying out the method of the present invention, for example, the above-mentioned amount of catalyst is dissolved in an 80 wt% acetic acid aqueous solution, and further, phenols are usually added in an amount of 30 wt% or less,
Preferably, it is dissolved in a concentration of 0.1 to 10 wt%, and the oxidizing agent component such as hydrogen peroxide solution is dropped in the above amount. The concentration of the oxidizing agent at this time is not particularly limited, but when hydrogen peroxide or a compound that releases hydrogen peroxide is used, it is suitable to use 3 to 30 wt% as hydrogen peroxide. When hydrogen peroxide is dropped, a temperature rise of about 1 to 50 ° C. is observed depending on the dropping rate and the concentration of the reaction substrate. The reaction is usually carried out at 0 to 30 ° C. and is completed in 5 to 30 minutes, but it may be heated or heated if necessary. After completion of the reaction, the reaction mixture may be diluted with about 5 times the amount of water, extracted with ether, benzene, etc., and p-benzoquinones produced by distilling ether, benzene, etc. from the extract may be obtained. it can.

[0020]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 12.5 m of 80 wt% acetic acid was added to a beaker having a content of 100 ml.
Take l, dissolve 0.0050 g (8 μmol) of hematin, and add 0.03 g of 2,3,6-trimethylphenol.
858 g (630 μmol) was dissolved. This was immersed in an ice water bath to adjust the liquid temperature to 2 ° C. While stirring, 3 ml (2.6 mmol) of 3 wt% hydrogen peroxide solution was added at once.
The liquid temperature rose to 4 ° C. After stirring for 10 minutes, 50 ml of water was added to stop the reaction. Ether 50
Extraction was performed twice with ml, and trimethyl-p-benzoquinone in the extract was quantified by GLC. As a result, the yield of trimethyl-p-benzoquinone was 82.1 wt%, and a trace amount of unreacted product was detected, but ether-soluble side reaction products were not detected at all.

Example 2 12.5 m of 80 wt% acetic acid was added to a beaker having a content of 100 ml.
Take l and 0.050 g (0.08 mmol) of hematin
Was dissolved, and 0.83 g (6.3 mmol) of 2,3,6-trimethylphenol was further dissolved. Soak this in an ice-water bath to bring the liquid temperature to 4 ° C and stir it to 30 wt%
3 ml of hydrogen peroxide solution was dropped for about 1 minute. Although the liquid temperature rose to a maximum of 40 ° C, stirring was continued as it was. After stirring for 15 minutes, acetaldehyde of 0.
The reaction was stopped by adding 1 ml and diluted with 50 ml of water. It was extracted 3 times with 50 ml of ether, and the extracts were combined and dried over anhydrous sodium sulfate. After the ether was distilled off using an evaporator, it was further held in a vacuum desiccator to obtain 0.832 g of orange crystals (yield as trimethyl-p-benzoquinone, 87.9 wt%). IR of this crystal
The spectrum was in perfect agreement with that of trimethyl-p-benzoquinone.

Example 3 12.5 m of 80 wt% acetic acid was added to a beaker having a content of 100 ml.
1), dissolve 0.025 g of hemoglobin, and add 0.0086 g of 2,3,6-trimethylphenol (6
3 μmol) was dissolved. Immerse this in an ice-water bath and keep the liquid temperature at 4 ℃
And 0.3m of 3wt% hydrogen peroxide while stirring
1 (0.26 mmol) was added at once. Although the liquid temperature rose to 6 ° C, stirring was continued for another 15 minutes. After injecting 50 ml of water, 2 with 50 ml of ether
It was extracted twice and trimethyl-p-benzoquinone in the extract was quantified by GLC. As a result, trimethyl-p
-The benzoquinone yield was 80.3 wt%.

The embodiments of the present invention will be listed below. 1. The following general formula (1)

Embedded image [In the formula, X represents hydrogen or a hydroxyl group,
R ¹ , R ² , R ³ and R ⁴ are hydrogen and an alkyl group which may have a substituent, an alkoxy group, an alkylsulfonyl group, an aryl group, an aryloxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and a halogen. Is a group independently selected from the group consisting of. ] The phenol represented by the following formula is oxidized with an oxidizing agent in the presence of a metalloporphyrin complex (the metal represents a complex salt-forming metal), and the following general formula (2)

Embedded image IN FORMULA, R < ¹ >, R < ² >, R < ³ > AND R < ⁴ > ARE THE SAME AS THE ABOVE-MENTIONED. ] The manufacturing method of p- benzoquinone shown by these. 2. In the general formulas (1) and (2), R ¹ ,
R ² , R ³ and R ⁴ are each hydrogen and an optionally substituted alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an alkylsulfonyl group having 1 to 4 carbon atoms, an aryl group, aryl The p according to the above item 1, which is a group independently selected from the group consisting of an oxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and halogen.
-Method for producing benzoquinones. 3. 3. The method for producing p-benzoquinones according to 1 or 2 above, wherein the metal is selected from the group consisting of Fe, Ni, Cr and Mn. 4. 4. The method for producing p-benzoquinones according to item 3, wherein the metal is Fe. 5. 5. The method for producing p-benzoquinones according to item 12, 3 or 4 above, wherein the metalloporphyrin complex is selected from the group consisting of hematins, hemins, hemes, hemoglobins and methemoglobins. 6. 1, wherein the oxidizing agent is selected from the group consisting of oxygen, hydrogen peroxide, a material that releases hydrogen peroxide, an organic hydroperoxide, and a percarboxylic acid.
The method for producing p-benzoquinones according to 3, 4, or 5. 7. 7. The method for producing p-benzoquinones according to item 6, wherein the oxidizing agent is hydrogen peroxide or a material that releases it. 8. A method for producing 2,3,6-trimethyl-p-benzoquinone, which comprises oxidizing 2,3,6-trimethylphenol with hydrogen peroxide or a material that releases hydrogen peroxide in the presence of an iron porphyrin complex.

[0025]

[Effect] According to the method of the present invention, the yield is 80 to 90 wt%.
It is surprising that the side reaction product soluble in ether was not detected although the unreacted product was detected. Therefore, purification of the target product is extremely easy, and its industrial result is tremendous.

[Brief description of the drawings]

FIG. 1 is a graph showing changes in the yield of a target product due to changes in the amounts of 2,3,6-trimethylphenol and hydrogen peroxide used.

Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location C07C 50/24 9049-4H C07C 50/24 50/28 9049-4H 50/28 50/30 9049-4H 50 / 30 315/04 7419-4H 315/04 323/22 7419-4H 323/22 // C07B 61/00 7419-4H C07B 61/00

Claims (7)

[Claims] 1. The following general formula (1): [In the formula, X represents hydrogen or a hydroxyl group,
R ¹ , R ² , R ³ and R ⁴ are hydrogen and an alkyl group which may have a substituent, an alkoxy group, an alkylsulfonyl group, an aryl group, an aryloxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and a halogen. Is a group independently selected from the group consisting of. ] The phenol represented by the formula [1] is oxidized with an oxidizing agent in the presence of a metalloporphyrin complex (the metal represents a complex salt-forming metal). [In the formula, R ¹ , R ² , R ³ and R ⁴ are the same as defined above. ] The manufacturing method of p- benzoquinone shown by these. 2. In the general formulas (1) and (2), R ¹ , R ² , R ³ and R ⁴ are hydrogen and an alkyl group having 1 to 4 carbon atoms which may have a substituent, and a carbon number of 1. ~
4. A group independently selected from the group consisting of a C4 alkoxy group, an alkylsulfonyl group having 1 to 4 carbon atoms, an aryl group, an aryloxy group, an arylsulfonyl group, an aralkyl group, a hydroxyl group and a halogen. A method for producing the described p-benzoquinones. 3. The metal is Fe, Ni, Cr and Mn.
The method for producing p-benzoquinones according to claim 1 or 2, which is selected from the group consisting of: 4. The p-benzoquinone according to claim 1, 2 or 3, wherein the metalloporphyrin complex is selected from the group consisting of hematins, hemins, hemes, hemoglobins and methemoglobins. Production method. 5. The oxidizing agent is selected from the group consisting of oxygen, hydrogen peroxide, a compound that releases hydrogen peroxide, an organic hydroperoxide, and a percarboxylic acid. A method for producing the described p-benzoquinones. 6. The method for producing p-benzoquinones according to claim 5, wherein the oxidizing agent is hydrogen peroxide or a material that liberates hydrogen peroxide. 7. A method of oxidizing 2,3,6-trimethylphenol with hydrogen peroxide or a material that releases hydrogen peroxide in the presence of an iron porphyrin complex.
A method for producing 6-trimethyl-p-benzoquinone.