JP2007223957A - Method for producing benzoic acid ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a benzoic acid ester compound, having a safe and simple process and a high yield. <P>SOLUTION: The method for producing a benzoic acid ester represented by general formula (IV) (R<SP>1</SP>is an electron-withdrawing substituted group; R<SP>2</SP>is a substituted or nonsubstituted alkyl group) comprises reacting a benzonitrile derivative with an alcohol represented by general formula HO-R<SP>2</SP>in the presence of a base to synthesize an imidic acid ester represented by general formula (III) and subjecting the compound to an acid hydrolysis. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing benzoic acid esters useful as pharmaceuticals, agricultural chemicals, electronic materials and the like or intermediates thereof.

  As a method of synthesizing a benzoic acid ester compound using a benzonitrile compound as a raw material, first, a method of synthesizing an ester compound by synthesizing an imidic acid ester or a salt thereof from a benzonitrile compound and then hydrolyzing it is known ( Non-patent document 1).

  In this method, as a method for synthesizing imidic acid esters or salts thereof as a synthetic intermediate, there is a method known as the Pinner method in which a nitrile and a alcohol are reacted in the presence of an acid catalyst. As an acid to be used, an acid gas such as hydrogen chloride is generally used. Therefore, in actual synthesis, complicated operations such as injection of hydrogen chloride gas in the reaction system and trapping of excessive gas are required. Met. Moreover, since the imidic acid esters or salts thereof were isolated in part, the yield decreased due to crystallization loss, and the yield decreased significantly when the solubility of the product was good. Further, the operation of taking out the hydrochloride of imidoesters is not preferable from the viewpoint of safety due to the diffusion of acid gas and the like, and special equipment such as forced exhaust equipment is required.

On the other hand, as a method known other than the above-described method for synthesizing imidoesters, a method of reacting a nitrile and an alcohol in the presence of a base catalyst is known (Non-patent Document 2). That is, a method of obtaining imidic acid esters by reacting an aromatic or aliphatic nitrile substituted with an electron-withdrawing group with an alcohol in the presence of a base such as sodium alkoxide or potassium cyanide. This reaction is an equilibrium reaction, and the equilibrium constant varies depending on the Hammett σ value of the substituent in the case of aromatic nitriles and on the σ ^* value of Taft of the substituent in the case of aliphatic nitriles, The larger the value, the larger the equilibrium constant, and thus the higher the reaction rate of imidic acid esters.

  However, according to the above document, it is described that the amount of base used is a catalytic amount, and the amount used is in the range of 0.01 to 0.25 equivalents relative to nitriles in any synthesis example. Yes. As a specific example, the relationship between different base concentrations at a reaction temperature of 25 ° C. and the conversion rate from nitriles to imidoesters, and the experimental results when p-nitrobenzonitrile is used as the nitrile are described. Yes. According to it, although the amount of base used with respect to nitriles is in the range of 0.01 to 0.2 equivalent, increasing the amount of base used tends to decrease the conversion rate to imidoesters. When the amount of sodium methoxide used for p-nitrobenzonitrile is 0.05 equivalent, the reaction rate of methyl-p-nitrobenzimidate is 80%. On the other hand, it is described that it is 81% when it is 0.1 equivalent and 78% when it is 0.2 equivalent.

  Moreover, although the reaction temperature in the synthesis example described in the said literature changes with nitriles used as a raw material, it exists in the range of 10-80 degreeC. Problems of the synthesis examples described in the same literature include that the conversion rate to imidoesters is insufficient depending on the compound, and that the reaction time is long.

  On the other hand, a method for synthesizing imidoesters by using nitriles under basic conditions and using a base in an amount of 0.5 to 3.0 equivalents relative to nitriles is also known. From the above, it was derived into an N-pyrazolylamide oxime compound (Patent Document 1).

In particular, no example has been known in which benzonitriles having an electron-withdrawing group at the meta position are reacted with alcohols in the presence of a base to synthesize imidic acid esters and then benzoic acid esters are synthesized.
JP 7-82252 A Chem. Ber. 1972, 105, 1778 Journal of Organic Chemistry, 1961, 26, 412

  An object of the present invention is to provide a process for producing a benzoate ester compound from a benzonitrile derivative, which is safe, simple in process and high in yield.

  The present inventor conducted intensive studies to develop a method capable of producing a benzoate compound having an electron-withdrawing group with a simple process and high yield. As a result, the synthesis of imidoesters, which are synthetic intermediates, is carried out under basic conditions, and in particular, the amount of base used is 0.5 to 3.0 equivalents with respect to nitriles, resulting in high yields of imidic acid. Esters were formed, and further, a method for deriving the ester compound in high yield by acid hydrolysis was found, and the present invention was achieved.

That is, the present invention
(1) The benzonitrile represented by the general formula (I) and the alcohol represented by the general formula (II) are added in an amount of 0.5 to 0.5 to the benzonitrile represented by the general formula (I).
The reaction is carried out in the presence of 3.0 equivalent of a base to synthesize imido acid esters represented by the general formula (III), and then this is acid-hydrolyzed, which is represented by the general formula (IV). A method for producing benzoic acid esters;

（式中、Ｒ¹は、電子吸引性の置換基を表わす。） Formula (I)

(In the formula, R ¹ represents an electron-withdrawing substituent.)

Formula (II)
HO-R ²
(In the formula, R ² represents a substituted or unsubstituted alkyl group.)

（式中、Ｒ¹及びＲ²はそれぞれ前記と同義である。） Formula (III)

(In the formula, R ¹ and R ² are as defined above.)

（式中、Ｒ¹及びＲ²はそれぞれ前記と同義である。） Formula (IV)

(In the formula, R ¹ and R ² are as defined above.)

(2) The method for producing a benzoic acid ester according to (1), wherein the acid hydrolysis is performed without isolating the imidic acid ester;
(3) The method for producing a benzoate ester according to (1) or (2), wherein R ¹ is a cyano group;
(4) The method for producing a benzoic acid ester according to any one of (1) to (3), wherein R ² is an alkyl group substituted with a hydroxy group;
(5) The method for producing a benzoate according to any one of (1) to (4), wherein R ¹ is a substituent bonded to the meta position.
About.

  According to the present invention, benzoic acid esters can be obtained from benzonitriles having an electron-withdrawing group in a high yield with a safe and simple operation.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be described in detail. In the present specification, a numerical range represented by using “to” means a range including numerical values described before and after “to” as a lower limit value and an upper limit value.
The production method of the present invention can be represented by the following reaction process formula.

First, R ¹ and R ^{2 in the} general formulas (I), (II), (III), and (IV) will be described in detail.
R ¹ represents an electron-withdrawing substituent. Examples thereof include a halogen atom (for example, fluorine, chlorine, bromine, iodine), a cyano group, a nitro group, an acyl group (preferably an acyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as formyl. , Acetyl, pivaloyl, tetradecanoyl, cyclohexylcarbonyl, benzoyl, trifluoroacetyl), an alkoxycarbonyl group (preferably an alkoxycarbonyl group having 2 to 50 carbon atoms, more preferably 2 to 18 carbon atoms, such as cyclohexyloxycarbonyl, methoxy Carbonyl, isopropoxycarbonyl, t-butoxycarbonyl), aryloxycarbonyl group (preferably an aryloxycarbonyl group having 7 to 50 carbon atoms, more preferably 7 to 25, for example, phenoxycarbonyl, naphthoxycarbonyl), carbamoyl group A carbamoyl group having preferably 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as carbamoyl, N-methylcarbamoyl, N, N-diethylcarbamoyl, N-mesylcarbamoyl), alkylsulfonyl group (preferably having 1 carbon atom) -50, more preferably 1-18 alkylsulfonyl groups such as methanesulfonyl, isopropylsulfonyl, cyclohexylsulfonyl, octylsulfonyl, 2-methoxyethylsulfonyl, 2-hexyldecylsulfonyl), arylsulfonyl groups (preferably having a carbon number) An arylsulfonyl group having 6 to 50, more preferably 6 to 25, such as benzenesulfonyl, p-toluenesulfonyl, 4-phenylsulfonylphenylsulfonyl, sulfamoyl group (preferably having 0 to 50 carbon atoms, and more) Mashiku a sulfamoyl group 0-25, for example, sulfamoyl, N- butylsulfamoyl, N, N- diethylsulfamoyl, N- methyl -N- (4- methoxyphenyl) sulfamoyl), and the like.

These substituents may be further substituted with a substituent. The substituent which R ¹ may have is an alkyl group (a linear or branched substituted or unsubstituted alkyl group, preferably an alkyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms). For example, methyl, ethyl, isopropyl, t-butyl, t-pentyl, cyclopropyl, cyclohexyl, 2-ethylhexyl, dodecyl), an alkenyl group (preferably having a carbon number of 2 to 50, more preferably 2 to 18). A substituted alkenyl group such as vinyl, an alkynyl group (preferably a substituted or unsubstituted alkynyl group having 2 to 50 carbon atoms, more preferably 2 to 18 carbon atoms such as ethynyl), a cycloalkyl group (preferably having 3 carbon atoms) ~ 50, more preferably 3-18 substituted or unsubstituted cycloalkyl groups such as cyclohexyl), aryl groups (preferably The substituted or unsubstituted aryl group having 6 to 50 carbon atoms, more preferably 6 to 25, for example, phenyl, naphthyl, anthryl),

A halogen atom (for example, fluorine, chlorine, bromine, iodine), an acylamino group (preferably an acylamino group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as acetylamino, butanoylamino, benzoylamino, trifluoro; Acetylamino, picolinoylamino), acyloxy group (preferably an acyloxy group having 1 to 50 carbon atoms, for example, acetoxy, tetradecanoyloxy, benzoyloxy), acyl group (preferably 1 to 50 carbon atoms, more preferably 1-18 acyl groups, for example, formyl, acetyl, pivaloyl, tetradecanoyl, cyclohexylcarbonyl, benzoyl, trifluoroacetyl), aryloxycarbonyl groups (preferably having 7 to 50 carbon atoms, more preferably 7 to 25 carbon atoms) An aryloxycarbonyl group For example, a carbamoyl group (preferably a carbamoyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as carbamoyl, N-methylcarbamoyl, N, N-diethylcarbamoyl, N- Mesylcarbamoyl), a carbamoyloxy group (preferably a carbamoyloxy group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as N, N-dimethylcarbamoyloxy), a carbonamido group (preferably having 1 to 50 carbon atoms). More preferably a carbonamide group having 1 to 18 carbon atoms such as formamide, N-methylacetamide, acetamide, N-methylformamide, benzamide), a sulfonamide group (preferably having 1 to 50 carbon atoms, more preferably 1 to 1 carbon atoms). 18 sulfonamide groups, for example Methanesulfonamide, dodecanesulfonamide, benzenesulfonamide, p-toluenesulfonamide), an alkoxy group (preferably an alkoxy group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as methoxy, propoxy, isopropoxy, Octyloxy, t-octyloxy, dodecyloxy, 2- (2,4-di-t-pentylphenoxy) ethoxy), aryloxy group (preferably having 6 to 50 carbon atoms, more preferably 6 to 25 aryloxy group) And, for example, phenoxy, 4-methoxyphenoxy, naphthoxy), a sulfamoyl group (preferably a sulfamoyl group having 0 to 50 carbon atoms, more preferably 0 to 25 carbon atoms such as sulfamoyl, N-butylsulfamoyl, N, N -Diethylsulfamoyl, N-methyl-N- ( 4-methoxyphenyl) sulfamoyl),

An alkoxycarbonyl group (preferably an alkoxycarbonyl group having 2 to 50 carbon atoms, more preferably 2 to 18 carbon atoms, such as cyclohexyloxycarbonyl, methoxycarbonyl, isopropoxycarbonyl, t-butoxycarbonyl), N-acylsulfamoyl group (Preferably an N-acylsulfamoyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as N-tetradecanoylsulfamoyl, N-benzoylsulfamoyl), an alkylsulfonyl group (preferably An alkylsulfonyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as methanesulfonyl, isopropylsulfonyl, cyclohexylsulfonyl, octylsulfonyl, 2-methoxyethylsulfonyl, 2-hexyldecylsulfonyl), arylsulfonyl A group (preferably an arylsulfonyl group having 6 to 50 carbon atoms, more preferably 6 to 25 carbon atoms, such as benzenesulfonyl, p-toluenesulfonyl, 4-phenylsulfonylphenylsulfonyl), an alkoxycarbonylamino group (preferably having 2 carbon atoms) To 50, more preferably 2 to 18 alkoxycarbonylamino groups such as ethoxycarbonylamino, isopropyloxycarbonylamino, cyclohexyloxycarbonylamino), aryloxycarbonylamino groups (preferably having 7 to 50 carbon atoms, more preferably 7-25 aryloxycarbonylamino group, for example, phenoxycarbonylamino, naphthoxycarbonylamino), amino group (preferably 0-50 carbon atoms, more preferably 0-18 amino group, , Methylamino, diethylamino, diisopropylamino, anilino), cyano group, nitro group, carboxyl group, hydroxy group, sulfo group, mercapto group, alkylsulfinyl group (preferably having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms). An alkylsulfinyl group such as methanesulfinyl, octanesulphinyl), an arylsulfinyl group (preferably an arylsulfinyl group having 6 to 50 carbon atoms, more preferably 6 to 25 carbon atoms such as benzenesulfinyl, 4-chlorophenylsulfinyl, p- Toluenesulfinyl), an alkylthio group (preferably an alkylthio group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as methylthio, octylthio, cyclohexylthio), an arylthio group (preferably having 6 to 50 carbon atoms, More preferably, it is an arylthio group having 6 to 25, for example, phenylthio, naphthylthio), ureido group (preferably a ureido group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as 3-methylureido, 3,3-dimethyl, etc. Ureido, 1,3-diphenylureido), a heterocyclic group (preferably a heterocyclic group having 2 to 50 carbon atoms, more preferably 2 to 25, and the hetero atom includes, for example, at least one of nitrogen, oxygen, sulfur and the like Including 3 to 12-membered monocyclic or condensed ring such as 2-furyl, 2-pyranyl, 2-pyridyl, 2-thienyl, 2-imidazolyl, morpholino, 2-quinolyl, 2-benzimidazolyl, 2 -Benzothiazolyl, 2-benzoxazolyl, 2-quinazolinon-3-yl, 1,1-dioxo-1,2,4-benzothiadi Din-3-yl, etc.), a sulfamoylamino group (preferably a sulfamoylamino group having 0 to 50 carbon atoms, more preferably 0 to 18 carbon atoms such as N-butylsulfamoylamino, N-phenylsulfuryl). Famoylamino), silyl group (preferably a silyl group having 3 to 50 carbon atoms, for example, trimethylsilyl, dimethyl-t-butylsilyl, triphenylsilyl), phosphonyl group (preferably 1 to 50 carbon atoms, more preferably 1 -18 phosphonyl groups such as phenoxyphosphonyl, octyloxyphosphonyl, phenylphosphonyl), azo groups (preferably azo groups having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as phenylazo), imide groups (Preferably an imide group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms such as N-succinimi , N- phthalimido), and the like.

Preferably, R ¹ is a cyano group.
The substitution position of R ¹ may be any of the ortho position, meta position, and para position, but the meta position and para position are preferred, and the meta position is most preferred.

R ² represents a substituted or unsubstituted alkyl group. This alkyl group represents a linear or branched substituted or unsubstituted alkyl group, preferably an alkyl group having 1 to 50 carbon atoms, more preferably 1 to 18 carbon atoms, such as methyl, ethyl, isopropyl, t-butyl. , T-pentyl, cyclopropyl, cyclohexyl, 2-ethylhexyl, dodecyl.

Examples of the substituent that the R ² optionally has, examples wherein R ¹ is mentioned as the substituent which may have can be mentioned.

R ² is preferably an unsubstituted alkyl group or an alkyl group substituted with a hydroxy group, more preferably an alkyl group substituted with a hydroxy group. That is, the alcohol represented by the general formula (II) is preferably selected from diols.

  Although the typical example of the imido acid ester compound represented by the said general formula (III) is shown below, this invention is not limited by this.

  Next, typical specific examples of the compound represented by the general formula (VI) are shown below, but the present invention is not limited thereto.

  In the present invention, the nitric acid ester represented by the general formula (III) is obtained by reacting the nitrile represented by the general formula (I) with the alcohol represented by the general formula (II) in the presence of a base. Generate. Bases that can be used in the present invention include simple alkali metals or alkaline earth metals (lithium, sodium, potassium, magnesium, etc.), metal hydrides (sodium hydride, potassium hydride, etc.), metal alkoxides (sodium methoxy). Metal alkoxide is preferable, and sodium methoxide, sodium ethoxide, and potassium t-butoxide are more preferable. In the present invention, the base is used in an amount of 0.5 to 3.0 equivalents based on the benzonitrile represented by the general formula (I). The amount of the base used is preferably 0.5 to 2.0 equivalents, more preferably 0.8 to 1.5 equivalents, relative to the benzonitriles.

  In the synthesis of imidoesters represented by the general formula (III), examples of the solvent used include alcohol solvents (for example, methanol, isopropanol), chlorine solvents (for example, dichloromethane, chloroform), aromatic solvents (for example) For example, benzene, toluene, chlorobenzene, xylene), amide solvents (for example, N, N-dimethylformamide, N, N-dimethylacetamide), ureido solvents (for example, 1,3-dimethyl-2-imidazolidinone), Nitrile solvents (eg acetonitrile), ester solvents (eg ethyl acetate, butyl acetate), ether solvents (eg diethyl ether, tetrahydrofuran), sulfone solvents (eg sulfolane), sulfoxide solvents (eg dimethyl) Sulfoxide), Ri Acid amide-based solvents (e.g., hexamethylphosphoric triamide), hydrocarbon solvents (e.g., hexane, cyclohexane) can be mentioned. These solvents may be used alone or in combination of two or more. Of these, alcohol solvents or ether solvents are preferred. The amount used is 0.5 to 500 parts by mass, preferably 1 to 50 parts by mass, per 1 part by mass of the nitriles represented by the general formula (I). When using a metal alkoxide as the alcohol and the base represented by the general formula (II), it is preferable to use the same carbon chain length as the reaction solvent.

  Although the reaction temperature in the synthesis | combination of the imido acid ester represented by general formula (III) can be performed at -20 degreeC-50 degreeC, 30 degreeC or less is preferable, More preferably, it is less than 10 degreeC and 5 degreeC or less is especially preferable. . The lower limit is preferably −10 ° C. or higher. In the present invention, as described above, it is preferable to have a step of performing the reaction of the imidoesters at less than 10 ° C., and this low-temperature reaction is preferably performed while maintaining the reaction from the initial stage to the end point. Also, the reaction can be improved to a certain degree compared to the reaction yield near room temperature by reacting at around room temperature to some extent and reacting at this low temperature state in the middle.

  The reaction time in the reaction between the benzonitriles of the general formula (I) and the alcohols of the general formula (II) varies depending on the compound type and reaction temperature, but is preferably 30 minutes to 24 hours, more preferably 2 hours to 10 hours. It can be done in about hours.

The imidic acid ester represented by the general formula (III) obtained by the above method may be isolated or not isolated, but is hydrolyzed using an acid without isolation to obtain the general formula (IV). It is preferable to use benzoic acid esters represented by the formula: Preferable acids to be used include hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid and the like.
The molar ratio between the imidoester represented by the general formula (III) and the acid is 1: 0.5 to 1: 100, preferably 1: 1 to 1:10. As the reaction solvent used in the acid hydrolysis reaction, the solvent used for the synthesis of the imidoesters can be used as it is, or another reaction solvent can be used. Although reaction temperature can be performed at 0-100 degreeC, Preferably it is 20-50 degreeC. Although the reaction time in this reaction also varies depending on the compound type, reaction temperature, etc., it can be carried out preferably for 30 minutes to 5 hours, more preferably for about 1 hour to 4 hours. In the acid hydrolysis reaction, the pH of the reaction solution is preferably 6 or less, more preferably 5 or less, further preferably 4 or less, and still more preferably 3 or less.

  The benzoic acid ester represented by the general formula (IV) is crystallized and isolated by a method such as adding water to the reaction solution, or is extracted if it is not crystallized. In some cases, it may be purified by column chromatography, distillation, recrystallization or the like.

The features of the present invention will be described more specifically with reference to examples and comparative examples. The materials, amounts used, ratios, processing details, processing procedures, and the like shown in the following examples can be changed as appropriate without departing from the spirit of the present invention. Therefore, the scope of the present invention should not be construed as being limited by the specific examples shown below.
Example 1 Synthesis of Exemplified Compound (IV-1)
To a solution of 10.0 g (0.068 mol) of m-nitrobenzonitrile in 50 ml of methanol was added 13.7 ml (0.10 mol) of a 28% methanol solution of sodium methoxide at room temperature, and the mixture was stirred at 0 ° C. for 3 hours. . The reaction solution was added to a mixture of 20 ml of concentrated hydrochloric acid and 180 ml of water, and stirred at 30 ° C. for 3 hours. After extraction with ethyl acetate and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and purified by column chromatography to obtain 10.4 g of exemplary compound (IV-1) as white crystals. The yield was 84.5%. Moreover, the measurement result of < ¹ > H-NMR of the obtained compound is shown below.
¹ H-NMR (solvent: CDCl ₃ , standard: tetramethylsilane) δ (ppm): 8.86 (1H, s), 8.45-8.32 (2H, m), 7.68 (1H, t ) 4.00 (3H, s).
Melting point of the obtained crystal m. p. Was 78 ° C.

Example 2 Synthesis of Exemplary Compound (IV-3)
To a 200 ml tetrahydrofuran solution of 52.0 g (0.50 mol) of 1,5-pentanediol was added 11.2 g (0.10 mol) of potassium tert-butoxide, and the mixture was stirred at room temperature for 1 hour. 12.8 g (0.10 mol) of isophthalonitrile was added and stirred at 5 ° C. for 8 hours, and then added to a mixture of 20 ml of concentrated hydrochloric acid and 180 ml of water, and stirred at 30 ° C. for 3 hours. After extraction with ethyl acetate and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography to obtain 15.7 g of exemplary compound (IV-3) as white crystals. The yield was 67.3%. The melting point of the obtained crystal m. p. Was 54-55 ° C. Moreover, the measurement result of < ¹ > H-NMR of the obtained compound is shown below.
¹ H-NMR (solvent: CDCl ₃ , standard: tetramethylsilane) δ (ppm): 8.32 (1H, s), 8.28 (1H, d), 7.84 (1H, d), 7. 59 (1H, t), 4.37 (2H, t), 3.70 (2H, t), 1.90 to 1.48 (7H, m).

[Comparative Example 1 Synthesis of Exemplary Compound (IV-1)]
Synthesis was performed in the same manner as in Example 1 except that the amount of sodium methoxide was changed to 0.10 equivalent in Example 2. As a result, the yield of the exemplary compound (IV-1) was 72.0%. there were.

[Comparative Example 2 Synthesis of Exemplary Compound (IV-3)]
Synthesis was performed in the same manner as in Example 2 except that the amount of potassium t-butoxide was changed to 0.25 equivalents in Example 2. As a result, the yield of the exemplary compound (IV-3) was 52.0. %Met.

  As described above, the present invention improves the yield by increasing the equivalent amount of the base, and induces the benzoic acid ester compound without isolating the imidic acid ester so that the imidic acid ester or its The operation of taking out the salt could be omitted, and the total yield was improved without any crystallization loss associated with the taking out. As described above, the present invention can greatly reduce the cost due to the simplification of the operation and the effect of improving the yield.

Claims (5)

A benzonitrile represented by the general formula (I) and an alcohol represented by the general formula (II) are mixed with 0.5 to 3.0 equivalents of a base of the benzonitrile represented by the general formula (I). A process for producing a benzoic acid ester represented by the general formula (IV), which comprises reacting in the presence to synthesize an imido acid ester represented by the general formula (III) and then hydrolyzing the imidic acid ester. .
Formula (I)

(In the formula, R ¹ represents an electron-withdrawing substituent.)
Formula (II)
HO-R ²
(In the formula, R ² represents a substituted or unsubstituted alkyl group.)
Formula (III)

(In the formula, R ¹ and R ² are as defined above.)
Formula (IV)

(In the formula, R ¹ and R ² are as defined above.) The method for producing a benzoic acid ester according to claim 1, wherein the imidic acid ester is subjected to acid hydrolysis without isolation. The method for producing a benzoic acid ester according to claim 1 or 2, wherein R ¹ is a cyano group. The method for producing a benzoic acid ester according to any one of claims 1 to 3, wherein R ² is an alkyl group substituted with a hydroxy group. The method for producing a benzoic acid ester according to any one of claims 1 to 4, wherein R ¹ is a substituent bonded to the meta position.