JPH0245451A - Production of nitrorifluoromethyltoluene - Google Patents

Abstract

PURPOSE:To readily obtain a compound useful as a synthetic intermediate for medicines and agricultural chemicals in high purity and yield by oxidizing and converting amino group of aminotrifluoromethyltoluene into nitro group. CONSTITUTION:Amino group of aminotrifluoromethyltoluene is subjected to oxidative reaction using an organic peracid, hydrogen peroxide-organic acid or hydrogen peroxide-organic acid anhydride at 0-100 deg.C temperature for 3-100hr to provide nitrotrifluoromethyltoluene. Performic, peracetic acids, etc., are cited as the organic peracid which is an oxidizing agent. Hydrogen peroxide in 3-95% concentration is used in the hydrogen peroxide-organic acid or hydrogen peroxide-organic acid anhydride. The nitrotrifluoromethyltoluene is especially useful as an intermediate for hypotensive agents, tranquilizers or herbicides.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing nitrotrifluoromethyltoluene, which is useful as a raw material for medicines and drugs, particularly as an intermediate raw material for antihypertensive agents, tranquilizers, and herbicides. It is related to.

[Prior art and problems to be solved] Method for producing nitrotrifluoromethyltoluene and u, s, p,
467125 (1984) u, s, p, 450
3276 (1985) u, s, p, , 隘4132
737 (1979) However, the method for producing ([) uses expensive trifluoromethyltoluene as a starting material, and the nitrated product gives various isomers, requires complicated separation, and has a low yield. The production method of (II) requires SF, which is difficult to obtain in large quantities as a fluorinating agent, expensive and highly toxic.
, and also has problems such as the need to react at high temperatures and high pressures.

[Means for solving the problem] As mentioned above, a method for obtaining nitrotrifluoromethyltoluene with high purity and industrially advantageous, which is useful as a raw material for medicines and agricultural chemicals, has not yet been developed. In view of the current situation, the present inventors have made extensive studies to solve these problems, and as a result, the present inventors have found that the amino group of aminotrifluoromethyltoluene is oxidized using an organic peracid or the like. The inventors have discovered that the desired nitrotrifluoromethyltoluene can be easily obtained by this method, and have arrived at the present invention.

That is, the present invention is characterized in that the amino group of aminotrifluoromethyltoluene is oxidized with an organic peracid, hydrogen peroxide-organic acid, or hydrogen peroxide-organic acid anhydride to convert it into a nitro group. This is a method for producing nitrotrifluoromethyltoluene.

According to the present invention, nitrotrifluoromethyltoluene (e.g. 2
-nitro-4-trifluoromethyltoluene, etc.),
Nitrotrifluoromethyltoluene, which could only be obtained in the form of a mixture with isomers (e.g. 2-trifluoromethyl-6-nitrotoluene, 3-trifluoromethyl-5-nitrotoluene, 2-trifluoromethyl Since methyl-4-nitrotoluene (such as methyl-4-nitrotoluene) can be obtained in a form that does not contain any isomers, it is advantageous that a highly purified product can be obtained that can be used as a raw material for medicines, agricultural chemicals, etc.

In addition, aminotrifluoromethyltoluene, which is a raw material of the present invention, is disclosed in the patent application filed in 1983, which has already been proposed by the applicant.
-106572. It can be easily obtained by the manufacturing method described in JP-A No. 63-45241 and the like. Examples of the organic peracid as an oxidizing agent include performic acid, peracetic acid, pertrifluoroacetic acid, perpropionic acid, or m-chlorobenzoic acid. Hydrogen peroxide used in the anhydride can have a concentration of 3 to 95%. If it is less than 3%, the concentration is too low and there is no reactivity;
If it is more concentrated than 5%, it is dangerous to handle as there is a risk of explosion. For ease of handling, it is preferable to use 20 to 60% hydrogen peroxide. Examples of organic acids or anhydrides of organic acids include formic acid, acetic acid, trifluoroacetic acid, propionic acid, and anhydrides of these organic acids. can be mentioned.

When using acetic acid, propionic acid, and these peracids, adding 0.01 to 5%, preferably 0.1 to 2% of sulfuric acid to the peracid as an acid catalyst accelerates the reaction rate. It is particularly effective.

In this reaction, the theoretical amount of peracid for oxidizing an amino group to a nitro group is 3 equivalents relative to aminotrifluoromethyltoluene, but there is no problem if more than 3 equivalents are used to complete the reaction. do not have. However, the use of an excessive amount is economically disadvantageous.

Furthermore, since there is a risk of explosion if the concentration of the oxidizing agent is high, a solvent that is stable under the reaction conditions may be used for dilution. When an organic peracid is used as the solvent, halogenated hydrocarbons such as methylene chloride and chloroform, organic acids and acid anhydrides corresponding to the organic peracid, and the like can be used. On the other hand, when using a hydrogen peroxide-organic acid system, it is possible to use an excess of the organic acid or acid anhydride.

The reaction temperature is 0 to 100°C. The reaction rate slows down below O''C0, and the peracid begins to decompose when the temperature rises above 100°C.
The reaction time is from 3 to 100 hours, although it cannot be generally specified.

Further, the reaction product can be easily recovered by adding water and separating and recovering the precipitated oil after the completion of the reaction, or by extracting with an organic solvent if necessary.

[Example J Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 501) In a eggplant-shaped flask, 1.0 g of 2-amino-6-trifluoromethyltoluene (5,7-maro O1) and 201.0 g of acetic acid were added. 2.6 g (34.2 gnol) of peracetic acid and 0.1 g of sulfuric acid were added, and the mixture was kept at 60° C. for 15 hours with stirring.

Next, the contents were transferred to 100 μl of ice water, and then 20 μl of ice water was added.
% aqueous sodium hydroxide solution was gradually added to make the mixture alkaline. After extracting the precipitated organic matter with ether, analysis by gas chromatography revealed that 2-amino-6
-Trifluoromethyltoluene conversion rate is 98.3%, 2
-Trifluoromethyl-6-nitrotoluene selectivity was 92.2%.

Example 2 In a 501 eggplant flask, 1.0 g (5.7 mmol) of 2-amino-6-trifluoromethyltoluene,
Trifluoroacetic acid 20ml 1. Pertrifluoroacetic acid 3.3
g (25.4m+wol) and heated to 35° while stirring.
C, tO waiting time.

Next, the contents were transferred to 100 ml of ice water, and
% aqueous sodium hydroxide solution was gradually added to make the mixture alkaline. The precipitated organic matter was extracted with ether and then analyzed by gas chromatography, and the conversion rate of 2-amino-6-trifluoromethyltoluene was 98.5.
%, the selectivity for 2-trifluoromethyl-6-nitrotoluene was 96.5%.

Example 3 2-amino-6-trifluoromethyltoluene (20 g (1) 4 mmol) and acetic acid 150 ml were placed in a 3001 Mitsuro flask.

Add 1 liter of sulfuric acid and add 66.5 g of 35% hydrogen peroxide (
685 wool) was added and kept at 70°C for 24 hours while stirring.

At this time, the conversion rate of 2-amino-6-trifluoromethyltoluene was 95.6%, and the conversion rate of 2-amino-6-trifluoromethyltoluene was 95.6%.
The selectivity of nitrotoluene was 90.1%.

Next, the contents were transferred to 500 μl of cold water, and the precipitated organic matter was extracted using 100 ra1 of methylene chloride, washed with 2001 ml of water, and then
01 and further washed with 200 ml of water.

Next, after drying with magnesium sulfate, 2-trifluoromethyl-6-nitrotoluene with a boiling point of 109°C/26+uiHg was obtained by concentrating and distilling under reduced pressure.
g (purity 99.2%) was obtained.

Example 4 1,001 liters of 2-amino-6-trifluoromethyltoluenroacetic acid was placed in a 2,001 ml Mitsuro flask, and 49 ml of 35% hydrogen peroxide was added.
Add 8g (513+mmol) and heat at 40° while stirring.
C. It was kept for 8 hours. At this time, the conversion rate of 2-amino-6-trifluoromethyltoluene was 98.2%, and the selectivity of 2-trifluoromethyl-6-nitrotoluene was 96.0.
%Met.

Next, the same post-treatment as in Example 3 was carried out, and 2-trifluoromethyl-6-nitrotoluene 17. 7g <purity 9
9. 3%).

Example 5 2-amino-6-trifluoromethyltoluene 1.0 g (5.7+*mol
), formic acid]0*I.

4.2g of 30% hydrogen peroxide (37.1*+++ol)
and stirred at room temperature for 48 hours.

Next, the contents were transferred to 1001 ice water and further 20%
Aqueous sodium hydroxide solution was gradually added to make the mixture alkaline. After extracting the precipitated organic matter with ether, it was analyzed by gas chromatography, and it was found that 2-amino-6-
The conversion rate of trifluoromethyltoluene was 99.0%. 2
-Trifluoromethyl-6-nitrotoluene selectivity was 66.2%.

Example 6 Into a 25-liter eggplant-shaped flask, 10 ml of 3-amino-5-trifluoromethyltoluene vinegar FIJ, 2.9 g of 30% hydrogen peroxide (2
5.6 mmol) and stirred at room temperature for 24 hours.

Next, the same post-treatment as in Example 5 was performed, and the conversion rate of 3-amino-5-trifluoromethyltono-renin was 95.3%. The selectivity of 3-trifluoromethyl-5-nitrotoluene was 94.1%.

Example 7 In a 25-liter eggplant-shaped flask, 1.0 g (5.7 mmol) of 4-amino-2-trifluoromethyltoluene was added.
) Refluoroacetic acid 10 theory 1.30% hydrogen peroxide 3.9g
(34.2+u+ol) was added and stirred at room temperature for 24 hours.

Next, the same post-treatment as in Example 5 was performed, and the conversion rate of 4-amino-2-trifluoromethyltoluene was 9.
0.7%. The selectivity for 2-trifluoromethyl-4-nitrotoluene was 94.4%.

Example 8 In a 25-liter eggplant-shaped flask, 1.0 g (5.71) 2-amino-4-trifluoromethyltoluene was added,
Acetic acid 10+al.

10ml of acetic anhydride. Add 0.1 g of sulfuric acid and 3.9 g (34.2 mmol) of 30% hydrogen peroxide, and heat at 60'C for 24 hours.
Stir for hours.

Next, the same post-treatment as in Example 5 was performed, and the conversion rate of 2-amino-4-trifluoromethyltoluene was 91.
．． The selectivity for 5%, 2-nitro-4-trifluoromethyltoluene was 94.3%.

[Effects of the Invention] In the present invention, by using aminotrifluoromethyltoluene as a raw material, which is easily obtained by the production method proposed by the applicant, it is possible to easily produce pharmaceuticals and agricultural chemicals with high yield and high purity. A nitrotrifluoromethyltoluene derivative useful as an intermediate can be obtained.

Claims (2)

[Claims] (1) A method for producing nitrotrifluoromethyltoluene, which comprises converting the amino group of aminotrifluoromethyltoluene into a nitro group by oxidizing it. (2) As an oxidizing agent, organic peracid, hydrogen peroxide-organic acid,
Or a method for producing nitrotrifluoromethyltoluene, characterized by using hydrogen peroxide-organic acid anhydride.