JPH07126198A - Production of allyl bromides - Google Patents

Abstract

PURPOSE:To obtain an allyl bromide compound useful as an intermediate for pharmaceuticals, agrochemicals, dyes, etc., in high volume efficiency, yield and selectivity by reacting an allyl chloride compound with a metal bromide in the presence of water and a phase-transfer catalyst. CONSTITUTION:The compound of the formula II is produced by slowly adding (A) a metal bromide to a mixture of (B) an allyl chloride compound of the formula I (R, R1 and R2 are H or lower alkyl), (C) water and (D) a phase- transfer catalyst such as quaternary ammonium salt while vigorously stirring the components to effect the reaction of the component B with the component A or by dropping the component C and the component D to a mixture of the component B and the component A or dropping the component C to a mixture of the component B, the component A and the component D while vigorously stirring the components.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing allyl bromides which is useful in the field of synthetic organic chemistry, particularly as an intermediate in the production of fine chemical products such as agricultural drugs and dyes. More specifically, it relates to an improved production method of allyl bromides by a halogen exchange reaction using allyl chlorides as a raw material.

[0002]

2. Description of the Related Art Formula (2) (Formula 3)

[0003]

[Chemical 3]

Various methods have been disclosed as methods for producing allyl bromides represented by the formula (wherein R, R ₁ and R ₂ each independently represent a hydrogen atom or a lower alkyl group). Looking at the known production method for allyl bromide (R = R1 = R2 = H} in the formula (2), which is the basic compound of the formula (2), generally, allyl alcohol is generally added to hydrogen bromide in the presence of sulfuric acid. It is produced by reacting with an acid.

For example, organic synthesis {Or
ganic Synthesis, Coll. , Volume 1,
According to p. 27 (1976)}, 5.9 mol of 48% hydrobromic acid and 4 mol of allyl alcohol are mixed, and 300 g of agricultural sulfuric acid is gradually added to this aqueous solution with stirring, followed by distillation. By doing so, allyl bromide can be obtained. According to this method, the target allyl bromide is 92
Although it can be produced in a quantitatively close yield of up to 96%, a large amount of acid wastewater is industrially generated due to the use of a large amount of sulfuric acid, and an operation such as neutralization treatment is required and the cost increases. It has drawbacks such as

Also known is a method for producing allyl bromide by brominating propylene with hydrogen bromide at a high temperature (350 to 450 ° C.) in the presence of pearlite catalyst (Soviet Patent No. 753,841 (1980)). However, this method not only has a low selectivity to allyl bromide due to by-product of 1-bromopropene, but also has a problem in separation from by-products.

On the other hand, a method for producing allyl bromides by a halogen exchange reaction of allyl chlorides is also known. Journal of the Organic Chemistry {J
o-urnal of the Organic Ce
mystery USSR Volume 10, 1122 (197)
4 years)}, allyl bromide or methallyl bromide is produced by subjecting allyl chloride or methallyl chloride to halogen exchange reaction with excess hydrobromic acid in the presence of cuprous chloride.

[0008] The Journal of the American Chemical Society {Jo-urnal of
the American Chemical Soc
e-ity, vol. 72, p. 4316 (1950)}, methallyl chloride is subjected to halogen exchange reaction with sodium bromide in methanol to give methallyl bromide.
Also disclosed is the method of making methallyl bromide with lithium bromide in acetone.

However, the former method not only has a low conversion rate of methallyl chloride of 70% or less, but requires special attention to wastewater measures because a heavy metal compound subject to industrial regulation is used as a catalyst. And have to. Even with the latter method, the yield of methallyl bromide is only 54%.

Regarding the halogen exchange reaction of an alkyl chloride to an alkyl bromide with a metal bromide using a phase transfer catalyst and water, conventionally, a synthesis {SYNT
H-ESIS 1 Vol. 34-5 (1984)} and Journal of the Chemical Society.
Chemical Communications {Journalof
the Chemical Society Che
medical Co-mmunications, 125
0 (1986)}, the allyl halides of the method of the present invention are reacted with allyl chlorides and metal bromides in the presence of a small amount of water and a phase transfer catalyst. There is no known method for producing bromides.

As a method for producing allyl bromides, some methods other than the above-mentioned methods are known, but none is satisfactory in terms of raw material or yield. The present applicants have previously proposed a method of reacting allyl chlorides with a metal bromide in an aprotic polar solvent to produce the corresponding allyl bromides in good yield (Japanese Patent Laid-Open No. 3-1 / 1993).
69830). However, it cannot be said that the method proposed by the present applicants is a sufficient method from an industrial viewpoint, and it has the following problems.

That is, it is necessary to use an aprotic polar solvent as a reaction solvent, and it is industrially necessary to recover and reuse this reaction solvent. In addition, there is a problem that it is difficult to apply to the production of allyl bromides having the same boiling point as that of the aprotic polar reaction solvent. Therefore, improvement of these problems is required.

[0013]

The present invention has been made in order to solve the problems of the above-mentioned conventional techniques, and is used in the field of synthetic organic chemistry, especially in the production of agricultural drugs and dyes. Formula (2) (Chemical Formula 4) useful as an intermediate

[0014]

[Chemical 4]

For the purpose of providing an improved and more industrial process for producing allyl bromides of the formula: wherein R, R ₁ and R ₂ each independently represent a hydrogen atom or a lower alkyl group. There is.

[0016]

Means for Solving the Problems As a result of intensive studies made by the present inventors to solve the problems of the prior art, based on the findings of the present inventors, allyl halides, especially allyl bromides Although they are compounds that are easily hydrolyzed when heated in the presence of water and easily converted to allyl alcohols, surprisingly, the halogen exchange reaction between allyl chlorides and metal bromides. By the presence of a small amount of water and a phase transfer catalyst, high conversion, it is possible to produce the target allyl bromides with a high yield, and the metal bromide is insoluble in allyl chlorides, In the reaction system in which water and the phase transfer catalyst do not exist, the halogen exchange reaction does not proceed at all.

On the other hand, even in the reaction system to which water is added, when the phase transfer catalyst is not present, a small amount of the allyl bromide is produced, but the conversion rate of the allyl chloride is low. Also, in the presence of a phase transfer catalyst, the conversion rate was similarly low in a reaction system in which water was not present, and it was discovered that a proper range of water content was necessary to obtain a sufficient conversion rate, and so on. As a result of repeating the above, it was previously proposed as a method for producing allyl bromides (Japanese Patent Application No. 5-111326).
However, in the subsequent investigation, depending on the charging method of the raw materials, the metal bromide solidified in the reaction vessel, and it was not possible to obtain a sufficient conversion rate, resulting in a decrease in the yield of the intended allyl bromides. It turns out that there is a problem. As a result of intensive studies, it was found that this solidification was caused by the nonuniform contact of the metal bromide and water in the reaction vessel. Therefore, in order to avoid the solidification of metal bromide, when charging the raw materials, either one of water or metal bromide is thoroughly mixed and stirred with allyl chlorides, while the other is gradually charged. The inventors have found that it is necessary to do so and have completed the present invention.
That is, the present invention uses the formula (1)

[0018]

[Chemical 5]

(In the formula, R, R ₁ and R ₂ each independently represent a hydrogen atom or a lower alkyl group.) While thoroughly mixing and stirring the allyl chlorides with water and a phase transfer catalyst. , Gradually charging the metal bromide therein to react, or while thoroughly mixing and stirring the mixture containing allyl chloride and the metal bromide or the phase transfer catalyst, water and the phase transfer catalyst Formula (2) (Chemical Formula 6) characterized by reacting by adding a mixture or water dropwise

[0020]

[Chemical 6]

(In the formula, R, R ₁ and R ₂ each independently represent a hydrogen atom or a lower alkyl group.).

The method of the present invention is an excellent industrially applicable production method. According to the method of the present invention, allyl chlorides can be reacted with high volumetric efficiency under relatively mild conditions. It is possible, and allyl bromides can be produced with high conversion and high yield. Also, after the reaction, the desired product can be isolated by adding water to the reaction mixture after completion of the reaction to dissolve the inorganic salt, and then obtaining a relatively high-purity allyl bromide only by a liquid separation operation. Highly pure allyl bromides can be obtained by performing distillation purification according to the above.

The allyl bromides obtained by the present invention have a high quality that can be sufficiently used as a useful intermediate for the production of organic synthetic chemistry, particularly agricultural medicine and dyes.
The method of the present invention will be described below.

In the present invention, the allyl chlorides of the formula (1) are used as a raw material. Specifically, allyl chloride, methallyl chloride, γ-methylallyl chloride,
γ, γ-dimethylallyl chloride, β-methyl-γ, γ
-Dimethylallyl chloride, γ-ethyl allyl chloride, γ-n-propyl allyl chloride, γ-isopropyl allyl chloride, γ-n-butyl allyl chloride, γ
-Sec-Butyl allyl chloride, γ-iso-butyl allyl chloride, γ-tertiary butyl allyl chloride and the like can be mentioned.

The metal bromide used as the halogen exchange agent for the allyl chlorides of the formula (1) is not particularly limited as long as it is a metal bromide, and specifically, lithium bromide, sodium bromide, potassium bromide, bromide. Calcium, magnesium bromide, barium bromide, ferrous bromide, ferric bromide, cupric bromide, rubidium bromide and the like can be mentioned, but from the industrial viewpoint, sodium bromide, odor Potassium iodide is preferred.

Although the amount of the metal bromide used is less than the theoretical amount, it will be reacted, but in consideration of the conversion rate of the starting allyl chlorides and the yield of the desired product, allyl bromides, it is usually used in the theoretical amount or more. It is appropriate to do. The upper limit of the amount used is preferably not more than 2 times the molar amount of allyl chloride as a raw material, from the viewpoint of stirring efficiency and economical efficiency.

The method of the present invention is characterized in that the reaction of allyl chlorides and metal bromide is carried out in the presence of a small amount of water and a phase transfer catalyst. If the amount of water added to the reaction system is too small, the reaction progresses remarkably slowly,
On the other hand, if the amount is too large, the yield is lowered. The amount of water used is in the range of 0.1 to 30% by weight, more preferably 0.2 to 20% by weight, and particularly preferably 1 to 15% by weight, based on the allyl chloride as a raw material.

Any type of phase transfer catalyst may be used as long as it is a compound having a property of transferring a bromine anion to an organic phase, such as quaternary ammonium salts, phosphonium salts, macrocyclic polyethers and chain polyethers. The compound (4) is not particularly limited, but quaternary ammonium salts are preferable from the economical point of view. Examples of quaternary ammonium salts include tetrabutylammonium bromide, tetrabutylammonium chloride, tetrahexylammonium bromide, tetrahexylammonium chloride, benzyltributylammonium bromide, benzyltributylammonium chloride, etc., but of course these compounds are not the only examples. It is not something that will be done. The upper limit of the amount of the phase transfer catalyst used is not particularly limited, but the smaller amount is preferable from the economical viewpoint, and the amount is 0.1 to 20% by weight based on the allyl chloride.
Is suitable, and a range of 0.5 to 10% by weight is more preferable.

The specific embodiment of the present invention is as follows. After charging a predetermined amount of a phase transfer catalyst and a predetermined amount of water to 1 mol of allyl chloride, a predetermined amount of metal bromide is gradually charged therein while thoroughly mixing and stirring, or allyl chloride is added. While thoroughly mixing and stirring the chlorides and the metal bromide, a mixture of water and the phase transfer catalyst is added dropwise thereto. After that, the temperature is raised to a predetermined temperature to carry out the reaction while continuing stirring. The reaction temperature is not particularly limited as long as it does not deteriorate the allyl chlorides or allyl bromides, but is preferably 20 to 100.
A range of ° C is suitable. Also, as the reaction method, a method of charging all the raw materials, a phase transfer catalyst and water to react, a method of charging metal bromide in a divided manner to react, a method of reacting while dropping allyl chlorides, etc. , Various methods can be used.

In the present invention, the progress of the reaction can be known by using a means such as gas chromatography. As the method for isolating the allyl bromides produced by the above halogen exchange reaction, after the reaction, the reaction mixture is cooled if necessary, and the amount of the metal chloride by-produced, the residual metal bromide and the phase transfer catalyst is dissolved. Allyl bromides produced by liquid separation are isolated by a very simple method. In the case of obtaining higher-purity allyl bromides, after separation, metal bromide in an amount corresponding to the residual methallyl chloride, a phase transfer catalyst and water are added and subjected to a halogen exchange reaction again, or the above isolation method. The allyl bromides obtained in step 1 can be purified by distillation, or the unreacted allyl chlorides can be distilled off to leave the allyl bromides in the distillation pot. As the method of distillation, either distillation under normal pressure or vacuum distillation can be used. The unreacted allyl chlorides recovered as the initial distillate can be subjected to the halogen exchange reaction again if necessary.

[0031]

The present invention will be described in more detail with reference to the following examples.

Example 1 76.5 g (1.0 mol) of allyl chloride and 3.2 g (10 mmol) of tetrabutylammonium bromide were placed in a 500 ml round-bottomed flask equipped with a cooling condenser.
And 3 g of water were charged. After sufficiently stirring so that the water was uniformly dispersed, 122.4 g (1.2 mol) of sodium bromide was gradually added while continuing stirring. Then, the temperature was raised and the reaction was carried out at 65 ° C for 6 hours. 16 reaction liquids
After cooling to 0 ° C., 300 g of water was added to the reaction solution to dissolve the inorganic salt and the layers were separated to obtain 117.1 g of crude allyl bromide as an oily substance. As a result of analyzing this crude allyl bromide by gas chromatography, the production rate of allyl bromide was 93.3% (vs. allyl chloride), and the raw material allyl chloride was 6.4% (vs. charged allyl chloride). Met. There were almost no by-products other than allyl bromide, and allyl bromide was selectively produced.
The obtained crude allyl bromide was distilled by a distillation apparatus equipped with a rectification column to obtain 105.5 g (purity of 98% or more) of allyl bromide having a boiling point of 70 to 71 ° C. Yield 87.2
% (Vs. allyl chloride). Also, as the first stay,
10.3 g of a mixture of allyl chloride and allyl bromide was obtained.

Example 2 90.6 g (1 mol) of methallyl chloride and 3.2 g (10 mmol) of tetrabutylammonium bromide were placed in a 500 ml round bottom flask equipped with a cooling condenser.
And 5 g of water were charged. After sufficiently stirring the water so that it is uniformly dispersed, sodium bromide 12
2.4 g (1.2 mol) was added slowly. After that, the temperature was raised and the reaction was carried out at 65 ° C. for 6 hours. After cooling the reaction solution, 300 g of water was added to the reaction solution to dissolve the inorganic salt and the layers were separated to obtain 131.4 g of crude methallyl bromide as an oil. When this crude methallyl bromide was analyzed by gas chromatography, the production rate of methallyl bromide was 94.1% (vs. methallyl chloride), and the raw material methallyl chloride was 5.5% (vs. charged methallyl chloride). It remains as ril chloride). There were almost no byproducts other than methallyl bromide, and methallyl bromide was selectively produced. The crude methallyl bromide obtained was distilled under reduced pressure of 200 mmHg by a distillation apparatus equipped with a rectification column,
Methallyl bromide having a boiling point of 52.0 to 53.0 ° C. 118.
9 g (purity of 98% or more) was obtained. Yield 88.1% (vs methallyl chloride).

Example 3 90.6 g (1 mol) of methallyl chloride and 3.2 g (10 mmol) of tetrabutylammonium bromide were placed in a 500 ml round-bottomed flask equipped with a cooling condenser.
Then, 122.4 g (1.2 mol) of sodium bromide was charged, and 5 g of water was slowly added dropwise thereto while being sufficiently mixed and stirred so as to be homogeneous. Then the temperature is raised to 6
The reaction was carried out at 5 ° C for 6 hours. After cooling the reaction solution, 300 g of water was added to the reaction solution to dissolve the inorganic salt,
The layers were separated to obtain 131.0 g of crude methallyl bromide as an oily substance. When the crude methallyl bromide was analyzed by gas chromatography, the production rate of methallyl bromide was 94.0% (vs methallyl chloride), and the raw material methallyl chloride was 5.6% (vs. the charged methallyl bromide). It remains as ril chloride).

Comparative Example 1 (Reaction under the condition that water was not added) Sodium bromide (24.5 g, 0.24 mol) and methallyl chloride (18.0 g, 0.2) were placed in a 100 ml round bottom flask equipped with a cooling condenser. Mol) and 0.6 g (1.9 mmol) of tetrabutylammonium bromide, and then the reaction was carried out at 65 ° C. for 6 hours while stirring. After cooling the reaction solution, 60 g of water was added to the reaction solution,
When an oily substance obtained by dissolving the inorganic salt and separating the liquid was analyzed by gas chromatography, the production rate of methallyl bromide was 6.4% (versus methallyl chloride).

Comparative Example 2 (Reaction under the condition that no phase transfer catalyst was added) 24.5 g (0.24 mol) of sodium bromide and 18.0 g (0) of methallyl chloride were placed in a 100 ml round bottom flask equipped with a cooling condenser. .2 mol) and water 1.0
After charging g, the reaction was carried out at 65 ° C. for 6 hours while stirring. After cooling the reaction solution, 60 g of water was added to the reaction solution to dissolve the inorganic salt, and the oil obtained by liquid separation was analyzed by gas chromatography to find that the yield of methallyl bromide was 0.68%. (Against methallyl chloride)
Met.

Comparative Example 3 In a 500 ml round-bottomed flask equipped with a cooling condenser, 122.4 g (1.2 mol) of sodium bromide, 90.6 g (1 mol) of methallyl chloride and 3.2 g of tetrabutylammonium bromide ( (10 mmol), and then 5 g of water was charged with gentle stirring. At the end of the water injection, some sodium bromide was observed to be solidified. After that, the temperature was raised with continuing stirring to carry out a reaction at 65 ° C. for 6 hours. The solidified sodium bromide remained in the same state during the reaction. After cooling the reaction solution, 300 g of water was added to the reaction solution and the layers were separated to obtain 106.5 g of crude methallyl bromide as an oily substance.
When this crude methallyl bromide was analyzed by gas chromatography, the production rate of methallyl bromide was 5
It was 1.7% (vs. methallyl chloride), and the raw material methallyl chloride was 47.1% (vs. charged methallyl chloride).

Examples 4 to 6 In Examples 4 to 6, the amount of water added to the reaction was examined. The other reaction conditions were the same as in Example 2. The results are shown in Table 1 (Table 1).

[0039]

[Table 1]

Examples 7 to 8 The types of metal bromide added to the reaction in Examples 7 to 8 were examined. The other reaction conditions were the same as in Example 2. The results are shown in Table 2 (Table 2).

[0041]

[Table 2]

Examples 9 to 10 The types of allyl chloride used in the reaction in Examples 9 to 10 were examined. The other reaction conditions were the same as in Example 2. The results are shown in Table 3 (Table 3).

[0043]

[Table 3]

[0044]

INDUSTRIAL APPLICABILITY According to the method of the present invention, allyl chlorides are used as raw materials, and the desired allyl bromides are efficiently produced in high volume efficiency under mild conditions with high volume efficiency without using a solvent. Can be converted to. Moreover, since the reaction selectivity is high, the isolation method is
Only the liquid separation operation with water is sufficient. When obtaining higher-purity allyl bromides, it is only necessary to remove residual allyl chlorides by distillation under mild conditions, and isolation and purification are easy. Further, there is an advantage that the mixture of residual allyl chloride and allyl bromide obtained by distillation can be used as it is as a raw material for the halogen exchange reaction. Therefore, the present invention is an industrially valuable method for producing allyl bromides, which are useful synthetic intermediates in the field of synthetic organic chemistry, particularly agricultural medicine and dyes.

[Procedure amendment]

[Submission date] December 10, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] 0025

[Correction method] Change

[Correction content]

The metal bromide used as the halogen exchange agent for the allyl chlorides of the formula (1) is not particularly limited as long as it is a metal bromide, and specifically, lithium bromide, sodium bromide, potassium bromide, bromide. Calcium, magnesium bromide, barium bromide, ferrous bromide, ferric bromide, cupric bromide, rubidium bromide and the like can be mentioned, but sodium bromide is preferred from the industrial viewpoint. .

[Procedure Amendment 2]

[Document name to be amended] Statement

[Name of item to be corrected] 0027

[Correction method] Change

[Correction content]

The method of the present invention is characterized in that the reaction of allyl chlorides and metal bromide is carried out in the presence of a small amount of water and a phase transfer catalyst. If the amount of water added to the reaction system is too small, the reaction progresses remarkably slowly,
On the other hand, if the amount is too large, the yield is lowered. The amount of water used is in the range of 0.1 to 30% by weight, preferably 0.5 to 20% by weight, particularly preferably 2 with respect to the raw material allyl chloride.
Is in the range of 15% by weight.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0041

[Correction method] Change

[Correction content]

[0041]

[Table 2]

Claims (2)

[Claims] 1. Formula (1) (Formula 1) (Wherein R, R ₁ and R ₂ each independently represents a hydrogen atom or a lower alkyl group), while thoroughly mixing and stirring water and a phase transfer catalyst, Gradually react with a metal bromide, or while thoroughly mixing and stirring a mixture of allyl chlorides and a metal bromide or a phase transfer catalyst, a mixture of water and a phase transfer catalyst therein, or , (2) (Chemical Formula 2) characterized by reacting by dropping water (In the formula, R, R ₁ and R ₂ each independently represent a hydrogen atom or a lower alkyl group.) A method for producing an allyl bromide. 2. Water is added in an amount of 0.1 to allyl chlorides.
The method according to claim 1, which is used in the range of 30% by weight.