JP2014208604A - Method for manufacturing an aromatic acyl compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve the Friedel-Crafts reaction, which is a renowned method for manufacturing an aromatic acyl compound, above all, to provide an improved method highlighting the catalytic activity loss of a Lewis acid used as a catalyst.SOLUTION: On an occasion for inducing a Friedel-Crafts reaction, the catalytic activity loss of a Lewis acid used as a catalyst can be inhibited by inducing the reaction while a gas stream is being generated in the liquid phase. Methods for generating the gas stream in the liquid phase are concretely instantiated by a method in which an inert gas is blown into the liquid phase and a method in which the pressure of a reaction system is reduced.

Description

The present invention relates to an improvement of Friedel-Crafts acylation reaction known as a method for producing an aromatic acyl compound.

A reaction for obtaining an aromatic acyl compound by reacting a compound having an aromatic ring with a carboxylic acid halide in the presence of a Lewis acid is called a Friedel-Crafts acylation reaction and is applied to various methods for producing aromatic acyl compounds. For example, Non-Patent Document 1 describes a reaction example in which aluminum chloride is used as a Lewis acid and biphenyl and acetyl chloride are reacted to obtain 4-acetylbiphenyl. In this way, aluminum chloride is typically used as the Lewis acid used in Friedel-Crafts acylation reactions, but aluminum chloride is highly reactive and unstable to carboxylic acid halides and compounds with aromatic rings. When there are various substituents, side reactions to these substituents may occur and the target compound may not be obtained.

On the other hand, various attempts have been made to suppress such side reactions by replacing highly reactive aluminum chloride with zinc chloride, boron trifluoride, etc., which have relatively low reactivity. It has been found that the catalyst activity may be reduced due to some by-product generated during the reaction, and as a result, problems such as incomplete reaction or a significant decrease in reaction rate may occur. did.

"Clam Organic Chemistry" <II> Third Edition, pages 694-695

The present invention is a novel Friedel-Crafts acylation which solves various problems such as a decrease in reaction rate due to a decrease in catalytic activity when a Friedel-Crafts acylation reaction is carried out using a Lewis acid having low reactivity. It is to provide a method for promoting the reaction.

The inventors of the present application have found that the above-described problems can be solved by carrying out the Friedel-Crafts acylation reaction while generating an air flow in the liquid phase. Specifically, the following invention is included.
[1]
A method for producing an aromatic acyl compound, comprising reacting a compound having an aromatic ring with a carboxylic acid halide in the presence of a Lewis acid while generating an air flow in a liquid phase.
[2]
The method for producing an aromatic acyl compound according to [1], wherein an air flow is generated in the liquid phase by blowing an inert gas into the liquid phase.
[3]
The method for producing an aromatic acyl compound according to [1], wherein an air flow is generated in the liquid phase by reducing the reaction system.

According to the present invention, when a conventionally known Friedel-Crafts acylation reaction is performed, the catalytic activity is reduced by some by-products generated during the reaction, and as a result, the reaction is not completed or the reaction rate is greatly reduced. Therefore, the amount of Lewis acid used for the reaction can be reduced. In addition, since a Lewis acid with low reactivity can be used in this reaction, a compound with an unstable substituent, which has conventionally been unable to be advantageously applied to this reaction by the formation of by-products due to the reactivity of Lewis acid. However, an inexpensive and simple Friedel-Crafts acylation reaction can be applied.

The compound having an aromatic ring and the carboxylic acid halide used in the present invention are not particularly limited as long as they are compounds to which Friedel-Crafts acylation reaction is generally applicable. Friedel-Crafts acylation reaction, for example, as described in the above-mentioned non-patent literature, carboxylic acid halide becomes a carbocation by the action of Lewis acid, this carbocation undergoes electrophilic substitution reaction on the aromatic ring, The reaction to obtain an aromatic acyl compound is shown. The general formula of Friedel-Crafts acylation reaction is shown below.

（Ｓｕｂ_１及びＳｕｂ_２は置換基を、Ｘはハロゲン原子を、ｎは０〜５の整数を表す。）

(Sub ₁ and Sub ₂ represent substituents, X represents a halogen atom, and n represents an integer of 0 to 5.)

The compound having an aromatic ring applicable to Friedel-Crafts acylation used in the present invention is a compound having an aromatic ring or a heterocyclic ring in which at least one site for Friedel-Crafts reaction remains. is there. Specifically, it has expanded aromatics including hydrocarbon aromatic compounds such as benzene, naphthalene and fluorene, and heterocyclic compounds such as pyrrole, thiophene, indole, furan and carbazole which are non-benzene aromatic compounds. Group compounds are exemplified. These compounds having an aromatic ring may have a substituent in the aromatic compound skeleton, and examples of these substituents include an alkyl group, a nitro group, an alkoxy group, an acetyl group, a halogen, and a halogen-containing group. Is done.

The carboxylic acid halide to which Friedel-Crafts acylation reaction can be used in the present invention generally refers to a compound in which the —OH portion of carboxylic acid is substituted with a halogen element. The carboxylic acid may be an aliphatic carboxylic acid or an aromatic carboxylic acid, and these carboxylic acids may have a substituent such as an alkyl group, a nitro group, an alkoxy group, an acetyl group, a halogen, or a halogen-containing group. Although the usage-amount of these carboxylic acid halides is not specifically limited, Usually, 0.8-5 mol times is used with respect to 1 mol of compounds which have an aromatic ring, Preferably it is used 1-3 mol times.

The Lewis acid used in the present invention is not particularly limited as long as it is a Lewis acid generally used for Friedel-Crafts acylation reaction. Examples of such Lewis acids include aluminum chloride, iron (III) chloride, aluminum bromide, zinc chloride, tin chloride, boron trifluoride, boron trifluoride diethyl ether complex, and the like. Among these Lewis acid catalysts, zinc chloride, boron trifluoride, or boron trifluoride diethyl ether complex that exhibits the effects of the present invention remarkably is preferable. The amount of these Lewis acids to be used is not particularly limited, but is usually 0.1 to 5 moles, preferably 0.5 to 3 moles per mole of the compound having an aromatic ring.

The present invention is usually carried out in the presence of a solvent. The solvent used in the present invention is not particularly limited as long as it does not react with a Lewis acid, a carboxylic acid halide, or a compound having an aromatic ring used in the reaction. For example, 1,1,2,2-tetrachloroethylene, 1, Halogenated hydrocarbons such as 2-dichloroethane, hydrocarbons and aromatic hydrocarbons having a nitro group such as nitromethane and nitrobenzene, halogens such as dichlorobenzene, pentafluorobenzene, tetrafluorobenzene and trifluorobenzene Aromatic hydrocarbons and the like are exemplified. The amount of these solvents used is not particularly limited, and is appropriately selected depending on the solubility of the Lewis acid, carboxylic acid halide, or compound having an aromatic ring used in the reaction.

“Reacting while generating an air flow in the liquid phase”, which is a feature of the present invention, means that a gas flow is generated from the liquid phase portion to the gas phase portion of the reactor. Specifically, a gas is introduced into the liquid phase by blowing an inert gas into the liquid phase, and a method of generating an air flow by the action of this gas rising to the gas phase, or by reducing the pressure of the reaction system Examples include a method of volatilizing a solvent in the liquid phase and the like, and a method in which the volatilized solvent is converted into a gas to generate an air flow by an action that rises from the liquid phase to the gas phase, and a method in which these methods are combined. . Among these, the method of blowing an inert gas into the liquid phase is preferable because it is simple.

When the inert gas is blown into the liquid phase, the inert gas to be used is not particularly limited, and examples thereof include rare gases such as helium and argon and nitrogen. The amount of the inert gas blown is usually not limited, and may be appropriately adjusted depending on the capacity of the reactor and the amount of Lewis acid, carboxylic acid halide, or compound having an aromatic ring used in the reaction. The effect of the present invention is sufficiently manifested by blowing 2 mL / min or more with respect to 1 g of the compound. Moreover, since the effect of this invention expresses the direction of blowing in of an inert gas more toward the lower part of a liquid phase than the upper part of a liquid phase, it is preferable.

When the reaction system is depressurized, the degree of depressurization is not particularly limited and is appropriately set according to the solvent used in the reaction, the carboxylic acid halide, and the compound having an aromatic ring, but the internal pressure is usually 53.2 to 80.0 kPa. And When the reaction system is decompressed, a gas introduction tube is provided in the liquid phase, and the reaction is performed while the reaction system is decompressed and a gas such as an inert gas is sucked from the gas introduction tube and an air flow is generated in the liquid phase. May be.

By reacting while generating an air flow in the liquid phase, when a Lewis acid, which is a subject of the present invention, particularly low reactivity, is used, its by-product produced during the reaction reduces its catalytic activity, As a result, the reason that the event is considered to occur in response to an event that the problem such as the reaction not being completed or the reaction rate being significantly reduced can be solved is as follows.

By generating a gas stream in the liquid phase, a substance that lowers or deactivates the catalytic activity by interacting with Lewis acid that is by-produced during the reaction, such as hydrogen halide, is generated outside the reaction system. It is estimated that the reason is that the catalyst activity decreases and the inactivation becomes less likely to occur. Therefore, the present invention is considered to be generally applicable to Friedel-Crafts acylation reaction using a compound having an aromatic ring and a carboxylic acid halide in the presence of a Lewis acid.

The temperature at which these reactions are carried out is appropriately selected depending on the Lewis acid, carboxylic acid halide, or compound having an aromatic ring used in the reaction, but is usually 0 to 200 ° C., preferably 30 to 100 ° C. In addition, the time for performing these reactions is also appropriately adjusted, and can be determined by a method in which the progress of the reaction is analyzed by, for example, high performance liquid chromatography to confirm disappearance of the raw materials.

The aromatic acyl compound thus obtained can be easily taken out and purified by applying conventional methods such as washing with water, distillation, crystallization, column chromatography and the like.

EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated in detail, this invention is not limited to these.

Each measurement value in this example and the comparative example was according to the following method and measurement conditions.

[1] Analysis conditions <high performance liquid chromatography>
Analyzer: LC-2010C manufactured by Shimadzu Corporation
Measurement wavelength: 240 nm
Developing solution: water / acetonitrile reverse phase column: Sumipax ODS A-212 (5 μm, 6.0 mmφ × 150 mm) manufactured by Sumika Chemical Analysis Co., Ltd.)
Column temperature: 40 ° C
Flow rate 1.0mL / min

[2] Reaction rate The reaction rates described in the examples and comparative examples are analyzed by high performance liquid chromatography under the above-mentioned conditions, unless otherwise specified. The area percentage was assumed to be the reaction rate.

<Example 1>
In a 500 ml glass reaction vessel equipped with a stirrer, cooler, thermometer and gas blowing tube, 34.6 g (0.25 mol) of benzoyl chloride as carboxylic acid halide and boron trifluoride diethyl ether complex as Lewis acid 64.0 g (0.45 mol) and 100 g of orthodichlorobenzene were added as a solvent. After the addition, stirring was started, and a solution prepared by previously dissolving 40.0 g (0.21 mol) of n-ethylcarbazole as a compound having an aromatic ring in 200 g of orthodichlorobenzene was added dropwise over 10 minutes. The temperature was raised to 75 ° C. while circulating nitrogen in the liquid phase at a flow rate of 170 mL per minute from the gas blowing tube, and stirring was continued at 75 to 80 ° C. for the time shown in Table 1. The reaction rate after stirring is shown in Table 1.

<Example 2, Comparative Example 1>
The experiment was performed in the same manner as in Example 1 except that the flow rate of nitrogen was set to 430 mL / min in Example 2 and nitrogen was not passed through the liquid phase in Comparative Example 1. The results are shown in Table 1.

<Example 3>
The experiment was performed in the same manner as in Example 1 except that the upper part of the gas blowing tube was sealed and the internal pressure during the reaction was changed to 66.7 kPa. The results are shown in Table 1.

<Example 4>
The reaction was carried out in the same manner as in Example 2 except that the Lewis acid catalyst was changed from boron trifluoride diethyl ether complex to zinc chloride and the amount used was changed to 14.0 g (0.10 mol). The results are shown in Table 1.

<Example 5>
The reaction was performed in the same manner as in Example 3 except that the Lewis acid catalyst was changed from boron trifluoride diethyl ether complex to zinc chloride and the amount used was changed to 14.0 g (0.10 mol). The results are shown in Table 1.

<Comparative example 2>
The reaction was performed in the same manner as in Example 5 except that the internal pressure during the reaction was changed to atmospheric pressure. The results are shown in Table 1.

As shown in Table 1, it was found that by generating an air flow in the liquid phase, there is a difference in reaction rate between using boron trifluoride diethyl ether complex and zinc chloride as Lewis acid. did.

<Example 6>
In a 100 ml glass reaction vessel equipped with a stirrer, cooler, thermometer and gas blowing tube, 2.3 g (0.016 mol) of benzoyl chloride as a carboxylic acid halide and boron trifluoride diethyl ether complex as a Lewis acid 4.9 g (0.035 mol) and nitrobenzene 5.0 g as a solvent were added. After the addition, stirring was started, and a solution in which 2.0 g (0.016 mol) of naphthalene was previously dissolved in 10 g of nitrobenzene as a compound having an aromatic ring was added dropwise over 5 minutes. The temperature was raised to 75 ° C. while circulating nitrogen in the liquid phase at a flow rate of 170 mL per minute from the gas blowing tube, and stirring was continued at 75 to 80 ° C. for the time shown in Table 2. The reaction rate after stirring is shown in Table 2.

<Comparative Example 3>
The experiment was performed in the same manner as in Example 6 except that nitrogen was not passed through the liquid phase. The results are shown in Table 2.

As shown in Table 2, it was found that by generating an air flow in the liquid phase, a difference in the reaction rate was caused even when naphthalene was used as the compound having an aromatic ring.

<Example 7>
In a 100 ml glass reaction vessel equipped with a stirrer, cooler, thermometer and gas blowing tube, 10.0 g (0.042 mol) of n-ethyl-3-nitrocarbazole as a compound having an aromatic ring and nitrobenzene as a solvent After adding 80 g, stirring was started and dissolved in advance, and then 7.45 g (0.044 mol) of 4-methoxybenzoyl chloride as a carboxylic acid halide and 12.40 g of boron trifluoride diethyl ether complex as a Lewis acid ( 0.087 mol) was charged. The temperature was raised to 75 ° C. while circulating nitrogen in the liquid phase at a flow rate of 60 mL per minute from the gas blowing tube, and stirring was continued at 75 to 80 ° C. for the time shown in Table 3. The reaction rate after stirring is shown in Table 3.

<Comparative example 4>
The experiment was performed in the same manner as in Example 7 except that nitrogen was not passed through the liquid phase. The results are shown in Table 3.

Claims (3)

A method for producing an aromatic acyl compound, comprising reacting a compound having an aromatic ring with a carboxylic acid halide in the presence of a Lewis acid while generating an air flow in a liquid phase. The method for producing an aromatic acyl compound according to claim 1, wherein an air flow is generated in the liquid phase by blowing an inert gas into the liquid phase. The method for producing an aromatic acyl compound according to claim 1, wherein an air stream is generated in the liquid phase by reducing the pressure of the reaction system.