JP5572421B2 - Method for producing 3,5-di-tert-butylhalogenobenzene - Google Patents

Description

  The present invention relates to a method for producing 3,5-di-tert-butylhalogenobenzene.

  Conventionally, as a method for producing 3,5-di-tert-butylhalogenobenzene, 1,3,5-tri-tert-butylbenzene is used as a raw material and produced by reacting iron and bromine in a carbon tetrachloride solvent. The method (for example, nonpatent literature 1) to do is proposed. However, this method cannot be said to be an industrially advantageous method such as requiring an equimolar amount or more of iron with respect to the raw material, complicated removal of the iron used, and the use of carbon tetrachloride. .

  As a method that does not use iron, a method in which 1,3,5-tri-tert-butylbenzene is used as a raw material and ferric chloride and bromine are allowed to act in a carbon tetrachloride solvent (for example, Non-Patent Document 2). ) Has been proposed. However, the yield is as low as 54%, and it is difficult to say that it is an industrially advantageous method such as using carbon tetrachloride.

  Also, a process for producing by using benzene as a raw material, reacting tert-butyl chloride and aluminum chloride in a 1,2-dichloroethane solvent to produce 1,3,5-tri-tert-butylbenzene and then reacting with bromine (For example, Non-Patent Document 3) has been proposed. However, this method is also difficult to say as an industrially advantageous method such as low yield and generation of many impurities.

  On the other hand, a method of producing 3,5-di-tert-butylaniline by bromination by a Sandmeyer reaction (for example, Non-Patent Document 4) has also been proposed. However, in the case of the Sandmeyer reaction, the aromatic amino compound used is highly toxic, the post-treatment after the reaction is complicated, and the yield is as low as 54%, which is not an industrially advantageous method.

Journal of the American Chemical Society 76, 2349-2353; 1954 Journal of the American Chemical Society 90, 2115-2123; 1968 Organic Preparations and Procedures Internationala 84, 1487-1503; 2006 Canadian Journal of Chemistry 80, 1487-1503; 2006

  An object of the present invention is to provide an industrially advantageous production method capable of producing 3,5-di-tert-butylhalogenobenzene with high purity and high yield.

  As a result of intensive studies to solve the above problems, the present inventor has completed the present invention. That is, the present invention is as follows.

で示される化合物とハロゲン化剤とをアンチモン化合物の存在下で反応させることを特徴とする下記一般式（２）：

（式中、Ｘは塩素または臭素原子を表す）
で示される化合物の製造方法。 [1] The following formula (1):

A compound represented by the following general formula (2), wherein a halogenating agent is reacted in the presence of an antimony compound:

(Wherein X represents a chlorine or bromine atom)
The manufacturing method of the compound shown by these.

[2] The method according to [1], wherein the antimony compound is one or more compounds selected from the group consisting of antimony trichloride, antimony pentachloride, antimony tribromide, and antimony pentabromide.

[3] The production method according to [1] or [2], wherein the amount of the antimony compound used is in the range of 1 to 50 mol% with respect to the compound of the general formula (1).

[4] The production method according to any one of [1] to [3], wherein the halogenating agent is chlorine or bromine.

[5] The production method according to any one of [1] to [4], wherein the reaction temperature is -20 to 20 ° C.

  The method for producing 3,5-di-tert-butylhalogenobenzene of the present invention can be obtained with high purity and high yield, and is suitable for industrial mass production.

（式中、Ｘは塩素または臭素原子を表す）
で示される３，５−ジ−ｔｅｒｔ−ブチルハロゲノベンゼンは、式（１）：

で示される化合物とハロゲン化剤とをアンチモン化合物の存在下で反応させることにより得ることができる。 Hereinafter, the present invention will be described in detail.
General formula (2) of the present invention:

(Wherein X represents a chlorine or bromine atom)
3,5-di-tert-butylhalogenobenzene represented by the formula (1):

And a halogenating agent can be obtained by reacting in the presence of an antimony compound.

  The 1,3,5-tri-tert-butylbenzene represented by the formula (1) used in the present invention is commercially available and can be easily obtained from a reagent company such as Aldrich. Moreover, it is also possible to synthesize | combine by a well-known method (For example, the method as described in Organic Letters 7 (24), 5365-5368; 2005).

The halogenating agent used in the present invention means a chlorinating agent, a brominating agent, a fluorinating agent and an iodinating agent, and a chlorinating agent and a brominating agent are preferred. Specific examples of the chlorinating agent include chlorine (Cl ₂ ), N-chlorosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin, sulfuryl chloride and the like. Specific examples of the brominating agent include bromine (Br ₂ ), bromine monochloride, N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, sulfuryl bromide and the like. Considering availability, use of chlorine (Cl ₂ ) and bromine (Br ₂ ) is preferable.

  The halogenating agent is preferably used in an amount of 1.0 to 5.0 mol equivalents relative to the compound represented by the formula (1), and 1.0 to 2.0 mol from the viewpoint of the reaction rate. It is more preferable to use in an equal amount range.

  The antimony compound used in the present invention is a compound containing antimony such as antimony hydride, antimony hydroxide, antimony halide, antimony oxide, antimony sulfide, etc., and these compounds are used alone or in combination of two or more. May be used. Specific examples of the antimony compound include antimony trichloride, antimony pentachloride, antimony tribromide, antimony pentabromide, antimony triiodide, antimony pentaiodide, antimony trioxide, antimony tetroxide, and dioxypentoxide. Antimony. From the viewpoint of selectively obtaining a monohalide, it is preferable to use antimony trichloride, antimony pentachloride, antimony tribromide, and antimony pentabromide.

  The amount of the antimony compound used is preferably 1 to 50 mol% with respect to the compound represented by the formula (1), and more preferably 5 to 30 mol% from the viewpoint of the reaction rate. .

  A solvent may be used for the reaction. The solvent to be used is not particularly limited as long as it is a solvent inert to the reaction. Solvents may be used alone or in admixture of two or more at any ratio. Specifically, halogenated aromatic hydrocarbons such as monochlorobenzene, dichlorobenzene and trichlorobenzene, halogens such as methylene chloride, methylene bromide, chloroform, carbon tetrachloride, ethylene dichloride, 1,1,1-trichloroethane and trichloroethylene And aliphatic hydrocarbons.

  The usage-amount of the said solvent is 50 to 1000 weight% with respect to the compound shown by Formula (1), Preferably it is 100 to 500 weight%.

  The reaction temperature is preferably in the range of -20 to 20 ° C. The reaction temperature is more preferably in the range of −10 to 10 ° C. from the viewpoint of suppressing side reactions.

  The reaction time varies depending on the type and amount of the antimony compound to be selected, but is preferably 1 to 24 hours, and more preferably 3 to 12 hours.

  After completion of the reaction, the obtained reaction solution can be post-treated by a usual method. The post-treatment method is not particularly limited. For example, washing with water, an aqueous acid solution (such as aqueous hydrochloric acid solution) and / or an alkaline aqueous solution (such as aqueous sodium hydroxide solution or aqueous sodium hydrogen carbonate solution) is performed to obtain an antimony compound and an inorganic material. A treatment method for removing salts and the like from the system can be mentioned.

  From the reaction solution thus obtained, the compound represented by the general formula (2) can be isolated by performing a general operation such as concentration. The isolated compound can be further purified by distillation, chromatography, recrystallization or the like, if necessary.

  Hereinafter, the present invention will be illustrated by specific examples, but the present invention is not limited to the contents of the examples.

<Reaction purity>
The purity in Examples and Comparative Examples was calculated by area percentage by analyzing the reaction solution by gas chromatography. Here, the reaction purity is defined as the purity of the target product (3,5-di-tert-butylhalogenobenzene) after removing the solvent and the alkyl halide by-produced by the reaction.

<Gas chromatography analysis conditions>
Apparatus: GC-2010 (manufactured by Shimadzu Corporation)
Column: ULTRA1 (manufactured by Agilent Technologies)
25 m × I. D 0.32 μm, 0.52 μm df
Column temperature: 150 ° C. → [Raise temperature at 10 ° C./min]→280° C.
Injection temperature: 300 ° C
Carrier gas: Helium gas detector: Hydrogen flame ionization detector (FID)

[Example 1]
Into a 1 L four-necked flask equipped with a condenser, a thermometer and a gas absorber, 1,3,5-tri-tert-butylbenzene 150 g (0.6 mol, manufactured by Aldrich), antimony trichloride 27.4 g (0 .12 mol) and 420 ml of methylene chloride were charged and cooled until the internal temperature became 5 ° C. or lower. Next, 153.4 g (0.96 mol) of bromine was dropped over 2 hours, and then the reaction was performed at an internal temperature of 5 ° C. or less for 3 hours. Table 1 shows the analysis results of the obtained reaction solution.

[Example 2]
The same operation as in Example 1 was performed except that the amount of bromine used was changed. Table 1 shows the analysis results of the obtained reaction solution.

[Comparative Example 1]
In a 200 mL four-necked flask equipped with a condenser, a thermometer and a gas absorption device, 30 g (0.122 mol) of 1,3,5-tri-tert-butylbenzene, 7.15 g (0.128 mol) of iron powder and chloride 84 ml of methylene was charged and cooled until the internal temperature became 5 ° C. or lower. Next, 23.3 g (0.146 mol) of bromine was added dropwise over 2 hours, and the reaction was carried out at an internal temperature of 5 ° C. or lower for 23 hours. Table 1 shows the analysis results of the obtained reaction solution.

[Comparative Example 2]
The same operation as in Comparative Example 1 was performed except that the iron powder was changed to ferric chloride. Table 1 shows the analysis results of the obtained reaction solution.

  According to the production method of the present invention, 3,5-di-tert-butylhalogenobenzene useful as a pharmaceutical, an electronic material, and an organic synthetic intermediate can be obtained in a high yield, high purity, and industrially usable method. Is possible.

Claims (5)

Following formula (1):

A compound represented by the following general formula (2), wherein a halogenating agent is reacted in the presence of an antimony compound:

(Wherein X represents a chlorine or bromine atom)
The manufacturing method of the compound shown by these.   The production method according to claim 1, wherein the antimony compound is one or more compounds selected from the group consisting of antimony trichloride, antimony pentachloride, antimony tribromide, and antimony pentabromide. The production method according to claim 1 or 2, wherein the amount of the antimony compound used is in the range of 1 to 50 mol% with respect to the compound of the general formula (1).   The production method according to claim 1, wherein the halogenating agent is chlorine or bromine.   The production method according to any one of claims 1 to 4, wherein the reaction temperature is -20 to 20 ° C.