JPH07224019A - Production of 2',3'-dichloro-3-ethoxymethoxybenzanilide - Google Patents

Abstract

PURPOSE:To provide a method for producing 2',3'-dichloro-4 ethoxymethoxybenzanilide by which steps for precipitating 2',3'-dichloro-4- hydroxybenzanilide with an acid, filtering and dehydrating the resultant crystal can be omitted to thereby remarkably improve the yield and economical effi ciency. CONSTITUTION:This method for producing 2',3'-dichloro-4- ethoxymethoxybenzanilide is to convert 2',3'-dichloro-4-hydroxybenzanilide obtained in the former step into an alkaline aqueous solution thereof, add the resultant aqueous solution to a mixed solution of an organic solvent having a low water solubility containing a quaternary ammonium salt as a catalyst added thereto without requiring a method for taking out the 2',3'-dichloro-4- hydroxybenzanilide such as filtration, further add chloromethyl ethyl ether thereto and carry out the reaction in a method for reacting the 2',3'-dichloro-4- hydroxybenzanilide with the chloromethyl ethyl ether and producing the 2',3' dichloro-4-ethoxymethoxybenzanilide. Thereby, the product can be obtained in good yield by continuous reactions.

Description

Detailed Description of the Invention

[0001]

The present invention relates to 2 ', 3'-dichloro-
The present invention relates to a method for producing 4-ethoxymethoxybenzanilide.

[0002]

2. Description of the Related Art A method for producing 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide is disclosed in JP-A-56-730.
Reported in 55. Among them, 2 ', 3'-dichloro-4-hydroxybenzanilide and chloromethyl ethyl ether (expressed as various alkoxyalkyl halides in patent specifications) are used as an inorganic base such as potassium carbonate or sodium carbonate, or pyridine. Or, in the presence of an organic basic substance such as triethylamine, acetone,
The reaction is carried out in an organic solvent such as N, N-dimethylformamide, or the potassium salt of 2 ', 3'-dichloro-4-hydroxybenzanilide and chloromethylethyl ether are mixed with acetone, N, N-dimethylformamide. It is said that 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide can be obtained by reacting in an organic solvent such as.

However, in these methods, 2 ', 3'
-When preparing dichloro-4-ethoxymethoxybenzanilide, its intermediate, 2 ', 3'-dichloro-4-
Since hydroxybenzanilide is poorly soluble in organic solvents, in order to use it in the subsequent etherification, it must be acid-deposited and filtered after alkali extraction.

Furthermore, due to the instability of chloromethylethyl ether used for etherification with respect to water, water must be removed from the filtered crystals.

[0005]

SUMMARY OF THE INVENTION The object of the present invention is to solve the problems of the conventional production method and to use the alkaline aqueous solution of 2 ', 3'-dichloro-4-hydroxybenzanilide obtained in the previous step. By directly using it for etherification, the steps of acid precipitation, filtration and dehydration are omitted, and the yield and economy are improved.

[0006]

According to the present invention, 2 ', 3'-dichloro-4-hydroxybenzanilide is reacted with chloromethylethyl ether to give 2', 3'-dichloro-
In the method for producing 4-ethoxymethoxybenzanilide, the 2 ', 3'-dichloro-4-hydroxybenzanilide obtained in the previous step is used as an alkaline aqueous solution, and is used as a catalyst without using extraction methods such as filtration. 2 ′, 3′-dichloro-4-ethoxymethoxybenzanilide is collected by adding it to a mixed solution of a low water-soluble organic solvent to which a primary ammonium salt has been added, and simultaneously or subsequently adding chloromethylethyl ether to react. A method for producing 2 ′, 3′-dichloro-4-ethoxymethoxybenzanilide, which is characterized by a continuous reaction which is obtained efficiently.

By reacting 2 ', 3'-dichloro-4-hydroxybenzanilide of the present invention with chloromethyl ethyl ether, 2', 3'-dichloro-4-
The reaction formula for producing ethoxymethoxybenzanilide is shown in [Equation 1].

[0008]

[Equation 1]

In carrying out this reaction, 2 ', 3'-dichloro-4-hydroxybenzanilide is used as an alkaline aqueous solution, and this alkaline aqueous solution and a mixed solution of a low water-soluble organic solvent to which a quaternary ammonium salt is added as a catalyst. The method of adding chloromethyl ethyl ether to the mixed solution of and can be adopted. Further, in a low water-soluble organic solvent mixed solution containing a quaternary ammonium salt as a catalyst,
An alkaline aqueous solution of 2 ', 3'-dichloro-4-hydroxybenzanilide and chloromethyl ethyl ether were added,
A method of dropping at the same time can also be adopted.

In this reaction, the amount of chloromethyl ethyl ether may be equimolar with respect to 2 ', 3'-dichloro-4-hydroxybenzanilide. Preference is given to using ethyl ether. That is, 2 ', 3'-dichloro-4-
1.3 to 1 mol of hydroxybenzanilide
It is desirable to use 2.0 moles, more preferably 1.3 to 1.7 moles. When used in excess, the reaction product, N-ethoxymethyl-2 ', 3'-dichloro-4-, represented by [Formula 1], is an excess reaction product.
Ethoxymethoxybenzanilide is obtained as a by-product, resulting in a decrease in yield.

[0011]

[Chemical 1]

The reaction temperature in this reaction is 0 ° C to 60 ° C.
Is preferred. More preferable reaction temperature is 40 ° C to 60 ° C.
Is.

Sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or the like can be used as an alkali source in order to form an alkaline aqueous solution of 2 ', 3'-dichloro-4-hydroxybenzanilide.

Examples of organic solvents having low water solubility include halogenated hydrocarbons such as dichloromethane and chloroform, aromatic hydrocarbons such as toluene and xylene, alkyl ethers such as diethyl ether and diisopropyl ether, and n-butanol. Alcohols having 4 or more carbons can be used.

As the quaternary ammonium salt added as a catalyst, so-called phase transfer such as tetrabutylammonium bromide, tetrabutylammonium chloride, benzyltriethylammonium chloride, cetyltrimethylammonium chloride, tri-n-octylmethylammonium chloride, etc. A catalyst (PTC) is used. The amount used is about 1 to 5 w / w%, preferably 2 to 3 w / w% with respect to 2 ', 3'-dichloro-4-hydroxybenzanilide.

After completion of the reaction, the reaction mixture is separated to remove the aqueous layer portion, and then the obtained organic layer portion is concentrated to remove the solvent, whereby 2 ', 3'-dichloro-4-ethoxy is obtained. Crude crystals of methoxybenzanilide are obtained. By recrystallizing this from an organic solvent, 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide can be obtained with a yield of 85% or more.

[0017]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1 56.4 g (0.2 mol) of 2 ', 3'-dichloro-4-hydroxybenzanilide, 21.6 g (0.54 mol) of sodium hydroxide and 170 of water.
While a mixture of 1 ml of dichloromethane and 280 ml of dichloromethane and 1.7 g of tetrabutylammonium bromide was heated and refluxed in the same container, 32.1 g (0.34 mol) of chloromethyl ethyl ether was added over 2 hours. Dropped. Then, post-reaction is carried out for 1 hour, the reaction mixture is allowed to stand still, and after liquid separation, from the obtained dichloromethane solution,
By distilling off dichloromethane, crude crystals of 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide are obtained. This was recrystallized from 200 ml of methanol to obtain 57.8 g of 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide. (Yield: 8
5%)

Example 2 56.4 g (0.2 mol) of 2 ', 3'-dichloro-4-hydroxybenzanilide, 35.6 g (0.54 mol) of potassium hydroxide and 170 m of water.
A mixture of 1 liter, 280 ml of dichloromethane and 1.7 g of tetrabutylammonium bromide was heated to reflux in the same vessel, while 32.1 g (0.34 mol) of chloromethylethyl ether was added over 2 hours. Dropped. Then, post-reaction is carried out for 1 hour, and the reaction mixture is allowed to stand still, liquid-separated, and then dichloromethane is distilled off from the obtained dichloromethane solution to obtain a crude 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide. Get crystals. This was recrystallized from 200 ml of methanol to obtain 60.0 g of 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide. (Yield: 8
8.2%)

[Example 3] While refluxing a mixed solution of 800 ml of dichloromethane and 3.4 g of tetrabutylammonium bromide, 112.8 g (0.4 mol) of 2 ', 3'-dichloro-4-hydroxybenzanilide and hydroxylation were prepared. Sodium 43.2 g (1.08 mol) and water 170 ml
49.2 g of chloromethyl ethyl ether
(0.52 mol) is added dropwise at the same time. Dropping is 2 ', 3'-
Alkaline solution of dichloro-4-hydroxybenzanilide was carried out for 2 hours and 30 minutes and chloromethyl ethyl ether was carried out for 2 hours and 40 minutes, and 2 ', 3'-dichloro-4-
The alkaline solution of hydroxybenzanilide was added dropwise so that the solution became faster. Then, post-reaction is carried out for 30 minutes, the reaction mixture is allowed to stand still, liquid separation is carried out, and then dichloromethane is distilled off from the obtained dichloromethane solution to obtain 2 ′, 3′-.
133.1 g (crude yield: 99.3%) of crude crystals of dichloro-4-ethoxymethoxybenzanilide were obtained. This was recrystallized using 400 ml of methanol to obtain 122.1 g of 2 ′, 3′-dichloro-4-ethoxymethoxybenzanilide. (Yield: 90%)

Example 4 While refluxing a mixed solution of 800 ml of dichloromethane and 3.4 g of tetrabutylammonium bromide, 112.8 g (0.4 mol) of 2 ', 3'-dichloro-4-hydroxybenzanilide and hydroxylation were prepared. A mixture of 71.3 g (1.08 mol) of potassium and 170 ml of water, and 49.2 g of chloromethyl ethyl ether.
(0.52 mol) is added dropwise at the same time. Dropping is 2 ', 3'-
Alkaline solution of dichloro-4-hydroxybenzanilide was carried out for 2 hours and 30 minutes and chloromethyl ethyl ether was carried out for 2 hours and 40 minutes, and 2 ', 3'-dichloro-4-
The alkaline solution of hydroxybenzanilide was added dropwise so that the solution became faster. Then, post-reaction is carried out for 30 minutes, the reaction mixture is allowed to stand still, liquid separation is carried out, and then dichloromethane is distilled off from the obtained dichloromethane solution to obtain 2 ′, 3′-.
134.1 g (crude yield: 100%) of crude crystals of dichloro-4-ethoxymethoxybenzanilide were obtained. This was recrystallized from 400 ml of methanol to obtain 23.5 g of 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide. (Yield: 91%)

Example 5 Continuous Reaction 231.5 g (1.42 mol) of 2,3-dichloroaniline
Is dissolved in 660 ml of toluene, and 37.3 g (0.28 mol) of phosphorus trichloride is added dropwise at room temperature over 20 minutes.
After the dropwise addition, the mixture is stirred for 1 hour, then 55.2 g (0.4 mol) of 4-hydroxybenzoic acid is added, and the mixture is reacted at 95 ° C. for 3 hours. After the reaction was completed, 120 ml of water was added, and 500 g of 20% NaOH aqueous solution was further added at 50 ° C.
After stirring for 2 hours, 2 ', 3'-dichloro-4-hydroxybenzanilide is extracted. This 2 ', 3'-dichloro-
4-hydroxybenzanilide alkaline extract 850
ml and 49.2 g of chloromethyl ethyl ether (0.
52 mol) are simultaneously added dropwise under reflux of a mixed solution of 800 ml of dichloromethane and 3.4 g of tetrabutylammonium bromide. Dropping is 2 ', 3'-dichloro-4
-Alkaline solution of hydroxybenzanilide for 2 hours 3
Chloromethyl ethyl ether was performed for 0 minutes and 2 hours and 40 minutes so that the alkaline solution of 2 ', 3'-dichloro-4-hydroxybenzanilide was always fast. Then, post-reaction is carried out for 30 minutes, the reaction mixture is allowed to stand still, and after liquid separation, dichloromethane is distilled off from the obtained dichloromethane solution to give a crude 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide. 133.1 g of crystals
(Crude yield: 99.3%). By recrystallizing this with 400 ml of methanol, 2 ', 3'-
Dichloro-4-ethoxymethoxybenzanilide 12
2.9 g was obtained. (Yield: 90.4%)

[0023]

According to the production method of the present invention, the alkaline aqueous solution of 2 ', 3'-dichloro-4-hydroxybenzanilide obtained in the previous step can be continuously used directly for the subsequent etherification. The acid precipitation, filtration, and dehydration steps of 2 ', 3'-dichloro-4-hydroxybenzanilide can be omitted, and the yield and economical efficiency can be remarkably improved.

Claims (1)

[Claims] 1. A method for producing 2 ′, 3′-dichloro-4-ethoxymethoxybenzanilide by reacting 2 ′, 3′-dichloro-4-hydroxybenzanilide with chloromethylethyl ether, 2 ′, 3′-Dichloro-4-hydroxybenzanilide obtained in the step is made into an alkaline aqueous solution, and a quaternary ammonium salt is added as a catalyst in a low water-soluble organic solvent mixture without taking out method such as filtration. It is a continuous reaction in which 2 ′, 3′-dichloro-4-ethoxymethoxybenzanilide can be obtained in good yield by adding chloromethylethyl ether to the solution and simultaneously or after adding chloromethylethyl ether to react. A method for producing 2 ', 3'-dichloro-4-ethoxymethoxybenzanilide.