JPH0237348B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing trifluoromethylbenzene derivatives, and more specifically, trifluoromethylhalogenobenzene is reacted with copper cyanide in a specific solvent in the presence of cupric bromide. The present invention relates to a method for producing trifluoromethylbenzonitrile. Aromatic halogen compounds have significantly lower reactivity than aliphatic halogen compounds, and unless they are activated with an appropriate electron-withdrawing group, they do not undergo normal S _N Ar type nucleophilic substitution reactions. The trifluoromethyl group is known to act as an electron-withdrawing group exhibiting -I and -E effects due to the electronegativity of the fluorine atom and the contribution of negative hyperconjugation, but it is not susceptible to nucleophilic attack. The degree of activation of aromatic rings is relatively small. Therefore, when trying to introduce a cyano group into trifluoromethylhalogenobenzene, even if an alkali cyanide is used directly, the reaction is more likely to occur on the trifluoromethyl side chain than on the aromatic ring. , it is difficult to obtain benzonitrile derivatives in a timely manner. The Rosenmund-von Braun reaction is well known as a method for obtaining a corresponding nitrile from an aromatic halogen compound. This reaction involves heating an aromatic bromine compound and copper cyanide to a high temperature of 250 to 260°C to replace the bromine atom with a cyano group.
However, since it requires extreme reaction conditions, it has the disadvantage of being accompanied by side reactions. Recently, a method of reacting in the presence of a palladium salt or a palladium-phosphine complex has been proposed, but this method is not suitable for industrial production. The applicant first proposed a simple and efficient method for obtaining the corresponding nitrile from trifluoromethylhalogenobenzene and its derivatives, which does not involve side reactions. We proposed a method of reacting in the presence of copper bromide or copper iodide in at least one solvent selected from triamide (hereinafter referred to as HMPA) and N-methylpyrrolidone (hereinafter referred to as NMP) ( Special request 1987
-Refer to specification No. 5215). As a result of further research to improve this method from an industrial standpoint, the present inventors have found that cupric bromide, which is not specifically disclosed in the above specification, is selectively used as copper bromide. Accordingly, compared to the case of using cuprous bromide described in the above specification,
When HMPA is used as a solvent, the desired product is obtained in almost the same yield, and when NMP, which is cheaper than HMPA, is used, the desired product is obtained in a significantly superior yield. The present inventors have discovered that the amount required is only about half that of cuprous oxide, which is very industrially advantageous, and have completed the present invention. That is, the gist of the present invention is that the formula: [In the formula, X represents a halogen, and Y represents hydrogen or a nitro group. ] Trifluoromethylhalogenobenzene shown by is reacted with copper cyanide to form the formula: [In the formula, Y has the same meaning as above. ] A method for producing a trifluoromethylbenzene derivative characterized by obtaining trifluoromethylbenzonitrile represented by the following. In addition, in the Rosenmund-von Braun reaction mentioned above, it is known that a divalent copper salt, for example, CuSO ₄ exhibits an excellent catalytic effect. However, according to the research of the present inventors, in the reaction of the present invention, divalent copper salts such as CuSO ₄ , CuCl ₂ , CuO, and Cu(NO ₃ ) ₂ do not contribute to the reaction at all, but only CuBr ₂ contributes to the reaction. It has been revealed that it exhibits a uniquely excellent catalytic effect. Examples of trifluoromethylhalogenobenzenes () used as starting materials in the present invention include o-chlorobenzotrifluoride, m-chloro-benzotrifluoride, p-chlorobenzotrifluoride, o-, p- or m- Bromobenzotrifluoride, o-, p- or m-iodobenzotrifluoride, 2-chloro-5-nitrobenzotrifluoride, 2-nitro-5-chlorobenzotrifluoride, 3-nitro-4-chlorobenzotrifluoride , 2-nitro-5-bromobenzotrifluoride, and the like. The proportion of copper cyanide used is at least 1 mol, preferably at least 2 mol, for example 2 mol, per 1 mol of trifluoromethylhalogenobenzene ().
~3 moles. It is also possible to use an alkali cyanide, such as potassium cyanide or sodium cyanide, in combination with copper cyanide. Cupric bromide is used in an amount of 0.02 to 2 times, preferably 0.3 to 1 times, mole relative to trifluoromethylhalogenobenzene (). As the solvent, aprotic polar solvents such as HMPA and NMP are used. These aprotic polar solvents can be used alone or in combination with other polar solvents. Preferred examples of other polar solvents include dimethylformamide, dimethylacetamide, dimethylsulfoxide, sulfolane, and glymes. When using a starting material that has a halogen atom at a position where a strong electron-withdrawing group represented by a nitro group and the electron effect of a trifluoromethyl group act synergistically, N-methylpyrrolidone is used as a solvent rather than HMPA. may be desirable. The reaction is usually carried out at normal pressure and at a temperature of 100 to 250°C, preferably 150 to 210°C, particularly 190 to 200°C. The reaction time is generally 1 to 10 hours. By hydrolyzing trifluoromethylbenzonitrile () obtained in this way,
It can be converted into benzoic acid and its derivatives or phthalic acid and its derivatives. Hydrolysis can be carried out by either acid or base hydrolysis. Hydrolysis with dilute or weak acids produces benzoic acid and its derivatives, although the reaction rate is very slow. On the other hand, when hydrolysis is performed with a strong acid, not only the cyano group but also the trifluoromethyl group is hydrolyzed to produce phthalic acid and its derivatives. When hydrolyzed with a base, the corresponding monocarboxylic acid is usually produced, but o-trifluoromethylbenzonitrile produces the corresponding acid amide, and when calcium hydroxide or barium hydroxide is used as a base, the corresponding monocarboxylic acid is produced. A mixture of amide and carboxylic acid is formed. This acid amide can be easily converted into a carboxylic acid by a nitrosation reaction. Next, examples and comparative examples will be shown to specifically explain the present invention. Example 1 In a 200 ml flask, 7.80 g (43 mmol) of p-chlorobenzotrifluoride and 7.17 g of copper cyanide
(80 mmol), 10 g (45 mmol) of cupric bromide, and 50 ml of HMPA were charged and reacted at 210° C. for 9 hours with stirring. The reaction mixture was subjected to gas chromatography (carrier SE-30), and it was confirmed that p-trifluoromethylbenzonitrile was produced in a yield of 99%. Examples 2 to 4 and Comparative Examples 1 to 5 Using the starting materials, divalent copper salts, and solvents shown in Table 1, reactions were carried out under the conditions shown in Table 1 to obtain p-trifluoromethylbenzonitrile. The yields are shown in Table 1. Example 5 The reaction was carried out under the same conditions as in Example 1, except that 9 g (40 mmol) of 3-nitro-4-chlorobenzotrifluoride was used in place of 7.8 g (43 mmol) of p-chlorobenzotrifluoride. The reaction mixture was subjected to gas chromatography to obtain 2-nitro-
Yield of 4-trifluoromethylbenzonitrile: 81
I confirmed that it was generated in %. 【table】

Claims (1)

[Claims] 1. In the presence of cupric bromide in at least one solvent selected from hexamethylphosphoric triamide and N-methylpyrrolidone, the formula: By reacting trifluoromethylhalogenobenzene represented by with copper cyanide, the formula: A method for producing a trifluoromethylbenzene derivative, which comprises obtaining trifluoromethylbenzonitrile represented by: [In the formula, X represents a halogen, and Y represents hydrogen or a nitro group. 2. The manufacturing method according to claim 1, wherein cupric bromide is used in an amount of 0.02 to 2 times mole relative to trifluoromethylhalogenobenzene. 3 Reaction temperature is 100-250℃, preferably 150-210℃
The manufacturing method according to claim 1 or 2, wherein the temperature is .degree.