JPH08311060A - Brominating agent - Google Patents

Abstract

PURPOSE: To obtain an industrially useful brominating agent, comprising a solution of an aromatic compound containing nitrogen dibromide hydrobromide and an aromatic compound containing nitrogen and capable of more raising the yield and selectivity of the product. CONSTITUTION: A brominating agent is a solution comprising (A) an aromatic compound containing nitrogen dibromide hydrobromide (preferably pyridine dibromide hydrobromide) and (B) an aromatic compound containing nitrogen (preferably pyridine) at >=0.5mol/l concentration of the component (A). Furthermore, the content of the component (B) is preferably >=1mol based on 1mol component (A). When the brominating agent is used for brominating 3- methylthiophene, 2-bromo-3-methylthiophene is selectively obtained and by- products are hardly formed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a brominating agent comprising a highly concentrated solution of a nitrogen-containing aromatic compound dibromide hydrobromide and a brominating method using the brominating agent.

[0002]

2. Description of the Related Art Conventionally, pyridine dibromide hydrobromide has been known as a reagent for selectively monobrominating aromatic amines [Synthetic Communication, 23, 855 (1993).
(Year) etc.]].

[0003]

The bromination reaction with pyridinedibromide hydrobromide is an extremely exothermic reaction, and exothermic suppression is essential for improving the yield and selectivity of the product, but it remains solid. When used, it is difficult to suppress heat generation, resulting in poor yield and selectivity (Comparative Example 1 described later).
reference). Therefore, it is desired to add pyridinedibromide hydrobromide in the form of a solution in order to facilitate suppression of heat generation and improve yield and selectivity. However,
The solubility of pyridinedibromide hydrobromide in organic solvents is extremely low, and the solubility in organic solvents such as dichloromethane and tetrahydrofuran is about 0.04 mol / liter or less. It is hard to say that the concentration is sufficiently high for industrial use. Therefore, an object of the present invention is to provide a high-concentration brominating agent capable of further increasing the yield and selectivity of the product and suitable for industrial use, and a bromination method using the brominating agent. It is in.

[0004]

According to the present invention, the above object is a solution containing a nitrogen-containing aromatic compound dibromide hydrobromide and a nitrogen-containing aromatic compound. The bromide concentration was 0.
It is achieved by providing a brominating agent characterized by being 5 mol / liter or more, and a bromination method using the brominating agent.

Examples of the nitrogen-containing aromatic compound in the brominating agent of the present invention and the nitrogen-containing aromatic compound in the nitrogen-containing aromatic compound dibromide hydrobromide include pyridine, quinoline and isoquinoline. The nitrogen-containing aromatic compound may have a substituent such as an alkyl group such as a methyl group and an ethyl group; a halogen atom such as a chlorine atom and a bromine atom. Examples of the nitrogen-containing aromatic compound dibromide hydrobromide include pyridine dibromide hydrobromide, lutidine dibromide hydrobromide, picoline dibromide hydrobromide, collidine dibromide hydrobromide, chloropyridine dibromide hydrobromide, quinoline dibromide hydrobromide. ,
Examples thereof include isoquinoline dibromide hydrobromide.

The nitrogen-containing aromatic compound dibromide hydrobromide is a product of the Journal of the American Chemical Society.
ociety), 70, 417 (1948), or according to the method.
That is, it is produced by dropping bromine into a mixture of a small excess of hydrobromic acid and a nitrogen-containing aromatic compound, and recrystallizing the obtained solid of the nitrogen-containing aromatic compound dibromide hydrobromide.

The reaction temperature of the reaction for preparing the nitrogen-containing aromatic compound dibromide hydrobromide is preferably in the range of -50 to 50 ° C, more preferably in the range of -20 to 20 ° C. The amount of the nitrogen-containing aromatic compound used is preferably in the range of 2.0 to 5.0 mol, and 2.0 to 3.0, per 1 mol of bromine.
A molar range is more preferred. The amount of hydrobromic acid is
The range of 1.0-2.0 mol is preferable to 1 mol of bromine.

The above reaction is carried out in the presence or absence of a solvent. As the solvent, halogenated hydrocarbon solvents such as dichloromethane, chloroform and dichloroethane; hydrocarbon solvents such as hexane and heptane are used. After the reaction, a solution of the nitrogen-containing aromatic compound dibromide hydrobromide can be obtained by separating the organic layer from the obtained two-layer solution. Crystals of the nitrogen-containing aromatic compound dibromide hydrobromide can be separated from the obtained solution by recrystallization or the like.

In the above reaction using a solvent, when hydrobromic acid or a nitrogen-containing aromatic compound is used in excess, these compounds contained in the separated aqueous layer are mixed with the nitrogen-containing aromatic compound. It can be reused in the preparation of bromide hydrobromide.

The crystals of the nitrogen-containing aromatic compound dibromide hydrobromide thus obtained are dissolved in an organic solvent and used as a solution having a concentration of 0.5 mol / liter or more. The concentration is 0.5 to 3 mol /
The range of liter is more preferable. If the concentration is lower than 0.5 mol / liter, the yield of the product and the selectivity are lowered, which is not preferable. As the organic solvent, it is preferable to use halogenated hydrocarbon solvents such as dichloromethane, chloroform and dichloroethane; hydrocarbon solvents such as hexane and heptane.

A nitrogen-containing aromatic compound dibromide hydrobromide solution having a concentration of 0.5 mol / liter or more is prepared by adding a nitrogen-containing aromatic compound to the solution. By adding a nitrogen-containing aromatic compound,
The solubility of the nitrogen-containing aromatic compound dibromide hydrobromide in an organic solvent is dramatically increased. For example, the solubility of pyridinedibromide hydrobromide in dichloromethane is
It is 0.01 mol / liter or less at room temperature, but when 1 mol of pyridine is added to 1 mol of pyridine dibromide hydrobromide, it becomes about 1 mol / liter,
The concentration is sufficient to withstand industrial use. The content of the nitrogen-containing aromatic compound is preferably 1 mol or more, and more preferably 1 to 10 mol, per 1 mol of the nitrogen-containing aromatic compound dibromide hydrobromide.
A concentration lower than 1 mol is not preferable because the solubility of the nitrogen-containing aromatic compound dibromide hydrobromide is low, and a concentration higher than 10 mol is not preferable because the cost of recovering the nitrogen-containing aromatic compound is high.

When the nitrogen-containing aromatic compound dibromide hydrobromide is prepared using an organic solvent, crystals of the nitrogen-containing aromatic compound dibromide hydrobromide are obtained from the obtained solution of the nitrogen-containing aromatic compound dibromide hydrobromide. It is also possible to prepare a brominating agent by adding a nitrogen-containing aromatic compound to the solution without separating. In such a case, a nitrogen-containing aromatic compound may be added to the solution of the nitrogen-containing aromatic compound dibromide hydrobromide, or before bromine is added dropwise in the step of preparing the nitrogen-containing aromatic compound dibromide hydrobromide. A nitrogen-containing aromatic compound may be added in advance.

Next, the bromination method using the obtained nitrogen-containing aromatic compound dibromide hydrobromide solution will be described. The bromination reaction is performed by adding a nitrogen-containing aromatic compound dibromide hydrobromide solution to the substrate. As the reaction solvent, a halogenated hydrocarbon solvent such as dichloromethane, chloroform or dichloroethane;
It is preferable to use a hydrocarbon solvent such as hexane or heptane. The reaction temperature is preferably -50 to 50 ° C,
The range of −5 to 10 ° C. is more preferable. The amount of the nitrogen-containing aromatic compound dibromide hydrobromide used is preferably in the range of 0.95 to 1.05 mol with respect to 1 mol of the substrate.

After completion of the bromination reaction, a nitrogen-containing aromatic compound hydrobromide is produced. After completion of the reaction, this can be separated by filtration or water extraction and reused for the preparation of the nitrogen-containing aromatic compound dibromide hydrobromide.

The isolation / purification of the brominated product thus obtained from the reaction mixture is carried out in the same manner as that used for the isolation / purification of ordinary organic compounds. For example, water is poured into the reaction mixture, extraction is performed with an organic solvent such as dichloroethane, hexane, etc., the extract is washed with water, an aqueous solution of sodium carbonate, etc., and then concentrated to obtain a crude product, and the crude product is distilled, etc. It is carried out by purifying by.

When the brominating agent of the present invention is used for the bromination of 3-methylthiophene, 2-bromo-3-methylthiophene can be selectively produced, and the dibromide (2,5-dibromo- The production of 3-methylthiophene) is significantly suppressed. The brominating agent of the present invention has a small amount of by-products and a high purity of 2 compared to the dioxane bromine complex conventionally known as a selective brominating agent for 3-methylthiophene.
A method for producing -bromo-3-methylthiophene can be provided (see Comparative Example 2 and Examples below).

[0017]

EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to these examples.

Example 1 A 50 ml three-headed flask equipped with a thermometer, a reflux condenser and a dropping funnel was charged with 2.25 ml of 47% hydrobromic acid and 14 ml of dichloromethane and cooled to 0 ° C. To this, 3.25 ml of pyridine was added dropwise at a rate such that the temperature of the reaction mixture did not exceed 10 ° C, and then the temperature of the reaction mixture was adjusted to 5
1.03 ml of bromine was added dropwise at a rate not exceeding ° C. After completion of dropping, the mixture was stirred at 0 ° C. for 30 minutes, and the organic layer was separated from the obtained two-layer reaction mixture. On the other hand, a 100 ml three-headed flask equipped with a thermometer, a reflux condenser and a dropping funnel was used to
-1.96 g of methylthiophene and dichloromethane 1
8 ml was charged and cooled to 10 ° C., and then the dichloromethane solution prepared above was added dropwise at such a rate that the temperature of the reaction mixture did not exceed 15 ° C. After 1 hour, the obtained yellow-orange slurry was analyzed by gas chromatography and the results are shown in Table 1.

Example 2 A 20-ml three-headed flask equipped with a thermometer, a reflux condenser and a dropping funnel was charged with 2.20 ml of 47% hydrobromic acid and 14 ml of dichloromethane and cooled to 0 ° C. To this, 3.15 ml of pyridine was added dropwise at a rate such that the temperature of the reaction mixture did not exceed 10 ° C, and then the temperature of the reaction mixture was adjusted to 5
1.00 ml of bromine was added dropwise at a rate not exceeding ° C. After completion of dropping, the mixture was stirred at 0 ° C. for 30 minutes, and the organic layer was separated from the obtained two-layer reaction mixture. On the other hand, a 100 ml three-headed flask equipped with a thermometer, a reflux condenser and a dropping funnel was used to
-1.91 g of methylthiophene and dichloromethane 1
8 ml was charged, the mixture was cooled to 0 ° C., and then the dichloromethane solution prepared above was added dropwise at such a rate that the temperature of the reaction mixture did not exceed 5 ° C. After 1 hour, the obtained yellow-orange slurry was analyzed by gas chromatography and the results are shown in Table 1.

Comparative Example 1 3-methylthiophene 1.9 in a 50 ml round bottom flask.
6 g and 15 ml of dichloromethane were charged and 6.40 g of pyridinedibromide hydrobromide obtained by recrystallization from acetic acid was added in 5 batches. After 1 hour, the obtained yellow-orange uniform solution was analyzed by gas chromatography. The results are shown in Table 1.

Comparative Example 2 A 50 ml three-headed flask equipped with a dropping funnel and a thermometer was used.
-Methylthiophene (1.96 g) and 1,4-dioxane (5 ml) were charged, and a solution of bromine (3.20 g) dissolved in 1,4-dioxane (10 ml) was added dropwise. After 1 hour, the obtained red-orange solution was analyzed by gas chromatography and the results are shown in Table 1.

[0022]

[Table 1]

Example 3 500 m equipped with a thermometer, mechanical stirrer and dropping funnel
A 1-liter three-headed flask was charged with 36.7 g of 47% hydrobromic acid and 240 ml of dichloromethane and cooled to 0 ° C. 76.6 g of pyridine was added dropwise to the reaction mixture at a rate such that the temperature of the reaction mixture did not exceed 10 ° C. Then, 20.0 ml of bromine was added dropwise at such a rate that the temperature of the reaction mixture did not exceed 5 ° C. After completion of dropping, the mixture was stirred at 0 ° C. for 30 minutes, and the organic layer was separated from the obtained two-layer reaction mixture. On the other hand, in a 1000 ml three-headed flask equipped with a thermometer, a mechanical stirrer and a dropping funnel, 38.3 g of 3-methylthiophene and 180 ml of dichloromethane were charged and cooled to 0 ° C.
Then, the organic layer previously separated was added dropwise at a rate such that the temperature of the reaction mixture did not exceed 5 ° C. After the addition is complete, continue at 0 ° C for 3
After stirring for 0 minutes, the reaction mixture was washed successively with 200 ml of water, 200 ml of 5% aqueous sodium carbonate solution and 200 ml of water. After distilling off the solvent under normal pressure, the residue was subjected to precision distillation to obtain 59.6 g (84.7%) of 2-bromo-3-methylthiophene as a fraction at 66 to 68 ° C. (20 mmHg).
I got As a result of analysis by gas chromatography, the purity was 99.6%.

[0024]

EFFECTS OF THE INVENTION According to the present invention, there are provided a high-concentration brominating agent capable of further increasing the yield and selectivity of a product and suitable for industrial use, and a bromination method using the brominating agent. To be done.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Manzo Shiono 1 2045 Sakata, Kurashiki City, Okayama Prefecture Kuraray Co., Ltd.

Claims (5)

[Claims] 1. A solution containing a nitrogen-containing aromatic compound dibromide hydrobromide and a nitrogen-containing aromatic compound, wherein the concentration of the nitrogen-containing aromatic compound dibromide hydrobromide is 0.5 mol / liter or more. Characterizing brominating agent. 2. The content of the nitrogen-containing aromatic compound is 1 with respect to 1 mol of the nitrogen-containing aromatic compound dibromide hydrobromide.
The brominating agent according to claim 1, which is in a molar amount or more. 3. The brominating agent according to claim 1, wherein the nitrogen-containing aromatic compound dibromide hydrobromide is pyridine dibromide hydrobromide, and the nitrogen-containing aromatic compound is pyridine. 4. A bromination method using the brominating agent according to any one of claims 1 to 3. 5. A method for producing 2-bromo-3-methylthiophene, which comprises reacting 3-methylthiophene with the brominating agent according to any one of claims 1 to 3.