JP2021054745A - Method for producing 2',3'-dimethyl aromatic ketone - Google Patents

Abstract

To provide a method for producing 2',3'-dimethyl aromatic ketone in which an inexpensive and easily available raw material is used and that can industrially manufacture 2',3'-dimethyl aromatic ketone that is inexpensive.SOLUTION: A 2',3'-Dimethyl aromatic ketone is produced by reacting 2,3-dimethylchlorobenzene with magnesium metal in the presence of lithium chloride of 0.2 mole times or more with respect to 2,3-dimethylchlorobenzene to convert into a Grignard reagent, and reacting the Grignard reagent with an acid anhydride at a reaction temperature of 10°C or lower, followed by subjecting to hydrolysis treatment.SELECTED DRAWING: None

Description

The present invention relates to a method for producing a 2', 3'-dimethyl aromatic ketone. In particular, the present invention relates to an industrially excellent method for producing a 2', 3'-dimethyl aromatic ketone.

2', 3'-dimethyl aromatic ketones are compounds useful as fine chemicals, raw materials for medical and agricultural chemicals, raw materials for resins and plastics, electronic information materials, optical materials and the like.
As a method for producing a 2', 3'-dimethyl aromatic ketone, in Patent Document 1, 2', 3'-benzoic acid is converted to acid chloride with thionyl chloride, and this is reacted with a malonic acid diester to produce a product. Is disclosed as a method for producing 2', 3'-dimethylacetophenone by hydrolyzing.

However, in the method described in Patent Document 1, the starting material 2', 3'-benzoic acid is expensive, and the reactant malonic acid ester is also expensive. In addition, the reaction steps are multi-stage, and the operation is complicated. As a result, the obtained 2', 3'-dimethyl aromatic ketone has become expensive.
Therefore, an inexpensive method for producing a 2', 3'-dimethyl aromatic ketone has been desired.

Chinese Patent Application Publication No. 102249921

An object of the present invention is to provide an inexpensive method for producing a 2', 3'-dimethyl aromatic ketone, which can be produced industrially by using an inexpensive and easily available raw material.

（但し、ｎは、１〜４の整数である） The method for producing a 2', 3'-dimethyl aromatic ketone of the present invention comprises using 2,3-dimethylchlorobenzene with a magnesium metal in the presence of 0.2 mol times or more of lithium chloride with respect to 2,3-dimethylchlorobenzene. The reaction is carried out at a reaction temperature of 40 ° C. or higher, converted to a Grignard reagent, the Grignard reagent is reacted with an acid anhydride at a reaction temperature of 10 ° C. or lower, and then hydrolyzed and represented by the following general formula (1). It is characterized by producing 2', 3'-dimethyl aromatic ketones.

(However, n is an integer of 1 to 4)

The method for producing a 2', 3'-dimethyl aromatic ketone of the present invention uses an inexpensive and easily available raw material of 2,3-dimethylchlorobenzene without using an expensive raw material or a reactant, and is industrial. It is an industrially excellent production method that can obtain 2', 3'-dimethyl aromatic ketones that can be produced and are inexpensive. The 2', 3'-dimethyl aromatic ketone obtained by the production method of the present invention can be used as a fine chemical, a raw material for medical and agricultural chemicals, a raw material for resins and plastics, an electronic information material, an optical material, and the like.

The acid anhydride may be acetic anhydride, propionic anhydride or butyric anhydride. The 2', 3'-dimethyl aromatic ketone may be 2', 3'-dimethylacetophenone, 2', 3'-propiophenone, or 2', 3'-butyrophenone. Further, the amount of lithium chloride can be increased by 0.2 to 2.0 mol times with respect to the 2,3-dimethylchlorobenzene.

Details of the present invention will be described below.
The method for producing a 2', 3'-dimethyl aromatic ketone of the present invention uses 2,3-dimethylchlorobenzene as a starting substrate. 2,3-Dimethylchlorobenzene is an inexpensive and readily available compound.

In the present invention, a Grignard reagent is prepared by reacting a chlorine atom of 2,3-dimethylchlorobenzene with a magnesium metal at 40 ° C. or higher in the presence of 0.2 mol times or more lithium chloride with respect to 2,3-dimethylchlorobenzene. Convert to. As the conversion reaction to the Grignard reagent, a normal conversion reaction can be utilized.
In the present invention, the magnesium metal used may be cutting chips, ribbon-like or powder-like ones, but cutting chips are preferable in terms of handling.
The amount of magnesium metal used is preferably 0.8 to 3 mol times that of 2,3-dimethylchlorobenzene.
It is preferable to add iodine, bromine, or an inexpensive compound containing these in order to remove the surface oxide film of the magnesium metal and enhance the reactivity. Examples of such compounds are preferably methyl iodide, methyl bromide, ethyl iodide, ethyl bromide and the like.

In the production of Grignard reagents, when 2,3-dimethylchlorobenzene is reacted with magnesium metal and converted to Grignard reagents, 0.2 mol times or more of lithium chloride can coexist with 2,3-dimethylchlorobenzene. is necessary. By coexisting 0.2 mol times or more of lithium chloride with 2,3-dimethylchlorobenzene, the Grignard reagent is rapidly produced, and the subsequent reaction with the acid anhydride occurs in a high yield.

The amount of lithium chloride is 0.2 mol times or more with respect to 2,3-dimethylchlorobenzene. Preferably, it is 0.2 to 2.0 mol times. When the amount of lithium chloride is 0.2 to 2.0 mol times that of 2,3-dimethylchlorobenzene, the Grignard reagent is produced more rapidly and lithium chloride is completely dissolved in the reaction system.

The reaction of reacting 2,3-dimethylchlorobenzene with a magnesium metal and converting it into a Grignard reagent is carried out at a reaction temperature of 40 ° C. or higher. The reaction temperature is preferably 40 to 60 ° C, more preferably 40 to 55 ° C. If the reaction temperature is less than 40 ° C., the reaction of conversion to Grignard reagent may not occur.

The reaction of conversion to Grignard reagents is carried out in a dehydrated system. Therefore, in the reaction, a solvent dehydrated in advance may be used, or before the reaction, an inexpensive Grignard reagent may be added to the solvent to remove water contained in the solvent.

As the solvent used in the production of the Grignard reagent, a solvent capable of efficiently advancing the reaction is used. The solvent used in the production of the Grignard reagent is preferably an ether solvent in which the Grignard reagent is easily produced. Specific examples of the solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-dioxane, 1,4-dioxane, cyclopropylmethyl ether. , Methyl-tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, benzene, toluene, xylene and the like. Of these, diethyl ether, diisopropyl ether, tetrahydrofuran, 1,3-dioxane, 1,4-dioxane, cyclopropylmethyl ether, and methyl-tert-butyl ether are preferable.

The amount of the solvent used is preferably determined according to the solubility of the 2,3-dimethylchlorobenzene or Grignard reagent, the slurry concentration, or the properties of the reaction solution. The amount of the solvent used is preferably 1 to 100 mol times that of 2,3-dimethylchlorobenzene. If the amount of the solvent used is less than 1 mol, the yield of the Grignard reagent may be low, and if it exceeds 100 mol, the productivity may be deteriorated, which may result in an uneconomical process.

In the production method of the present invention, a Grignard reagent and an acid anhydride are reacted at a reaction temperature of 10 ° C. or lower and then hydrolyzed to produce a 2', 3'-aromatic ketone. The acid anhydride is an anhydride of a carboxylic acid having an alkyl group having 1 to 4 carbon atoms.

Specific examples of the acid anhydride to be reacted with the Grignard reagent include acetic anhydride, propionic anhydride, butyric anhydride, and valeric anhydride. The acid anhydride is preferably acetic anhydride, propionic anhydride, or butyric anhydride.

The amount of the acid anhydride used is preferably 0.5 to 10 mol times, more preferably 1 mol to 5 mol times, with respect to 1 mol of 2,3-dimethylchlorobenzene. If it is less than 0.5 mol times, unreacted Grignard reagent may remain, the yield may decrease, and the isolation and purification of the target product may be burdensome. If it is more than 10 mol times, unreacted acid anhydride may remain and productivity may deteriorate, and the load on separation of unreacted acid anhydride and 2', 3'-dimethyl aromatic ketone will increase. There is.

A solvent may be used for the reaction between the Grignard reagent and the acid anhydride. The solvent is preferably a solvent that does not inhibit the reaction and can proceed efficiently. Specific examples of the solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, 1,3-dioxane, 1,4-dioxane, cyclopropylmethyl ether. , Methyl-tertiary butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, benzene, toluene, xylene and the like. Of these, tetrahydrofuran, 1,3-dioxane, cyclopropylmethyl ether, benzene, toluene and xylene are preferable. Mesitylene.

The amount of the solvent used is preferably 0.05 to 50 times by mass with respect to 2,3-dimethylchlorobenzene. If the amount of the solvent used is less than 0.05 times by mass, it is difficult to remove the heat of reaction, and the reaction may run out of control. If it exceeds 50 times by mass, productivity may be poor.

As a method for reacting a Grignard reagent with an acid anhydride, a solution containing an acid anhydride may be put into a Grignard reagent solution, or a Grignard reagent solution may be put into a solution containing an acid anhydride. In order to prevent sudden exothermic reaction and reaction runaway, the solution to be added is added while controlling the temperature in the reaction system so that it is within the set range, such as continuously or dividedly added over time. It is preferable to adjust the speed. The time required for charging is preferably 0.5 to 6 hours.

The reaction temperature of the Grignard reagent and the acid anhydride is 10 ° C. or lower. Preferably, it is -40 to 0 ° C. When the reaction temperature exceeds 10 ° C., the Grignard reagent further reacts with the produced 2', 3'-dimethyl aromatic ketone, and the reaction yield of the 2', 3'-dimethyl aromatic ketone decreases.

The reaction time of the Grignard reagent and the acid anhydride is usually 0.5 to 40 hours after mixing the entire amount of the Grignard reagent solution and the solution containing the acid anhydride.

After completion of the reaction of the Grignard reagent with the acid anhydride, the product forms a salt consisting of a 2', 3'-dimethyl aromatic ketone and magnesium halide. Therefore, by hydrolyzing the salt, a 2', 3'-dimethyl aromatic ketone can be obtained. Water, acidic water or alkaline water is preferably added to the reaction completion solution to hydrolyze the salt consisting of 2', 3'-dimethyl aromatic ketone and magnesium halide. A method of isolating the 2', 3'-dimethyl aromatic ketone from the obtained oil phase after removing the produced magnesium halide in the aqueous phase is preferable.

（但し、ｎは、１〜４の整数である） The 2', 3'-dimethyl aromatic ketone produced in the production method of the present invention is represented by the following formula (1).

(However, n is an integer of 1 to 4)

The 2', 3'-dimethyl aromatic ketone represented by the above formula (1) is 2', 3'-dimethylacetophenone, 2', 3'-propiophenone, 2', 3'-butyrophenone, 2', It is 3'-valerophenone, preferably 2', 3'-dimethylacetophenone, 2', 3'-propiophenone, 2', 3'-butyrophenone.

Methods for isolating the desired 2', 3'-dimethyl aromatic ketone from the reaction solution include a distillation method, a crystallization method, an extraction method, a column separation using silica, a pseudo-moving bed adsorption separation method, and the like. You may combine the methods of. For example, in the distillation method, simple distillation, rectification, vacuum distillation, atmospheric distillation are preferable, and vacuum distillation is more preferable.

Since the 2', 3'-dimethyl aromatic ketone obtained by the production method of the present invention is a compound useful in a wide range of fields, it is of great significance to efficiently obtain it industrially.

Hereinafter, the present invention will be described in more detail with reference to Examples. The manufacturer grades of the reagents used here are all equivalent to the first grade level or higher.

[Example 1]
Thermometer containing 106.7 g of tetrahydrofuran (1.48 mol; manufactured by nacalai tesque), 7.19 g of magnesium powder (0.296 mol; manufactured by Chuo Kosan Co., Ltd.), and 3.62 g of lithium chloride (0.0853 mol; manufactured by nacalai tesque). The mixture was placed in 300 ml of a four-necked flask and stirred while replacing the inside of the system with nitrogen. To this, 0.5 g of a 1 mol / L ethylmagnesium bromide tetrahydrofuran solution (manufactured by Tokyo Kasei Co., Ltd.) was added to remove water in the system. Subsequently, 1.24 g of ethyl bromide (0.0114 mol; manufactured by Wako Pure Chemical Industries, Ltd.) was added. After stirring for a while, it was confirmed that heat generation occurred. Next, while maintaining the reaction solution temperature at 40 to 50 ° C., 40.0 g (0.284 mol; manufactured by Wako Pure Chemical Industries, Ltd.) of 2,3-dimethylchlorobenzene was gradually added dropwise. After completion of the dropping, the mixture was aged with stirring at 50 ° C. for 10 hours, and 15.2 g of toluene (0.38% by mass / 2,3-dimethylchlorobenzene: manufactured by Wako Pure Chemical Industries, Ltd.) was added to obtain a Grignard reagent solution. ..

Next, 48.2 g of acetic anhydride (0.28 mol; manufactured by Wako Pure Chemical Industries, Ltd.) and 45.4 g of toluene (1.14 mass times / 2,3-dimethylchlorobenzene: manufactured by Wako Pure Chemical Industries, Ltd.) with a thermometer. It was put into a 300 ml mouth flask, and the inside of the system was stirred in a cooling bath at −5 ° C. while substituting with nitrogen. The Grignard reagent solution was added dropwise thereto while controlling the reaction solution temperature to be −5 to 5 ° C. After the whole amount of the Grignard reagent solution was added dropwise, the mixture was stirred at room temperature for 2 hours. This was gradually added dropwise to 500 ml of a four-necked flask equipped with a thermometer containing 222 g of a 10 mass% acetic acid aqueous solution. Hydrolysis was completed by stirring for 1 hour after the dropping. After hydrolysis, stirring was stopped and an oil phase containing 2', 3'-dimethylacetophenone was obtained by static separation.

As a result of analyzing the obtained oil phase by gas chromatography (GC), the reaction yield of 2', 3'-dimethylacetophenone was 79.2% (based on the raw material 2,3-dimethylchlorobenzene).

[Example 2]
In Example 1, 7.88 g (0.324 mol; manufactured by Chuo Kosan Co., Ltd.) of magnesium powder and 6.03 g (0.142 mol; manufactured by nacalai tesque) of lithium chloride were used in the same manner as in Example 1. The reaction was carried out. As a result of analyzing the obtained oil phase by gas chromatography (GC), the reaction yield of 2', 3'-dimethylacetophenone was 83.9% (based on the raw material 2,3-dimethylchlorobenzene).

[Comparative Example 1]
In Example 1, the reaction was carried out in the same manner as in Example 1 except that lithium chloride was not added. As a result of analyzing the obtained oil phase by a gas chromatography method, the reaction yield of 2', 3'-dimethylacetophenone was 64.4% (based on the raw material 2,3-dimethylchlorobenzene).

[Comparative Example 2]
In Example 1, in the Grignard reagent synthesis, the reaction was carried out in the same manner as in Example 1 except that 2,3-dimethylchlorobenzene was gradually added dropwise while maintaining the reaction solution temperature at 35 ° C., but 2,3-dimethyl. It was confirmed that chlorobenzene was not converted and Grignard reagent was not produced.

[Comparative Example 3]
In Comparative Example 2, the reaction was carried out in the same manner as in Comparative Example 2 except that 7.88 g of magnesium powder (0.324 mol; manufactured by Chuo Kosan Co., Ltd.) and 6.03 g of lithium chloride (0.142 mol; manufactured by nacalai tesque) were used. However, it was confirmed that 2,3-dimethylchlorobenzene was not converted and the Grignard reagent was not produced.
The results of Examples 1 and 2 and Comparative Examples 1 to 3 are shown in Table 1 below.

表中、「２，３−ＤＭＣＢ」は２，３−ジメチルクロロベンゼンを表し、「２，３−ＤＭＡＰ」は２′，３′−ジメチルアセトフェノンを表す。

In the table, "2,3-DMCB" represents 2,3-dimethylchlorobenzene and "2,3-DMAP" represents 2', 3'-dimethylacetophenone.

[Example 3]
The oil phase obtained in Example 1 was distilled under reduced pressure (vacuum degree 2.9 to 4.0 kPa, distillation temperature 125 to 130 ° C.), and as a result, the total yield was 71.4% (based on raw material 2,3-dimethylchlorobenzene). ), 2', 3'-dimethylacetophenone having a GC purity of 99.1% was obtained.

In the method for producing a 2', 3'-dimethyl aromatic ketone of the present invention, a Grignard reagent is produced as an intermediate in the presence of lithium chloride using 2,3-dimethylchlorobenzene, which is an inexpensive raw material, and this Grignard is produced. A 2', 3'-dimethyl aromatic ketone can be produced by efficiently reacting a reagent with an acid anhydride at a reaction temperature of 10 ° C. or lower. The method for producing a 2', 3'-dimethyl aromatic ketone of the present invention is an industrially excellent production method.

The 2', 3'-dimethyl aromatic ketone produced by the method for producing a 2', 3'-dimethyl aromatic ketone of the present invention is a fine chemical, a pesticide raw material, a resin / plastic raw material, an electronic information material, an optical material, etc. Can be used as.

Claims (4)

2,3-Dimethylchlorobenzene was reacted with magnesium metal at a reaction temperature of 40 ° C. or higher in the presence of 0.2 mol times or more of lithium chloride with respect to 2,3-dimethylchlorobenzene, and converted into a Grignard reagent. A method for producing a 2', 3'-dimethyl aromatic ketone represented by the following general formula (1) by reacting a Grignard reagent with an acid anhydride at a reaction temperature of 10 ° C. or lower and then hydrolyzing the reagent.

(However, n is an integer of 1 to 4) The method for producing a 2', 3'-dimethyl aromatic ketone according to claim 1, wherein the acid anhydride is acetic anhydride, propionic anhydride or butyric anhydride. Claim 1 or 2 where the 2', 3'-dimethyl aromatic ketone is 2', 3'-dimethylacetophenone, 2', 3'-dimethylpropiophenone, or 2', 3'-dimethylbutyrophenone. The method for producing a 2', 3'-dimethyl aromatic ketone according to. The 2', 3'-dimethyl aromatic ketone according to any one of claims 1 to 3, wherein the amount of lithium chloride is 0.2 to 2.0 mol times that of 2,3-dimethylchlorobenzene. Manufacturing method.