JP2001039929A - Production of chloronitrobenzotrifluoride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply obtain the subject compound useful as an intermediate for medicines and agrochemicals from readily preparable raw materials by a short process by treating aminochlorobenzotrifluoride with an oxidizing agent in a solvent. SOLUTION: An aminochlorobenzotrifluoride of formula I (e.g. 4-amino-3- chlorobenzotrifluoride of formula II, etc.), is treated with an oxidizing agent (e.g. a peroxide such as sodium perborate, sodium percarbonate, etc.), in a solvent (preferably water, a lower alcohol, a lower carboxylic acid or a nitrile, to be concrete, especially methanol, acetic acid, etc., may be cited) to give the objective compound of formula III (e.g. a compound of formula IV). The amount of the solvent used is preferably 3-30 times as much as parts by weight of the compound of formula I and the amount of the oxidizing agent is preferably 1-20 equivalents based on the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing chloronitrobenzotrifluoride which is useful as an intermediate for medical and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, as a method for producing chloronitrobenzotrifluoride, for example, 4-amino-3-
A method is known in which chlorobenzotrifluoride is used as a starting material, amino groups are diazotized, and nitrated with sodium nitrite in the presence of a copper catalyst to produce 3-chloro-4-nitrobenzotrifluoride in a yield of 47%. Have been.
[Chem. Pharm. Bull. , 40,2399
(1992)].

[0003]

The conventional method is a two-stage reaction via a diazotization reaction, so that the operation is complicated and an expensive copper catalyst is required. In addition, there was a problem that mass production was difficult due to low yield.

[0004]

SUMMARY OF THE INVENTION The present invention has been made for the purpose of providing an efficient production method which solves the drawbacks of the prior art. Provided is a method for producing nitrobenzotrifluoride, especially 3-chloro-4-nitrobenzotrifluoride. That is, the present invention provides a method for producing chloronitrobenzotrifluoride represented by the following formula 2, wherein an oxidizing agent is allowed to act on aminochlorobenzotrifluoride represented by the following formula 1 in a solvent.

[0005]

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[0006]

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[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
The substitution position of the amino group and the chlorine atom on the benzene ring in aminochlorobenzotrifluoride (formula 1) is not particularly limited. Examples of aminochlorobenzotrifluoride (Formula 1) include the following compounds. 2-amino-
3-chloro-benzotrifluoride, 2-amino-4-
Chloro-benzotrifluoride, 2-amino-5-chloro-benzotrifluoride, 2-amino-6-chloro-
Benzotrifluoride, 3-amino-2-chloro-benzotrifluoride, 3-amino-4-chloro-benzotrifluoride, 3-amino-5-chloro-benzotrifluoride, 3-amino-6-chloro-benzotrifluoride Lido, 4-amino-2-chloro-benzotrifluoride, 4-amino-3-chloro-benzotrifluoride.
Among these, 4-amino-3-chlorobenzotrifluoride (Formula 3) is preferable as aminochlorobenzotrifluoride (Formula 1) in the present invention because of its usefulness as a pharmaceutical intermediate. The aminochlorobenzotrifluoride (Formula 1) in the present invention is a known compound or a compound that can be synthesized from a known compound by a known method. For example, in the case of 4-amino-3-chlorobenzotrifluoride, it can be synthesized by chlorinating 4-aminobenzotrifluoride in a solvent using a chlorinating agent such as N-chlorosuccinimide or chlorine gas.

In the present invention, an oxidizing agent is allowed to act on aminochlorobenzotrifluoride (formula 1) in a solvent.
As the solvent, water, lower alcohols, lower carboxylic acids, and nitriles are preferable. As lower alcohols, methanol and ethanol are preferable, and as lower carboxylic acids, formic acid, acetic acid and propionic acid are preferable,
As the nitriles, acetonitrile is preferred.

The oxidizing agent in the present invention includes an oxidizing agent having an action of oxidizing an amino group to a nitro group. For example, sodium perborate, sodium percarbonate, peracetic acid prepared from 90% aqueous hydrogen peroxide and acetic anhydride, peracetic acid prepared from 90% aqueous hydrogen peroxide and trifluoroacetic anhydride, pertrifluoroacetic acid Acetic acid, peroxodisulfuric acid and the like can be mentioned. In particular, sodium perborate and sodium percarbonate are preferable because they are easy to handle and can be used for mass synthesis. These oxidizing agents may be hydrates. As the oxidizing agent in the present invention, a commercially available one can be used as it is. When sodium perborate or sodium percarbonate is used as the oxidizing agent, it is particularly preferable to use methanol or acetic acid as the solvent, since the yield becomes particularly high.

The amount of the solvent used is preferably 3 to 30 parts by weight, particularly preferably 5 to 15 parts by weight, based on aminochlorobenzotrifluoride (formula 1). The amount of the oxidizing agent is preferably 1 equivalent to 20 equivalents, particularly preferably 1 equivalent to 10 equivalents, based on aminochlorobenzotrifluoride (formula 1).

In the reaction of the present invention, usually, aminochlorobenzotrifluoride (formula 1) and a solvent and an oxidizing agent are charged and reacted in a reaction vessel, or the solvent and the oxidizing agent are charged in a reactor. The reaction can be carried out by charging and reacting while adding aminochlorobenzotrifluoride (formula 1). The reaction temperature is preferably in the range of 20C to 100C, particularly preferably 50C to 70C. The reaction time is preferably 1 to 24 hours. The reaction pressure is not particularly limited, and is preferably under atmospheric pressure. The reaction of the present invention
The desired product can be obtained without using a catalyst. The preferred embodiment of the solvent, oxidizing agent, and reaction conditions used for the reaction is particularly preferable when 4-amino-3-chlorobenzotrifluoride (formula 3) is used as aminochlorobenzotrifluoride (formula 1). preferable.

In the reaction of the present invention, the amino group in Formula 1 is oxidized to produce chloronitrobenzotrifluoride (Formula 2) in which the amino group has become a nitro group. The relative positions of the chlorine atom, nitro group, and trifluoromethyl group substituted on the benzene ring in chloronitrobenzotrifluoride (Formula 2) are the same as the corresponding positions in aminochlorobenzotrifluoride (Formula 1). . For example, when the reaction of the present invention is carried out using 4-amino-3-chlorobenzotrifluoride (formula 3), 3-chloro-4-nitrobenzotrifluoride (formula 4) is obtained.

Specific examples of chloronitrobenzotrifluoride (formula 2) other than formula 4 include the following compounds. 2-chloro-3-nitro-benzotrifluoride, 2-chloro-4-nitro-benzotrifluoride,
2-chloro-5-nitro-benzotrifluoride, 2-
Chloro-6-nitro-benzotrifluoride, 3-chloro-2-nitro-benzotrifluoride, 3-chloro-
5-nitro-benzotrifluoride, 3-chloro-6-
Nitro-benzotrifluoride, 4-chloro-2-nitro-benzotrifluoride, 4-chloro-3-nitro-
Benzotrifluoride. In general, the nitrobenzotrifluoride (formula 2) obtained by the present invention is preferably post-treated and further purified to obtain high-purity chloronitrobenzotrifluoride (formula 2). Examples of the purification method include distillation, chromatography and the like.

In the production method of the present invention, the reaction can be carried out by a simple operation without using any special reagent or catalyst.
The desired product is obtained in a one-step reaction. The chloronitrobenzotrifluoride (formula 2) obtained according to the present invention is a compound useful as a pharmaceutical and agricultural chemical intermediate.

[0015]

The present invention will be described in detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Acetic acid (15 mL: 1) was placed in a 100 mL flask equipped with an internal thermometer, a condenser, and a dropping funnel.
4.3 g) and sodium perborate tetrahydrate.
05 g (32.8 mM) were suspended. 4 for the dropping funnel
1.25 g of -amino-3-chlorobenzotrifluoride
(6.4 mM) in acetic acid (15 mL: 14.3 g). The contents of the flask were heated to 50 ° C, and while maintaining the internal temperature at 50 to 60 ° C, 4-amino-3 was added.
A solution of chlorobenzotrifluoride in acetic acid was added dropwise over 35 minutes. After 5.5 hours, the reaction was stopped and the precipitate was filtered. The filtrate was diluted with ice water and extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, then with a saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was distilled to obtain 1.02 g of 3-chloro-4-nitrobenzotrifluoride. The yield from 4-amino-3-chlorobenzotrifluoride was 71%.

Example 2 A 100 mL flask was charged with methanol (18 mL: 22.7 g), sodium percarbonate 1.94 g (corresponding to 14.4 mM hydrogen peroxide), 4-amino-3-chlorobenzotrifluoride 1.41 g (7.2 mM), water (0.7 mL), and acetonitrile (5.4 mL: 6.9 g) were added, and the mixture was irradiated with ultrasonic waves. The reaction was allowed to proceed for 23 hours while maintaining the internal temperature at 50 ° C. Water was added to the reaction solution, which was extracted with dichloromethane. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure.
The obtained crude product was distilled to obtain 4.03 g of 3-chloro-4-nitrobenzotrifluoride. 4-amino-3
The yield from -chlorobenzotrifluoride was 56%.

[0018]

According to the present invention, chloronitrobenzotrifluoride (formula 2) can be easily and easily produced from aminochlorobenzotrifluoride (formula 1) which is easily prepared.

Claims (6)

[Claims] 1. A method for producing chloronitrobenzotrifluoride represented by the following formula 2, wherein an oxidizing agent is allowed to act on an aminochlorobenzotrifluoride represented by the following formula 1 in a solvent. Embedded image Embedded image 2. A 3-chloro-4-nitro compound represented by the following formula 4, wherein an oxidizing agent is allowed to act on 4-amino-3-chlorobenzotrifluoride represented by the following formula 3 in a solvent. A method for producing benzotrifluoride. Embedded image Embedded image 3. The method according to claim 1, wherein the oxidizing agent is a peroxide. 4. The method according to claim 1, wherein the oxidizing agent is sodium perborate or sodium percarbonate. 5. The reaction according to claim 1, wherein the reaction is carried out in the absence of a catalyst.
5. The production method according to any one of items 1 to 4. 6. The production method according to claim 1, wherein the solvent is methanol or acetic acid.