JP4183461B2 - Process for producing 6-bromo-2-naphthalenecarboxylic acid - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing high-purity 6-bromo-2-naphthalenecarboxylic acid, which is suitable as an intermediate material for pharmaceuticals and agricultural chemicals, in a high yield under mild conditions.
[0002]
[Prior art]
In Japanese Patent Application Laid-Open No. Hei 10-195018, the applicant applied molecular oxygen in the presence of an oxidation catalyst comprising a heavy metal compound and a bromine compound in a solvent containing a lower aliphatic carboxylic acid. Discloses a process for producing 6-bromo-2-naphthalenecarboxylic acid by oxidation. 6-Bromo-2-naphthalenecarboxylic acid is then used as a raw material for pharmaceuticals and agricultural chemicals as a methyl ester.
[0003]
When the above methyl ester is used as these raw materials, mixing of impurities is disliked, and therefore, as high purity as possible as 6-bromo-2-naphthalenecarboxylic acid as the raw material is desired. However, when 6-bromo-2-naphthalenecarboxylic acid is produced under the conditions specifically described in the above publication, there is a problem that a non-negligible amount of impurities are generated and the purification thereof is not easy. That is, in the above publication, it is recommended to adopt a reaction temperature of 120 to 200 ° C. and a reaction pressure of 10 to 30 kg / cm ² (0.98 to 2.94 MPa) as suitable conditions for the oxidation reaction. The reaction conditions of 175 ° C. and 30 kg / cm ² are employed. Such reaction conditions were certainly satisfactory from the viewpoint of productivity, but the purity of the product obtained was not so high, and it was necessary to carry out advanced purification treatment for high purity. . In addition, since the reaction is performed under high pressure, a special material facility is required, which increases the cost.
[0004]
[Problems to be solved by the invention]
The present inventor considers that purification of 6-bromo-2-naphthalenecarboxylic acid recovered from the reaction solution obtained by the oxidation reaction as described above is not easy, and relaxes restrictions on apparatus materials. In order to reduce the cost, the inventors examined the method for producing 6-bromo-2-naphthalenecarboxylic acid with few impurities in high yield by devising the oxidation conditions. First, by adopting reaction conditions at lower temperature and lower pressure than recommended by the above proposal, it is possible to produce 6-bromo-2-naphthalenecarboxylic acid with high purity without any special purification. However, it was a big problem that the reaction yield was lowered. Therefore, as a result of further investigation, high-purity 6-bromo-2-naphthalenecarboxylic acid was obtained by oxidizing 6-bromo-2-methylnaphthalene under the conditions of addition of acetic anhydride, preferably under mild temperature and pressure conditions. It came to discover that an acid can be manufactured with a high yield. Accordingly, an object of the present invention is to oxidize 6-bromo-2-methylnaphthalene with molecular oxygen in the presence of an oxidation catalyst to produce highly pure 6-bromo-2-naphthalenecarboxylic acid industrially advantageously. It is to provide a method.
[0005]
[Means for Solving the Problems]
That is, the present invention relates to a molecular form of 6-bromo-2-methylnaphthalene in a solvent containing a lower aliphatic carboxylic acid having 1 to 4 carbon atoms in the presence of an oxidation catalyst composed of a heavy metal compound and a bromine compound and acetic anhydride. It is a method for producing 6-bromo-2-naphthalenecarboxylic acid, wherein a reaction product oxidized by oxygen is cooled to separate a precipitate .
[0006]
DETAILED DESCRIPTION OF THE INVENTION
6-Bromo-2-methylnaphthalene used as a raw material of the present invention can be preferably obtained by bromination of 6-hydroxy-2-methylnaphthalene, as described in the above publication, It is not limited and may be manufactured by any manufacturing method.
[0007]
The solvent containing the lower aliphatic carboxylic acid having 1 to 4 carbon atoms used as the solvent may be composed only of the lower aliphatic carboxylic acid having 1 to 4 carbon atoms , and the lower aliphatic carboxylic acid is mainly used. It may be a mixed solvent in which other components that do not adversely affect the reaction are mixed. Examples of the lower aliphatic carboxylic acid having 1 to 4 carbon atoms include formic acid, acetic acid, propionic acid, butyric acid, and a mixture thereof, and the use of acetic acid is particularly preferable. The amount of the solvent used is preferably 10 to 40 times by weight, particularly 15 to 30 times by weight, based on the raw material 6-bromo-2-methylnaphthalene.
[0008]
The oxidation catalyst comprising a heavy metal compound and a bromine compound used in the present invention is generally a combination of a heavy metal compound and a bromine compound as already known, but in the case of using bromide as the heavy metal compound. Can also be used alone. As the heavy metal compound, a metal compound that dissolves in the reaction system is preferable, and specifically, carboxylates of heavy metals such as cobalt, manganese, cerium, for example, acetate, propionate, naphthenate, carbonate, bromide, A hydroxide etc. can be mentioned. In these, it is preferable to use a cobalt compound or to use a cobalt compound and a manganese compound together, and as a compound, use of acetate and bromide is preferable. The bromine compound may be any compound that dissolves in the reaction system and generates bromine ions. For example, inorganic compounds such as alkali metal bromide, alkaline earth metal bromide, hydrogen bromide, hydrobromic acid, etc. Examples of the bromine compound include organic bromine compounds such as ethyl bromide and bromoacetic acid. Inorganic bromine compounds are particularly preferred.
[0009]
The heavy metal compound in the oxidation catalyst is 0.03 to 2.0 times mol, especially 0 in the case of a cobalt compound or a mixture of a cobalt compound and a manganese compound with respect to 6-bromo-2-methylnaphthalene which is an oxidation raw material on a heavy metal basis. It is preferably used in the range of 1 to 1.0 mole. Moreover, when using a cobalt compound and a manganese compound together, it is preferable to use it in the ratio from which Co / Mn (atomic ratio) will be 0.1-100, especially 0.3-3. The amount of bromine compound used is 0.015 to 2.0 times mol, particularly 0.05 to 0.5 times mol, based on bromine (Br), relative to the raw material 6-bromo-2-methylnaphthalene. It is preferred to use.
[0010]
In the oxidation reaction of the present invention, acetic anhydride is added. A suitable addition amount of acetic anhydride is 0.01 to 10 times mol, particularly 0.1 to 2.0 times mol for the raw material 6-bromo-2-methylnaphthalene. The addition of acetic anhydride makes it possible to produce 6-bromo-2-naphthalenecarboxylic acid with high yield and high purity at a mild reaction temperature and pressure.
[0011]
The oxidation reaction of the present invention comprises a solvent comprising the above-mentioned lower aliphatic carboxylic acid having 1 to 4 carbon atoms , raw material 6-bromo-2-methylnaphthalene, an oxidation catalyst comprising a heavy metal compound and a bromine compound, and acetic anhydride. This is done by blowing molecular oxygen into the chamber. Examples of the gas containing molecular oxygen include air, pure oxygen, a mixture of oxygen and an inert gas in an arbitrary ratio, and the use of air is preferred industrially.
[0012]
The oxidation reaction may employ any system such as a batch system, a semi-batch system, or a continuous system. The temperature of the oxidation reaction is preferably in the range of 80 to 120 ° C., particularly 95 to 115 ° C., and the reaction pressure is preferably 0.098 to 0.98 MPa, particularly preferably 0.098 to 0.48 MPa. By adopting such mild conditions, 6-bromo-2-naphthalenecarboxylic acid with few impurities can be easily produced. Since 6-bromo-2-naphthalenecarboxylic acid can be precipitated by cooling the reaction solution obtained by the oxidation reaction to room temperature, 6-bromo-2-naphthalenecarboxylic acid having a high purity can be obtained by filtering it off. Can be recovered. The heavy metal catalyst in the filtrate can be recovered and reused.
[0013]
【Example】
[Example 1]
In a 500 ml glass container equipped with a reflux condenser, a gas blowing tube and a discharge tube, a temperature measuring tube and a magnetic stirrer, 210 g (3.5 mol) of acetic acid and 1.66 g (6.66 mmol) of cobalt acetate tetrahydrate Manganese acetate tetrahydrate 1.65 g (6.73 mmol), potassium bromide 1.06 g (8.91 mmol), 6-bromo-2-methylnaphthalene 10.0 g (45.2 mmol) and acetic anhydride 5 .2 g (51.0 mmol) was charged, the mixture was kept at 110 ° C., and the reaction was carried out for 8 hours while stirring and blowing air at a rate of 0.2 liters / minute under normal pressure.
[0014]
After completion of the reaction, the reaction solution was cooled to 30 ° C., and the precipitate was separated by filtration and dried to obtain 9.1 g of 6-bromo-2-naphthalenecarboxylic acid having a purity of 99.1%. Combined with the analysis result of 6-bromo-2-naphthalenecarboxylic acid dissolved in the filtrate, the yield of 6-bromo-2-naphthalenecarboxylic acid based on 6-bromo-2-methylnaphthalene was 88.5 mol%. Met.
[0015]
[Example 2]
The reaction was performed in the same manner as in Example 1 except that the oxidant air was changed to pure oxygen and the reaction time was 4.5 hours. After completion of the reaction, the reaction solution was cooled to 30 ° C., and the precipitate was filtered and dried to obtain 8.3 g of 6-bromo-2-naphthalenecarboxylic acid having a purity of 99.2%. Combined with the analysis result of 6-bromo-2-naphthalenecarboxylic acid dissolved in the filtrate, the yield of 6-bromo-2-naphthalenecarboxylic acid based on 6-bromo-2-methylnaphthalene was 96.0 mol%. Met.
[0016]
[Comparative Example 1]
210 g (3.5 mol) of acetic acid, 3.34 g (13.4 mmol) of cobalt acetate tetrahydrate, 3.30 g (13.5 mmol) of manganese acetate tetrahydrate, 2.12 g (17.8 mmol) of potassium bromide ) And 20.0 g (90.4 mmol) of 6-bromo-2-methylnaphthalene, the mixture is kept at a temperature of 150 ° C., and compressed air is supplied at a pressure of 2.94 MPa with stirring at 1.0 liter / min. The reaction was carried out for 30 minutes while blowing at a rate of. After completion of the reaction, the reaction solution was cooled to 30 ° C., and the precipitate was filtered and dried to obtain 20.14 g of 6-bromo-2-naphthalenecarboxylic acid having a purity of 97.6%. Although purification was attempted by dissolving this 6-bromo-2-naphthalenecarboxylic acid in an aqueous alkali solution and acidifying it, the purity was not improved. Combined with the analysis result of 6-bromo-2-naphthalenecarboxylic acid dissolved in the filtrate, the yield of 6-bromo-2-naphthalenecarboxylic acid with respect to 6-bromo-2-methylnaphthalene was 92.4 mol%. It was .
[0017]
【The invention's effect】
According to the present invention, high-purity 6-bromo-2-naphthalenecarboxylic acid useful as a pharmaceutical intermediate can be produced in high yield.

Claims (1)

A reaction in which 6-bromo-2-methylnaphthalene is oxidized with molecular oxygen in a solvent containing a lower aliphatic carboxylic acid having 1 to 4 carbon atoms in the presence of an oxidation catalyst composed of a heavy metal compound and a bromine compound and acetic anhydride. A method for producing 6-bromo-2-naphthalenecarboxylic acid, wherein the precipitate is separated by cooling the product .