JPS62106029A - Production of ether compound - Google Patents

Abstract

PURPOSE:The reaction between a halogenated aromatic compound and a metal salt of organic hydroxy compound is carried out using a mixture of a cuprous compound and a cupric compound as a catalyst to produce the titled compound which is used as an intermediate of agricultural chemicals or medicines in high selectivity and high yield. CONSTITUTION:In the production of an ether such as 2-ethoxythiophene or 3-methoxythiopene by reaction of a halogenated aromatic organic hydroxyl compound such as sodium ethylate or sodium methylate in the presence of a catalyst, a mixture of a cuprous compound such as cuprous oxide, cuprous iodide, or cuprous cyanide with a cupric compound such as cupric oxide, cupric iodide, cupric chloride, or cupric cyanide is used as a catalyst. EFFECT:The objective compound is produced in a shortened time.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing ether compounds with good selectivity and high yield.

[Problems to be solved by conventional technology and invention]

Ether compounds having an aromatic ring are useful compounds that can be widely used as intermediates for agricultural chemicals, medicines, and the like. Until now, cuprous oxide has been used as a catalyst for the synthesis reaction of ether compounds having an aromatic ring. As an example of this reaction, Alkiv Kemi, Vol. 23, p. 239, 1958, describes a method for synthesizing methoxythiophene using cuprous oxide as a catalyst. According to this report, for 1 equivalent of 3-bromothiophene, 2.8 equivalents of sodium methylate and 0
．． Using 5 equivalents of cuprous oxide, heating under reflux for 100 hours,
3-methoxythiophene was obtained with a yield of 81%.

This synthesis method not only requires complicated separation and purification steps because the boiling points of the raw material 6-bromothiophene, 5-7'O muchiophene, and the product 3-methoxythiophene are similar. However, the reaction time was extremely long and the yield was not good.

[Failure to solve the problem]

In view of the above facts, the present inventors have studied the amount of a method for producing an ether compound by reacting a non-logogenated aromatic compound with a metal salt of an organic hydroxy compound.

As a result, they discovered that when a mixture of a primary copper compound and a secondary copper compound was used as a catalyst, an ether compound could be produced in a short time and with good selectivity, and the present invention was completed.

The present invention relates to the production of an ether compound by reacting a halogenated aromatic compound and a metal salt of an organic hydroquine compound in the presence of a catalyst, using a monovalent copper compound and a divalent copper compound as catalysts. This is a method for producing an ether compound, characterized by using a mixture of compounds.

The halogenated aromatic compound used as a raw material in the present invention is a compound in which hydrogen bonded to an aromatic ring is replaced with a halogen atom.

It is expressed in the general formula as follows.

R, -X (1) (However, R1 represents a substituted or unsubstituted isoaromatic ring group or a substituted or unsubstituted heteroaromatic ring group, and represents an X\i halogen atom.) The above general formula In (1), any isotropic aromatic ring group represented by R1 can be used without any limitations. However, from the viewpoint of easy availability of raw materials, those having 6 to 14 carbon atoms are preferred. Specific examples of the allotropic aromatic ring group include phenyl, naphthyl, anthryl, and phenanthryl groups.

Further, in the above general formula (1), any heteroaromatic ring group represented by R1 can be used without any limitation. Nuclear heteroaromatic ring group and 1- include furyl group, chenyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, pyridyl group, benzofuryl group, benzothenyl group, and indolyl group.

Quinolyl group, pyrazinyl group, bi1)midyl group.

Examples include a pyridazyl group, a quinoxalinyl group, a thiazolyl group, a benzothiazolyl group, and an inoxasilyl group.

In addition, in the above general formula (1), any substituent of the substituted homologous aromatic ring group and the substituted heteroaromatic ring group represented by R1 may be particularly selected as long as it reacts with the reagent used in the reaction. Can be used without restrictions. Specific examples of the substituent include alkyl groups such as methyl, ethyl, and propyl groups; alkenyl groups such as vinyl and furyl groups; alkynyl groups such as propynyl; alkoxy groups such as methoxy and ethoxy; methylthio groups. , alkylthio group such as ethylthio group; alkoxyalkyl group such as methoxymethyl group: phenyl group; nitro group; cyano group; amino group; alkoxycarbonyl group; sulfonyl group: formyl group: monoalkylamino group, dialkylamino group, trifluoro Examples include polyfluoroalkyl groups such as methyl groups. Actually, fluorine does not inhibit the etherification reaction.

It may be substituted with a halogen atom such as chlorine or a hydroxy group.

Furthermore, the halogen atom represented by X in the above general formula (1) can be any of fluorine, chlorine, bromine, and iodine, but bromine or iodine is preferably used because of its good reactivity.

The other raw material used in the present invention is a metal salt of an organic hydroxy compound. Metal salts of organic hydroxy compounds are
It is known as alcolade or phenolate.
In the present invention, such known metal salts of organic hydroxy compounds can be used without any restriction. A metal salt of an organic hydroxy compound that can be particularly preferably used in the present invention is represented by the following general formula.

R2-0 to M(2) (However, R2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted homoaromatic ring group.

It represents a substituted or unsubstituted heteroaromatic ring group, and M represents an alkali metal atom. ) is a metal salt of an organic hydroxy compound.

In the above general formula (2), the alkyl t5 represented by R2 may be a linear monobranched b-shifted one, and the number of carbon atoms is not particularly limited. However, from the viewpoint of easy availability of raw materials, it is preferable that the number of carbon atoms is 1 to 6. Specific examples of the alkyl group include methyl group, ethyl group, n-propyl group,
1s○-propyl group, n-butyl group.

Examples include iso-7'thyl group, t-butyl group, n-pentyl group, n-hexyl group, and the like.

Furthermore, in the above general formula (2), as the homoaromatic ring group and the heteroaromatic ring group represented by R2, each group explained in the above general formula (1) can be used as is without any restriction.

In the general formula (2), the substituents for the substituted alkyl group represented by R2 include the substituents for the substituted homoaromatic ring group and the substituted heteroaromatic ring group described for the general formula (1).
It can be used by removing the alkyl group. Further, as the substituents for the substituted alloaromatic ring group and the substituted heteroaromatic ring group, the substituents explained for the general formula (1) can be directly applied.

In the general formula (2), the alkali metal atom represented by M is lithium or sodium.

Potassium, etc. can be mentioned, but from the top of Handling A.

Sodium and potassium are preferably used.

Among the metal salts of organic hydroxy compounds represented by the general formula (2), R2 is an alkyl group.

Alternatively, a substituted alkyl group is particularly preferred in the present invention because the yield of the target ether compound increases.

Further, as the @monovalent copper compound and the divalent copper compound which are the catalysts of the present invention, known compounds can be used without particular restriction.

Suitable primary copper compounds include cuprous oxide and cuprous iodide.
Examples include copper, cuprous bromide, cuprous chloride, cuprous fluoride, cuprous cyanide, and the like. Suitable divalent copper compounds include cupric oxide, cupric bromide, cupric chloride, cupric fluoride, cupric cyanide, and the like. 1st valence and 2nd valence
The combination of copper compounds of the same type, as well as different types of compounds, has the effect of accelerating the etherification reaction of the present invention and increasing the yield and selectivity of the produced ether compound. Furthermore, even better effects can be found by adding metallic steel to the combination of the first-valent copper compound and the second-valent copper compound.

According to the present invention, a mixture of a primary copper compound and a secondary copper compound is used as a catalyst, and when an ether compound is produced from the above-mentioned halogenated aromatic compound and a metal salt of an organic hydroxy compound, an inorganic compound is usually used. Preference is given to using active organic solvents. All kinds of inert organic solvents can be used as the inert organic solvent, and specific examples include benzene, hexane, and cyclohexane.

Decalin, toluene, xylene, N,N-dimethylformamide (hereinafter abbreviated as DMF -i).

Dimethyl sulfoxide (hereinafter abbreviated as DMSO), diethyl needle, dibutyl ether.

Examples include dimethoxyethane, diethylene glycol dimethyl ether, alcohol, and the like.

When alcohol is used as a solvent, the above general formula (
It is desirable to use an alcohol corresponding to R2-0-M shown in 2), that is, an alcohol represented by the general formula R2-OH. For example, it is preferable to use methanol for an R2h''-methyl group, ethanol for an ethyl group, and isopropyl alcohol for an isopropyl group in terms of yield and selectivity.

In carrying out the invention, a halogenated aromatic compound, a metal salt of an organic hydroxy compound and a first
The order of addition of the mixture of the valent copper compound and the second valent copper compound is not particularly limited. - For example, considering the use of alcohols, especially as solvents for etherification reactions, lower alcohols such as methanol, ethanol or isopropyl alcohol are reacted with alkali metals to prepare alcoholic solutions containing alcoholades; For example, a method of adding a halogenated aromatic compound and a mixture of a primary copper compound and a secondary copper compound may be mentioned.

Also, halogenated aromatic compounds and organic humans.

The molar ratio of the metal salt of the organic hydroxy compound is not particularly limited, but is generally 1:01 to 1:100, preferably a large amount of the metal salt of the organic hydroxy compound to the halogenated aromatic compound. It is preferable to use the molar ratio in the range of 1:1.1 to 1:10 because by adding the ether compound, the ether compound can be obtained more selectively and in a high yield in a short period of time.

The mixing ratio of the primary copper compound and the secondary copper compound, which are catalysts, can be selected from a wide range, but it is usually 0.01 to 100 mol per 1 mol of the primary copper compound. A range of secondary valent copper compounds may be used. Preferably, the molar ratio of the primary copper compound to the secondary copper compound is 0.1.
: 10-10 : [], selected from the range of 1.

When metallic copper is added to a mixture of a primary nitrate compound and a secondary copper compound, the molar ratio of the former to the latter is 0.01 to
Range of 100 to 100:0.01, preference 0.1
: It is suitable to select from the range of 10 to 10:0.1.

In addition, the mixture of the primary copper compound and the secondary copper compound, which are catalysts, has a ratio of 0.01 to 8
It is suitable to choose from the range of 0 mole percent, preferably from 1 to 50 mole percent.

Furthermore, the weight ratio of the halogenated aromatic compound to the inert organic solvent is generally from 1:1 to 1:20, preferably from 1:1 to
It is preferable to choose from a range of 1:10.

The temperature in the reaction of the present invention is not particularly limited and can be selected within a wide temperature range, but it is generally selected from the range of 50 to 150°C, preferably 80 to 150°C.

The method for purifying the ether compound obtained in the present invention is not particularly limited. Generally, after filtering off the catalyst, the reaction solution is neutralized and mixed with benzene, toluene, methylene chloride, or chloroform.

After extraction with an inert organic solvent such as carbon tetrachloride or ether, drying, distillation under normal pressure, distillation under reduced pressure, and recrystallization, the material can be purified by chromatography. Furthermore, it is also possible to adopt a method in which the reaction solution is neutralized and then the catalyst is separated by steam distillation.

〔effect〕

According to the method of the present invention described above, an ether compound can be obtained in a shorter time and in a higher yield than when a primary copper compound and a secondary copper compound are used alone as catalysts. be able to. Moreover, the obtained ether compound has good selectivity and is easy to purify.

That is, according to the method of the present invention, the ether compound was obtained in 100 hours with a yield of 81%, compared to the conventional method.
The ether compound can be obtained in less than an hour and with a yield of 85% or more. Furthermore, since no dehalogenation reaction, which is a side reaction, occurs, there are almost no by-products, and the selectivity for the target ether compound is extremely high.

Examples are given below to specifically explain the present invention, but the present invention is not limited to these Examples.

Example 1 30.9 (184 mmole) of 2-bromothiophene was added to a 200-cm three-neck flask equipped with a reflux condenser and a stirrer.
), sodium ethylate 27.5! (405!
TII]]01+3), a mixture of cuprous oxide and cupric oxide prepared in advance 8,! i' CCu0(5,0!
j−+ 57.7 mmole), Cu2O(5
g-.

34.9 mmole)] and ethanol 100-
The mixture was heated under reflux (oil bath temperature: 120° C.) and stirred vigorously for 20 hours under a nitrogen atmosphere. The reaction solution was returned to room temperature, neutralized with dilute hydrochloric acid, and then steam distilled. As a result of separating the obtained oil layer and analyzing it by gas chromatography, it was confirmed that thiophene was not produced and no dehalogenation reaction occurred. The oil layer was then distilled under reduced pressure to 64°C/18 m
2-ethoxythiophene, a colorless liquid with mHy, is
．． 5 g wo? G.

The yield is 95% based on the raw material 2-bromothiophene.
It was 7%.

Example 2 100 Mg of methanol (!: 12.31 (53 D + nmole) of sodium gold FfA) was added to a 200-cm three-neck flask equipped with a reflux condenser and a stirrer.
A sodium methylate-methanol solution was prepared in advance. 55 g of 3-bromothiophene (214 mmo
le) and pulverized oxidized steel 6J9CCuO2,21(2
7 mmole), Cu202.7g (19 mmole)
1.1 g (1.7 mmole) of Cu) were added sequentially, and the mixture was heated under rapid flow conditions (oil bath temperature 120°C).
Stir vigorously for 0 hours. Thereafter, the reaction solution was returned to room temperature 1, neutralized with dilute hydrochloric acid, and then steam distilled. As a result of analyzing the obtained oil layer in the same manner as in Example 1, it was confirmed that a dehalogenation reaction had occurred and b was reduced. The oil layer was then extracted with 50% of methylene chloride, and the methylene chloride layer was dried with calcium chloride. After distilling off methylene chloride, atmospheric distillation was performed to obtain 231 6-ethoxythiophene, which is a four-color liquid with a boiling point of 159°C.

The yield was 94.9% based on the raw material 3-bromothiophene.
It was 5%.

Example 3 Oxide oxide is a representative monovalent copper compound.

A combination of cuprous chloride and cuprous iodide with cupric oxide, cupric chloride, and cupric bromide, which are typical cupric compounds, was used as a catalyst for the following reaction.

That is, 6-bromothiophene 16.3,! i'(I
D.

mm01θ) and 15 g of sodium ethylate (220
mmole ) in ethanol 70-, add a predetermined amount of the above combination of catalysts (entered in Table 1), and heat at 100°C.
The mixture was heated and stirred vigorously. After 3 hours, the reaction solution was analyzed by gas chromatography to calculate the production rate of 3-ethoxythiophene.

Table 1 Example 3 An ether compound was synthesized in the same manner as in Example 1 using the halogenated aromatic compounds, metal salts of organic hydroxy compounds, and catalysts shown in Table 2. The results are also listed in Table 2.

As a result of analysis in the same manner as in Example 1, it was confirmed that the dehalogenation reaction had occurred.

It＼j″：tJ

Claims (1)

[Claims] When producing an ether compound by reacting a halogenated aromatic compound and a metal salt of an organic hydroxy compound in the presence of a catalyst, a primary valent copper compound and a secondary valent copper compound are used as catalysts. A method for producing an ether compound, characterized by using a mixture of.