DE2537288A1 - MANUFACTURE OF TRIFLUOROMETHYL SUBSTITUTED AMINOBENZONITRILE - Google Patents

Description

Bayer Aktiengesellschaft

Central Patents Department. Trademarks and licenses

509 Leverkusen. Bayerwerk

Jo / Pt

ü,

Production of trifluoromethyl-substituted aminobenzonitriles

The invention relates to an improved process for the preparation of aminobenzonitriles with CF ^ groups.

CF ^ -substituted aminobenzonitriles are excellent intermediates for the manufacture of azo dyes (British Patents 756 079 and 757 361) and for manufacture of biologically active compounds such as pesticides (US Pat. No. 3,012,058).

Those to be produced according to the invention are of great technical importance However, compounds have not yet been obtained because there has been no manufacturing method available that the compounds delivered in a simple manner and with high yields.

So far, two chemically different manufacturing processes have been proposed. One method is based on CF, -substituted anilines, which are nitrated to give the corresponding nitro compounds. The amino group is converted to the cyano group with nitrous acid and subsequent reaction with a heavy metal cyanide in the sense of a Sandmeyer reaction (J. Am. Chem. Soc. 73, 5125-27 (1951) and 76, 1151-54 (1954) and J. Chem. Soc. B, 1967 «449-454).

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The last reaction step is the reduction of the Nitro to amino group (British Patents 756 079 and 757 361).

The second method, so far only used for compounds in which the CF ^ group is in the m-position to the amino group, is based on CF ^ -substituted chloroaniline, which, according to Sandmeyer, is converted to CF -., - substituted chlorobenzonitrile, which is reacted in the last stage under pressure with liquid ammonia to form CF, -substituted aminobenzonitrile.

A common feature of all of the previously known processes is the poor yield. Although the importance of CF ₁ , -substituted aminobenzonitriles has been recognized in the previous literature, no production processes proceeding in high yields could be proposed.

It has now been found that GF, -substituted cyananilines of the general formula (i)

(D

in which

the CN group in o- or p-position to the amino group and the CF ^ group is in ρ- or o-position to the amino group, R denotes a substituent, in particular hydrogen,

Halogen such as fluorine, chlorine, bromine, iodine or a CF, group, is obtained in high yields,
if one CF ^ -substituted halobenzonitriles of the formula (II)

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in which

X means halogen such as fluorine, chlorine, bromine, iodine, the CF ₅ - and

the CN groups are each arranged in the o or p position to X.

and
R has the meaning given above,

with ammonia in a dipolar aprotic solvent
Temperatures between 100 and 250 ⁰ C, preferably 130 to
200 ⁰ C converts.

The method according to the invention can be used with particularly good success on 3-trifluoromethylcyananilines of the formula (III)

CN

- NH ₂ (III)
R '"CF ₃

apply in which

R ^{1 represents} hydrogen, chlorine or trifluoromethyl and the

Amino group is in the 2-, 4- or 6-position.

Preferably the process is carried out with an excess of ammonia carried out.

It can be described as extremely surprising that there is practically no reaction under the conditions according to the invention the CN group occurs and the nitriles of the formula (I) or (III) are obtained in high yields. According to the state of the art

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it was to be expected that at high pressure, an excess of ammonia and in the presence of ammonium salts under the reaction conditions, the nitrile group would preferentially be attacked ("The Chemistry of Functional Groups", Zvi Rappoport and S, Patai, 1970, 271-272 (Interscience Publisher )). As shown in the case of similar compounds (US Pat. No. 3,012,058, Example 3), this should at least lead to severe reductions in yield and to the formation of by-products.

Suitable dipolar aprotic solvents are, for example, dimethylformamide, pyrrolidone, N-methylpyrrolidone, dimethyl sulfoxide, Hexamethylphosphoric acid diamide and SuIfοlan. However, pyridine, alkylpyridines and glycol dialkyl ethers are preferred, where alkyl is preferably C.-C 1-4 alkyl.

The CF ^ -substituted halobenzonitriles used as starting materials are known, or can be obtained from the corresponding benzoic acid halides by known processes as follows represent:

+ 2 NH,

-NH ₄ Y

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Y means Cl, F and X and R have the meanings given.

Examples are:

3-trifluoromethyl-4-chlorobenzonitrile, 3-trifluoromethyl-4-bromobenzonitrile, 3-trifluoromethyl-4-fluorobenzonitrile, 3-trifluoromethyl-4,5-dichlorobenzonitrile; 3-trifluoromethyl-4-chloro-5-bromobenzonitrile, 3-trifluoromethyl-4-ood-benzonitrile, 3-trifluoromethyl-4,5-dibromobenzonitrile; 3-trifluoromethyl-4-fluoro-5-chlorobenzonitrile; 3-trifluoromethyl-4-chloro-5-dodbenzonitrile; 3,5-bis (trifluoromethyl) -4-chlorobenzonitrile; 3,5-bis (trifluoromethyl) -4-bromobenzonitrile; 2-chloro-5-trifluoromethylbenzonitrile; 2,3-dichloro-5-trifluoromethylbenzonitrile; 2-bromo-5-trifluoromethylbenzonitrile; 2,3-dibromo-5-trifluoromethylbenzonitrile; 2 ~ fluoro-5-trifluoromethylbenzonitrile; 2-fluoro-3,5-bis (trifluoromethyl) -benzoni tril; 2-chloro-3,5-bis (trifluoromethyl) benzonitrile; 2-chloro-3-trifluoromethylbenzonitrile ; 2,5-dichloro-3-trifluoromethylbenzonitrile, 2,5-dibromo-3-trifluoromethylbenzonitrile; 2-fluoro-3-trifluoromethyl-5-chlorobenzonitrile; 2-trifluoromethyl-4-chlorobenzonitrile.

As bases for the hydrogen halide released during the reaction the ammonia used in excess is generally used. To avoid corrosion, however, you can also use Presence of inorganic bases such as alkali or alkaline earth carbonates or - oxides, preferably soda, sodium hydrogen carbonate or calcium carbonate work.

The reaction according to the invention is carried out at elevated pressure. In general, one works with which by the concentration of the ammonia, the solvent and the given one Volume of the pressure vessel by temperature

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self-adjusting pressure. Pressure ranges from 50 to 150 bar are particularly preferred.

The concentration of that to be used for the chlorine-ammonia exchange anhydrous ammonia is generally between 10 and 60 percent by volume, preferably 20 to 50 percent by volume, based on the solvent. For the substituted halobenzonitrile used, an excess of 6 20 Moles, preferably 8-16 moles, of ammonia per mole of halobenzonitrile are used.

The process according to the invention can be carried out by adding 1-4 times the amount of diluent such as pyridine, 1 to 2.5 moles, preferably 1 to 1.5 moles of anhydrous, to 1 mole of halotrifluoromethylbenzonitrile in a suitable VA autoclave Soda or sodium hydrogen carbonate is added and 8 to 16 mol of liquid ammonia are pumped in. The mixture is stirred for 1 to 7 hours, preferably 1.5 to 5 hours at 130 to 200 ^° C. After cooling, the autoclave is depressurized. The inorganic salts are filtered off, the solvent is distilled off and the residue is purified either by recrystallization or by distillation. The yield can be up to 90 % of theory.

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226.5 g (1 mole) of 3-trifluoromethyl-4-chloro-benzoyl fluoride are added dropwise at 40 to 50 ⁰ C under cooling in 200 ml of concentrated aqueous ammonia (3 mol). The precipitated colorless crystal slurry is filtered off with suction, washed with water and dried. This gives 221 g (98%) of 3-trifluoromethyl-4-chlorbenzoesäureamid, mp 128-131 ⁰ C. The dry carbonamide is entered and at 20 to 25 ⁰ C in 220 ml (3 moles) of thionyl chloride, the thick suspension was cooled to 80 to 90 ⁰ C heated, with a strong gas evolution begins. The mixture is stirred until the evolution of gas has ceased (about 4 to 5 hours) and the excess thionyl chloride is distilled off from the clear solution, initially at normal pressure and finally in vacuo. The product 3-trifluoromethyl-4-chlorobenzonitrile is _{distilled at boiling point 1} ^ 100 ° C. as a colorless liquid which quickly solidifies (melting point 58 to 60 ^° C.). 190 g are obtained, that is 93 % of theory, based on the benzoyl fluoride used. All listed trifluoromethyl-substituted halobenzonitriles can be prepared analogously from the corresponding benzoic acid halides in high yields.

Example 2

135 g (0.66 mol) of 3-trifluoromethyl-4-chlorobenzonitrile are placed in a 0.7 l V4A autoclave 70 g of anhydrous soda and

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Submitted 140 ml of pyridine and injected 250 ml (10 mol) of liquid ammonia. The mixture is ^{stirred at 180 °} C. for 2 hours. The initial pressure of 125 bar falls rapidly to 110 bar. After cooling, the pressure in the autoclave is released. 50 ml of pyridine are stirred in, the thin mixture is filtered off with suction, washed thoroughly and the solvent is removed in vacuo. 100 g (89 %) of 3-trifluoromethyl-4-aminobenzonitrile are obtained from the residue by distillation at boiling point _{Q 1} 100 to 125 ^° C. as a colorless liquid which rapidly solidifies (melting point 60 to 63 ^° C.). Similarly, 3-trifluoromethyl-4-fluorobenzonitrile and 3-trifluoromethyl-4-bromobenzonitrile are obtained under the same conditions from 3-trifluoromethyl-4-aminobenzonitrile with 88 and 86 % yield, respectively.

Example 3

145 g (0.6 mol) of 3-trifluoromethyl-4,5-dichlorobenzonitrile (melting point 63 to 65 ° C), 50 g of sodium hydrogen carbonate and 300 ml of dimethylformamide are in a 0.7 1 VA autoclave with 150 ml (6 mol) liquid ammonia is added and the mixture is stirred ^{at 145 ° C. for 4 hours.} After releasing the pressure, the thin mixture is filtered off with suction, the solvent is distilled off in vacuo and the residue is stirred out with hot water. The almost colorless 3-trifluoromethyl-4-amino-5-chlorobenzonitrile crystallizes out on cooling. 130 g of crude product with a melting point of 65 to 70 ^° C. with an amino group content of 87 % are obtained, which is an 84 % yield. Are obtained analogously from 3-trifluoromethyl-4,5-dibromobenzonitrile under the same conditions, the 3-trifluoromethyl-4-amino-5-bromobenzonitrile, melting at 81 to 84 ⁰ C in 91% yield. The 3-trifluoromethyl-4-chloro-5-iodobenzonitrile is formed

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under the same conditions the 3-trifluoromethyl-4-amino-5-iodobenzonitrile of mp 87 to 92 ⁰ C in a yield of 76 %,

Example 4 cn

55 g (0.2 mol) of 3,5-bis (trifluoromethyl) -4-chlorobenzonitrile, 20 g of sodium hydrogen carbonate and 120 ml of N-methyl pyrrolidone are placed in a 0.3 l VA autoclave and 40 ml (1 , 6 mol) of liquid ammonia are added. The mixture is stirred for five hours at 130 ^° C., the autoclave is let down and the solvent is distilled off in vacuo. The distillation residue is blown out with steam. The 3,5-bis- (trifluoromethyl) -4-aminobenzonitrile crystallizes out on cooling. 40 g (79 %) of product with a melting point of 58 to 62 ^° C. are obtained.

Example 5

70 g of 2-chloro-3-trifluoromethyl-benzonitrile, bp ₁₂ 107 ⁰ C, m.p. 39 ° C are introduced into 350 ml of pyridine in an autoclave. 100 ml of liquid ammonia are injected and the mixture is stirred for 6 hours at 180 ^° C. A pressure of 56 bar is established. It is cooled, relaxed and filtered. Distillation gives 49 g of 2-amino-3-trifluoromethylbenzonitrile with a boiling point of ₁₀ 105 ^° C., melting point 68 to 69 ^° C. Purity according to gas chromatogram 97.5 %.

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Example 6

200 g of 2-chloro-5-trifluoromethyl-benzonitrile, bp ₁₇ 97 ⁰ C, m.p. 37 ⁰ C in an autoclave with 1 1 of pyridine and 200 ml NH-, liquid and stirred for 5 hours at 170 C. A pressure of 39 bar is established. After working up as in Example 5, 140 g of 2-amino-5-trifluoromethylbenzonitrile (bp ₁₄ 143 ° C, m.p. 75 to 77 ⁰ C) are 77.5% of theory.

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Claims (3)

Claims; /. Οό / Ζοο 1. Process for the preparation of CF, -substituted cyananilines the formula NC NH ₂ R CF, in which the CN group in o- or p-position to the amino group * ■ and the CF, group is in the p- or o-position to the amino group, R denotes a substituent, in particular hydrogen or halogen or CF ,, characterized in that CF, -substituted halobenzonitriles the formula in which X is halogen and CF means - and the CN group are each arranged o- or p-position to X and R are as defined above is reacted with ammonia in a dipolar aprotic solvent at temperatures between 100 and 250 ⁰ C. 2. The method according to claim 1, characterized in that one carries out the reaction in pyridine, alkyl pyridines or glycol dialkyl ethers. 3. The method according to claim 1, characterized in that the reaction is carried out at temperatures from 130 to 200 ⁰ C. Le A 16 671 -11- 709809/1099 ORIGINAL