JPH04234825A - Process for producing benzotrifluoride compound - Google Patents

Abstract

PURPOSE: To provide the producing method of the benzotrifluoride compound without having complicated operation nor using dangerous starting material to obtain a little by-product and with high yield.

CONSTITUTION: The characterized method for producing benzotrifluoride compound is provided by allowing the para-halobenzotrifluoride compound of the formula to react with hydrogen transfer agent selected from alkali metal formate, ammonium formate and these mixture in the presence of at least about 0.05% metal hydrogenation catalyst of group VIII. In the formula, X is chlorine or bromine, and each of R is independently selected among hydrogen, nitro and amino.

COPYRIGHT: (C)1992,JPO

Description

[Detailed description of the invention]

FIELD OF THE INVENTION This invention relates to a process for preparing benzotrifluoride compounds by reacting para-halobenzotrifluoride compounds with hydrogen transfer agents in the presence of metal hydrogenation catalysts.

BACKGROUND OF THE INVENTION Up to now, benzotrifluoride could only be produced by complicated processes involving the use of difficult-to-handle substances. In one method, benzoic acid was reacted with sulfur tetrafluoride, and in another method, benzotrichloride was reacted with hydrofluoric acid. A less complex route using safer reactants reduces the cost of producing benzotrifluoride and related compounds. In Example 2 of US Pat. No. 4,022,795 it is suggested that 2-aminobenzotrifluoride can be prepared from 5-chloro-2-aminobenzotrifluoride. The reaction occurs in water using sodium hydroxide, a surface active agent such as a phase transfer catalyst (benzyltriethylammonium chloride in Example 2), and palladium on charcoal. Although the reaction conditions remove the halogen from the benzene ring and also reduce the nitro group to an amino group, a competitive reaction also occurs in which two or more aromatic or heteroaromatic nuclei are separated from the nuclear chlorine or bromine atom. Bonded together at positions previously occupied by atoms. In the examples, these dimers accounted for 60% of the product.
The above may be configured. The presence of these undesirable by-products reduces the yield of the benzotrifluoride compound, adds cost to the production of the desired product, and complicates purification of the product.

[Means for Solving the Problems] The present inventors have discovered that a benzotrifluoride compound is paralyzed in the presence of a metal hydrogenation catalyst.
It has been discovered that halobenzotrifluoride compounds can be prepared by reacting with hydrogen transfer agents. Unlike some conventional methods of making benzotrifluoride compounds, the method of the present invention does not involve complicated operations or the use of hazardous starting materials. Although U.S. Pat. No. 4,022,795 suggests that the use of phase transfer catalysts is necessary to reduce dimer formation (see Examples 1 and 2), , we found that using our para-halobenzotrifluoride compounds, the presence of a phase transfer catalyst was not required to reduce dimer formation. By using at least 0.05% by weight of a metal hydrogenation catalyst, we have discovered that U.S. Pat.
The production of undesirable dimeric by-products of the type produced in the '795 reaction can be greatly reduced. Even though our reactions require a solid catalyst to catalyze a possible reaction between two immiscible liquids,
We have unexpectedly found that the reaction proceeds completely even in the absence of surfactant. The para-halobenzotrifluoride compounds used in the method of the invention have the general formula

embedded image where X is chlorine or bromine and each R is independently selected from hydrogen, nitro, and amino. In the formula, X is preferably chlorine. If anything,
This is because these compounds are not very expensive. Further, in the formula, both R groups are preferably hydrogen. This is because it produces a valuable product, benzotrifluoride (referred to as BTF). It is also preferred that one R group is hydrogen and the other R groups are nitro. This is because it also produces a valuable product, m-aminobenzotrifluoride (designated MABTF). Furthermore, it is preferred that both R groups are amino groups. This is because it also produces a valuable product, 3,5-diaminobenzotrifluoride (referred to as DABTF). Most of the starting materials included within the general formula are commercially available. For example, 4-chloro-3,5-dinitrobenzotrifluoride (CDNB
TF) and 4-chlorobenzotrifluoride (referred to as TF) and 4-chlorobenzotrifluoride (referred to as
PCBTF) is commercially available in large quantities, 3-nitro-4-chlorobenzotrifluoride can be produced by nitration of 4-chlorobenzotrifluoride, and 4-chloro-3,5-diaminobenzotrifluoride (referred to as CDABTF) can be easily obtained by reduction of CDNBTF. The para-halobenzotrifluoride compound is reacted with a hydrogen transfer agent, which can be an alkali metal formate, ammonium formate, or a mixture thereof. The alkali metal formate or ammonium formate can be used as is or can be generated in situ by reacting formic acid with a base. Alkali metal formates are preferred. After all, they work well;
This is because they are inexpensive and the by-products produced during the reaction are easy to handle. Particularly preferred is sodium formate. This is because it is cheap. Although a stoichiometric amount of hydrogen transfer agent may be present to remove chlorine and reduce any nitro groups present to amino groups, an excess of up to 10 mol % hydrogen transfer agent may be used to ensure completion of the reaction. It is preferable to do so. The reaction is catalyzed by a metal hydrogenation catalyst (this is VII
(Group I metals). Examples of such catalysts include activated nickel and noble metals such as palladium, platinum, rhodium, and ruthenium. A preferred catalyst is palladium supported on a carbon substrate (Pd/C).
It is. After all, it has been found to work very well. To avoid the formation of large amounts of dimeric by-products, it is necessary to use at least about 0.05% by weight catalyst, based on the weight of halobenzotrifluoride. More than about 1% by weight catalyst can be used, but the small additional benefit is usually not worth the additional cost. Although it is possible to carry out the reaction by melting the reactants, it is preferable to carry out the reaction in a solvent. Since some of the reactants are relatively insoluble in most solvents, they may exist as solids until a dissolved starting material is reacted and another solid starting material is dissolved. Polar solvents, either protic or aprotic, may be used. Examples of suitable polar aprotic solvents include dimethylformamide, dimethyl sulfoxide, and n-methylpyrrolidinone. Examples of suitable polar protic solvents include water and alcohols such as methanol, n-octanol and diethylene glycol. Preferably, the solvent is sufficiently different in boiling point from the benzotrifluoride compound product so that either the solvent or the benzotrifluoride compound is readily boiled away. When the starting material is a nitro-halobenzotrifluoride, the solvent is preferably water or an alkanol up to C3. This is because the aminobenzotrifluoride product has a higher boiling point than the solvent and the solvent can be easily separated by distillation. When the starting material is PCBTF, the solvent is preferably diethylene glycol or n-octanol. This is because the benzotrifluoride compound can be distilled off and thereby separated from the solvent. Although any amount of solvent may be used, it is preferred to use a ratio of about 5 to about 20 parts by weight of solvent to 1 part by weight of halobenzotrifluoride compound. The reaction proceeds by heating the reactants to a temperature between about room temperature and about the boiling point of the solvent, if a solvent is present. The reactants are about 60~
Preferably, it is heated to about 90°C. p of the reaction mixture
H is not critical, but it is usually basic. When a palladium on carbon catalyst is used, it is preferred to blanket the reaction mixture with an inert atmosphere such as nitrogen to prevent ignition of palladium in the air. The reaction can be monitored by gas chromatography to determine when it is complete. Benzotrifluoride products can be used to make a variety of products. for example,
Diaminobenzotrifluoride can be used to make specialty polymers, meta-aminobenzotrifluoride and benzotrifluoride can be used to make pesticides and herbicides, and benzotrifluoride can be used to make pharmaceuticals. .

EXAMPLES The following examples further illustrate the invention. Example 1 Preparation of BTF by hydrodechlorination of PCBTF using sodium formate in methanol In a 20 ml round bottom flask, 1.01 g of PCBTF,
0.56 g of sodium formate and 10 ml of methanol were charged. After purging the flask with nitrogen atmosphere,
0.10 g of 10% Pd/C was added and the reaction mixture was heated in an oil bath with stirring (45-95° C., 1.5 hours). After diluting the reaction mixture with methanol and filtering, gas chromatography (GC) analysis showed a yield of BTF of 98%.
．． It showed 3%. Example 2 PCBTF using ammonium formate in methanol
Preparation of BTF by hydrodechlorination of ammonium formate (0.50 g
) was used to perform the above experiments. A yield of 99.5% was determined after 1.1 hours at 67-71°C (bath temperature). Example 3 Example 1 was repeated using different solvents and reaction conditions. The results are summarized in the table below. Example 4 P using sodium formate in diethylene glycol
Preparation of BTF by Hydrodechlorination of CBTF In a 500 ml round bottom flask equipped with a magnetic stirrer and condenser, the PC
20.07 g of BTF, 32.16 g of sodium formate, and 200 g of diethylene glycol were charged and purged with nitrogen. Then, add 10% Pd/C1.0111 to this.
Add 60-6 g and immerse the flask in a preheated oil bath.
The mixture was stirred at 6°C for 10 hours. After cooling to room temperature, the flask is distilled and the BT is extracted by distillation at water aspirator pressure.
F11.0g (yield 68.1%, purity by GC 96.0g)
0%) were collected. After that, a new PCBTF (20.6
The reaction mixture was reused by adding g) and fresh sodium formate (30.4 g). After heating (60-90° C.) for 18.5 hours, 11.02 g of BTF (yield 66.1%, purity 91.1% by GC) was recovered by the same distillation. The catalyst from the reaction mixture was then washed with methanol (4X100m
l), then washed with water (4X100ml) followed by methanol (4X100ml) and then dried under full vacuum (~0.5mmHg, 7 hours, 0.97g recovered)
Therefore, it was reused three times. Then convert this to PCBTF
(10.05g), sodium formate (16.22g),
and diethylene glycol (100 ml).
ml flask and heated at 80-84°C for 7.4 hours. In the same manner as above, BTF5.94 was obtained by distillation.
g (73.1% yield, 96.5% purity by GC) was recovered. Example 5 Preparation of MABTF m-nitro-p-chlorobenzotrifluoride (MNP
Example 1 was repeated using CBTF). The table below shows the conditions and results. 1 m-nitrobenzotrifluoride intermediate 2 G
C, Internal Standard 3 Reused Catalyst from Previous Experiment 4 Tricaprylmethylammonium chloride sold by Aldrich Chemical Company. This is a phase transfer catalyst and therefore this experiment is outside the scope of this invention. Example 6 Preparation of MABTF using aqueous sodium formate 6.6
Example 1 was repeated using an equivalent amount of sodium formate.

embedded image 1 Outside the scope of the invention 2 5.6 equivalents of HCOONa were used in this experiment. MABTF Reaction Equilibrium Two reactions are occurring: hydrogenolysis of the aryl chlorine and reduction of the nitro group to the amino group. The individual reaction formulas are as follows.

[C4] Thus, the overall reaction equation is as follows.

[Chemical formula 5] Example 7 MABTF by reduction/hydrodechlorination of MNPCBTF
Preparation of MNPC in a 250 ml one-necked flask equipped with a condenser.
BTF25.09g (Marshal
lton), 111.2 mmol), sodium formate 5
0.24 g (738.7 mmol, 6.6 molar equivalent) was charged. It was then purged with nitrogen and 10% P
d/C (Aldrich) 2.57g
(10.2% by weight) was added and the reaction flask was immersed in a 79°C preheated oil bath. After stirring under reflux for 2.3 hours, the reaction mixture was cooled to room temperature and treated with 1 each of water and methylene chloride.
50ml was added with stirring. The reaction mixture was filtered to recover the catalyst, which was washed with 3×100 ml of methylene chloride and the washings were added to the filtrate. The layers were separated and the aqueous layer was further extracted with 100 ml of methylene chloride. Analysis of the extract by gas chromatography using n-hexadecane as internal standard yielded MA corresponding to a yield of 87.8%.
This showed the presence of BTF. The extract was dried over anhydrous sodium sulfate, filtered, and stripped on a rotary evaporator to yield 17.21 g of MABTF (96.0% yield, gc
Purity of 97.5% according to istd) was obtained. Example 8 Preparation of DABTF by Hydrodechlorination of CDABTF in Water 1.0 g (4.76 mmol) of CDABTF was added to 10 ml of water. Solid sodium formate (0.39g,
5.73 mmol) on activated carbon 10% palladium 0
．． Added with 1g. The mixture was heated at 90°C until completion. The catalyst was filtered off and washed with ethyl acetate. The aqueous layer was extracted twice with ethyl acetate and dried over magnesium sulfate. To remove the solvent, 0.76 g of crude DABTF (91.5
%) were isolated. Melting point: 89-90°C. Example 9 DA by hydrodechlorination of CDABTF in methanol
Preparation of BTF Add 10.0 g (0.0 g) of CDABTF to 100 ml of methanol.
0476 mol) was added. Solid sodium formate (8
．． 1 g, 0.119 mmol) was added along with 1.0 g of 10% palladium on activated carbon. The mixture was heated at 70° C. until complete and 200 ml of water was added to dissolve the salt. The catalyst was filtered off and washed with toluene. The aqueous layer was extracted with toluene and the combined extracts were dried over magnesium sulfate. After removal of the solvent, 6.75 g of crude DABTF (80.
5%) were isolated.

Claims (21)

[Claims] 1. A para-halobenzotrifluoride compound having the general formula: [Image Omitted] wherein X is chlorine or bromine, and each R is independently selected from hydrogen, nitro, and amino. in the absence of a phase transfer catalyst and at least about 0.05% VII based on the weight of the para-halobenzotrifluoride compound described above.
1. A method for producing a benzotrifluoride compound, which comprises reacting the compound with a hydrogen transfer agent selected from the group consisting of an alkali metal formate, ammonium formate, and mixtures thereof in the presence of a Group I metal hydrogenation catalyst. 2. The method according to claim 1, wherein X is chlorine. 3. The method according to claim 1, wherein one R is hydrogen and the other R is nitro. 4. A process according to claim 3, wherein water or an alkanol up to C3 is present in the reaction. 5. The method of claim 1, wherein both R are hydrogen. 6. A process according to claim 5, wherein diethylene glycol or n-octanol is present during the reaction. 7. The method of claim 1, wherein both R are amino. 8. A process according to claim 7, wherein water or an alkanol up to C3 is present in the reaction. 9. The method of claim 1, wherein a polar solvent is present during the reaction. 10. The method of claim 9, wherein the weight ratio of said para-halobenzotrifluoride compound to said solvent is about 1 to about 5-20. 11. The method of claim 1, wherein the Group VIII metal hydrogenation catalyst is a noble metal catalyst. 12. The method of claim 11, wherein the noble metal catalyst is palladium supported on carbon. 13. The amount of said catalyst is from about 0.05 to about 0.05 based on the weight of said para-halobenzotrifluoride compound.
12. The method of claim 11, wherein the amount is about 1% by weight. 14. The method of claim 1, wherein said reaction is conducted at a temperature of about 60 to about 90°C. 15. The method of claim 1, wherein said hydrogen transfer agent is sodium formate. 16. (A) (1) para-chlorobenzotrifluoride; (2) at least a substantially stoichiometric amount of an alkali metal formate; (3) about 0 based on the weight of said para-chlorobenzotrifluoride; .05 to about 1% by weight Group VIII metal catalyst;
and (4) a polar solvent in a weight ratio of about 5 to 20 to said para-chlorobenzotrifluoride; and then (B) said composition is heated between room temperature and the boiling point of said solvent. A process for producing benzotrifluoride in the absence of a phase transfer catalyst, characterized by heating at a temperature of . 17. The method of claim 16, wherein the Group VIII metal catalyst is palladium on carbon. 18. (A) (1) 3-nitro-4-chlorobenzotrifluoride; (2) at least a stoichiometric amount of an alkali metal formate; (
3) from 0.05 to about 1% by weight Group VIII metal catalyst based on the weight of the 3-nitro-4-chlorobenzotrifluoride described above; and (4) by weight based on the 3-nitro-4-chlorobenzotrifluoride described above. a polar solvent in a ratio of about 5 to about 20, and then (B) heating said composition at a temperature between room temperature and the boiling point of said solvent. A process for producing meta-aminobenzotrifluoride in the absence of. 19. The method of claim 18, wherein the Group VIII metal catalyst is palladium on carbon. 20. (A) (1) 4-chloro-3,5-diaminobenzotrifluoride; (2) at least a stoichiometric amount of an alkali metal formate; (
3) about 0.05 to about 1% by weight VII based on the weight of the 4-chloro-3,5-diaminobenzotrifluoride described above;
a Group I metal catalyst; and (4) a polar solvent in a weight ratio of about 5 to about 20 to the 4-chloro-3,5-diaminobenzotrifluoride described above;
3 in the absence of a phase transfer catalyst, characterized in that: (B) heating said composition at a temperature between room temperature and the boiling point of said solvent;
, 5-diaminobenzotrifluoride manufacturing method. 21. The method of claim 20, wherein the Group VIII metal catalyst is palladium on carbon.