CA2037517A1 - Method of making benzotrifluoride compound - Google Patents

Abstract

METHOD OF MAKING A BENZOTRIFLUORIDE COMPOUND
ABSTRACT OF THE DISCLOSURE
Discloses a method of making a benzotrifluoride compound by reacting a para-halobenzotrifluoride compound having the general formula

Description

2~7~17 Case 6146~59/60 RDF/kmf METHOD OF MAXING BENzorRIFLuoRID~ CONPOUND
Background of the_Invention This invention relates to a method of making a benzotrifluoride compound by reacting a para-halobenzotrifluoride compound with a hydrogen transfer agent in the presence of a metal hydrogenation catalyst.
Until now, benzotrifluoride could be made only by complicated processes that involved the use of materials that are difficult to handle. In one process, benzoic acid was reacted with sulfur tetrafluoride, and, in another process, benzotrichloride was reacted with hydrofluoric acid. A less complicated route that uses safer reactants would reduce the cost of producing benzotrifluoride and related compounds.
In U.S. Patent 4,022,795, Example 2, 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 (benzyl triethylammoniu~ chloride in Example 2), and palladium on charcoal. While the reaction conditions remove halogen ~rom a benzene ring, and will also reduce nitro ; ; groups to amino groups, a competing reaction also occurs in which two or more aromatic or heteroaro~atic nuclei are joined together at the positions formerly occupied by nuclear chlorine or bromine atoms. In the Examples, these dimers can constitute over 60% of the product. The presence of these unde~irable ~ 022690 ': ' ', ' ., ' . ~' ' ' '. ', ' ' . ' .': ' ,' ' '' ': " ' . ; '. ' ',: ' .' ' ' ' 2~37~17 by-products reduces the yield of the benzotrifluoride compound, adds to the expense of producing the desired product, and ;
complicates purification of the product.
Summary of the Invention We have discovered that benzotrifluoride compounds can be ~, -made by reacting a para-halobenzotrifluoride compound with a hydrogen transfer agent in the presence of a metal hydrogenation catalyst. Unlike some prior methods of making benzotrifluoride compounds, the method of this invention does not involve complicated procedures or the use of dangerous starting materials.
While U. S. Patent 4,022,795 suggests that the use of a phase transfer catalyst is necessary to reduce the formation of dimers (see Examples 1 and 2), we have found that with our para-halobenzotrifluoride compounds, the presence of a phase transfer catalyst is not required to reduce the formation of dimers. By using at least 0.05 wt% of a metal hydrogenation cotalyst we are able to greatly reduce the production of undesiroble dimer by-products of the type that were formed in the reactions in U.S. Patent 4,022,795. Surprisingly, even though in our reaction the solid catalyst must catalyze a r-action thot can be betwe-n two immiscible liquids, we have ound~that the reaction proceeds to completion, even in the abs-nce of a surface active agent.

- 2~37~:~7 escription of the T~v8a~a The para-halobenzotrifluoride compounds used in the process of this invention have the general formula R~R ~ ~

where X is chlorine or bromine and each R is independently selected from hydrogen, nitro, and amino. In the formula, X is preferably chlorine as those compounds are less expensive.
Also in the formula, both R groups are preferably either hydrogen, as that produces benzotrifluoride (BTF), a valuable product, or one R group is hydrogen and the other R group is nitro as that produces m-aminobenzotrifluoride (MABTF), which is also a valuable product. M ditionally, both R groups are preferably amino groups, as that produces 3,5-diaminobenzotrifluoride (DABTF), which is al80 a valuable product. Most of the starting materials included w$thin the scope in the general formula are commercially available. For example, 4-chloro-3,5-dinitrobenzotrifluoride (CDNBTF) and 4-chlor3benzotrifluorSde~(PCBTF) are commercially available in bulk,~3-nltro-4-chlorobenzotrifluoride can be made by nitrating 4-oh~lorob-nzotrifluoride, and 4-chloro-3,5,-diamSnobenzo-trifluoride (CDA~TF) is readily available via r~duction of ~ ~ -CDNBTF.

The~para-halobenzotrifluoride compound is reacted with a hydrogen~transfer agent, which can be an alkali metal formate, _ 3 _ 2~37~ 7 ammonium formate, or a mixture thereof. The alkali metal formate or ammonium formate can be added as such, or can be formed in situ by reacting formic acid with a base. Alkali metal formates are preferred because they work well, they are ;
inexpensive, and the by-products formed in the reaction are easier to handle; sodium formate is especially preferred because it is inexpensive. A stoichiometric amount of the hydrogen transfer agent can be present to remove the chlorine and to reduce any nitro groups that are present to amino groups, but it is preferable to use up to 10 mole% excess of the hydrogen transfer agent in order to insure completion of the reaction.
The reaction is catalyzed by a metal hydrogenation -catalyst, which is a Group VIII metal; examples of such catalysts include activated nickel and precious metals such as, for example, palladium, platinum, rhodium, and ruthenium. The preferred catalyst is palladium on a carbon substrate (Pd/C) as lt has been found to work very well. In order to avoid the production of large amounts of dimer by-product, it is necessary to use at least about 0.05% by weight catalyst, based on the weight of the halobenzotrifluoride. While more catalyst than about 1% by weight can be used, the small additlonal beneflt 1- usually not worth the additional expense.
It~1- poss1ble to conduct the reaction by melting the reactants, but it is preferable to conduct the reaction in a solv-nt.~ Since some of the starting materials are relatively iD~soluble in~most solvents, they may be present as solids until the~dissolved starting~material reacts and additional solid . : ~. . . - . , , . ~

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2~37~ 7 starting material dissolves. A polar solvent, either protic or aprotic, can be used. Examples of suitable polar aprotic solvents include dimethylformamide, dimethylsulfoxide, and n-methylpyrrolidinone. Examples of suitable polar protic solvents include water and alcohols such as methanol, n-octanol, and diethylene glycol. Preferably, the solvent should differ sufficiently in boiling point from the benzotrifluoride compound product so as to permit one to easily boil off either the solvent or the benzotrifluoride compound.
If the starting material is a nitro-halobenzotrifluoride, the solvent is preferably water or an alkanol up to C3, as the aminobenzotrifluoride product will have a higher boiling point than the solvent and the solvent can be easily separated by distillation. If the starting materiaI is PCBTF, the solvent is preferably diethylene glycol or n-octanol as the benzotrifluoride product can then be distilled off a~d, thereby, separated from the solvent. Any amount of solvent can be used but it is preferable to use a ratio of about S to about 20 parts by weight solvent to 1 part by weight halobenzotrifluoride compound.
The reaction proceeds by heating the reactants to a temperature between about room temperature and about the bolllng;point of the solvent, ir a solvent is present.
Preferably, the~reactants are heated to about 60 to about 90oC.
While the pH of the reaction mixture is not critical, it is usually basic. Mhen a palladium on carbon catalyst is used, it is~preferable to cover~the reaction mixture with an inert atmospheré such as nitrogen to prevent the ignition of the .

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palladium in air. The reaction can be monitoxed by gas chromatography to determine when it is complete.
The benzotrifluoride products can be used for making a variety of products. For example, the diaminobenzotrifluorides can be used to make specialty polymers, meta-aminobenzotri-fluoride and ~enzotrifluoride can be used in making pesticides and herbicides, and benzotrifluoride can be used to make p~armaceuticals.
The following examples further illustrate this invention.

Preparation o BTF by the Hydrodechlorination of PCBTF
using Sodium Formate in Methanol A 20 mL round-bottom flask was charged with 1.01 g PCBTF, 0.56 g sodium formate, and lO mL methanol. After purging the flask with a nitrogen atmosphere, 0.10 g of 10% Pd/C was added and the reaction mixture was heated, with stirring, in an oil bath (45 to 95C, 1.5 h). After diluting the reaction mixture with methanol and filtering, gas chromatographic (GC) analysis indicated a 98.3% yield of BTF.
EXAMPLE 2 ~ -Prepa~ 5lon of BTF by the Hydrodechlorination of PCBTF
using Ammonium Formate in Methanol Th~ above experiment was run using ammonium formate (0.50 g) in place of sodium formate; a 99.5% yield was determined after 1.1 h at 67 to 71C (bath temperature).

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2~7~17 ~ xample 1 was repeated using different solvents and reactions conditions: the results are summarized in the following table.

Pd/C Catalvst GC ANALYSIS
Solvent _~ Wt% hours BTF PCBTF Dimer methanol 1 10 1 85.8 0 14~2 methanol 5 lo 3 93.2 o 6.8 methanol 10 10 3 97.7 0 1.8 methanol 10 1 5 81.0 0 16.0 methanol 10 5 3 97.6 o 2.4 methanol l 1 18 54.1 13 32.4 n-octanol 10 11.6 3.2 78.2 o.s 14.0 diethylene 10 12.1 1 87.4 0 11.7 glycol Preparation of BTF by the Hydrodechlorination of PCBTF -usin~ Sodium Formate in Diethylene Glycol A 500 mL round-bottom flask equipped with a magnetic stirrer and a condenser was charged with 20.07 g PCBTF, 32.16 g sodium formate, and 200 mL diethylene glycol, and was purged with nitrogen. To this was then added 1.0111 g 10% Pd/C and the flask was immersed in a preheated oil bath and stirred at 60 to 66~C for lO h. After allowing to cool to room temperature, the flask was adapted for distillation and 11.05 g ~!-BTF ~68.1% yield, 96.0% purity by GC) was collected by distillation at water aspirator pressure (15 to 25 mm Hg, 60 to 65C).
The reaction mixture was then reused by adding fresh PCBTF
(20.6 g) and fresh sodium formate (30.4 g). After heating for , 18.5 h (60 to 90~C), 11.02 g of BTF (66.1% yîeld, 91.1% purity by GC) were collected by distillation in a æimilar fashion.

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20~7~ 7 The catalyst from the reaction mixture was then reused a third time by first filtering and washing it with methanol (4 X
loo mL), then water (4 X 100 mL), followed by methanol (4 X 100 mL), then drying under full vacuum ( about 0.5 mm Hg, 7h., 0.97 g recovered). This was then charged in a 250 mL flask with PCBTF (10.05 g), sodium formate (16.22 g), and diethylene glycol (100 mL), and heated at 80 to 84OC for 7.4 h. In a similar fashion to above, 5.94 g of BTF (73.1% yield, 96.5 purity by GC) was collected by distillation.

Preparation of MABTF
Example 1 was repeated using m-nitro-p-chlorobenzotrifluoride (MNPCBTF). The following table gives the conditions and the results.
Sodium NNPCBTF Formate Methanol Temp. h GC Area %
grams equiv. mL MABTFMNBTF

1 1.9 10 69-88C 215.2%79 9%
1 4.0 10 66-77C 986.7%11 0%
+1.9 69--80C 2 94-0% 0,0%
1006.4 1000 56-68C 2100.0%0.0%
1 6.4 5 69-70C 1 60.7S MNBTF gc istd2 (78.6% conversion) 1 6.4 5 85-98C 4.4 13.3% 78.4%
~3.2 10 57.5~ ~ABTF gc istd 6.6 100 78-79C 2.3 87.8% MAB~F gc istd 96.0% i801. (97.5% pure) Catalyst Recycle:
25 6.6 100 80-84C 4.5 72.1% MABTF gc istd 65.5% isolated Water + 4.4 wt~ ~Aliquat-336~ -no solvent:
6.6 10 mL H20 81-82C 2.5 16.9 39.6%
~5~ mL H20 75-82C 6.6 78.4% ~ABTF gc istd 77.1% isolated ' ~

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2~37~1.7 Other catalyst loadinas:
10 wt% Pd-C: MABTF MNBTF
25 4.0 100 73-86C 22 o 57.3%
(69% conversion) +4.0 75-81C 22.8 84.6% 0 5 wt% 10% Pd-C: 54.1% MABTF gc istd 4.0 100 73-83C 22 44.4~ 46.1%
+4.0 81-85C 22.8 90.0% 0 78.1% MABTF qc istd 1 m-nitro benzotrifluoride intermediate 2 GC, internal standard 3 reused catalyst from previous experiment 4 tricaprylmethylammonium chloride sold by Aldrich Chemical Co. This is a phase transfer catalyst and this experiment is, therefore, outside the scope of this invention.

Preparation o~_~ABTF using ~queous sodium ~ormate Example 1 was repeated using 6.6 equivalents of sodium .
formate 105-110C ~ `
Y~N2H2O/HCO2Na NH2 '~
MNPCBTFFd/C - MA8TF
., .

Com~ents EL 10% Pd-C h YI~L~
- Water GC IS~ Iso~a~ç~
"standard" 100 10 wt% 4.6 86.3 +4.4 wt% 1100 10 wt% 23.3 5%
"Aliquat 336"
les~ water 35 10 wt% 1.~ 82.1% 91.3%
recycle cat.35 reuse 1.1 99.6% 92.0%
recycIe again35 reuse 13.4 60.5%
less catalyst35 2 wt% 8.3 84.4% 89.9%
les~ cat~lyst35 3 wt% 2.1 85.5% 93.6%
rèpéat 3S~e~ t.35 3 wt% 2.7 90.0% 92 9%
le6s~ HCOONa35 3 wt~ 8.6 73%
50 g scale 175 3 w~% 1.4 94.8% 88.3%
rècycle c~t.175~ reuse 20.5 9g.2% 100%
outsid- the scope of thi~ invention 2 ~ 5.6~equiv. of HCOONa were used in this experiment 2~7 ~ 7 ~
B~ ~e~ction Balance Two reactions are taking place hydrogenolysis of an aryl chlorine and reduction of a nitro-group to an amine The separate equations are ArCl + NaOOCH -----> ArH + NaCl + C02 ArN02 + 3 NaOOCH -----> ArNH2 + Co2 ~ Na2C03 + Na~CO
also 2NaHCo3 <======> Na2C03 + H20 + Co2 Thus, the overall eguation is:

~ + 4NaOOCH ~ ~

+ NaCl - . -+ 2.5 CO2 + 1.5 Na2CO3 * 0 5 H20 EXAMPLE ~
Pre~aration of MABTF by the Reduction/Hydrodechlorination of MN~C~TF
A~250 mL ~ingle-neck flask equipped with a condenser was :
charged with~25 09 g ~NPC8TF (Marshallton, 111 2~mmol), 50 24 g sodium~formate (738 7 l,~ 6 6~ 1e -quiv ), and lOO mL
methanol; This w~ th-n purged with nitrogen, 2 57 g (10 2 wt~) o~10%~Pd~on C~(Aldrich~ was~added,~and the reaction flask was~im~me~rsed~in;a~pr-h~ated oil bath~;at 79 C Aft-r stirring -;
2 3~h under r flux~the~r action mixture wa cooled to room - -er~tyr-~and~l50~mL~eaoh-of~wat-r and methylen chloride w~ro~dded~with ~tirring ~ The~r~action mixture was filtered to ~37~:~ 7 recover the catalyst, and this was washed with 3 X 100 mL of methylene chloride, the washings being added to the filtrate.
The layers were separated and the aqueous layer was extracted with a further 100 mL or methylene chloride. Analysis of the extracts by gc using n-hexadecane as internal standard indicated the presence of MABTF amounting to an 87.8% yield.
The extracts were dried over anhydrous ssdium sulfate, filtered, and stripped on a rotary evaporator to yield 17.21 g of MABTF (96.0% yield, 97.5% purity by gc istd).

Preparation of DABTF by Hydrodechlorination of CDABTF in Water To 10 m~ of water was added 1.0 g (4.76 mmol) of CDABTF.
Solid sodium formate was added (0.39 g, 5.73 mmol), along with 0.1 g of 10% palladium on activated carbon. The mixture was heated at 90DC until complete. The catalyst was filtered cff and washed with ethyl acetate. The aqueous layer was extracted twice with ethyl acetate and dried over magnesium sulfate.
After removal of the solvent, 0.76 g (91.5%) of crude DABTF was isolated, mp 89 to 90C.

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2~7~ 7 EXAMPLE g Preparation of DABTF by HYdrodechlorination of CDABTF in Methanol To 100 mL of methanol was added 10.0 g (0.0476 mol) of CDABTF. Solid sodium formate was added (8.1 g, o.l19 mmol), along with l.0 g of 10% palladium on activated carbon. The mixture was heated at 70C until complete and 200 mL of water was added to dissolve the salts. 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 (80.5%) of crude DABTF was isolated.

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Claims (21)

1. A method of making a benzotrifluoride compound comprising reacting a para-halobenzotrifluoride compound having the general formula with a hydrogen transfer agent selected from the group consisting of alkali metal formates, ammonium formate, and mixtures thereof, in the absence of a phase transfer catalyst and in the presence of at least about 0.05 % by weight, based on the weight of said para-halobenzotrifluoride compound, of a Group VIII metal hydrogenation catalyst, where X is chlorine or bromine, and each R is independently selected from hydrogen, nitro, and amino.

2. A method according to Claim 1 wherein X is chlorine.

3. A method according to Claim 1 wherein one R is hydrogen and the other R is nitro.

4. A method according to Claim 3 wherein water or an alkanol to C3 is present during said reaction.

5. A method according to Claim 1 wherein both R's are hydrogen.

6. A method according to Claim 5 wherein diethylene qlycol or n-octanol is present during said reaction.

7. A method according to Claim 1 wherein both R's are amino.

8. A method according to Claim 7 wherein water or an alkanol to C3 is present during said reaction.

9. A method according to Claim 1 wherein a polar solvent is present during said reaction.

10. A method according to Claim 9 wherein the weight ratio of said para-halobenzotrifluoride compound to said solvent is about 1 to about 5 to 20.

11. A method according to Claim 1 wherein said Group VIII
metal hydrogenation catalyst is a precious metal catalyst.

12. A method according to Claim 11 wherein said precious metal catalyst is palladium on carbon.

13. A method according to Claim 11 wherein the amount of said catalyst is about 0.05 to about 1 wt.%, based on the weight of said para-halobenzotrifluoride compound.

14. A method according to Claim 1 wherein said reaction is conducted at a temperature of about 60 to about 90°C.

15. A method according to Claim 1 wherein said hydrogen transfer agent is sodium formate.

16. A method of making benzotrifluoride in the absence of a phase transfer catalyst comprising (A) forming a composition which comprises (1) para-chlorobenzotrifluoride;
(2) at least about a stoichiometric amount of alkali metal formate;
(3) about 0.05 to about 1 wt.%, based on the weight of said para-chlorobenzotrifluoride, of a Group VIII metal catalyst; and (4) a polar solvent in a weight ratio to said para-chlorobenzotrifluoride of about 5 to about 20; and (B) heating said composition at a temperature between room temperature and the boiling point of said solvent.

17. A method according to Claim 16 wherein said Group VIII
metal catalyst is palladium on carbon.

18. A method of making meta-aminobenzotrifluoride in the absence of a phase transfer catalyst comprising (A) forming a composition which comprises (1) 3-nitro-4-chlorobenzotrifluoride;
(2) at least a stoichiometric amount of alkali metal formate:
(3) about 0.05 to about 1 wt.%, based on the weight of said 3-nitro-4-chlorobenzotrifluoride, of a Group VIII metal catalyst; and (4) a polar solvent in a weight ratio to said 3-nitro-4-chlorobenzotrifluoride of about 5 to about 20; and (B) heating said composition at a temperature between room temperature and the boiling point of said solvent.

19. A method according to Claim 18 wherein said Group VIII
metal catalyst is palladium on carbon.

20. A method of making 3,5-diaminobenzotrifluoride in the absence of a phase transfer catalyst comprising (A) forming a composition which comprises (1) 4-chloro-3,5-diaminobenzotrifluoride;
(2) at least a stoichiometric amount of alkali metal formate;
(3) about 0.05 to about 1 wt.%, based on the weight of said 4-chloro-3,5-diaminobenzotrifluoride, of a Group VIII metal catalyst; and (4) a polar solvent in a weight ratio to said 4-chloro-3,5-diaminobenzotrifluoride of about 5 to about 20; and (B) heating said composition at a temperature between room temperature and the boiling point of said solvent.

21. A method according to Claim 20 wherein said Group VIII
metal catalyst is palladium on carbon.