JPS5951241A - Process for producing benzotrifluoride derivatives - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for producing benzo-11 fluoride derivatives,
2-21-rho-5-chlorobenzotrifluoride, 2
-amino-5-chlorobenzotrifluoride, 3-nitro-4-hydroxypenzotrifluoride, 3-amino-4-hydroxypenzotrifluoride, 3-nitro-
4-(substituted or non-substituted) aminobenzo-1-refluoride, 3-amino-4-(substituted or unsubstituted) aminobenzotrifluoride, and other benzene-refluoride derivatives with high monomer ratio and purity. , and relates to an efficient manufacturing method.

The above-mentioned penzotrifluoride derivatives, which are known as intermediate compounds for the synthesis of various useful chemicals (pharmaceuticals, agriculture, etc.), are usually produced by using penzotrifluoride as a raw material, which is chlorinated, and then further nitrated and reduced. The desired target compound is obtained using reactions such as amination, amination, etc., but various types of compounds are generated during the process, and their separation requires complicated operations. An example is penzotrifluoride.
When converted to jA, 0-chlor body, m-chlor body υ and P
- A mixture of chlorine compounds is produced. If this is distilled,
Although the 0-chlor form can be separated, the Nf of the m-chlor form and the P-chlor form is difficult to separate. Also, can you nitrate this mixture of m-chloride and p-chloride? G gets 2-
It is difficult to separate the mixture of nitro-5-chloride and 3-nitro-4-chloride by distillation, and if separation is forced, a method such as cooling and assimilation should be adopted. become. Such a method is unsuitable for industrial production, and moreover, it is a trade-off in purity! It is also not easy to obtain goods.

The present inventors have conducted four other studies in search of a method for industrially and efficiently producing benzotrifluoride derivatives, and found that 2-nitro-5-chlorobenzotrifluoride and
- Nitro-4-chlorpenzotrifluoride shows a remarkable difference of +11 in the reactivity of their chlorines, and if an excessive amount of reaction reagent is used, there is essentially no reaction with respect to the 5-position chlorine of the former. The reaction did not proceed, and the reaction proceeded only for the latter 4-position chlorine, and as a result, the proportion of both 1i41F became 1
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The present invention was completed based on the above findings, and
The gist is that @1'! Alternatively, 2-nitro-5-chlorobenzo! is obtained from the reaction mixture obtained by reacting with a secondary amine or ammonia, or from the reaction mixture obtained by further reducing the reaction mixture.・Separating and recovering at least one of refluoride or the reaction product produced therefrom and the reaction product produced into 3-nitro-4-chlorobenzotrifluorideff: Production of a characterized penzotrifluoride derivative F to the law.

The light emitting substance of the method of the present invention is a mixture containing 2-nitro-5-chlorobenzotrifluoride and 3-21.rho-4-chlorobenzotrifluoride, and... For example, a mixture of commercially available 3-chlorobenzotrifluoride (containing about 10% by weight and 7'L of 4-chlorobenzotrifluoride) is added dropwise to a mixed acid of sulfuric acid and nitric acid kept at room temperature to 50°C.
After several hours of ill-stirring, the mixed acid can be separated, washed with water and dried if necessary, and then prepared.

The primary or secondary amine or ammonia is added to the MiJ nitro mixture in the presence or absence of an inert m-ray (e.g. alcohol, alkane, halogenated alkane, benzene, ether, water). 1 or more, preferably 2 IU per 2 times amine or ammonia
A small excess of 110 times equivalents was used (and these used 7ii
-Nitro-4-chlorpents River Refluorite h(
Use k standard. ) can be applied. The reaction is usually -5
The process proceeds at a temperature of 0 to 200°C and under normal pressure to increased pressure. In addition, the first
Alternatively, as the secondary amine, an alkylamine or a dialkylamine is commonly used, and those having an alkyl group having a Fuki number of 1 to 6 are preferably used. By this reaction, the 4-position chlorine atom of 3-nitro-4-chlorobenzotrifluoride is displaced by a substituted or unsubstituted amino group (i.e., amino, alkylamino or dialkylamino), and 3-nitro-4-( mt replacement reed or non-rt replacement)
It becomes aminobensito jJ fluoride. On the other hand, 2-nitro-5-chlorobenzotrifluoride is virtually unreacted! Since it remains in the reaction mixture, it can be recovered by washing the reaction mixture with water and, if necessary, distilling it.

In the above, a mixture containing 2-nitro-5-chlorobenzotrifluoride and 3-nitro-4-chlorobenzotrifluoride is reacted with a first casing or a secondary amine or ammonia, and the resulting reaction mixture is Direct 2-nitro-5-chlorobenzotrifluoride and 3-nitro-
Although the reaction mixture resulting in 4-chlorobenzotrifluoride is completely separated, it is also possible to further subject the reaction mixture to a reduction reaction and then separate the reaction mixture for each reaction. For example, 3-nitro-4-(
Hydrogenation of a mixture containing substituted or (91:substituted) aminobenzotrifluoride in the presence of a catalyst such as palladium or platinum, usually supported on a support such as carbon, results in that each nitro group is far from the amino group. be excused. A separation operation may be performed on this mixture of J-cousin products. Of course, the same results can be obtained by performing a separation operation on the reaction mixture before subjecting it to the above-mentioned glue reduction reaction and then carrying out hydrogenation as described above.

Next, the present research will be specifically explained with reference to examples.

Reference Example 1 Commercially available 3-chlorobenzotrifluoride 361y containing 5059ft of 4-chlorpenzotrifluoride was added to #14
1.5F (specific gravity d=1.52), nitric acid 5009 (98%
) into the mixed acid at ￥ - 50 ℃. After the dripping is finished,
After continuing the reaction at the same temperature for 1 hour, the liquid was separated and 443.71% of tr2-nitro-5-chlorobenzotrifluoride (I
Ix rate of 98.4%).

Example 1 22.5 y of the nitro mixture obtained in Reference Example 1, 2.5 y of dimethylamine in 150 y of ethanol. OP'i cotton was mixed, reacted with stirring at room temperature for 3 hours, and distilled to give 2-nitro-5
17.52 of -chlorobenzotrifluoride was obtained. 99% purity.

Example 2 22.5 F of the nitro sludge mixture obtained in Reference Example 1 was added with 3.0 F of n-hexylamine in 150 ml of ethanol, reacted under heating under reflux for 8 hours, and then distilled to obtain 2-nitro 5-
18.6 units of chlorpenzotrifluoride were obtained. Purity 9
8% 0 Example 3 The nitro powder mixture 1002υ and 50% dimethylamine water bath a16.0 as described in Reference Example 1 was reacted by pressing at 150° C. for 4 hours. The organic layer was separated from the reaction mixture, washed with water, and distilled to give 2-nitro-5-chlorobenzotrifluoride 8.
I got 05no. Over 99% purity.

Example 4 2-nitro-5-chlorobenzotrifluoride 20. (1, methanol 100-1
5% palladium/sealed with 0.52% hydrogen (4k'=
9/oi). The temperature is maintained at 35-45°C and the reaction is carried out under stirring. After the reaction is completed, the catalyst is separated and distilled to give 2-amino-5-chlorobenzotrifluoride 1
9.2F (yield 96.0%) is obtained.

Example: Meta/-/ of the nitro mixture 22.59 obtained in Reference Example 1
l/100 mtFIM with dimethylamine a, oy@
The mixture was mixed and allowed to react with stirring at room temperature for 1 hour. Place in a 300-valley autoclave and add 5% platinum/hydrogen to the anti-J core mixture.
52 and add hydrogen (7 cm on the 4th floor). temperature 40
While maintaining the temperature at ~45°C, carry out Jiyuan, and after the reaction is complete,
Distribute the catalyst door to door. By distillation, 2-amino-5-chlorobenzotrifluoride 14.4F (yield 85.7%, purity 99% or more) is obtained.

Note that throughout this specification, unless otherwise specified, percentages are expressed as 9,
Represents weight %.

Patent applicant: Yuikin Kogyo Co., Ltd. Representative Patent Attorney Aoyama Aoyama (2 others)

Claims (1)

[Scope of Claims] A mixture containing 1, 2-ditro-5-chlorobenzotrifluoride and 3-ditro-4-chlorobenzotrifluoride is reacted with a primary amine or a secondary amine or ammonia, and is obtained by 2-nitro-5-
A penzotrifluoride characterized by separating and recovering at least one of chlorobenzotrifluoride or a reaction product derived from the same and a reaction product derived from 3-nitro-4-chlorobenzotrifluoride. Derivative l! i! Construction method. 2, 2-nitro-5-chlorobenzotrifluoro! Jl
' and 3-nitro-4-chlorobenzotrifluoride is obtained by nitrating a mixture containing 3-chlorobenzotrifluoride and 4-chlorobenzotrifluoride.Claim 1. How to make kisen. 3. The first or second amine or ammonia is used twice in mole or more, and the process is carried out at -50 to 200°C under normal pressure to increased pressure. ! The manufacturing method described in Disciple Section 1. 4. 2-nitro-5-chlorobenzo-1- from the reaction mixture
The manufacturing method described in Clause 1 of Patent No. 51''I, which separates and recovers refluoride. 6. A process for producing 3-nitro-4-(substituted or unsubstituted) aminobenzotrifluoride '(il'') from the reaction mixture.
[, the manufacturing method according to claim 1 to be recovered. 7. The production method according to claim 1, wherein the obtained reaction mixture is further subjected to a reduction reaction. 8. The production method according to claim 7, wherein the reduction is carried out by hydrogenation in the presence of palladium or platinum.