JP2003012597A - Method for producing monoiodo compound of methyl benzoate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To solve conventional technical difficulties in obtaining the monoiodo compound of methyl benzoate by one step process at low cost in high conversion ratio. SOLUTION: The monoiodo compound of methyl benzoate is produced by directly iodizing methyl benzoate, a raw material, by using an iodizing agent together with an acid catalyst in a solvent.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing a monoiodo form of methylbenzoic acid.

[0002]

2. Description of the Related Art Generally, in the iodination of methylbenzoic acid, direct iodination inevitably produces and contaminates isomers. Due to the difficulty of the subsequent separation step, nitration of methylbenzoic acid is followed by reduction. The corresponding aminomethyl benzoic acid was synthesized and used as the raw material for Sandmeyer (Sa
The main method is a synthetic method utilizing the ndmeyer reaction. Fork
A method of reacting sulfuric acid, sodium nitrite, and iodine with methyl benzoic acid as a raw material in a carbon tetrachloride solvent (J. Indian
Chem. Soc. 1930) or a synthetic method of reacting thallium trifluoroacetate with KI as a catalyst (J. Chem. Soc. 197).
Although there is a description of 4), it was not satisfactory in terms of toxicity, reactivity or handling.

As a method for direct iodination of aromatic compounds, a method using iodine, nitrogen dioxide or nitric acid as an oxidizing agent is known. However, when these are used, there is a problem that an aromatic nitro compound is produced as a by-product, and problems such as separation and purification from isomers and toxicity problems occur.

On the other hand, a method using hydrogen peroxide (Japanese Patent Application Laid-Open No. 6-58242)
3-91336) or a method using persulfate or peracetic acid,
Alternatively, a method using iodine monochloride is also known,
All of these had low yields. Further, a method using a silver salt such as silver sulfate, silver nitrate or silver trifluoroacetate is also known, but it involves a problem that waste liquid treatment is required.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the prior art.

[0006]

The present invention is a method for producing a monoiodo form of methylbenzoic acid by direct iodination of methylbenzoic acid as a raw material with an iodizing agent in a solvent together with an acid catalyst.

In the present invention, iodine, iodide, periodate or periodate can be used as the iodination agent. Further, in the present invention, iodic acid, iodate or a compound thereof can be used as the iodizing agent, and in that case, they can be used in combination with hydrogen peroxide solution.

According to the present invention, in the direct iodination of methylbenzoic acid, the desired monoiodo compound can be selectively and stepwise reacted by reacting iodine with periodate or periodic acid in a solvent using an acid catalyst. It can be synthesized.

In the present invention, the monoiodo compound can be synthesized by using an inexpensive iodate or a combination of iodic acid instead of periodate. In some cases, the monoiodo compound can be selectively synthesized in a short time by using hydrogen peroxide together. However, the starting material, methylbenzoic acid, is not limited to the 2-methylbenzoic acid mentioned in the examples, and this synthetic method is effective even when isomers are used.

The solvent used for the iodination is a halogenated hydrocarbon solvent such as dichloromethane, dichloroethane, trichloroethane, chloroform, tetrachloroethylene, carbon tetrachloride, chlorobenzene, dichlorobenzene, etc., an aromatic nitro compound such as nitrobenzene, nitrotoluene, acetic acid, chlorobenzene. Carboxylic acids such as acetic acid and trifluoroacetic acid are used. Preferred solvents include halogenated hydrocarbons, acetic acid, a mixed solvent of acetic acid and water, and 3 of these solvents.
A mixed solvent of component systems can be used. The amount of the solvent is not particularly limited as long as it can be handled easily, but it is usually used in an amount of 1 to 50 times the amount of methylbenzoic acid.

Paraperiodic acid, orthoperiodic acid or metaperiodic acid, and their salts or solutions can be used as the periodic acid of the iodizing agent. As the iodic acid, iodic acid or salts thereof or a solution thereof can be used. At this time, the reaction can be completed in a short time by using the hydrogen peroxide solution together.

Instead of iodine, iodides such as potassium iodide, sodium iodide and other alkali iodides can be used.

As the catalyst to be used, inorganic acids such as sulfuric acid, nitrosyl sulfuric acid, a mixed acid of sulfuric acid and nitric acid, and organic acids such as p-toluenesulfonic acid are used, but sulfuric acid is inexpensive and a side reaction such as nitration. Is preferable because it does not occur. The amount of the catalyst is 0.01 to 10 with respect to 1 part of methylbenzoic acid.
0 part, preferably 0.05 to 3.0 parts, and more preferably 0.1 to 1.0 parts are used. When the amount of sulfuric acid used is small, iodine easily sublimes, resulting in increased loss. On the other hand, if the amount of sulfuric acid used is too large, not only is there no effect, but it also promotes the oxidation reaction of methylbenzoic acid and side reactions such as the diiodo form.

The reaction is carried out by heating and stirring, but since iodine has a subliming property, it is preferable to carry out the reaction while refluxing the solvent to prevent precipitation. The reaction is completed in 4 to 20 hours depending on the temperature conditions, and the conversion rate to monoiodomethylbenzoic acid does not fall below 90%.

In this reaction, although the conversion rate is high, the solubility of the product is relatively high, so that many of them remain in the solvent, and it is possible to sufficiently increase the yield by recycling the reaction mother liquor. Therefore, recycling is recommended.

Further, as the recrystallization solvent, suitable solvents such as toluene, ethyl acetate, methanol and ethanol can be used alone or in combination, and if necessary, a solvent diluted with water can be used.

[0017]

EXAMPLES The present invention will be described in more detail based on the following examples, but it goes without saying that the present invention is not limited to these examples.

[Example 1] 300 to which a reflux condenser was connected
15 g of 2-methylbenzoic acid, 12 g of iodine, 7.2 g of periodic acid solution (50% solution), 92 ml of acetic acid, 4.7 g of concentrated sulfuric acid were charged into a 3-ml flask with three-necked flask, and the temperature of the oil bath was raised to about 120 ° C. The reaction was conducted for 7 hours under the reflux condition. After cooling to room temperature, the precipitated crystals were filtered off, dissolved with about 500 ml of methylene chloride and washed with 5% hypo,
After washing with 10% sodium carbonate and distilled water, the solvent was dried. Then, the solvent was distilled off under reduced pressure to obtain a solid content.
The crude yield was about 54%, and the purity was measured by HPLC as 2-methylbenzoic acid / 3-iodo-2-methylbenzoic acid / 5-
Iodo 2-methylbenzoic acid = 0.7% / 3.2% / 9
It was 5.7% and diiodo compound was 0.3%.

Example 2 In a 300 ml flask, 2
Methylbenzoic acid 15g, iodine 11.3g, iodic acid solution 18.5g (34% solution), acetic acid 115ml, concentrated sulfuric acid 7
g, and 15 ml of 30% hydrogen peroxide solution at 60 ° C for 3 times
Added over 0 minutes. After the addition was completed, the temperature of the oil bath was raised to about 120 ° C., and the reaction was conducted for 3 hours under reflux conditions. After the iodine color disappeared, the mixture was cooled to room temperature, the precipitated crystals were filtered off, and the same operation as in Example 1 was performed. The crude yield is about 65% and the purity is 2 as measured by HPLC.
・ Methylbenzoic acid / 3 ・ Iodo ・ 2 ・ Methylbenzoic acid /
5-iodo2-methylbenzoic acid = 0.7% / 2.9% /
It was 95.8% and diiodo compound was 0.5%.

Example 3 In a 300 ml flask, 2
Methylbenzoic acid 15g, iodine 11.3g, iodic acid solution 11.2g (34% solution), acetic acid 115ml, concentrated sulfuric acid 6
g, raise the temperature of the oil bath to about 120 ° C,
The reaction was carried out under reflux conditions for 5 hours. Hereinafter, Example 1
The same operation was performed. The crude yield is about 52% and the purity is H
Measured by PLC: 2 · Methylbenzoic acid / 3 · Iodine · 2
・ Methylbenzoic acid / 5 ・ iodo2-methylbenzoic acid =
It was 1.1% / 2.9% / 95.6% and the diiodo form was 0.2%.

Example 4 In a 300 ml flask, 2
Methylbenzoic acid (15 g), iodine (9.7 g), potassium iodate (8.0 g), acetic acid (115 ml) and concentrated sulfuric acid (6.8 g) were added, and 30% hydrogen peroxide solution (15 ml) was added at 60 ° C over 30 minutes. Then, the same operation as in Example 1 was performed.
The crude yield is about 65% and the purity is 2-methylbenzoic acid / 3-
Iodo-2-methylbenzoic acid / 5-iodo2-methylbenzoic acid = 0.4% / 3.7% / 93.7%, and the diiodo form was 1.5%.

Example 5 To the reaction mother liquor of Example 1 were added 15 g of 2-methylbenzoic acid, 12 g of iodine, 7.2 g of a periodic acid solution (50% solution), and a shortage of acetic acid and sulfuric acid. Then, the same operation as in Example 1 was performed. The crude yield increased to about 70%, and the purity was 2-methylbenzoic acid / 3-iodo-2-methylbenzoic acid / 5-iodo2-methylbenzoic acid = 1.4% / 7.4% / 90. At 4%, the diiodo form was 0.5%.

COMPARATIVE EXAMPLE 1 The sulfuric acid of Example 2 was replaced with phosphoric acid 7.8.
When the same reaction was performed except that g (85% liquid) was replaced, sublimation iodine increased, the reactivity deteriorated, and the crude yield drastically decreased to about 21%.

As shown in these Examples, according to the present invention, the methyliodoic acid monoiodo compound (5
-Iodo-2-methylbenzoic acid, 3-iodo-2-methylbenzoic acid) can be obtained at a high conversion rate.

[0025]

INDUSTRIAL APPLICABILITY The present invention has the effect that a monoiodo form of methylbenzoic acid can be obtained from methylbenzoic acid as a raw material in a single step, and has a high conversion rate and a low cost without using a highly toxic amino compound. It has an effect of being able to obtain a monoiodo form of methylbenzoic acid and has an extremely high practical value.

Continued front page    (72) Inventor Akira Aizawa             4017 Ushigome, Shirako-cho, Chosei-gun, Chiba Prefecture Iseka             Gaku Kogyo Co., Ltd. F-term (reference) 4H006 AA02 AC30 BA66 BB17 BC10                       BC34 BE05 BE32 BE53 BJ50                       BM30 BM74 BS30                 4H039 CA54 CD10

Claims (4)

[Claims] 1. A process for producing a monoiodo form of methylbenzoic acid, which comprises direct iodination of methylbenzoic acid as a raw material in a solvent together with an acid catalyst using an iodizing agent. 2. Iodine, iodide,
The method for producing a monoiodo form of methylbenzoic acid according to claim 1, wherein periodate or periodate is used. 3. The method for producing a monoiodo form of methylbenzoic acid according to claim 1, wherein iodic acid, iodate or a compound thereof is used as the iodizing agent. 4. The method for producing a monoiodo form of methylbenzoic acid according to claim 3, wherein iodic acid, iodate or a compound thereof is used in combination with hydrogen peroxide solution.