JP2000154171A - Production of cyanobenzoic acid compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce the subject high-purity compound useful as a raw material for medicines and agrochemicals from a readily available compound in high yield under mild conditions by reacting a specific amide compound with a specified nitrosonium salt compound. SOLUTION: (A) A cyanobenzamide compound represented by formula I [CONH2 and Xn denote each a substituent group on the benzene ring; CONH2 is located at the m- or the p-position with respect to CN; X is Cl or F; (n) is 0-4] is reacted with (B) a nitrosonium salt compound (e.g. NOClO4) under acidic conditions to produce a compound represented by formula II. The above reaction is preferably carried out in the presence of an organic solvent without substantially containing water, e.g. acetonitrile and the component A is preferably m-cyanobenzamide or p-cyanobenzamide. The compound represented by formula II is preferably the corresponding m-cyanobenzoic acid or p- cyanobenzoic acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to medical and agricultural chemicals and liquid crystals,
The present invention relates to a method for producing a cyanobenzoic acid or a nucleus-substituted product thereof with a chlorine or fluorine atom, which is useful as a raw material or an intermediate of various fine chemicals such as functional polymer monomers.

[0002]

2. Description of the Related Art As a method for producing cyanobenzoic acid, a sand Meyer reaction in which p-aminobenzoic acid is diazotized and then reacted with copper cyanide [Lucas et al., J. Am.
Chem. Soc., 51 (1929) 2718] is known. In addition, a method of oxidizing tolunitrile with a strong reagent oxidizing agent such as chromic acid or permanganic acid to synthesize it [Levine et al., J. Org.
m., 24 (1959) 115], [Kattwinkel et al., Chem. Ber., 3
7 (1904) 3226]. However, the Sandmeyer method requires dangerous copper cyanide, and it is difficult to isolate and purify p-cyanobenzoic acid under acidic conditions under which hydrogen cyanide is released. When a reagent oxidizing agent such as chromic acid or permanganic acid is used, toxic heavy metal waste is generated in a stoichiometric amount or more, and a large amount of waste liquid containing toxic heavy metal is generated, which is a problem for the environment. Recently, a method of synthesizing p-cyanobenzoic acid by reacting a halogen-substituted benzonitrile such as chlorobenzonitrile with carbon monoxide using a catalyst [Japanese Patent Laid-Open No. 64-47, Dokl. Akad. .Nauk.SSSR, 312,
5,1129, (1990), J. Organomet.Chem., 358, 1-3, 563, (198
8)], and a method of synthesizing p-cyanobenzoic acid by enzymatically hydrolyzing a nitrile group on one side of terephthalonitrile using mononitrase or the like [Japanese Patent Laid-Open No. 61-85194] has been reported. Further, as a prior art related to the present invention, a method of hydrolyzing a terephthalonitrile with aqueous ammonia under pressure to a nitrile group [Arkhipova et al., J. Gen. Che.
m.USSR, 33 (1963) 631]. According to the authors, the amide group of p-cyanobenzamide generated by one-sided hydration of terephthalonitrile undergoes hydrolysis to form p-cyanobenzoic acid. However, in the above-mentioned methods, raw materials are difficult to obtain and the price is high, and the synthesis is complicated and severe conditions are required. In any case, the methods are still insufficient as industrially inexpensive and advantageous methods.

[0003]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above circumstances, and is intended to obtain a cyanobenzoic acid compound from a relatively easily available cyanobenzamide compound under mild conditions with high purity and high yield. The present invention provides an industrially advantageous production method which can be obtained at a high rate.

[0004]

Means for Solving the Problems The present inventors have conducted various studies in order to achieve the above object, and as a result, using a cyanobenzamide compound as a starting material, without damaging a cyano group on a benzene ring (-CONH _2). ) Was converted to a carboxyl group (-COOH) to find a method for synthesizing a cyanobenzoic acid compound, thereby completing the present invention. That is, the present invention relates to the following matters. (1) The following general formula (I)

Embedded image (Wherein -CONH ₂ and -Xn represent a substituent on a benzene ring, -CONH ₂ is at the m or p position of -CN, X represents a chlorine atom or a fluorine atom, and n is 0
Represents an integer of ４4. However, when n is 2 or more, X may be the same or different. ) And a nitrosonium salt compound are reacted under acidic conditions.
I)

Embedded image (Wherein -COOH and -Xn represent a substituent on a benzene ring, -COOH is at the m-position or p-position of -CN, X represents a chlorine atom or a fluorine atom, and n represents 0 to 0.
Represents an integer of 4. However, when n is 2 or more, X may be the same or different. The method for producing a cyanobenzoic acid compound represented by the formula: (2) The method for producing a cyanobenzoic acid compound according to the above (1), wherein the reaction is carried out in an organic solvent substantially free of water. (3) the cyanobenzamide compound of the general formula (I)
The cyanobenzoic acid according to the above (1) or (2), which is -cyanobenzamide or p-cyanobenzamide, and wherein the cyanobenzoic acid compound of the general formula (II) is a corresponding m-cyanobenzoic acid or p-cyanobenzoic acid. A method for producing an acid compound.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION In the reaction of the present invention for producing a cyanobenzoic acid compound, a cyanobenzamide compound and a nitrosonium salt compound are stirred under a predetermined temperature at a predetermined temperature for a predetermined time in the presence of an organic solvent. This is done by: The charging and reaction of the reaction raw materials are not particularly limited, but generally can be performed under atmospheric pressure. As a reactor to be used, glass and a strong acid-resistant metal container are suitable.

The cyanobenzamide compound used in this reaction is unsubstituted or halogen-substituted cyanobenzamide. Unsubstituted cyanobenzamide compounds have p
-Cyanobenzamide and m-cyanobenzamide, respectively, a hydrolysis reaction of one side nitrile group of terephthalonitrile and isophthalonitrile [Berther et al.,
Chem. Ber., 92 (1959) 2616]. Next, a halogenated cyanobenzamide compound will be described. Chlorinated cyanobenzamide compounds such as 4-cyano-2,3,5,6-tetrachlorobenzamide and 3-cyano-2,4,5,6-tetrachlorobenzamide can be obtained by chlorinating terephthalonitrile and isophthalonitrile. The chlorinated terephthalonitrile compound such as tetrachloroterephthalonitrile and the chlorinated isophthalonitrile compound such as tetrachloroisophthalonitrile can be easily synthesized by a hydrolysis reaction of one side nitrile group. Fluorinated cyanobenamide compounds such as 4-cyano-2,3,5,6-tetrafluorobenzamide and 3-cyano-2,4,5,6-tetrafluorobenzamide are chlorinated terephthalolines such as tetrachloroterephthalonitrile. Of fluorinated isophthalonitrile compounds such as tetrafluoroterephthalonitrile and tetrafluoroisophthalonitrile such as tetrafluoroterephthalonitrile obtained by a fluorination reaction of chlorinated isophthalonitrile compounds such as nitrile compounds and tetrachloroisophthalonitrile It can be easily synthesized by a hydrolysis reaction of one side nitrile group.

In the present invention, a nitrosonium salt compound is reacted with a cyanobenzamide compound. Nitrosonium salt compound of the general formula NO ⁺ X ^- (X is a monovalent cation) is indicated by a predominantly ionic crystalline solid. The nitrosonium salt compound used in this reaction is NOCl
O ₄ , NOSO ₃ F, NOHSO ₄ , NOSCN, NO
BF ₄ , NOPF ₄ , NOAsF ₄ , NOSbF ₄ , N
OFeCl ₄ , NOMoF _{6 and the} like. Preferably, NOHSO ₄ or NOBF ₄ is used. The nitrosonium salt compound may be separately synthesized and used, or prepared and used in the reaction system. The amount of the nitrosonium salt compound to be used is preferably 1 to 5 in a molar ratio with respect to the cyanobenzamide compound.

This reaction is preferably carried out in an organic solvent substantially free of water. Examples of the organic solvent that can be used include polar amides such as formamide and dimethylformamide; sulfur-containing systems such as dimethylsulfoxide and sulfolane; imidazolidones such as 1,3-dimethyl-2-imidazolidione; dioxane; -Dimethoxyethane, ethers such as diglyme, dichloromethane, chloroform, halogens such as 1,2-dichloroethane, aromatic hydrocarbons such as benzene and toluene, acetic anhydride, acid anhydrides such as propionic anhydride, acetonitrile, Nitriles such as propionitrile are preferably used. More preferably, acetonitrile having high solubility of various nitrosonium salt compounds is used. These organic solvents may be used alone or in combination of two or more. In addition, water can be used instead of the organic solvent. However, since the nitrosonium salt compound is rapidly hydrolyzed with water, it is limited to a reaction system of NO ⁺ HSO ₄ ⁻ and concentrated sulfuric acid. The amount of the solvent in this reaction is preferably 5 to 100 times the weight of the cyanobenzamide compound.

The reaction temperature in the present invention is -30 to 10
0 ° C is preferred, and -10 to 50 ° C is more preferred. If the reaction temperature is too high, the nitrosonium salt compound is decomposed, and if the reaction temperature is too low, the solubility of the cyanobenzamide compound is low and the reaction is difficult. The reaction time in this reaction varies depending on the composition of the solvent, but is preferably about 10 minutes to 10 hours.

The isolation and purification of a cyanobenzoic acid compound will be described. In this reaction, an organic solvent is usually used. After completion of the reaction, the cyanobenzoic acid compound is precipitated or remains dissolved by the solvent. If precipitated, filter, wash with water,
It can be isolated and purified only by drying. When the cyanobenzoic acid compound is dissolved, the solvent is distilled off under reduced pressure and low temperature, and water is added to the residue to precipitate cyanobenzoic acid. The same applies hereinafter. Even when an organic solvent is used, the purity of cyanobenzoic acid reflects the purity of the cyanobenzamide compound used.

[0011]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which by no means limit the present invention. The measurement conditions of the liquid chromatography are as follows. Column: Shodex (registered trademark: Showa Denko KK)
DE-513L, precolumn Column temperature: 40 ° C, Eluent flow rate: 1 ml / min, Eluent: water / acetonitrile / acetic acid = 2250/750
/ 15 (ml) sodium 1-octanesulfonate6.
45 g detector: UV 254 nm,

Example 1 In a 100 ml three-necked flask, 20 ml of acetonitrile and 2.92 g of p-cyanobenzamide were added to form a solution in an ice bath, and after cooling sufficiently, a solution of 2.57 g of nitrosonium tetrafluoroborate in 20 ml of acetonitrile was stirred. While dropping over 5 minutes.
After the completion of the dropwise addition, the stirring was further continued until the generation of gas stopped. The solution was distilled off under reduced pressure, and 10 ml of water was added to the residue.
The precipitated crystals were collected by filtration, washed with water and dried to obtain 2.77 g (yield 95%) of p-cyanobenzoic acid. The purity of p-cyanobenzoic acid obtained by high performance liquid chromatography analysis was 99% or more.

Example 2 A 200 ml three-necked flask was charged with 100 ml of a 70% strength by weight aqueous sulfuric acid solution and 2.92 g of m-cyanobenzamide and stirred. Next, 5g of sulfuric acid
10 g of a 50% by weight nitrosyl sulfuric acid sulfuric acid solution in which 5 g of nitrosyl sulfuric acid were dissolved was added dropwise.
The reaction was allowed to proceed for 0 minutes at room temperature. The precipitated crystals were collected by filtration, washed with water, and dried to obtain 2.68 g of m-cyanobenzoic acid (yield 92).
%). Purity was over 98%.

[0014]

According to the present invention, a cyanobenzoic acid compound can be easily produced with high yield and purity from a cyanobenzamide compound easily obtained from a phthalonitrile compound and an inexpensive nitrosonium salt. It is useful for the production of cyanobenzoic acid or a chlorinated or fluorine-substituted product as a raw material or intermediate of various fine chemicals such as liquid crystals and functional polymer monomers.

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Claims (3)

[Claims] 1. A compound represented by the following general formula (I) (Wherein -CONH ₂ and -Xn represent a substituent on a benzene ring, -CONH ₂ is at the m or p position of -CN, X represents a chlorine atom or a fluorine atom, and n is 0
Represents an integer of ４4. However, when n is 2 or more, X may be the same or different. ) And a nitrosonium salt compound are reacted under acidic conditions.
I) (Wherein -COOH and -Xn represent a substituent on a benzene ring, -COOH is at the m-position or p-position of -CN, X represents a chlorine atom or a fluorine atom, and n represents 0 to 0.
Represents an integer of 4. However, when n is 2 or more, X may be the same or different. The method for producing a cyanobenzoic acid compound represented by the formula: 2. The process for producing a cyanobenzoic acid compound according to claim 1, wherein the reaction is carried out in an organic solvent substantially free of water. 3. The cyanobenzamide compound of the general formula (I) is m-cyanobenzamide or p-cyanobenzamide, and the cyanobenzoic acid compound of the general formula (II) corresponds to the corresponding m-cyanobenzoic acid or p-cyanobenzamide. The method for producing a cyanobenzoic acid compound according to claim 1 or 2, which is benzoic acid.