JPWO2006064897A1 - Method for producing 2-alkoxyethyl bromide - Google Patents

Abstract

The present invention provides 2-alkoxyethanol and thionyl bromide in the presence of a compound having one or more amide bonds or urea bonds in the molecule in an amount of 0.8 equivalent mole or more per mole of 2-alkoxyethanol. And a process for producing 2-alkoxyethyl bromide. According to the present invention, high-purity 2-alkoxyethyl bromide can be produced in high yield while suppressing by-product impurities.

Description

  The present invention relates to a process for producing 2-alkoxyethyl bromide using thionyl bromide.

  2-Alkoxyethyl bromide is expected to increase its use in various industrial raw materials, particularly pharmaceutical intermediates, raw materials for electrolyte compounds of electric devices and raw materials for liquid crystal compounds of liquid crystal display elements, and polymer modifiers. .

  2-Alkoxyethyl bromide has been conventionally synthesized by the following method.

  Bulletin of the Chemical Society of Japan, Vol. 50 (9), P2271-2282 (1977) (Reference 1) discloses a two-step process for obtaining 2-alkoxyethyl bromide by chlorination of 2-alkoxyethanol and then halogen exchange reaction with sodium bromide. Are listed. There is no description of the yield in this document.

  Journal of American Chemical Society, Vol. 67, P290-293 (1945) (Document 2) describes a method of obtaining 2-methoxyethyl bromide by allowing dimethyl sulfate to act on ethylene bromohydrin.

  Journal of Organic Chemistry, Vol. 27, P807-814 (1962) (reference 3) describes a method of obtaining 2-methoxyethyl bromide by reacting 2-methoxyethanol with phosphorus tribromide.

  Chemical Abstracts, Vol. 58, P3308 (reference 4) and ORGANIC SYNTHESIS COLLECTIVE, VOLUME 3, P370-371 (reference 5), there is a method of obtaining 2-methoxyethyl bromide by allowing phosphorus tribromide to act on 2-methoxyethanol in pyridine. Are listed.

  All of the above-described conventional production methods have disadvantages such as low yield of the target product and generation of by-products, resulting in failure to obtain a high-purity product, which is not preferable as an industrial production method. .

  For example, the yield is 48% in the method described in Reference 2, 29% in the method described in Reference 3, 56% in the method described in Reference 4, and 56 to 66% in the method described in Reference 5. In any production method, a satisfactory yield as an industrial production method cannot be obtained.

  Moreover, although there is no description regarding the purity of a target object in the literatures 1-4, since the impurity produces | generates by the method as described in these literatures, it is difficult to obtain 2-alkoxyethyl bromide of high purity. For example, in the method described in Document 3, since 11 to 12% of ethyl bromide is generated as an impurity, purity and yield are low. Also, by-products such as ethyl bromide are not preferable in the environment.

  On the other hand, a method for bromination or chlorination by allowing bromide or thionyl chloride to act on alcohol in the presence of a catalytic amount of DMF has been known.

  Tetrahedron Letters, 41 (2000) P3011-1014 (Reference 6) discloses a method for obtaining β-aminobromide in a high yield by reacting thionyl bromide with β-aminoalcohol in the presence of a catalytic amount of DMF. Are listed. This document reports that the presence of amino groups in the reaction substrate contributes to bromination.

  In JP-A-61-238750 (Reference 7), thionyl chloride is allowed to act on a terminal alcohol of a polyoxyethylene chain in the presence of a catalytic amount (0.1 to 5% by weight with respect to the alcohol) of DMF. A method for chlorination is described. There is no description of the yield in this document.

  In these production methods, bromide or thionyl chloride is allowed to act in the presence of a catalytic amount of DMF. Surprisingly, the reaction conditions in these production methods are as follows. Even if it is applied to bromination, a satisfactory yield as an industrial production method cannot be obtained.

  Thus, until now, there is no known method for obtaining 2-alkoxyethyl bromide with high yield and high purity by suppressing the formation of by-products. In fact, the purity of available 2-methoxyethyl bromide is as low as 92% by gas chromatography and contains many impurities.

  Accordingly, an object of the present invention is to provide a method for producing 2-alkoxyethyl bromide with higher yield and purity than conventional.

  As a result of intensive studies, the present inventors brominated 2-alkoxyethanol using thionyl bromide in the presence of a compound having a specific amount of amide bond or urea bond in the molecule, The present inventors have solved the above problems and found that 2-alkoxyethyl bromide can be obtained with high quality and high yield without producing impurities, and have reached the present invention.

式中、
Ｒは、炭素数１〜２０の直鎖または分岐鎖のアルキル基及び炭素数３〜２０のシクロアルキル基からなる群から選択した基を表わし、ここで、これらの基は、１以上のハロゲン原子で置換されていてもよく、
Ｘは、酸素原子を表し、
Ｒ_１及びＲ_２は、それぞれ独立して、水素、メチル、エチル、プロピル、ｎ−プロピル、ｉ−プロピル、ｎ−ブチル、ｉ−ブチル、ｓ−ブチル、ｔ−ブチル、ｎ−アミル、ｉ−アミル、ｎ−ヘキシル、ネオヘキシル、ｎ−ヘプチル、２−エチルヘキシル、ｎ−オクチル、ｉ−オクチル、ｓ−オクチル、ｔ−オクチル、シクロプロピル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル、ビシクロプロピル、シクロデシル、ノルボルニル、アダマンチルからなる群から選択される基を表す、
で示される２−アルコキシエタノールと臭化チオニルとを、前記２−アルコキシエタノール１モルに対し０．８等量モル以上の、１種以上のアミド結合または尿素結合を分子内に持つ化合物の存在下に、反応させることを含む、一般式（２）：

式中、Ｒ、Ｘ、Ｒ_１及びＲ_２は、一般式（１）におけるものと同義である、
で示される２−アルコキシエチルブロマイドの製造方法である。The present invention relates to a general formula (1):

Where
R represents a group selected from the group consisting of a linear or branched alkyl group having 1 to 20 carbon atoms and a cycloalkyl group having 3 to 20 carbon atoms, wherein these groups are one or more halogen atoms. May be replaced with
X represents an oxygen atom,
R ₁ and R ₂ are each independently hydrogen, methyl, ethyl, propyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-amyl, i- Amyl, n-hexyl, neohexyl, n-heptyl, 2-ethylhexyl, n-octyl, i-octyl, s-octyl, t-octyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopropyl, cyclodecyl, Represents a group selected from the group consisting of norbornyl and adamantyl,
In the presence of a compound having one or more amide bonds or urea bonds in the molecule in an amount of 0.8 equivalent mole or more of 2-alkoxyethanol and thionyl bromide represented by And reacting with general formula (2):

In the formula, R, X, R ₁ and R ₂ have the same meaning as in general formula (1).
It is a manufacturing method of 2-alkoxyethyl bromide shown by these.

  The present invention can produce a high-purity 2-alkoxyethyl bromide in a high yield by suppressing the by-product of impurities by coexisting a compound having a specific amount of an amide bond or urea bond in the molecule during the reaction. It is characterized by that. When 2-alkoxyethanol and thionyl bromide are reacted in the absence of a compound having an amide bond or urea bond in the molecule, or in the presence of a small amount called a so-called catalytic amount, acetaldehyde or 1,2 -A large amount of impurities such as dibromoethane are by-produced to reduce the yield of the target 2-alkoxyethyl bromide (for example, 20%) as well as the purity (for example, 75%). Highly pure 2-alkoxyethyl bromide cannot be obtained in a yield.

  In the general formulas (1) and (2), R represents a group selected from the group consisting of a linear or branched alkyl group having 1 to 20 carbon atoms and a cycloalkyl group having 3 to 20 carbon atoms. These groups may be substituted with one or more halogen atoms.

  Examples of the linear or branched alkyl group having 1 to 20 carbon atoms include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-amyl, i-amyl, n-hexyl, neohexyl, n-heptyl, 2-ethylhexyl, n-octyl, i-octyl, s-octyl, t-octyl, n-nonyl, n-decyl, n-lauryl, myristyl, cetyl, Examples include stearyl and icosyl, and methyl, ethyl and i-propyl are preferable.

  Examples of the cycloalkyl group having 3 to 20 carbon atoms include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopropyl, cyclodecyl, norbornyl, and adamantyl, and cyclopentyl and cyclohexyl are preferable.

  The above alkyl group and cycloalkyl group may be substituted with one or more halogen atoms (for example, chlorine, bromine, iodine, fluorine).

  R preferably represents an alkyl group having 1 to 8 carbon atoms, and particularly preferably a methyl group or an ethyl group.

  X in the general formulas (1) and (2) is an oxygen atom.

R ₁ and R ₂ in the general formulas (1) and (2) are each independently hydrogen, methyl, ethyl, propyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-amyl, i-amyl, n-hexyl, neohexyl, n-heptyl, 2-ethylhexyl, n-octyl, i-octyl, s-octyl, t-octyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclo A group selected from the group consisting of heptyl, cyclooctyl, bicyclopropyl, cyclodecyl, norbornyl and adamantyl. R ₁ and R ₂ are preferably hydrogen, methyl or ethyl, and particularly preferably hydrogen.

  As 2-alkoxyethanol represented by the general formula (1), 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, 2-butoxyethanol, 2-hexyloxyethanol, 2-ethylhexyloxyethanol, chloroethoxyethanol, Bromoethoxyethanol and the like are preferable, and these are industrially produced and easily available compounds.

  Thionyl bromide can be easily produced by reacting thionyl chloride with hydrogen bromide. The amount of thionyl bromide to be used is 0.8-5 equivalent moles, preferably 0.9-2 equivalent moles relative to 1 mole of the compound represented by the general formula (I).

  The compound having an amide bond or urea bond in the molecule of the present invention is limited as long as it has at least one amide group (—CO—N <) or urea bond (> N—CO—N <) in the molecule. Specifically, acetamide, acrylamide, N, N-dimethylformamide, N, N-dimethylacetamide, N, N-diethylacetamide, N, N-diisopropylacetamide, 2-pyrrolidone, 1-methyl-2- Pyrrolidone, N, N-dimethylpropanamide, 2-cyano-N, N-dimethylacetamide, 1-methyl-2-piperidinone, 1-butyrylaziridine, 1-isobutyrylaziridine, 1-ethyl-2-pyrrolidinone, 1,5-dimethylpyrrolidinone, N, N, 2-trimethylpropionamide, 3-methyluracil, ε-ca Loractam, N-methylcaprolactam, 3-ethyl-2,4-imidazolidinone, 1-acetylimidazolidinone, 4-acetylmorpholine, N, N-diethylpropanamide, N, N-dimethylpentanamide, 3-methyl 2-thioxo-4-imidazolidinone, 1-acetyl-4-piperidinone, 1-acetylazepane, 1-acetyl-3-methylpiperidine, 1-butyl-2-pyrrolidine, 1-acetyl-4-methylpiperidine 1,4-dimethyl-2,5-piperazinedione, 1-ethyl-2,3-piperazinedione, 3,5,5-trimethyl-1,3-oxaziridine-2,4-dione, N, N, N ', N'-tetramethylethanediamide, 1,3-dimethyl-2-thioxo-4-imidazolidinone, 1-methyloxyindo 2-methyl-1-oxyindolinone, N, N-dimethylbenzamide, N-methylacetanilide, 1-acetyl-2-pyrrolidinecarboxamide, acetylpiperidine, urea, N, N-dimethylurea, 1 , 3-dimethylimidazolidinone, more preferably 2-pyrrolidone, N-methylpyrrolidone, acetamide, N, N-dimethylformamide, N, N-dimethylacetamide, 1,3-dimethylimidazolidinone, ε-caprolactam, acetyl piperidine, urea, N, N-dimethylurea and the like are included. Particularly preferable compounds as compounds having an amide bond or a urea bond in the molecule are N, N-dimethylformamide, N, N-dimethylacetamide and urea. These may be used alone or in combination of two or more.

  The amount of the compound having an amide bond or urea bond in the molecule is 0.8 to 50 moles, preferably 0.9 to 5 moles per mole of the compound represented by formula (I). Most preferably, it is 1-2 equivalent mole.

  In the present invention, a reaction solvent can be used, but it may not be used. When used, the reaction solvent is not particularly limited, but is selected in consideration of easiness of stirring during the reaction, and can be added before the reaction or may be added during the reaction. . The reaction solvent used is preferably a solvent that separates layers when mixed with water. Specifically, halogenated solvents such as dichloromethane, chlorobenzene, o-dichlorobenzene, methylene bromide, bromobenzene, and fluorobenzene, diisopropyl Examples thereof include ether solvents such as ether and dibutyl ether, ester solvents such as ethyl acetate and butyl acetate, and aromatic hydrocarbon solvents such as toluene, xylene and mesitylene. Although the usage-amount of a solvent is not specifically limited, It is 0-100 times with respect to the weight of a reaction mixture, Preferably it is 0-10 times. In the present invention, the reaction solvent can also serve as an extraction solvent, and the amount of solvent used in that case is 0.01 to 100 times, preferably 0.1 to 10 times the weight of the reaction mixture. It is. In the present invention, as one embodiment, a solvent can be added after the reaction.

  Although the reaction temperature in this invention is not specifically limited, Preferably it is -20-150 degreeC, Most preferably, it is 0-60 degreeC.

  The reaction time in the present invention is not particularly limited because it depends on the reaction conditions, but it is preferably 0.5 to 40 hours, and particularly preferably 1 to 24 hours.

  After completion of the reaction in the present invention, the reaction mixture is cooled, water is added to decompose excess thionyl bromide and the target product is separated. When fractionating the target product, an extraction solvent may be added if necessary. The extraction solvent is not particularly limited, and examples thereof include aromatic hydrocarbon solvents such as toluene and xylene, halogen solvents such as methylene chloride, chlorobenzene, o-dichlorobenzene, and trichlorobenzene, or ether solvents such as dimethyl ether. Used.

  When the target product is a liquid, distillation or rectification can be performed as necessary. Moreover, when a target object is a solid, it can refine | purify by performing recrystallization.

  The purity of 2-alkoxyethyl bromide can be measured by gas chromatography or high performance liquid chromatography.

  Next, although the specific example of this invention is shown, this invention is not limited to these.

In addition, the reaction yield in the following examples was calculated by the following method.
(Reaction yield calculation method)
Quantitative analysis (internal standard method) by ¹ H-NMR was used. In a screw tube, 1.0 g of toluene (internal standard substance) and 5.0 g of the organic layer after the reaction were accurately weighed and mixed well. An appropriate amount of this mixed solution was dissolved in deuterated chloroform, and ¹ H-NMR was measured as a sample solution. Of the obtained signals, the integral intensity ratio between the peak of the methyl group of toluene and the appropriate peak in general formula (2) (when R is a linear or branched alkyl group, the peak of the methyl group at the end) The target product in the reaction solution was quantified and the reaction yield was calculated.

Example 1
A 500 mL capacity four-necked flask was equipped with a stirrer, reflux condenser, thermometer and gas absorption device, 76.1 g (1.0 M) of 2-methoxyethanol, 95.7 g (1.1 M, N, N-dimethylacetamide). 1.1 equivalent mole) and 150 ml of methylene chloride were added, and 228 g (1.1 M, 1.1 equivalent mole) of thionyl bromide was added dropwise under ice cooling. The time required for the dropping was 2 hours. After completion of the dropwise addition, the mixture was refluxed and stirred for 5 hours, and then 50 g of water was added. The organic layer was separated and distilled under reduced pressure (20 kPa) to obtain 108.4 g (yield 78%) of 2-methoxyethyl bromide as a colorless and clear liquid. Purity 99% (gas chromatography). Boiling point 61-62 ° C. (18.7 kPa).

Example 2
A 500 mL four-necked flask is equipped with a stirrer, reflux condenser, thermometer, and gas absorption device, and 90.1 g (1.5 M, 1.5 equivalents) of 2-methoxyethanol (76.1 g, 1.0 M) Mol) was added, and 228 g (1.1 M, 1.1 equivalent mol) of thionyl bromide was kept at 60 ° C. or lower and dropped in 2 hours. When half the amount of thionyl bromide was dropped, 150 ml of o-dichlorobenzene was added and the dropping was continued. After completion of the dropwise addition, the mixture was stirred at 50 ° C. for 24 hours, 100 g of water was added, and the organic layer was separated. In addition, as a result of quantifying 2-methoxyethyl bromide in the organic layer according to the above-described reaction yield calculation method, the reaction yield was 87.8%. The separated organic layer was distilled under reduced pressure to obtain 114 g (81% yield) of 2-methoxyethyl bromide as a colorless and clear liquid. Purity 99% (gas chromatography). Boiling point 61-62 ° C. (18.7 kPa).

Examples 3-5, Comparative Examples 1-3
The amount of urea added was 0.01 equivalent mole (Comparative Example 1), 0.2 equivalent mole (Comparative Example 2), 0.6 equivalent mole (Comparative Example 3), 0.8 equivalent mole (implemented). Example 3) Same as Example 2 except 1.0 equivalent mole (Example 4), 1.1 equivalent mole (Example 5) and 1.2 equivalent mole (Example 6). By the method, 2-methoxyethyl bromide was obtained. According to the reaction yield calculation method described above, 2-methoxyethyl bromide in the organic layer was quantified. The results are shown in FIG.

  When 2-methoxyethanol, which is a substrate of the present invention, was used, the yield improved as the amount of urea added increased and reached saturation at 1.2 equivalent moles or more. Addition in a low concentration range (0.01-0.6 equimolar), called a so-called catalyst amount, yielded about 20% or less, and could not be adopted as an industrial production method. .

Example 7
A 500 mL capacity four-necked flask is equipped with a stirrer, reflux condenser, thermometer and gas absorber, and 53.1 g (0.88 M, 1.5 equivalents) of urea is added to 53.8 g (0.6 M) of 2-ethoxyethanol. Mol) was added, and 137 g (0.66 M, 1.1 equivalent mol) of thionyl bromide was kept at 30 ° C. or lower and dropped in 2 hours. After completion of the dropping, the mixture was stirred at 50 ° C. for 12 hours, 150 ml of o-dichlorobenzene was added, 200 ml of water was added, and the organic layer was separated. As a result of quantifying 2-ethoxyethyl bromide in the organic layer according to the above-described reaction yield calculation method, the reaction yield was 93.5%. The separated organic layer was distilled under reduced pressure to obtain 72.9 g (yield 80%) of 2-ethoxyethyl bromide as a colorless and clear liquid. Purity 99% (gas chromatography). Boiling point 71-72 ° C (16.0 kPa).

Examples 8-11, Comparative Examples 4-6
The amount of urea added was 0.01 equivalent mole (Comparative Example 4), 0.2 equivalent mole (Comparative Example 5), 0.6 equivalent mole (Comparative Example 6), 0.8 equivalent mole (implemented). Example 8), similar to Example 7 except that 1.0 equivalent mole (Example 9), 1.1 equivalent mole (Example 10) and 1.2 equivalent mole (Example 11). By the method, 2-ethoxyethyl bromide was obtained. According to the reaction yield calculation method described above, 2-ethoxyethyl bromide in the organic layer was quantified. The results are shown in FIG.

  When 2-ethoxyethanol, which is the substrate of the present invention, was used, the yield improved as the amount of urea added increased, reaching saturation at 1.0 equimolar or more. Addition in a low concentration range (0.01 to 0.6 equivalent mole) called a so-called catalyst amount has a yield of 30% or less, and cannot be employed as an industrial production method.

Example 12
A 500 mL four-necked flask was equipped with a stirrer, a reflux condenser, a thermometer and a gas absorption device, and 142.1 g (1.0 M) of 2- (hexyloxy) ethanol and 72.1 g of urea (1.2 M, 1.M). 2 equivalent moles) was added, and 137 g (1.1 M, 1.1 equivalent moles) of thionyl bromide was kept at 30 ° C. or lower and dropped in 2 hours. After completion of dropping, the mixture was stirred at 50 ° C. for 12 hours, 150 ml of o-dichlorobenzene was added, and then 200 ml of water was added. The organic layer was separated and distilled under reduced pressure to obtain 186.3 g (yield 89.1%) of colorless and clear liquid 2- (hexyloxy) ethyl bromide. Purity 99% (gas chromatography). Boiling point 91 ° C. (1.3 kPa).

Comparative Example 7
28.0 g (13.5% yield) of 2- (hexyloxy) ethyl bromide was obtained in the same manner as in Example 12 except that the amount of urea added was 0.02 equivalent mole.

  With respect to 2- (hexyloxy) ethanol, which is the substrate of the present invention, the same tendency as the above-mentioned 2-methoxyethanol and 2-ethoxyethanol was observed. That is, when the amount of urea added is low (0.02 equivalent mole), the yield is only 13.5%, while when the amount of urea added is 1.2 equivalent mole, the yield Reached 89.1%. In addition, when the amount of urea added was low (0.02 equivalent mole), a large amount of hexyl bromide was by-produced as an impurity and was not usable as an industrial production method.

Comparative Example 8
A stirrer, a reflux condenser, and a thermometer were attached to a 500 mL four-necked flask, 76.1 g of 2-methoxyethanol and 39.6 g of pyridine were added, and 81.2 g of phosphorus tribromide was added dropwise at 10 to 100 ° C. After completion of the reaction, distillation under reduced pressure was performed to obtain 52.7 g (yield 42.1%) of 2-methoxyethyl bromide as a pale yellow clear liquid. Purity 94.9% (gas chromatography).

  According to the present invention, high-purity 2-alkoxyethyl bromide can be produced in a high yield. High-purity 2-alkoxyethyl bromide is expected to expand its use in various industrial raw materials, especially pharmaceutical intermediates, raw materials for electrolyte compounds in electrical devices, raw materials for liquid crystal compounds in liquid crystal display elements, and polymer modifiers. Is done.

The change of the reaction yield of 2-methoxyethyl bromide (MEB) and 2-ethoxyethyl bromide (EEB) by the amount of urea addition is shown.

Claims (3)

General formula (1):

Where
R represents a group selected from the group consisting of a linear or branched alkyl group having 1 to 20 carbon atoms and a cycloalkyl group having 3 to 20 carbon atoms, wherein these groups are one or more halogen atoms. May be replaced with
X represents an oxygen atom,
R ₁ and R ₂ are each independently hydrogen, methyl, ethyl, propyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-amyl, i- Amyl, n-hexyl, neohexyl, n-heptyl, 2-ethylhexyl, n-octyl, i-octyl, s-octyl, t-octyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopropyl, cyclodecyl, Represents a group selected from the group consisting of norbornyl and adamantyl,
In the presence of a compound having one or more amide bonds or urea bonds in the molecule in an amount of 0.8 equivalent mole or more of 2-alkoxyethanol and thionyl bromide represented by And reacting with general formula (2):

In the formula, R, X, R ₁ and R ₂ have the same meaning as in general formula (1).
The manufacturing method of 2-alkoxyethyl bromide shown by these.   The compound having an amide bond or a urea bond in the molecule is at least one selected from the group consisting of urea, N, N-dimethylformamide, and N, N-dimethylacetamide. A method for producing 2-alkoxyethyl bromide. The method for producing 2-alkoxyethyl bromide according to claim 1 or 2, wherein R ₁ and R ₂ are hydrogen.

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