JP3449800B2 - Method for producing 2-methyl-1,4-naphthoquinone - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing 2-methyl-1,4-naphthoquinone by oxidizing 2-methylnaphthalene in a liquid phase.

[0002]

2. Description of the Prior Art 2-Methyl-1,4-naphthoquinone is
It is called menadione or vitamin K3 and has a hemostatic effect when the animal body bleeds. Not only vitamin K3, but also its derivatives such as vitamins K1, K2, K4, vitamin K3 sodium bisulfite adduct, vitamin K3 dimethyl bisulfite dimethylpyrimidinol salt adduct, etc. are used as human medicines and feed additives. It has been used and is a useful compound.

Conventionally, as an industrial production method of 2-methyl-1,4-naphthoquinone, there is a method of oxidizing 2-methylnaphthalene using chromic anhydride, dichromate such as sodium dichromate, or the like. Has been done. However, due to the pollution problem caused by chromium compounds in recent years, it has become difficult to manufacture by this method.

On the other hand, various oxidation methods which do not use chromium compounds have been proposed so far. As one of the methods, there is a method in which 2-methylnaphthalene is subjected to oxygen oxidation in the gas phase using a vanadium catalyst (Japanese Patent Laid-Open No. 6-9485, etc.). However, in this method, a high selectivity is obtained. In addition, the conversion rate must be kept very low. Further, as a liquid-phase oxidation method, a method using a cerium compound is known (JP-A-63-26442).
No. 8, etc.). According to this method, the target compound can be obtained in a relatively high yield, but since a stoichiometric amount of the cerium compound is used, it is necessary to regenerate the cerium compound by electrolysis or the like.

Another known method is to oxidize 2-methylnaphthalene in a liquid phase using hydrogen peroxide or an organic peracid. As an example of the reaction in this method, a method of oxidizing in a solvent such as acetic acid without using a catalyst (Japanese Patent Publication No.
No. 9-53252), a method using an acid as a catalyst (Japanese Patent Laid-Open No. 53-50147), and the like are known, but the yields are low at less than 40%.
There is also an attempt to use an ion exchange resin impregnated with palladium as a catalyst (Japanese Patent Laid-Open No. 61-227548),
Although a yield of over 50% has been obtained by this method, since a large amount of ion exchange resin is used for the reactants,
From the viewpoint of the cost of the ion exchange resin and the prevention of contamination by the eluate from the ion exchange resin, it is necessary to impart a very high degree of durability to the ion exchange resin. Chem. Phe
rm. Bull. , 34 (2) 445-449.
(1986) is a 2-methylnaphthalene in acetic acid solvent,
We report the experimental results when the oxidation reaction with hydrogen peroxide was repeated using a palladium-ion exchange resin catalyst. According to this, the yield of the first time was 60.2%, which was 50.5% at the fourth time, which was about 16% lower, and the result of additional tests by the present inventors showed that the catalyst was repeatedly used for 5-6%. The number of times was the limit. This means that the catalyst cost becomes very large, and industrial adoption is difficult from an economical point of view. Further, when the ion exchange resin is used in a batch reaction apparatus, the ion exchange resin is agitated together with the reaction solution, and therefore the physical strength is required for the ion exchange resin. On the other hand, when a continuous flow reactor is used, this reaction is extremely difficult to remove because it involves a very large amount of heat generation.
Further, in this method, in order to obtain a sufficient conversion rate of 2-methylnaphthalene, a large amount of hydrogen peroxide of 6 times mol or more, that is, 2 times or more of the theoretically necessary amount, relative to 2-methylnaphthalene. Must be used. This not only increases the cost of hydrogen peroxide in the raw material chemical cost, but also causes generation of oxygen gas due to excess hydrogen peroxide and / or accumulation of peroxide in the reaction system, It is likely to increase the risk of ignition and explosion during operational operation.

[0006]

SUMMARY OF THE INVENTION The present invention provides a method for producing 2-methyl-1,4-naphthoquinone by oxidizing 2-methylnaphthalene with an oxidizing agent such as hydrogen peroxide.
Not only to improve the yield from 2-methylnaphthalene, but also to increase the utilization efficiency of oxidizing agents such as hydrogen peroxide,
To make 2-methyl-1,4-naphthoquinone economically and industrially advantageous as compared with the prior art by making the reaction system homogeneous to facilitate heat removal and reducing the catalyst cost. It is intended.

[0007]

The present inventors have surprisingly found that the conventional technique of oxidizing 2-methylnaphthalene with hydrogen peroxide using palladium and an ion exchange resin is unexpectedly replaced with an ion exchange resin. By using a relatively large amount of sulfuric acid, the utilization efficiency of hydrogen peroxide is significantly improved, and 2-methyl-
They have found that 1,4-naphthoquinone can be obtained and have reached the present invention.

That is, according to the present invention, in a solvent containing carboxylic acid in 2-methylnaphthalene, the weight is 5 g to 100 per 1 liter of the palladium compound and the carboxylic acid solvent.
A method for producing 2-methyl-1,4-naphthoquinone, which comprises reacting hydrogen peroxide and / or an organic peracid in the presence of g sulfuric acid.

In the conventionally known method, the conditions similar to those of the present invention are adopted, and the above-mentioned Chem. Phe
rm. Bull. , 34 (2) 445-449.
Describes an example of performing oxidation with hydrogen peroxide using palladium sulfate ( PdSO ₄ ) as a catalyst. In this example, PdSO ₄ was synthesized by mixing palladium acetate ( Pd (OAc) ₂ ) with the corresponding mineral acid, that is, sulfuric acid in acetic acid, and used as it is. It is considered that the amount used is about equimolar to Pd (OAc) _2, and the concentration is significantly lower than the amount specified in the present invention. Further, this document describes that the reaction rate is relatively fast, but does not describe the yield. Also, Chem. Pherm. Bull. ，
34 (11) 4467-4473 includes palladium-
An experimental method for determining the rate equation for the oxidation reaction of naphthalene and methylbenzene with hydrogen peroxide in the presence of an ion exchange resin catalyst is described, which is 4.6 mg for 5 ml of acetic acid (ie for 1 liter of acetic acid). The concentration is 0.92 g), which is also lower than the amount specified in the present invention, and the oxidation reaction is carried out, but the initial rate is only measured and the yield is not described. The inventors of the present invention conducted a comparative experiment in order to confirm the reaction performance of the method described in this document. The results are shown in Comparative Example 7, but neither the conversion nor the selectivity was satisfactory as compared with the results obtained in the present invention. As described above, it is unexpected that not only the reaction rate but also the conversion rate and the selectivity are improved by increasing the amount of sulfuric acid used in the reaction, and especially the utilization efficiency of hydrogen peroxide is improved. Is quite surprising.

The reason why such an improvement in the efficiency of hydrogen peroxide is recognized is not yet clear.

The carboxylic acid used as a solvent in the present invention may be any carboxylic acid which is miscible with the reaction raw materials and sulfuric acid and which is liquid under the reaction conditions. Specific examples thereof include acetic acid, propionic acid, butyric acid, caprylic acid, caproic acid, capric acid, etc., but usually the reaction raw material, product, by-product, sulfuric acid, hydrogen peroxide, generated water, etc. Acetic acid, which has good solubility and is inexpensive, is preferably used.

The carboxylic acid may be used alone or as a mixture with a solvent inert to the reaction.

The palladium compound used in the present invention is preferably one which forms a homogeneous system when added to the reaction system. Specifically, carboxylic acid salts such as palladium acetate and palladium caprylate, halides such as palladium chloride and palladium bromide, acid salts such as palladium sulfate and palladium nitrate, palladium acetylacetonato complex, dichlorobis (triphenylphosphine). Examples thereof include complex compounds such as palladium and tris (dibenzylideneacetone) chloroformdipalladium, and the use of palladium acetate and palladium sulfate is particularly preferable.

If the amount of the palladium compound used is too small, a sufficient effect cannot be obtained in terms of yield and hydrogen peroxide efficiency, and if it is too large, it is not preferable from the economical viewpoint. Therefore, the amount used thereof is generally 25 to 500 mg / liter, preferably 45 to 200 mg / liter, as the amount of palladium with respect to the solvent at the end of the reaction. The sulfuric acid used in the reaction may be concentrated sulfuric acid or a sulfuric acid aqueous solution, or may be added as a carboxylic acid solution.

Sulfuric acid is used in an amount of 5 to 100 g, preferably 15 to 50 g, based on 1 liter of the carboxylic acid solvent . If this amount is too small, a sufficient yield cannot be achieved, and if it is too large, it is not desirable in terms of cost and device corrosion.

Hydrogen peroxide used as an oxidizing agent is usually used in an aqueous solution of 30 to 60% by weight, but 100%
There is no problem in using hydrogen peroxide. Further, as the oxidizing agent, an organic peracid such as peracetic acid or m-chloroperbenzoic acid can be used. These can be used as a pure organic peracid or as a solution in a suitable solvent. Alternatively, hydrogen peroxide may be reacted with a carboxylic acid in advance to form an organic peracid, and this may be used as it is for oxidation. If the amount used is too small, it will not be possible to obtain a sufficient raw material conversion rate, and if it is too large, it will be economically disadvantageous. The rate may decrease. Therefore, the preferable amount of hydrogen peroxide used is 0.5 to 10 mol, and more preferably 1 to 4 mol, per 1 mol of 2-methylnaphthalene. The method of adding hydrogen peroxide is
A predetermined amount may be added to the reaction system at once, or may be added at a constant rate over time. Further, hydrogen peroxide may be added in the form of a mixture with carboxylic acid which is a solvent, or carboxylic acid and sulfuric acid.

If the concentration of the reaction raw material, 2-methylnaphthalene, in the solution is too high, the yield of 2-methyl-1,4-naphthoquinone will be low, and if it is too low, the volumetric efficiency will be poor, which is not practical. Absent. Usually, the concentration of 2-methylnaphthalene is 0.1 to 20 as the charged amount with respect to the final solution amount.
0 g / liter, preferably 1.0 to 100 g /
It is a liter.

The reaction temperature is preferably in the range of 25 ° C to 100 ° C, more preferably 40 to 90 ° C. If the reaction temperature is lower than 25 ° C, the yield will be lowered, and if it exceeds 100 ° C, decomposition of the oxidant will start and its efficiency will be deteriorated. The reaction time is usually about 5 minutes to 8 hours, but can be arbitrarily adjusted depending on the addition rate of hydrogen peroxide, reaction conditions and the like.

The 2-methylnaphthalene used as a reaction raw material in the present invention is industrially produced by a method such as separation from a tar fraction, and can be easily obtained.

2-methyl-obtained by this reaction method
1,4-naphthoquinone can be taken out from the reaction mixture by a generally known method. For example, there is a method in which the reaction solution is concentrated, water is added to the solution, and 2-methyl-1,4-naphthoquinone is precipitated as a solid.

[0021] The catalyst used in this reaction is palladium.
Beam can also be recovered by adding an appropriate post-treatment. Examples of the post-treatment method include a method of precipitating metallic palladium by adding a reducing agent, a method of forming a solution of an appropriate solvent and then adsorbing and collecting the solution.

[0022]

EXAMPLES Next, the present invention will be described in more detail with reference to examples. In the following examples, 2-methylnaphthalene is abbreviated as MN, and 2-methyl-1,4-naphthoquinone is abbreviated as VK3. The conversion rate, selectivity and yield were determined according to the following formulas.

[0023]

[Equation 1]

Example 1 0.7 g (4.92 m) of 2-methylnaphthalene (MN)
mol) and 800 mg of sulfuric acid ( 40 g per 1 liter of acetic acid at the end of the reaction) in 13 ml of acetic acid,
4.0 ml of 0.2% acetic acid solution of palladium acetate was added,
The temperature was raised to 70 ° C. with stirring, and then a mixture of 60% hydrogen peroxide solution 0.7 ml (15.32 mmol) and acetic acid 3.0 ml was added dropwise over 15 minutes. 1 after completion of dropping
After stirring at 70 ° C. for 5 minutes, the reaction solution was cooled and HPL
Raw materials and products were quantified by the C internal standard method. As a result, the conversion rate of 2-methylnaphthalene was 96.2%,
The selectivity of methyl-1,4-naphthoquinone (VK3) is 6
The yield was 7.3% and the yield was 64.7%.

Examples 2 to 6 Reactions were carried out in the same manner as in Example 1 except that the amount of sulfuric acid was changed to the amount shown in Table 1 and the reaction time was set to 1 hour after completion of dropping.
The amount of sulfuric acid and the reaction results are shown in Table 1.

[0026]

[Table 1]

Examples 7 to 8 Using the amount of MN shown in Table 2, 400 mg of sulfuric acid was dissolved in 16 ml of acetic acid, 1.0 ml of 0.2% acetic acid solution of palladium acetate was added, and the mixture was heated to 70 ° C. with stirring. The temperature was raised, and then the amounts of 60% hydrogen peroxide and acetic acid described in Table 2 were added to 3.0
The ml mixture was added dropwise over 15 minutes. After completion of dropping, the mixture is stirred for 1 hour at 70 ° C., then the reaction solution is cooled and
Raw materials and products were quantified by the PLC internal standard method.
Table 2 shows the amount added and the reaction results.

[0028]

[Table 2]

Examples 9-11 0.7 g of MN and 400 mg of sulfuric acid are dissolved in 16 ml of acetic acid, and a 0.2% acetic acid solution of palladium acetate 1.0
ml, and the mixture was heated to a predetermined temperature shown in Table 3 with stirring, and then 0.7 ml of 60% hydrogen peroxide solution and 3.0 ml of acetic acid were added.
The ml mixture was added dropwise over 15 minutes. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hour (2.5 hours for Example 11), the reaction solution was cooled, and raw materials and products were quantified by the HPLC internal standard method. Table 3 shows the reaction temperature and the reaction results.

[0030]

[Table 3]

Examples 12 to 15 MN (0.7 g) and sulfuric acid (400 mg) were dissolved in acetic acid (13 ml), a predetermined amount of a 0.2% acetic acid solution of palladium acetate was added, and acetic acid was further added to adjust the acetic acid amount in the solution to 17 ml.
After that, the temperature was raised to 70 ° C. with stirring, and then a mixture of 60% hydrogen peroxide solution 0.7 ml and acetic acid 3.0 ml was added dropwise over 15 minutes. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hour, cooled, and the raw materials and products were quantified by the HPLC internal standard method. Table 4 shows the amount of palladium acetate added and the reaction results.

[0032]

[Table 4]

Example 16 A reaction was carried out in the same manner as in Example 14 except that 15 μl (8.9 μmol) of a 12% palladium sulfate aqueous solution was used instead of the acetic acid solution of palladium acetate. The reaction results were such that the MN conversion was 89.2% and the VK3 selectivity was 60.3%.

Example 17 Tris (dibenzylideneacetone) chloroform dipalladium (0) 9.5 mg in place of the palladium acetate solution
The reaction was performed in the same manner as in Example 14 except that was used. The reaction results were as follows: MN conversion 92.5%, VK3 selectivity 64.
It was 1%.

Example 18 The reaction was performed in the same manner as in Example 14 except that 6.2 mg of dichlorobis (triphenylphosphine) palladium was used instead of the palladium acetate solution. The reaction results were such that the MN conversion was 92.5% and the VK3 selectivity was 62.5%.

Example 19 A mixture of 1.4 ml of 60% hydrogen peroxide solution, 19.6 ml of acetic acid and 400 mg of sulfuric acid was reacted at 70 ° C. for 30 minutes while stirring. After the reaction, peracetic acid and hydrogen peroxide in the solution were quantified by titration to be 1.24 mol / liter and 0.08 mol / liter, respectively. 10 ml of this peracetic acid solution was used for the reaction. The reaction is MN 0.
7 g and 400 mg of sulfuric acid were dissolved in 20 ml of acetic acid, 1.0 ml of 0.2% acetic acid solution of palladium acetate was added, the temperature was raised to 70 ° C. with stirring, and then the peracetic acid solution 1 was prepared.
0 ml was added dropwise over 15 minutes. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hour, cooled, and the raw materials and products were quantified by the HPLC internal standard method. The reaction results were such that the MN conversion was 79.6% and the VK3 selectivity was 60.8%.

Example 20 The reaction was carried out in the same manner as in Example 4 except that all the acetic acid was replaced with propionic acid. The reaction results were 88.0% MN conversion.
%, VK3 selectivity was 60.3%.

Comparative Example 1 For comparison, the reaction was carried out using only sulfuric acid as a catalyst. The reaction was performed in the same manner as in Example 14 except that palladium acetate was not added and the reaction time was 3 hours. As a result of post-reaction analysis, the conversion rate of MN was 80.0%,
The selectivity of VK3 was 45.6% and the yield was 36.5%.

Comparative Example 2 For comparison, sulfuric acid was not added and the reaction was carried out using only palladium acetate as a catalyst. The reaction was performed in the same manner as in Example 1 except that sulfuric acid was not added and the reaction time was 4 hours. As a result of post-reaction analysis, the conversion rate of MN was 5
7.7%, VK3 selectivity 39.6%, yield 22.
It was 8%.

Comparative Example 3 Catalyst Preparation: Sulfonic Acid Type Ion Exchange Resin (DOWEX
50W-X8, 200-400 mesh) 1 g of acetic acid 1
After immersing in 0 ml and removing the supernatant acetic acid by decantation, 10 ml of acetic acid was added, then 2 mg of palladium acetate was added with stirring, and the mixture was stirred for 5 hours as it was.
After standing overnight, excess acetic acid was removed before use.

Reaction: 10 ml of acetic acid and MN to the above catalyst
0.35 g was added and the temperature was raised to 50 ° C. with stirring to 60%.
0.35 ml of hydrogen peroxide water was added to start the reaction.
After 4 hours, 0.35 ml of 60% aqueous hydrogen peroxide was further added, and the reaction was continued for another 4 hours. After cooling, the reaction solution was analyzed by the HPLC internal standard method to calculate the reaction results. As a result, the MN conversion rate was 75.4% and the VK3 selectivity was 4
The yield was 9.0% and the yield was 36.9%.

The prior art document (Japanese Patent Laid-Open No. 61-22754).
No. 8) describes that a conversion rate of 88.8% and a selectivity rate of 59.0% can be obtained by carrying out the reaction under such conditions. Could not be reproduced.

Comparative Example 4 Comparative Example 3 except that the same catalyst as prepared in Comparative Example 3 was used, the amount of hydrogen peroxide used was only 0.35 ml at the beginning and no additional hydrogen peroxide was added after 4 hours. The reaction was carried out in the same manner as in. As a result, MN conversion rate 42.0%, V
K3 selectivity of 44.2%, VK3 yield of 18.5%,
It was not possible to obtain satisfactory reaction results. This means that about 80% of hydrogen peroxide was consumed in side reactions such as decomposition into oxygen or oxidation of products.

Comparative Examples 5 and 6 The reaction was carried out in the same manner as in Example 4 except that other acid was used instead of sulfuric acid. The type, amount and reaction results of the acid used are shown below.

[0045] Comparative Example 5: Phosphoric acid 800 mg (reaction for 2 hours) … MN conversion rate 64.2%, VK3 selectivity 42.8% Comparative Example 6: Trifluoromethanesulfonic acid 800 mg … MN conversion rate 86.4%, VK3 selectivity 38.9%

Comparative Example 7 The reaction was carried out in the same manner as in Example 2 except that the amount of sulfuric acid was changed to 20 mg. The reaction results are as follows: MN conversion rate 80.9%, V
The K3 selectivity was 48.1%, and the VK3 yield was 38.9%. We couldn't raise enough MN conversion rate, so VK3
The selectivity does not exceed 50%.

[0047]

According to the present invention, the following effects can be obtained. (1) 2-methyl-1,4-naphthoquinone can be obtained with a high selectivity without sacrificing the conversion rate of the raw materials by the one-step reaction. (2) With a theoretically required amount of hydrogen peroxide, a high conversion rate can be obtained, and the efficiency of hydrogen peroxide can be dramatically increased as compared with the conventional method, which is economically and safety advantageous. Two
-Methyl-1,4-naphthoquinone can be prepared. (3) The heat can be easily removed because the reaction can be performed under a homogeneous system and mild conditions. (4) It is economically advantageous because an expensive ion exchange resin that deteriorates in the reaction system is not used.

As described above, according to the present invention, without using a substance having an environmental problem such as a chromium compound,
A method for industrially producing 2-methyl-1,4-naphthoquinone can be provided.

Claims (4)

(57) [Claims] 1. Hydrogen peroxide and / or organic peracid is allowed to act on 2-methylnaphthalene in a solvent containing a carboxylic acid in the presence of 5 to 100 g of sulfuric acid in a weight of 1 liter of a palladium compound and a carboxylic acid solvent. A method for producing 2-methyl-1,4-naphthoquinone, which comprises: 2. The method according to claim 1, wherein the carboxylic acid is a saturated aliphatic carboxylic acid having 8 or less carbon atoms. 3. The production method according to claim 1, wherein the palladium compound is a palladium compound which is soluble in the reaction system. 4. The method according to claim 1, 2 or 3, wherein hydrogen peroxide is used in a ratio of 1 to 4 mol per 1 mol of 2-methylnaphthalene.