GB2194533A

GB2194533A - Dichlorotrifluoromethyl nitrotoluenes and their amino derivatives

Info

Publication number: GB2194533A
Application number: GB08719062A
Authority: GB
Inventors: Takeshi Kondo; Toshikazu Kawai; Hideki Oshio
Original assignee: Central Glass Co Ltd
Current assignee: Central Glass Co Ltd
Priority date: 1986-08-13
Filing date: 1987-08-12
Publication date: 1988-03-09
Anticipated expiration: 2007-08-12
Also published as: FR2602766A1; GB8719062D0; GB2194533B; DE3726891A1; FR2602766B1

Description

GB2194533A 1

SPECIFICATION

Compounds useful in the preparation of pharmaceuticals and herbicides This invention relates to novel isomeric compounds named dichlorotrifluoromethyinitrotoiuenes 5 and a method of preparing aminotrifluoromethyltoluenes from the novel compounds.

Aminotrifluoromethyltoluenes (abbreviatqd to ATFT) are of use as intermediate materials of some medicines, particularly of tranquilizers and antiphlogistic anodynes, and agricultural chemi cals represented by herbicides. At present, 2-amino-6- trifluoromethyitoluene (or 2-methyl-3-am ino-benzotrifluoride) is in industrial use for such purposes. 10 The following methods are known for preparation of ATFT.

(1) US 3,390,172 (1968) CH BOOC,,&NO2 SF4 cr C33 NO 2 E 15 3-50 V Pd1C -1 0O.C 70c CH 3 C10 >_&NE 2 20 0 (AT-FT) (2) FR 1,522, 956 (1968) 25 Ofi CH 3 H 2' '->do HNO 3 CH 3 coon 6 1 30 W 3 W 3 C113 No2 H 2' Pd/C 0 NH 2 35 W 3 Cr 3 (3) US 4,209,464 (1980) CH 40 CF,,_,_,_,NH 2 O=S CH W 3 N S C111 3 Q'Cl 25-3 C 3 QJ1 cl CH 3 85-9-c 45 CH 3 CH 3 cr 3 NH2 CF3,,[:NE2 R-Ni Cl 7VC 50 (4) BE 899,927 (1984) 2 GB2194533A 2 CF 3 CF 3 CF3 cl cl, 0 C12 " + - 0 - HN0,j &CH3 6CH 3 ci CH3 _&CH 3 5 CF 3 cl + C1 H21 catalylt CF3 1'&CH3 acceptor CH N024CH N acid N02,-& - 3 2 ci 3 02 10 CF 3 k NH_&CH 2 3 15 However, these methods have disadvantages in some points, respectively. In the method (1), SF, used as fluorinating agent is difficult to acquire in large quantities and is expensive and highly toxic, and the reaction has to be carried out under high- temperature and high-pressure conditions. In the method (2) the starting material, 3trifluoromethylbenzyl alcohol is a very 20 expensive material. In the method (3) the starting material, 2-halogeno-5- trifluoromethylaniline is an expensive material, and each reaction in this method consumes a considerably long time. The method (4) Uses expensive 3-trifluorometyltoluene as the starting material.

SUMMARY OF THE INVENTION 25

It is an object of the present invention to provide a more favorable method of preparing aminotrifluoromethyltoluenes.

It is another object of the invention to provide novel isomeric compounds which can be converted into aminotrifluoromethyltoluenes by the method according to the invention.

It is still another object of the invention to provide a method of preparing said novel com- 30 pounds.

The present invention provides novel isomeric compounds represented by the general formula (1). That is, the novel compounds are dichlorotrifluoromethylnitrotoluenes (abbreviated to DCTFNT).

CH 3 35 CF3,6NC2 (1) C1 C1 40 According to the invention, a DCTFNT is obtained by nitrating a dichlorotrifluoromethyltoluene (abbreviated to DCTFT).

Furthermoie, this invention provides a method of preparing an aminotrifluoromethyltoluen (ATFT), characterized in that a dichlorotrifluoromethylnitrotoluene is reacted with hydrogen in the 45 presence of hydrogenation catalyst and an acid acceptor to thereby accomplish reduction of the nitro group of the DCTFNT and dechlorination of the DCTFNT.

By this method ATFT's including 2-amino-6-trifluoromethyltoluene can easily be prepared with high yields and at relatively low costs.

50 DETAILED DESCRIPTION OF THE INVENTION

Nitration of DCTFT into DCTFNT of the invention is accomplished by reaction with fuming nitric acid in the presence of concentrated sulfuric acid. Usually the fuming acid is 94% nitric acid, and the concentrated sulfuric acid is 96-98% sulfuric acid. In this reaction it is suitable to use 1 to 2 mols, and preferably 1.05 to 1.20 mol, of nitric acid per 1 mole of DCTFT, and the 55 reaction is carried out in the presence of 3 to 6 mols of sulfuric acid per 1 mol of DCTFT. A suitable range of the reaction temperature is from 30 to 120'C, and a preferable range is from to 100'C. The reaction time is usually 2-5 hr, though it is considerably variable depending on various factors.

The position of the nitro group introduced by this reaction is determined by the positions of 60 chorine, methyl and trifluoromethyl substitutions in the DCTFT. That is, a nitro group is selec tively introduced in the 2-position of 3,4-dichloro-6- trifluoromethyltoluene, in the 6-position of 2,3-dichloro-4-trifluoromethyltoluene, in the 4-position of 2,3-dichloro6-trifluoromethyltoluene, in the 3-positicn of 2,4-dichloro-5-trifluoromethyltoluene, in the 6- position of 2,5-dichloro-4-trifluo romethyltolu-3ne, and in the 5-position of 2,6-dichloro-3- trifluoromethyltoluene. 65 3 GB 2 194 533A 3 It is known that 3,4-dichloro-6-trifluoromethyltoluene can be formed by reacting dichlorotoluene with hydrogen fluoride and carbon tetrachloride, but this method is very low in the yield of the DCTFT. As disclosed in our copending patent application of the same date, DCTFT is obtained at good yield by first forming a dichlorotrichloromethyltoluene (abbreviated to DCTCT) by react ing dichlorotoluene with carbon tetrachloride in the presence of an aluminum halide and then 5 fluorinating DUCT by hydrogen fluoride.

Typical examples of aluminum halide used in the initial reaction are anhydrous aluminum chloride and anhydrous aluminum bromide. The quantity of the aluminum halide is 1 to 6 mols, and preferably 1 to 3 mols, per 1 mole of the starting dichlorotoluene. Since the aluminum halide used in this reaction combines with DUCT to form a complex, in case of shortage of the 10 aluminum halide there is selectively formed a dichlorobis (dichloromethylphenyl) methane (abbrevi ated to DCBM) as a by-product. On the other hand, selectivity of the reaction to DUCT does not significantly augment even if an excessively large quantity of aluminum halide is used. This reaction is carried out at a temperature in the range from 0 to 100'C, and preferably from 20 to 800C. The reaction time is usually from 20 min to 4 hr though it is widely variable. In this 15 reaction it is preferable to use an organic solvent selected from, for example, dichloromethane, chloroethanes and chlorofluoroethanes. The best solvent is 1,2- dichloroethane by which the selectivity to DUCT is remarkably enhanced. After the reaction the aforementioned complex is decomposed to thereby obtain DUCT by mixing the reaction product with water.

The fluorinaion of DCTCT is carried out in an autoclave by reacting DUCT with hydrogen 20 fluoride in a quantity not less than the theoretical quantity at a temperature in the range from 0 to 150'C, and preferably from room temperature to 100'C. The reaction pressure is 3-20 kg/cm2, and preferably 8-10 kg/CM2. It is suitable to use 3.2 to 12 mols, and preferably 6 to 9 mols, of hydrogen fluoride per 1 mol of DUCT. The reaction time is usually 3-6 hr though it is considerably variable. After the reaction, high purity DCTFT can easily be recovered by first 25 washing the re action product with an aqueous alkali solution for removal of unreacted fluorinating agent and then subjecting the product to distillation under reduced pressure for separation of the solvent and by-products having higher boiling points.

The reaction between DCTFNT and hydrogen to form ATFT is carried out in an autoclave by passing hydrogen gas through a mixture of DCTFNT, a neutral or basic liquid medium, an acid 30 acceptor and a hydrogenation catalyst, while stirring and heating the mixture, until saturation of absorption of hydrogen in the mixture at the employed reaction temperature and under the employed reaction pressure.

The liquid medium is either water or an organic solvent inactive to the reactants. Examples of useful organic solvents are alcohols preferably having not more than 7 carbon atoms, such as 35 methanol, ethanol, isopropanol, n-propanol, isobutanol, 2-butanol and ethylene glycol, ethers such as glycol methyl ether, glycol dimethyl ether, tetrahydrofuran, dioxane and anisol and hydrocarbons such as cyclohexane, methylcyclohexane, toluene and xylene. The liquid medium may be a mixture. It is preferred to use water and/or ethanol as the liquid medium. The concentration of the starting DCTFNT in the liquid medium is widely variable though concentra- 40 tions not lower than 15 wt% are favorable.

The acid acceptor can be selected from various types of basic compounds such as alkali metal hydroxides, carbonates and acetates, alkaline earth metal hydroxides, oxides, carbonates and acetate, ammonia and amines, particularly tertiary amines. More specifically, good examples are sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, lithium carbo- 45 nate, calcium oxide, magnesium oxide, ammonia, trimethylamine, triethylamine, pyridine and pi coline. The quantity of the acid acceptor is at least 2 mols per 1 mol of ATFT to be formed or DCTFNT to be converted into ATFT. In the case of a tertiary amine it is possible to excessively increase its quantity to thereby use it also as the above described liquid medium.

The hydrogenation catalyst can be selected from conventional catalysts, preferably from ones 50 comprising palladium, platinum and/or nickel. It is best to use a catalyst comprising palladium carried on active carbon. It is suitable that the quantity of the catalyst is 0.01-10 wt%, and preferably 1-5 wt%, of the DCTFNT.

The hydrogenation reaction is carried out at a temperature of 80-120'C and under a pressure of 6-10 kg/CM2. 55 The invention is further illustrated by the following nonlimitative examples.

EXAMPLE 1 A

A mixture of 27.0 g (0.203 mol) of anhydrous aluminum chloride and 100.0 g of carbon tetrachloride was kept stirred, and a solution of 16.1 g (0.1 mol) of 3,4- dichlorotoluene in 54 g 60 of carbon tetrachloride was dropped into the mixture in a total period of 2 hr while the temperature of the reaction system was maintained at 50-52'C. The total quantity of carbon tetrachloride reached 1.0 mol. After than stirring of the reaction liquid was continued for another 2 hr. The reaction liquid was left to cool down and then was poured into 700 ml of iced water, followed by stirring at room temperature. After that aluminum chloride was removed, and an 65 4 GB2194533A 4 organic phase was extracted from the aqueous liquid with carbon tetrachloride. The thus reco vered organic phase was washed with 5% aqueous solution of sodium hydroxide, followed by drying with anhydrous calcium chloride, and the organic solvent was dissipated by distallation under reduced pressure. As the rsult 25.2 g of crude DUCT was obtained. By gas chromato graphy the crude product was proved to contain 73.3 wt% of 3,4-dichioro-6- trichloromethyitolu- 5 ene, referred to as DUCT-(1), (yield 66.3%) and 16.2 wt% of dichlorobis(3, 4-dichloro-6-methyi- phenyi)methane (yield 20.3%), while neither unreacted dichlorotoluene nor 3,4-dichlorobis(trichio romethyl)toluene was detected.

The whole quantity (25.2 g) of the crude DUCT and 10.9 g of hydrogen fluoride were charged in a 100 m] autoclave, and these reactants were stirred and kept heatd at 60-80'C 10 while the pressure in the autocalve was kept at about 8 kg/cm2 by continuously extracting hydrogen chloride gas formed as a by-product of the reaction from the top of reflux tower by means of a primary pressure regulating valve. After the lapse of about 3 hr the pressure in the autoclave was no longer rising, so that it was decided that the fluoronating reaction had been completed. The reaction product was taken out of the autoclave and washed with 10% aqueous 15 solution of sodium hydroxide to remove unreacted hydrogen fluoride, and then distillation under reduced pressure was performed to obtain 1'2.82 g (0.0550 mol, yield 55. 0%) of 3,4-dichloro-6 trifluoromethyltoiuene, referred to as DUFT-(1), of which purity was 98. 2%. This compound had a boiling point of 97-100'C at 23 mmHg.

In a 500 mi round-bottomed flask, 135 g (0.590 mol) of DUFT-(1) was charged together 20 with 230 g of 96% concentrated sulfuric acid, and 47.5 g (0.708 mol) of 94% fuming nitric acid was dropped into the flask in a total period of 1 hr while the temperature of the reaction system was maintained at 4WC under normal pressure. Then the.temperature was raised up to 90'C, and stirring was continued for additional 2 hr. Then 150 g of 1,2- dichloroethane was added to dissolve the reaction product. The resultant solution was allowed to separate into two 25 phases, and the organic phase was washed with 10 wt% aqueous solution of sodium hydroxide to remove unreacted HNO,. After that 1,2-dichloroethane was removed by distillation to obtain 154 g (0.552 mol, yield 93.6%) of 3,4-dichloro-6-trifluoromethyl-2- nitrotoluene, referred to as DCTFNT(1), having purity of 98.3%. The purity of this product was enhanced to 99.3% by reerystailization using n-hexane. The melting point of the purified product was 57.9-58.4'C. The 30 structure of the obtained compound was confirmed by mass spectrometry (MASS) (M+ 273), H NMR spectrometry (in CC14, 6 2.43 3H (CH,) s, 3 7.87 1H (5-H)) and infrared adsorption characteristics (NO, 1565, 1302 cm 1; CH3 1378 cm-'; CF3 1124, 1143, 1179 cm-l; H- 910 cm-1). EI ementary analysis gave the following result.

- 35 Theoretical (%): C 35.04, H 1.46, N 5.11 Found (%): C 34.98, H 1.43, N 5.19 There was no doubt that the chemical formula of the obtained compound was as indicated below. 40 CH 3 CF 3,N02 cl 45 h - 1 In a 500 mi autoclave equipped with a stirrer, 91 9 (0.332 mol) of DUFNT- (1) was charged together with 380 g (1.32 mol) of 28.5 wt% aqueous solution of sodium acetate used as an acid acceptor, 180 mi of ethanol as solvent and 4.5 g of a hydrogenation catalyst which 50 comprised 5 wt% of palladium carried on active carbon. The gas atmosphere in the autoclave was replaced by hydrogen gas, and a hydrogenating and dechlorinating reaction was carried out for 8 hr by feeding hydrogen gas to the mixture in the autoclave with continuous stirring while maintaining the temperature in the autoclave at WC and the pressure at 10 kg/CM2. After that 100 g of 1,2-dichloroethane and 300 g of 10 wt% aqueous solution of sodium hydroxide were 55 added and mixed with the reaction liquid. The mixed liquid was allowed to separate into two layers and the aqueous layer was removed. The organic phase was filtered to remove the catalyst, and the filtrate was dried with anhydrous calcium chloride. Then 1,2-dichloroethane was dissipated from the dried filtrate by simple distillation. By gas chromatography, the organic product was proved to contain 98.5 wt% of 2-amino-6- trifluoromethyitoluene, ATFT-(1). The 60 yield of ATFT-(1) on the basis of DCTFNT-(1) was 96.4 moi%.

EXAMPLE 1 B

In the process of Example 1 A, the reaction to convert DCTFNT-(1) into ATFT-(1) was re- peated except that neither ethanol nor any alternative solvent was used. In this case the organic 65 G82194533A 5 product contained 98.3 wt% of ATFT-(1). The yield of ATFT-(1) on the basis of DUFNT-(1) was 95.7 mol%.

EXAMPLE 1 C

The reaction in Example 1 B was further modified by using 56.2 9 of disodium hydrogenphos- 5 phate as an acid acceptor in place of 108 g of sodium acetate (380 9 of 28.5% solution) in Examples 1A and 1B. In this case the organic product weighed 56.7 9 and contained 98.6 wt% of ATFT-(1). The yield of ATFT-(1) on the basis of DUFNT-(1) was 96.8 mo]O/o.

EXAMPLE 1 D 10 The reaction in Example 1 C was modified by using 29 g of sodium hydroxide as an acid acceptor in place of disodium hydrogenphosphate and omitting the addition of the aqueous solution of sodium hydroxide after the reaction. In this case the organic product weighed 55.8 g and contained 99.0 wt% of ATFT-(1). The yield of ATIFT-(1) on the basis of DCT17NT-(1) was 95.7 moi%. 15 EXAMPLE 2

A mixture of 108 g (0.812 mol) of anhydrous aluminum chloride, 125 9 (0. 812 mol) of carbon tetrachloride and 205 g of 1,2-dichloroethane was kept stirred, and a solution of 65.4 g (0.406 mol) of 2,3-dichlorotoluene in 78.0 g of 1,2-dichloroethane was dropped into the mixture in a 20 total period of 30 min while the temperature of the reaction system was maintained at 50-52'C.

After that stirring of the reaction system was continued for 2 hr, and thereafter the reaction liquid was left to cool down. Then the reaction liquid was poured into 1000 mi of iced water, followed by stirring at room temperature. After removing aluminum chloride, an organic phase was extracted from the aqueous liquid with carbon tetrachloride. The organic phase was washed 25 with 5% aqueous solution of sodium hydroxide, followed by drying with anhydrous calcium chloride, and the solvent was dissipated by distillation under reduced pressure. As the result 102 g of crude DUCT was obtained. By gas chromatography the crude product was proved to contain 42.8 wt% (yield 37.6%) of 2,3-dichloro-4-trichloromethyitoluene, referred to as DUCT (2), 27.1 wt% (yield 23.8%) of 2,3-dichloro-6-trichloromethyltoluene, referred to as DUCT-(3), 30 and 30.1 wt% (yield 36.6%) of DCBM, while unreacted Z,3-dichlorotoluene was not detected.

The whole quantity (102 g) of the crude DUCT and 109 g of hydrogen fluoride were charged in a 300 mi stainless steel autoclave, and these reactants were stirred and kept heated at 95-100'C while the pressure in the autoclave was kept at about 8 kg/CM2 by continuously extracting hydrogen chloride gas formed as a by-product of the reaction in the same manner as 35 in Example 1A. After the lapse of about 3 hr the pressure in the autoclave was no longer rising, so that the fluorinating reaction was terminated. The reaction product was washed with aqueous solution of sodium hydroxide to remove unreacted hydrogen fluoride, followed by distillation under reduced pressure. The thus treated product was a mixture of 7.42 9 (0.0319 mol, yield 16.6%) of 2,3-dichloro-4 trifluoromethyltoluene (purity 98.3%, boiling point 115-118'C at 35 40 mmHg), referred to as DCTFT-(2), and 7.45 9 (0.0323 mol, yield 28.3%) of 2,3-dichloro-6 trifluoromethyltoluene (purity 99.2%, boiling point 108-1 1WC at 35 mmHg), referred to as DCTFT-(3). The structure of DUFT-(2) was confirmed by MASS (M+ 228), H- NMR (in CDO, (5 2.48 3H (CH3) S, 7.24 1 H (6-H) s, 7.52 1 H (5-H) s) and F-NIVIR (in CIDC13, 61.5 ppm 3F (C173) S, standard substance was CKI.). Similarly the structure of DUFT-(3) was confirmed by MASS 45 (M+ 228), H-NMR (in. CIDC1, (5 2.58 3H (CH,) s, 7.48 2H (4,5-H) s) and F- NMR (in CDC13, 63.3 ppm 3F (CF,) s, standard substance was WC13).

In a round-bottomed flask, 7.42 9 (0.0319 mol) of DUFT-(2) obtained by the above process, 16.3 g (0.160 mol) of 96% sulfuric acid and 2.60 9 (0.0388 mol) of 94% fuming nitric acid were stirred and subjected to reaction for 1 hr at WC under normal pressure. After completing 50 the reaction 30 9 of 1,2-dichloroethane was added to dissolve the reaction product. The resultant solution was allowed to separate into two layers, and the organic layer was washed with an aqueous solution of sodium hydroxide to remove acid matter. Then, in an evaporator 1,2-dichloroethane was dissipated from the organic phase to thereby obtain 8.28 g (0.0296 mol, yield 92.7%) of 2,3-dichloro-4-trifluoromethyi-6-nitrotoluene (purity 92. 7%), referred to as 55 DUFNT-(2). The purity of this DUffiT-(2) was enhanced to 99.2% by recrystallization using n hexane. The melting point of the purified product was 44.5-45.7'C. The structure of DUFNT (2) was confirmed by MASS (M+ 273), H-NMR (in WCl., & 2.17 3H (CH3) s, 8. 04 1H (5-H) s) and F-NMR (in WC1, 63.8 ppm 3F (CF,) s, stanard substance was WC13).

In a 100 mi stainless steel autoclave provided with a stirrer, 15.4 9 (0. 0552 mol) of DCTFNT- 60 (2) prepared by the above process was charged together with 53.0 9 of 10 wt% aqueous solution of sodium hydroxide (0.132 mol) used as an acid acceptor and 0. 77 9 of a hydrogena tion catalyst which comprise 5 wt% of I'd carried on active carbon. The atmosphere in the autoclave was replaced by hydrogen gas, and a hydrogenating and dechlorinating reaction was carried out for 4 hr by passing hydrogen gas through the liquid phase, which was under stirring, 65 6 GB2194533A 6 while maintaining the temperature in the autoclave at 1OWC and the pressure at 10 kg/CM2.

After that 30 g of 1,2-dichloroethane was added to and mixed with the reaction liquid, and the mixed liquid was filtered to remove the catalyst. The filtrate was allowed to separate into two layers, and the separated organic layer was dried with anhydrous calcium chloride. Then 1,2 dichloroethane was dissipated by distillation under reduced pressure to obtain 9.29 9 (yield 5 95.7%) of 2-amino-4-trifluoromethyitoluene of which purity was 99.5%.

EXAMPLE 3

In a round-bottomed flask, 7.45 g (0.0323 mol) of DCTFT-(3) prepared in Example 2, 16.5 9 of 96% sulfuric acid (0.162 mol) and 2.60 g of 94% fuming nitric acid (0. 0388 mol) were 10 subjected to reaction in the same manner as in the nitration of DUFT-(2) in Example 2, and the reaction product was treated in the same manner. As the result, 8.36 9 (0. 0302 moi, yield 93.4%) of 2,3-dichloro-6-trifluoromethy]-4-nitrotoluene (purity 98.9%), referred to as DWIFNT-(3), was obtained. The purity of this DUFNT-(3) was enhanced to 99.1% by recrystallization using n-hexane. The melting point of the purified product was 25.5-27.0'C. The structure of DCTFNT- 15 (3) was confirmed by MASS (M+ 273), WNMR (in CDC13, J 0.48 3H (CHJ s, 5. 87 1 H (5-H) s) and F-NMR (in CDCI,, 62.1 ppm 3F (CF,) s, standard substance was CF0J.

In a 100 mi stainless steel autoclave provided with a stirrer, 8.36 9 (0. 0302 mol) of DCTW- (3)-prepared by the above process was charged together with 29.0 9 of 10 wt% aqueous solution of sodium hydroxide (0.0725 mol) used as an acid acceptor and 0. 42 9 of a hydrogena- 20 tion catalyst which comprised 5 wt% of Pcl carried on active carbon. Then the hydrogenating and dechlorinating reaction in Example 2 and the treatment of the reaction product were re peated. In this case the final product was 4.92 9 (yield 92.2%) of 4- amino-2-trifluromethy[tolu ene of which purity was 92.2%.

25 EXAMPLE 4

The initial process (preparation of DUCT) in Example 1A was repeated except that 16.1 g (0.1 mol) of 2,4-dichlorotoluene was used in place of 3,4-dichlorotoluene in Example 1A. As the result 24.3 9 of crude DUCT was obtained. By gas chromatography the crude product was proved to contain 70.2 wt% (yield 61.3%) of 2,4-dichloro-5- trichloromethyitoluene, referred to 30 as DUCT-(4), and 29.8 wt% (yield 35.9%) of the DCBM while unreacted dichlorotoluene was not detected.

The whole quanitity (24.3 9) of the crude DUCT and 10.0 g of hydrogen fluoride were subjected to reaction in the same manner as in Example 1A except that the reaction temperature was raised to 95-102'C. The reaction product was washed with an aqueous solution of sodium 35 hydroxide to remove unreacted hydrogen fluoride and then subjected to distillation under reduced pressure. As the result 12.3 g (0.0527 mol, yield 86.0%) of 2,4-dichloro- 5-trifluoromethyltoluene (purity 98.2%, boiling point 83-85'C at 6 mmHg), referred to as DUFT-(4), was obtained. The structure of this compound was confirmed by MASS (M+ 228), H-NMR (in CDCI, , (5 2.36 3H (CH) s, 7.43 1 H (6-H) s, 7.50 1 H (3-H) s) and F-NMR (in CDO, 62.8 ppm 3F (CF,) s, standard 40 substance was CFC13), In a round-bottomed flask, 14.3 9 (0.0616 mol) of DUFT-(4) prepared by the above process, 31.4 9 of 96% sulfuric acid (0.308 mol) and 4.95 9 of 94% fuming nitric acid (0.0738 mol) were subjected to reaction in the same manner as in the nitration of DUFT- (2) in Example 2, and the reaction product was treated in the same manner. As the result, 16.2 9 (0.0578 mol, 45 yield 93.9%) of 2,4-dichforo-5-trifluoromethyl-3-nitrotoluene (purity 97. 8%), referred to as DUFNT-(4), was obtained. The purity of this product was enhanced to 99.5% by recrystalliza tion using n-hexane. The melting point of the purified product was 58.1- 58.8'C. The structure of DUFNT-(4) was confirmed by MASS (M' 273), H-NMR (in CDO, (5 2.49 3H (CH3) s, 7.68 50; 1H (6-H) s) and F-NIVIR (in CIDC1, 61.3 ppm 3F (CF,) s, standard substance was CFC1,). 50 In a 500 m] stainless steel autoclave provided with a stirrer, 91 9 (0. 322 mol) of DU17NT-(4) prepared by the above method was charged together with 380 g of 28.5 wt% aqueous solution of sodium acetate (1.32 mol) used as an acid acceptor, 180 mi of ethanol as additional solvent and 4.5 9 of a hydrogenation catalyst which comprises 5 wt% of Pcl carried on active carbon.

Then the hydrogenating and dechlorinating reaction in Example 1A and the treatment of the 55 reaction product were repeated. In this case the final product was 57.2 g (yield 97.3%) of 3 amino-5-trifluoromethyltoluene of which purity was 98.9%.

The above hydrogenating and dechlorinating reaction was repeated except that 319 9 of 10 wt% aqueous solution of sodium hydroxide was used in place of the the sodium acetate solution and that the addition of aqueous solution of sodium hydroxide after the reaction was omitted. In 60 this case. the final product was 56.3g (yield 96.2%) of 3-arnino-5trifluoromethyitoluene of which purity was 99.2%.

EXAMPLE 5

The initial process (preparation of DUCT) in Example 1A was repeated except that 16.1 9 65 7 GB2194533A 7 (0.1 mol) of 2,5-dichlorotoluene was used in place of 3,4-dichlorotoluene in Example 1 A and that the quantity of the iced water was increased to 1000 mi. As the result 24.1 9 of crude DUCT was obtained. By gas chromatography the crude product was proved to contain 72.1 wt% (yield 62.4%) of 2,5-dichloro-4-trichloromethyltoluene, referred to a DUCT-(5), and 27.9 wt% (yield 33.3%) of DCBM while unreated dichlorotoluene was not detected. The crude DUCT 5 was dissolved in 50 mi of n-hexane to remove insoluble matter, and the filtrate was subjected to concentration under reduced pressure and distillation under reduced pressure to thereby obtain 11.5 9 (0.0410 mol, yield 41.0%) of DUCT-(5) which had a purity of 99.2% and a melting point of 41.6-42.5'C. The structure of this compound was confirmed by MASS (M+ 276) and WNMR (in CDCI,, (5 2.39 3H (CHJ s, 7.40 1 H (3-H) s, 8.13 1 H (6- H) s). 10 24.1 g of the aforementioned crude DUCT and 10.0 9 of hydrogen fluoride were subjected to reaction in the same manner as in Example 1A except that the reaction temperature was raised to 95-102'C, and the reaction product was treated in the same manner. As the result 11.3 g (0.0483 mol, yield 77.3%) of 2,5-dichloro-4-trifluoromethyitoluene (purity 97.8%, boiling point 83-85'C at 6 mmHg), referred to as DUFT-(5), was obtained. The strcture of this 15 compound was confirmed by MASS (M+ 228), H-NMR (in CIDID13, (5 2.35 3H (CH3) s, 7.32 1 H (3 H) s, 7.61 1 H (6-H) s) and F-NIVIR (in CIDW13, 63.1 ppm 3F (CF3) s, standard substance was CFCW' In a round-bottomed flask, 13.6 9 of DUFT-(5) prepared by the above method, 29.4 g of 96% sulfuric acid (0.289 mol) and 4.64 9 of 94% fuming nitric acid (0. 0692 mol) were 20 subjected to reaction is the same manner as in the nitration reaction in Example 2, and the reaction product was treatd in the same manner. As the result, 15.4 9 (0. 0552 mol, yield 95.7%) of 2,5-dichloro-4-trifluoromethyi-6-nitrotoluene (purity 98.2%), referred to as DCT17NT-(5), was obtained. The purity of this product was enhanced to 99.2% by recrystallization using n hexane. The melting point of the purified product was 48.5-49.4"C. The structure of DUFNT- 25 (5) was confirmed by MASS (M+ 273), H-NMR (in CDCI,, 8 2.41 3H (CH,) s, 7. 85 1H (3-H) s) and F-NIVIR (in CDCI,, 63.2 ppm 3F (CF,) s, standard substance was WC1,).

In a 100 mI stainless steel autoclave provided with a stirrer, 8.28 9 (0. 0296 mol) of DCTFNT- (5) prepared by the above process was charged together with 28.4 g of 10 wt% aqueous solution of sodium hydroxide (0,0710 mol) used as an acid acceptor and 0. 42 9 of a hydrogena- 30 tion catalyst comprising 5 wt% of I'd carried on active carbon. Then the hydrogenating and dechlorinating reaction in Example 2 was repeated and the reaction product was treatd in the same way. In this case the final product was 4.91 g (yield 94.1%) of 2- amino-4-trifluoromethy lene of which purity was 99.2%.

35 EXAMPLE 6

A mixture of 27.0 g (0.203 mol) of anhydrous aluminum chloride, 31.5 g (0. 205 mol) of carbon tetrachloride and 50.5 g of 1,2-dichloroethane was keptstirred, and a solution of 16.1 9 (0.1 mol) of 2,6 dichlorotoluene in 19.1 g of 1,2-dichloroethane was dropped into the mixture in a total period of 2 hr while the temperature of the reaction system was maintained at 50-52'C. 40 After that stirring of the reaction sytem was continued for 2 hr, and thereafter the reaction liquid was left to cool down. Then the reaction liquid was treated in the same way as in the preparation of DUCT in Example 2. As the result 26.0 g of crude DUCT was obtained. By gas chromatography the crude product was proved to contain 88.4 wt% (yield 82. 7%) of 2,6 dichloro-3-trichloromethyitoluene, referred to as DCTCT-(6), and 11.6 wt% (yield 15.0%) of 45 DCBM while unreacted dichlorotoluene was not detected.

In a 100 m] stainless steel autoclave, 26.0 9 of the crude DUCT obtained by the above process and 10.0 9 of hydrogen fluoride were subjected to reaction in the same manner as in Example 1A except that the reaction temperature was raised to 95-102'C, and the reaction product was treated in the same way. As the result 16.6 9 (0.0527 mol, yield 87.8%) of 2,6dichloro-3-trifluoromthyitoluene (purity 98.7%, boiling point 83-85'C at 8 mmHg), referred to as DCTFT-(6), was obtained. The structure of this compound was confirmed by MASS (M+ 228), H-NMR (in CDO, (5 2.58 3H (CH,) s, 7.33 1 H (5-H) s, 7.43 1 H (4-H) s) and F-NIVIR (in WC13, 62.8 ppm 3F (CF3) s, standard substance was WC13), In a round-bottomed flask, 16.6 g (0.0715 mol) of DCTFT-(6) prepared by the above method, 55 36.5 9 of 96% sulfuric acid (0.358 mol) and 5.75 9 of 94% fuming nitric acid (0.0858 mol) were subjected to reaction in the same manner as in the nitration reaction in Example 2, and the reaction product was treated in the same way except that the quantity of 1,2-dichloroethane as solvent was increased to 50 9. As the result, 18.9 9 (0.0674 mol, yield 94.2%) of 2,6-dichloro 3-trifluoromethyl-5-nitrotoluene (purity 97.5%), referred to as DUFNT- ffi), was obtained. The 60 purity of this product was enhanced to 99.5% by recrystallization using n- hexane. The melting point of the purified product was 40.7-41.5"C. The structure of DCTFNT- (6) was confirmed by MASS (M+ 273), WNMR (in CDCI,, 6 2.68 3H (CHJ s, 8.07 1 H Q-1-1) s) and F- NIVIR (in CDC13, 63.7 ppm 3F (CF,) s, standard substance was CFC13), In a 100 m] stainless steel autoclave provided with a stirrer, 8.36 9 (0. 0302 mol) of DCTINT- 65 8 GB 2 194 533A 8 (6) prepared by the above process was charged together with 29 g of 10 wt% aqueous solution of sodium hydroxide (0.0725 moll used as an acid acceptor and 0.42 g of a hydrogenation catalyst comprising 5 wt% of Pd carried on active carbon. Then the hydrogenating and dechlori nating reaction in Example 2 was repeated and the reaction product was treated in the same way. In this case the final product was 4.98 g (yield 93.3%) of 3-amino-5trifluoromethyltoluene 5 of which purity was 99.0%.

Claims

1. A compound of formula.

10 CF374N02 (1) C1 C1 f 2, 3,4-dichloro-6-trifluoromethyl-2-nitrotoluene.

3. 2,3-dichloro-4-trifluoromethyl-6-nitrotoluene.

4. 2,3-dichloro-6-trifluoromethyl-4-nitrotoluene.

5 2,4-dichloro-5-trifluoromethyl-3-nitrotoluene. 20

6. 2,5-dichloro-4-trifluoromethyl-6-nitrotoluene.

7. 2,6-dichloro-3-trifluoromethyl-5-nitrotoluene.

8. A method of preparing a compound as defined in claim 1 which comprises nitrating a dichlorotrifluoromethyltoluene.

9. A method according to claim 8 wherein the dichlorotrifluoromethyltoluene is nitrated with 25 fuming nitric acid in the presence of concentrated sulfuric acid.

10. A method according to claim 9 wherein the nitric acid is present in an amount of from 1.05 to 1.20 mol and the sulfuric acid is present in an amount of from 3 to 6 mols, per 1 mol of dichlorotrifluoromethyltoluene.

11. A method of preparing a compound as defined in claim 1 substantially as hereinbefore 30 described in any one of Example 1 A or 2 to 6.

12. A method of preparing an aminotrifluoromethyltoluene wherein a dichlorotrifluoromethylni- trotoluene is reacted with hydrogen in the presence of an acid acceptor and a hydrogenation catalyst.

13. A method according to claim 12 wherein the reaction is carried out in a liquid medium. 35

14. A method according to claim 13 wherein the liquid medium comprises water.

15. A method according to claim 13 or 14 wherein the liquid medium comprises an organic solvent.

16. A method according to claim 15 wherein the organic solvent is enthanol.

17. A method according to any one of claims 12 to 16 wherein the acid acceptor is a basic 40 compound which is an alkali metal salt, alkaline earth metal salt, ammonia or amine.

18. A method according to any one of claims 12 to 17 wherein the acid acceptor is present in an amount of at least 2 mols per 1 mol of dichlorotrifluromethylnitrotoluene.

19. A method according to any one of claims 12 to 18 wherein the catalyst comprises palladium. 45

20. A method according to claim 19 wherein the catalyst further comprises active carbon.

21. A method according to any one of claims 12 to 20 wherein the reaction is carried out at a temperature of from 80 to 120'C under a pressure of from 6 to 10 kg/cm2.

22. A method according to any one of claims 12 to 21 wherein the dichlorotrifluoromethylto- luene is 3,4-dichloro-6-trifluoromethyl-2-nitrotoluene, 2,3-dichloro-4trifluoromethyl-6-nitrotoluene, 50 2,3-dichloro-6-trifluoromethyl-4-nitrotoluene, 2,4-dichloro-5trifluoromethyl-3-nitrotoluene, 2,5-di chloro-4-trifluoromethyl-6-nitrotoluene or 2,6-dichlor.o-3trifluoromethyl-5-nitrotoluene.

23. A method of preparing an aminotrifluoro'm"ethyltoluene substantially as hereinbefore de- scribed in any one of the Examples.

Published 1988 at The Patent Office, State House, 66/71 High Holborn, London WC113 4TP. Further copies maybe obtained from The Patent Office, Sales Branch, St Mary Cray, Orpington, Kent BR5 3RD. Printed by Burgess & Son (Abingdon) Ltd. Con. 1/87.