JPS60136530A - Method for producing halogen-substituted ether compounds - Google Patents

Abstract

PURPOSE:To produce a variety of the titled compounds in the same reactor, in one step, efficiently and economically, by using an OH-substituted compound as a raw material, and reacting with a dihalogen-substituted compound in the presence of a suspension of a strongly basic substance. CONSTITUTION:The reaction of an OH-substituted compound such as n-butyl alcohol with a dihalogen-substituted compound of formula (X is halogen; n is 3-20) is started in an aprotic polar solvent in the presence of a suspension of a strongly basic substance such as NaOH flakes, etc., at -20-+100 deg.C. The objective compound such as 1-bromo-4-n-butoxybutane, etc. can be produced by the reaction within 20hr. The OH-substituted compound is a compound having aliphatic hydrocarbon group, carbon ring or heterocyclic group substituted with OH group. EFFECT:Suitable for the production of a variety of products in small quantities. USE:When the objective compound is bonded with a functional group, it is useful as an intermediate raw material to introduce said functional group to an amide compound, an amine, an OH-substituted compound, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing halogen-substituted ether compounds. More specifically, the present invention relates to a method for producing a halogen-terminated ether compound using a hydroxyl-substituted compound as a starting material.

...Since halogen-substituted ether compounds have a highly reactive halogen atom in their molecules, they can be reacted with amide compounds, amines, hydroxyl-substituted compounds, etc. in the same manner as general halogen-substituted compounds.

In particular, when a functional group is bonded to a halogen-substituted ether compound, it becomes an extremely useful intermediate material for introducing those functional groups into amide compounds, amines, hydroxyl-substituted compounds, etc. However, since no industrial production method has been established for versatile non-rogen-substituted ether compounds that meet the above-mentioned objectives, they have not been used in large quantities.)

Conventionally known methods for producing halogen-substituted ether compounds include, for example, a method for producing a halogen-substituted ether compound by reacting a hydroxyl-substituted ether compound with a brominating agent such as phosphorus tribromide, and a method for producing a halogen-substituted ether compound by reacting a hydroxyl-substituted ether compound with a brominating agent such as phosphorus tribromide. -1. A method of producing a halogen-substituted ether compound by reacting a compound with a dihalogen-substituted compound is known. However, with these methods, the types of compounds that can be produced are limited due to the troublesome handling of raw materials and the high cost of the products, and their applications are also limited to specific fields. This is the current situation.

In view of the above-mentioned actual situation regarding the production of halogen-substituted ether compounds, the present inventors have conducted extensive studies with the aim of adopting a highly versatile hydroxyl-substituted compound as a starting material. Initiating a reaction with the substitution compound. It was discovered that a halogen-substituted ether compound could be produced, and the present invention (C) was achieved.

That is, the present invention provides a method for producing a halogen-substituted ether compound, which comprises starting a reaction between a hydroxyl-substituted compound and a dihalogen-substituted compound in an aprotic polar solvent under suspension of a strongly basic material. It is.

In the present invention, a specific method for starting the reaction while suspending a strong basic substance is a method of simultaneously supplying and mixing the three substances to an aprotic polar solvent and causing the strong basic substance to become cloudy and react; A method in which a strong basic substance is suspended in an aprotic polar solvent, and then a hydroxyl-substituted compound and a dihalogen-substituted compound are simultaneously supplied for reaction, and a method in which a hydroxyl-substituted compound and a dihalogen-substituted compound are added to an aprotic polar solvent. An appropriate method may be employed, such as dissolving or suspending, and then adding and suspending a strong basic substance.

The hydroxyl-substituted compounds targeted by the present invention include compounds in which an aliphatic hydrocarbon group is substituted with a hydroxyl group, compounds in which a carbocyclic ring is substituted with a hydroxyl group, compounds in which a heterocyclic ring is substituted with a hydroxyl group, and the like.

Placement of a hydroxyl group on an aliphatic hydrocarbon group: Examples of deep compounds include methyl alcohol, ethyl alcohol, n-
Propyl alcohol, 1so-furobyl alcohol, n
-butyl alcohol, 1so-butyl alcohol, 5e
These include compounds in which a saturated hydrocarbon group such as c-butyl alcohol is substituted with a hydroxyl group, and compounds in which an unsaturated hydrocarbon group is substituted with a hydroxyl group such as allyl alcohol and methallyl alcohol. Examples of compounds in which a hydroxyl group is substituted on a carbon ring include compounds in which a hydroxyl group is substituted in an aromatic carbocycle such as phenol, methylphenol, dimethylphenol, nitrophenol, fluorophenol, chlorophenol, and nitrochlorophenol, and for example, cyclohexanol, Bromocyclopentanol, bromocyclohexanol, ethylcyclohexanol, n-
These are compounds in which a hydroxyl group is substituted for an alicyclic hydrocarbon group, such as propylcyclohexanol, cycloheptatool, and cyclooctatool. Examples of compounds in which a hydroxyl group is substituted on a heterocyclic ring include tetrahydropyranyl alcohol. Among the above-mentioned hydroxyl group-substituted compounds, the carbon substituted by the hydroxyl group is preferably a primary or secondary carbon.

The dihalogen-substituted compound to be reacted with the hydroxyl-substituted compound is a polymethylene cybaride represented by the following general formula, where X is a halogen atom, such as chlorine, bromine, iodine and may be different. n is an integer from 3 to 20. Examples of polymethylene cybalides represented by the above general formula, where X is bromine, include 1,6-dibromopropane, 1,4-dibromobutane, 1,5-dibromohebutane, 1,6-dibromohexane, 1, 8-dibromooctane, 1,1°-dibromodecane, 1,12-
Dibromododecane, 1゜14-dibromotetradecane,
1,16-dibromohexadecane, 1. ．． 18-dibromooctadecane, 1.20-sipromoeicozan, etc. Among the polymethylene cybarides listed in -, compounds with short methylene chains, such as compounds in which n is 12 or less in the above general formula, are convenient because they can be easily separated after the reaction.

The reaction solvent used in the present invention may be any aprotic polar solvent, such as acetonitrile, N,N-dimethylacetamide, N,N-dimethylacetamide, dimethylsulfoxide, sulborane, tetraglyme, dioxane, N-methylpyrrolidone. etc. can be mentioned.

In the reaction system of the method of the present invention, it is necessary to start the reaction in a state where at least a part of the strong basic substance is suspended, and the amount of water in such a state is determined by the amount of water in the reaction system. The amount is usually about 6% by weight. If the amount of water exceeds this value, side reactions such as hydrolysis of the dihalogen-substituted compound are likely to occur, resulting in a significant decrease in yield. To conduct the reaction efficiently and increase the yield of the target product,
It is preferable that the water content of the reaction system is 5% by weight or less.

The amount of the solvent to be used is not particularly limited, but is in the range of 5 to 95% by weight, preferably 10 to 90% by weight, based on the total amount of the reactants including the solvent.

Next, the strong basic substance used in the present invention is a solid substance, and when dissolved or suspended in water, the pI-T of the aqueous solution is
It can be used as long as it is 10 or more, preferably 11 or more. Such basic substances include, for example, alkali metal hydroxides, alkali metal oxides, alkali metal carbonates, alkaline earth metal hydroxides, alkaline earth metal oxides, alkali metal hydrides, and alkaline earth metals. Examples include hydrides, alkali metal amides, alkali metal alkoxides, and the like.

To specifically illustrate the above substances, examples of the alkali metal hydroxides include sodium hydroxide, potassium hydroxide, lithium hydroxide, rubidium hydroxide, and cesium hydroxide; examples of the alkali metal oxides include, for example, Sodium oxide, potassium oxide, lithium oxide, rubidium oxide, decium oxide, but as alkali metal carbonates,
For example, carbonic acid) IJ thy rum, potassium carbonate, lithium carbonate, coal rice rubidium,
Cesium carbonate is an alkaline earth metal hydroxide.
Examples of alkaline earth metal oxides include benzene hydroxide, red sea bream hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. , strontium oxide, barium oxide, and examples of alkali metal hydrides include sodium hydride,
Potassium hydride, lithium hydride, and alkaline earth metal hydrides include, for example, beryllium hydride,
Examples include magnesium hydride and calcium hydride. Further, alkali metal amides are compounds in which ammonia is substituted with an alkali metal, such as sodium amide, potassium amide, lithium amide, etc.Alkali metal alkoxides are compounds in which the proton of the hydroxyl group of an alcohol is substituted with an alkali metal, such as sodium amide. Examples include methoxide, sodium ethoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide, potassium t-butoxide, and the like.

Among the above-mentioned basic substances, those suitable for carrying out the method of the present invention are, for example, alkali metal hydroxide 1, alkaline earth metal hydroxide, alkali metal oxide, alkaline earth metal oxide, alkali It is Kinpeng Charmbeak Salt.

These strongly basic substances are usually used in the reaction in solid form, and the reaction is initiated with a small amount (or at least a portion) suspended in the reaction solution.

In carrying out the present invention, a hydroxyl-substituted compound as a raw material,
The relative amounts of the dihalogen-substituted compound and the strong basic substance to be used vary depending on the reactivity of the dihalogen-substituted compound and the hydroxyl-substituted compound, and cannot be uniformly defined.

However, when the relative ratio of the hydroxyl-substituted compound and the dihalogen-substituted compound approaches 1, a side reaction occurs in which two halogen atoms of the dihalogen-substituted compound are replaced with the hydroxyl-substituted compound, resulting in a decrease in yield. On the other hand, when the dihalogen-substituted compound is present in large excess, the dihalogen-substituted compound disappears due to the reaction between the strong basic substance and the dihalogen-substituted compound, resulting in a decrease in yield. Generally, the amount of dihalogen-substituted compound used is 0.5 to hydroxyl-substituted compound.
-30 times the mole, preferably 0.8-15 times the mole, and the amount of the strong basic substance used is 0.3-15 times the mole of the hydroxyl group-substituted compound, preferably 0.5-10 times the mole. is within the range of

For the reaction method, a normal reaction pot may be used, or if a strongly basic substance with low solubility is used, it is packed in a column and a mixed solution of a hydroxyl-substituted compound and a dihalogen-substituted compound is prepared. A flow type method in which the liquid is passed through and circulated may also be used. However, a reaction vessel is more convenient for equipment maintenance and management.

The reaction temperature depends on the reactivity of the amide compound and halogen-substituted compound used, but if the reaction temperature is low, the reaction progresses slowly, and if the actual temperature is high, bright reactions such as hydrolysis of the amide compound may occur, resulting in the formation of a product. The income and particular decline. Therefore, the reaction is usually carried out at a temperature range of -20 to 100°C, preferably -10 to 70'C. ,・preferably 0~
It is carried out in a temperature range of 50°C.

As long as the temperature is within this range, it is not necessarily necessary to keep the humidity constant during the reaction, but it is sufficient to keep track of the progress of the reaction and set the central temperature appropriately to allow the reaction to occur efficiently.

In addition, the reaction time, like the reaction temperature, varies depending on the water, compound, and dino-log/substituted compound used, but it is at most 60 hours, and usually within 20 hours. The progress of the reaction can be grasped by determining changes in the properties of the reaction system and the concentrations of raw materials and target products in the reaction solution using gas chromatography or high performance liquid chromatography.

After the reaction, the by-produced metals) and halides are filtered out and distilled under reduced pressure using a conventional method to obtain the desired product with high purity. However, if the metal nologenide is dissolved in the reaction solution or remains, use a solvent that forms two layers, such as hexane-water, benzene-water, or chloroform-water, after distilling off the solvent. After removing the above-mentioned substances by combining with silk, the target product with high purity can be obtained by distillation under reduced pressure. Furthermore, if the desired product has a high boiling point or is thermally decomposable, it can be purified by methods such as solvent extraction and recrystallization.

If the reaction solvent has a high affinity for water, such as dimethyl phorophyside (or if the target product is highly lipophilic, such as a long-chain alkyl ether), add a fat such as hexane to the reaction solution after the reaction. A method in which the target product is extracted by adding a group hydrocarbon solvent, a method in which the target product is separated as an oil layer by adding water to the reaction solution, or a bath that forms two layers of water such as benzene, toluene, and chloroform. A method of extracting and separating the target substance using a reagent can also be applied.

According to the present invention, a wide variety of halogen-substituted ether compounds can be produced in one step at low cost, and since the present invention uses the same reaction mode, a wide variety of halogen-substituted ether compounds can be produced in the same reactor. The compound can be produced and is suitable for producing products with a high variety of products in small quantities.

Next, the present invention will be further explained by examples.

Actual example 1 Production of 1-bromo-4-n-butoxybutane: N, N-
Dimethylformamide 150+++J and n-butyl alcohol 11.1? and 1,4-dibromobutane 81
Added 0 g of flaked water and crushed in a mortar while stirring. oy was added and suspended, and the reaction was carried out at 25 to 60°C for 7 hours. After reacting for a predetermined period of time, insoluble substances in the reaction solution are separated in a furnace, and 150 m/! of n-hexane is added to the solution. was added to extract the target product. This extraction operation was repeated two more times. N-hexane was distilled off from the n-hexane layer, and the remaining liquid was heated at 109-111°C/30°C.
Distilled under the distillation conditions of 1-bromo-4-n-butoxybutane22. oy (yield 70%) was obtained.

Comparative Example 1 Production of 1-bromo-4-11-butoxybutane: Actual %t
i) In Example 1, the flaky sodium hydroxide was replaced with 40% hydroxide) l) The reaction was carried out in exactly the same manner as in Example 1, except that 60.0% of the rum aqueous solution was used, and the post-reaction treatment was also the same. I went to In this reaction, when a 40% aqueous sodium hydroxide solution was added, the reaction solution was homogeneous. Distilled 1-bromo-4-0-butoxypukun 722
(yield 26%).

Examples 2 to 5 Reactions were carried out using the combinations of raw materials, strong basic substances, and solvents listed in Table 1 under the conditions listed in Table 1. After the reaction, treatment was carried out in exactly the same manner as in Example 1, and the results shown in Table 2 were obtained.

Example 7 Preparation of (4-bromobutoxy)benzene: 150 m7 of N,N-dimethylformamide! phenol 1412
and 115.4 f of 1,4-dibromobutane were added, and while stirring, 6.67 g of flaked sodium hydroxide ground in a mortar was added, and the reaction was carried out at 10 to 15°C for 4 hours. After the reaction for a predetermined period of time, remove the undissolved substances from the reaction solution,
The solvent and unreacted raw materials were distilled off from the P solution. The residual liquid was extracted with benzene-water to obtain the desired product in the benzene layer. Benzene was distilled off from the benzene layer, and the remaining liquid was distilled at 153~b to (4-bromobutoxy)benzene at 296?
(yield 86%).

Example 8 Production of (4-bromobutoxy)cyclohexane: Completely the same as Example 7 except that 150 g of cyclohexanol was used instead of phenol 1412 and the reaction was carried out at 25 to 30°C for 10 hours. The reaction and subsequent treatments were carried out. Distilled under distillation conditions of 110 to 11215 mnIT9, and (4-bromobutoxy)cyclohexane 1
5.2f (yield 43%) was obtained.

Example 9 Production of 1-(4-bromobutoxy)-4-nitrobenzene: The reaction and reaction were carried out in exactly the same manner as in Example 7, except that P-nitrophenol 2102 was used instead of phenol 1417 in Example 7. In the subsequent treatment, benzene was distilled off from the benzene layer, and 1-(4-bromobutoxy)-4-
Nitrobenzene 34.5F (yield 84%) was obtained.

In addition, the melting point was 68 to 69°C. −□２′　1 peek

Claims (1)

[Claims] 1. A method for producing a halogen-substituted ether compound, which comprises starting a reaction between a hydroxyl-substituted compound and a dihalogen-substituted compound in an aprotic polar solvent under suspension of a strong basic substance.