JP2001220363A - Method for producing aryl esters by using phosphorus oxychloride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing aryl esters, especially the aryl esters of benzotriazolcarboxylic acid under a mild condition in high yield and high purity by using a comparatively inexpensive reagent. SOLUTION: This method for producing the aryl esters comprises reacting a carboxylic acid with phosphorus oxychloride in the presence of a base, and carrying out the esterification reaction of the resultant product by using a phenol compound in an amount of >=3 molar times as much as that of the phosphorus oxychloride in the presence of the same or different kind of a base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a low-cost and efficient method for producing aryl esters.

[0002]

2. Description of the Related Art Aryl esterified carboxylic acid compounds are important as intermediates or final compounds for the synthesis of fine chemicals such as pharmaceuticals, agricultural chemicals and photographic materials. In particular, aryl ester derivatives of benzotriazole carboxylic acids are useful compounds as a development inhibitor in silver halide photographic materials, and various synthetic methods have been conventionally developed. For example, JP-A-57-151944 describes a multi-step synthesis method using 3,4-dinitrobenzoic acid as a starting material. That is, 3,4-dinitrobenzoic acid is converted into a carboxylic acid chloride with thionyl chloride, and this acid chloride is reacted with phenol to synthesize 3,4-dinitrobenzoic acid phenyl ester. The group is reduced to 3,4-diaminobenzoic acid phenyl ester. By reacting the aqueous acetic acid solution of 3,4-diaminobenzoic acid phenyl ester thus obtained with a sodium nitrite solution, benzotriazole-5-carboxylic acid is obtained at a 60% yield from 3,4-dinitrobenzoic acid. It is stated that a phenyl ester is obtained.

In the above-mentioned conventional method, when synthesizing a phenyl ester, it is necessary to synthesize highly reactive 3,4-dinitrobenzoic acid chloride under high-temperature conditions. There was a disadvantage that the load was large. Also, from the viewpoint of the production of benzotriazole-5-carboxylic acid phenyl ester, 3,4-dinitrobenzoic acid is difficult to obtain, industrial waste such as iron mud is generated in the reduction process, and production in multiple steps. It was difficult to say that the method was advantageous in terms of cost due to poor properties. JP-A-62-34150 describes a method of condensing benzotriazole-5-carboxylic acid and phenol using dicyclohexylcarbodiimide (DCC). However, with this method,
Benzotriazole is problematic in that the yield is as low as about 32%, DCC is expensive and easily rash, and it is difficult to remove dicyclohexylurea as a by-product.
It was hardly enough for an industrial synthesis method of -5-carboxylic acid phenyl ester. Further, Japanese Unexamined Patent Application Publication No.
No. 1-269156 discloses the reaction of benzotriazole-5-carboxylic acid with triphenyl phosphite in the presence of a p-toluenesulfonic acid catalyst to give benzotriazole-5 in a yield of 74% (HPLC purity 98.4%). -Methods for obtaining carboxylic acid phenyl esters are described. However, this method has a problem that a high temperature and a long time are required until the reaction is completed. Further, neither the yield nor the purity was satisfactory.

[0004]

SUMMARY OF THE INVENTION It is an object of the present invention to produce aryl esters, in particular, benzotriazole carboxylic acid aryl esters, at low yields and high purity under mild conditions using inexpensive reagents. It is to provide a way to do it.

[0005]

According to the present inventor, in order to solve the above-mentioned problems, the following manufacturing method is provided. (1) After reacting a carboxylic acid with phosphorus oxychloride in the presence of a base, further performing an esterification reaction in the presence of the same or a different base with a phenol compound at least 3 times the amount of phosphorus oxychloride. A method for producing aryl esters, characterized by the following. (2) After reacting the compound represented by the general formula (I) with phosphorus oxychloride in the presence of a base, the phenol compound is mixed with phosphorus oxychloride in an amount of at least 3 times the amount of phosphorus oxychloride in the presence of the same or a different base. A method for producing a compound represented by the general formula (II), wherein the compound is subjected to an esterification reaction using

[0006]

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Here, R ₁ represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an acyl group, an alkylsulfonyl group, an arylsulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbamoyl group, or a sulfamoyl group. , R ₂ represents a substituent, m
Represents an integer of 0 to 3, and Ar represents an aryl group. However,
When R ₁ in the general formula (I) is a group other than a hydrogen atom, the case where R ₁ in the general formula (II) represents a hydrogen atom is also included. (3) After converting the compound represented by the following general formula (Ia) into a compound represented by the general formula (Ib), the compound is reacted with phosphorus oxychloride, and further reacted with phosphorus oxychloride in the presence of a base. A method for producing a compound represented by the general formula (IIa), wherein an esterification reaction is carried out using a phenol compound in a molar amount of twice or more.

[0008]

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Here, R ₂ , m and Ar have the same meanings as above, R ₃ represents an alkyl group, an aryl group, an alkoxycarbonyl group and an aryloxycarbonyl group, and M represents a hydrogen atom, an alkali metal or ammonium. Represent. (4) After acetylating 1H-benzotriazole-5 or 6-carboxylic acid, react with phosphorus oxychloride, and further, in the presence of a base, use a phenol compound at least three times the molar amount of phosphorus oxychloride to form an ester. A method for producing 1H-benzotriazole-5 or 6-carboxylic acid phenyl ester, which comprises subjecting the compound to a chlorination reaction.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a method for producing an aryl ester of the present invention will be described in detail. In the present invention, the carboxylic acid is preferably an aliphatic carboxylic acid having 1 to 30 carbon atoms, more preferably 1 to 20 carbon atoms (eg, acetic acid, propionic acid, hexadecanoic acid), and preferably 6 carbon atoms.
To 30, more preferably an aromatic carboxylic acid having 6 to 20 carbon atoms (e.g., benzoic acid, 1-naphthoic acid, 1H-benzotriazole-5 (or 6) -carboxylic acid). Among them, those represented by the general formula (I) are preferable. Further, as the phenol compound used in the present invention, a phenol compound having no substituent having a greater nucleophilicity than a phenolic hydroxyl group in the molecule is preferable, for example, phenol, 2,4-dichlorophenol, p-nitro Phenol, p-chlorophenol,
p-fluorophenol, p-trifluoromethylphenol, p-methylphenol. In the above general formulas (I), (II), (Ia), (Ib) and (IIa), R ₁ is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an acyl group, an alkylsulfonyl group, Arylsulfonyl group, alkoxycarbonyl group,
Represents an aryloxycarbonyl group, a carbamoyl group, a sulfamoyl group, R ₂ represents a substituent, m represents an integer of 0 to 3, Ar represents an aryl group, R ₃ represents an alkyl group, an aryl group, an alkoxycarbonyl group And an aryloxycarbonyl group, and M represents an alkali metal or ammonium. The alkyl group represented by R ₁ represents a linear, branched, or cyclic substituted or unsubstituted alkyl group, preferably having 1 to 30 carbon atoms, for example, methyl, ethyl, n-
Propyl, isopropyl, t-butyl, n-octyl,
Eicosyl, 2-chloroethyl, 2-cyanoethyl, 2
-Ethylhexyl, cyclohexyl, cyclopentyl,
4-n-dodecylcyclohexyl, bicyclo [1,2,
2] heptane-2-yl and bicyclo [2,2,2] octan-3-yl. The alkenyl group represented by R ₁ represents a linear, branched, or cyclic substituted or unsubstituted alkenyl group, preferably having 2 to 30 carbon atoms, for example, vinyl, allyl, prenyl, geranyl, oleyl, 2- Cyclopenten-1-yl, 2-cyclohexen-1-yl, bicyclo [2,2,1] hept-2-en-1-yl, bicyclo [2,2,2] oct-2-en-4-yl Represent. The alkynyl group represented by R ₁ represents a linear, branched, or cyclic substituted or unsubstituted alkynyl group, preferably having 2 to 30 carbon atoms, and represents, for example, an ethynyl, propargyl, or trimethylsilylethynyl group.

The aryl group represented by R ₁ represents a substituted or unsubstituted aryl group, preferably having 6 to 30 carbon atoms.
More preferably, it is 6 to 20, for example, phenyl, p-
Represents tolyl, naphthyl, m-chlorophenyl, o-hexadecanoyloxyphenyl. The acyl group represented by R ₁ preferably has 1 to 30 carbon atoms, more preferably 1 to 2 carbon atoms.
0, for example, formyl, acetyl, pivaloyl, 2
-Represents chloroacetyl, stearoyl, benzoyl, pn-octyloxyphenylcarbonyl. The alkylsulfonyl group represented by R ₁ represents a substituted or unsubstituted alkylsulfonyl group, preferably 1 to 30 carbon atoms, more preferably 1 to 20 carbon atoms, for example, methylsulfonyl and ethylsulfonyl. The arylsulfonyl group represented by R ₁ represents a substituted or unsubstituted arylsulfonyl group, preferably having 6 to 30 carbon atoms, more preferably 6 to 2 carbon atoms.
0 and represents, for example, phenylsulfonyl, p-methylphenylsulfonyl. The alkoxycarbonyl group represented by R ₁ represents a substituted or unsubstituted alkoxycarbonyl group, preferably having 2 to 30 carbon atoms, more preferably 2 to 30 carbon atoms.
20 and represents, for example, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, n-octadecyloxycarbonyl.

The aryloxycarbonyl group represented by R ₁ represents a substituted or unsubstituted aryloxycarbonyl group, preferably having 7 to 30 carbon atoms, more preferably 7 to 2 carbon atoms.
0, for example, phenoxycarbonyl, o-chlorophenoxycarbonyl, m-nitrophenoxycarbonyl, p-
Represents t-butylphenoxycarbonyl. The carbamoyl group represented by R ₁ represents a substituted or unsubstituted carbamoyl group, preferably having 1 to 30 carbon atoms, more preferably 1 to 2 carbon atoms.
0, for example, carbamoyl, N-methylcarbamoyl, N, N-dimethylcarbamoyl, N, N-di-n-
Represents octylcarbamoyl and N- (methylsulfonyl) carbamoyl. The sulfamoyl group represented by R ₁ represents a substituted or unsubstituted sulfamoyl group, preferably having 0 to 30 carbon atoms, more preferably 0 to 20 carbon atoms, for example, N-ethylsulfamoyl, N- (3-dodecyl) (Oxypropyl) sulfamoyl, N, N-dimethylsulfamoyl, N-acetylsulfamoyl, N-benzoylsulfamoyl, N- (N′-phenylcarbamoyl)
Represents sulfamoyl.

When R ₁ in the general formula (I) represents an acyl group, a sulfonyl group, an alkoxycarbonyl group, or an aryloxycarbonyl group, R ₁ in the general formula (II) is the same acyl group, sulfonyl group, alkoxycarbonyl group, respectively. May be an aryloxycarbonyl group,
It may be a hydrogen atom. Examples of the substituent represented by R ₂ include a halogen atom, an alkyl group (including a cycloalkyl group and a bicycloalkyl group), an alkenyl group (including a cycloalkenyl group and a bicycloalkenyl group), an alkynyl group,
Aryl group, heterocyclic group, cyano group, nitro group, alkoxy group, aryloxy group, silyloxy group, heterocyclic oxy group, acyloxy group, carbamoyloxy group, alkoxycarbonyloxy group, aryloxycarbonyloxy, acylamino group, aminocarbonyl Amino group, alkoxycarbonylamino group, aryloxycarbonylamino group, sulfamoylamino group, alkyl and arylsulfonylamino group, alkylthio group, arylthio group, heterocyclic thio group, sulfamoyl group, alkyl and arylsulfinyl group, alkyl and aryl Sulfonyl group, acyl group, aryloxycarbonyl group, alkoxycarbonyl group, carbamoyl group, aryl and heterocyclic azo group, imide group, phosphino group, phosphinyl group, phosphine group Iniruokishi group, phosphinyl amino group, a silyl group.

More specifically, R ₂ is a halogen atom (eg, a chlorine atom, a bromine atom, an iodine atom), an alkyl group
[Indicates a linear, branched, or cyclic substituted or unsubstituted alkyl group. An alkyl group (preferably an alkyl group having 1 to 30 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, t-butyl, n-octyl, eicosyl, 2-
Chloroethyl, 2-cyanoethyl, 2-ethylhexyl), cycloalkyl group (preferably having 3 to 30 carbon atoms)
A substituted or unsubstituted cycloalkyl group such as cyclohexyl, cyclopentyl, 4-n-dodecylcyclohexyl), a bicycloalkyl group (preferably a substituted or unsubstituted bicycloalkyl group having 5 to 30 carbon atoms,
That is, it is a monovalent group obtained by removing one hydrogen atom from a bicycloalkane having 5 to 30 carbon atoms. For example, bicyclo [1,2,2] heptan-2-yl, bicyclo [2,2
2,2] octan-3-yl), and a tricyclo structure having more ring structures. An alkyl group (for example, an alkyl group of an alkylthio group) among the substituents described below represents an alkyl group having the same meaning. ],

Alkenyl group [represents a linear, branched, or cyclic substituted or unsubstituted alkenyl group; An alkenyl group (preferably a substituted or unsubstituted alkenyl group having 2 to 30 carbon atoms, for example, vinyl, allyl, prenyl, geranyl,
Oleyl), a cycloalkenyl group (preferably a substituted or unsubstituted cycloalkenyl group having 3 to 30 carbon atoms,
That is, it is a monovalent group obtained by removing one hydrogen atom of a cycloalkene having 3 to 30 carbon atoms. For example, 2-cyclopenten-1-yl, 2-cyclohexen-1-yl),
Bicycloalkenyl group (substituted or unsubstituted bicycloalkenyl group, preferably a substituted or unsubstituted bicycloalkenyl group having 5 to 30 carbon atoms, ie, a monovalent obtained by removing one hydrogen atom of a bicycloalkene having one double bond) For example, bicyclo [2,2,1] hept-2-en-1-yl, bicyclo [2,2,2] oct-2-en-4-yl)], an alkynyl group (preferably A substituted or unsubstituted alkynyl group having 2 to 30 carbon atoms, for example, ethynyl, propargyl, trimethylsilylethynyl group,

An aryl group (preferably a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, such as phenyl, p
One hydrogen atom from a tolyl, naphthyl, m-chlorophenyl, o-hexadecanoyloxyphenyl), heterocyclic group (preferably a 5- or 6-membered substituted or unsubstituted aromatic or non-aromatic heterocyclic compound) And more preferably a monovalent group having 3 to 30 carbon atoms.
Is a 5- or 6-membered aromatic heterocyclic group. For example, 2-furyl, 2-thienyl, 2-pyrimidinyl, 2
-Benzothiazolyl), cyano group, nitro group, alkoxy group (preferably substituted or unsubstituted alkoxy group having 1 to 30 carbon atoms, for example, methoxy, ethoxy, isopropoxy, t-butoxy, n-octyloxy, 2-
Methoxyethoxy),

An aryloxy group (preferably having 6 carbon atoms)
To 30 substituted or unsubstituted aryloxy groups, for example, phenoxy, 2-methylphenoxy, 4-t-butylphenoxy, 3-nitrophenoxy, 2-tetradecanoylaminophenoxy), silyloxy group (preferably carbon number A 3-20 silyloxy group, for example, trimethylsilyloxy, t-butyldimethylsilyloxy), a heterocyclic oxy group (preferably having 2 to 30 carbon atoms);
Substituted or unsubstituted heterocyclic oxy group, 1-phenyltetrazol-5-oxy, 2-tetrahydropyranyloxy), acyloxy group (preferably formyloxy group, substituted or unsubstituted alkylcarbonyl having 2 to 30 carbon atoms) An oxy group, a substituted or unsubstituted arylcarbonyloxy group having 6 to 30 carbon atoms, for example, formyloxy, acetyloxy, pivaloyloxy, stearoyloxy, benzoyloxy, p-methoxyphenylcarbonyloxy), a carbamoyloxy group (preferably A substituted or unsubstituted carbamoyloxy group having 1 to 30 carbon atoms, for example, N, N-dimethylcarbamoyloxy, N, N-diethylcarbamoyloxy, morpholinocarbonyloxy, N, N-di-n-octylaminocarbonyloxy N-n-octyl carbamoyloxy)

An alkoxycarbonyloxy group (preferably a substituted or unsubstituted alkoxycarbonyloxy group having 2 to 30 carbon atoms, for example, methoxycarbonyloxy,
Ethoxycarbonyloxy, t-butoxycarbonyloxy, n-octylcarbonyloxy), an aryloxycarbonyloxy group (preferably a substituted or unsubstituted aryloxycarbonyloxy group having 7 to 30 carbon atoms, for example, phenoxycarbonyloxy, p -Methoxyphenoxycarbonyloxy, pn-hexadecyloxyphenoxycarbonyloxy), an acylamino group (preferably a formylamino group, a substituted or unsubstituted alkylcarbonylamino group having 1 to 30 carbon atoms, A substituted or unsubstituted arylcarbonylamino group, for example, formylamino, acetylamino,
Pivaloylamino, lauroylamino, benzoylamino, 3,4,5-tri-n-octyloxyphenylcarbonylamino),

An aminocarbonylamino group (preferably,
C1-C30 substituted or unsubstituted aminocarbonylamino, for example, carbamoylamino, N, N-dimethylaminocarbonylamino, N, N-diethylaminocarbonylamino, morpholinocarbonylamino), alkoxycarbonylamino group (preferably carbon Number 2-3
0 substituted or unsubstituted alkoxycarbonylamino group, for example, methoxycarbonylamino, ethoxycarbonylamino, t-butoxycarbonylamino, n-octadecyloxycarbonylamino, N-methyl-methoxycarbonylamino), aryloxycarbonylamino group (preferably Is a substituted or unsubstituted aryloxycarbonylamino group having 7 to 30 carbon atoms, for example, phenoxycarbonylamino, p-chlorophenoxycarbonylamino, mn-octyloxyphenoxycarbonylamino), sulfamoylamino group (preferably Is a substituted or unsubstituted sulfamoylamino group having 0 to 30 carbon atoms, for example, sulfamoylamino, N, N-dimethylaminosulfonylamino, Nn-octylaminosulfonylamino), Alkyl and arylsulfonylamino groups (preferably substituted or unsubstituted alkylsulfonylamino having 1 to 30 carbon atoms, substituted or unsubstituted arylsulfonylamino having 6 to 30 carbon atoms, for example, methylsulfonylamino, butylsulfonylamino, phenyl Sulfonylamino, 2,3,5-trichlorophenylsulfonylamino, p-methylphenylsulfonylamino),

An alkylthio group (preferably having a carbon number of 1 to
30 substituted or unsubstituted alkylthio groups such as methylthio, ethylthio, n-hexadecylthio) and arylthio groups (preferably substituted or unsubstituted arylthio having 6 to 30 carbon atoms such as phenylthio, p-chlorophenylthio, m-methoxy) Phenylthio), a heterocyclic thio group (preferably a substituted or unsubstituted heterocyclic thio group having 2 to 30 carbon atoms, for example, 2-benzothiazolylthio, 1-phenyltetrazol-5-ylthio), a sulfamoyl group (preferably Is a substituted or unsubstituted sulfamoyl group having 0 to 30 carbon atoms, for example, N-ethylsulfamoyl, N- (3-dodecyloxypropyl) sulfamoyl, N, N-dimethylsulfamoyl, N-
Acetylsulfamoyl, N-benzoylsulfamoyl, N- (N'-phenylcarbamoyl) sulfamoyl), sulfo group, alkyl and arylsulfinyl group (preferably substituted or unsubstituted alkylsulfinyl group having 1 to 30 carbon atoms) A substituted or unsubstituted arylsulfinyl group having 6 to 30 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, phenylsulfinyl,
p-methylphenylsulfinyl),

Alkyl and arylsulfonyl groups (preferably substituted or unsubstituted alkylsulfonyl groups having 1 to 30 carbon atoms, substituted or unsubstituted arylsulfonyl groups having 6 to 30 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, Phenylsulfonyl, p-methylphenylsulfonyl), acyl group (preferably formyl group, substituted or unsubstituted alkylcarbonyl group having 2 to 30 carbon atoms, substituted or unsubstituted arylcarbonyl group having 7 to 30 carbon atoms, for example, Acetyl, pivaloyl, 2-chloroacetyl, stearoyl, benzoyl, pn-octyloxyphenylcarbonyl), an aryloxycarbonyl group (preferably a substituted or unsubstituted aryloxycarbonyl group having 7 to 30 carbon atoms, for example, phenoxy Carbonyl, - chlorophenoxy carbonyl, m
-Nitrophenoxycarbonyl, pt-butylphenoxycarbonyl), an alkoxycarbonyl group (preferably a substituted or unsubstituted alkoxycarbonyl group having 2 to 30 carbon atoms, for example, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, n- Octadecyloxycarbonyl),

A carbamoyl group (preferably having a carbon number of 1 to
30 substituted or unsubstituted carbamoyls such as carbamoyl, N-methylcarbamoyl, N, N-dimethylcarbamoyl, N, N-di-n-octylcarbamoyl, N- (methylsulfonyl) carbamoyl), aryl and heterocyclic azo Group (preferably a substituted or unsubstituted arylazo group having 6 to 30 carbon atoms, a substituted or unsubstituted heterocyclic azo group having 3 to 30 carbon atoms, for example, phenylazo, p-chlorophenylazo, 5-ethylthio-
1,3,4-thiadiazol-2-ylazo), an imide group (preferably N-succinimide, N-phthalimide), a phosphino group (preferably a substituted or unsubstituted phosphino group having 2 to 30 carbon atoms, for example, Dimethylphosphino, diphenylphosphino, methylphenoxyphosphino), phosphinyl group (preferably having 2 to 2 carbon atoms)
30 substituted or unsubstituted phosphinyl groups, for example,
Phosphinyl, dioctyloxyphosphinyl, diethoxyphosphinyl), phosphinyloxy group (preferably a substituted or unsubstituted phosphinyloxy group having 2 to 30 carbon atoms, for example, diphenoxyphosphinyloxy, Dioctyloxyphosphinyloxy),

A phosphinylamino group (preferably a substituted or unsubstituted phosphinylamino group having 2 to 30 carbon atoms, for example, dimethoxyphosphinylamino, dimethylaminophosphinylamino), a silyl group (preferably ,
Represents a substituted or unsubstituted silyl group having 3 to 30 carbon atoms, for example, trimethylsilyl, t-butyldimethylsilyl, phenyldimethylsilyl).

Among the above functional groups, those having a hydrogen atom may be removed and further substituted with the above group. Examples of such functional groups include alkylcarbonylaminosulfonyl, arylcarbonylaminosulfonyl, alkylsulfonylaminocarbonyl,
An arylsulfonylaminocarbonyl group is exemplified.
Examples include methylsulfonylaminocarbonyl,
p-methylphenylsulfonylaminocarbonyl, acetylaminosulfonyl, and benzoylaminosulfonyl groups. m represents an integer of 0 to 3, and when m is 2 or 3, each R ₂ may be the same or different, and adjacent R ₂ may form a ring.
m is preferably 0 or 1. Aryl group represented by Ar has the same meaning as the aryl group described for R _2. Ar is preferably a substituted or unsubstituted phenyl group, more preferably an unsubstituted phenyl group. An alkyl group represented by R ₃ ,
Aryl group, an alkoxycarbonyl group and an aryloxycarbonyl group are an alkyl group described by R _2, respectively,
Synonymous with an aryl group, an alkoxycarbonyl group and an aryloxycarbonyl group. R ₃ is preferably an alkyl group, and more preferably a methyl group.

The alkali metal represented by M is, for example, lithium, sodium or potassium. The ammonium represented by M is preferably a tertiary amine (eg, trimethylamine, triethylamine, tributylamine, N, N-diethylisopropylamine, 1,8-diazabicyclo [5,4,0]
Undecene (DBU)) ammonium. Specific examples of the compound represented by formula (II) obtained by the production method of the present invention are shown below, but it should not be construed that the invention is limited thereto.

[0026]

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[0027]

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Next, the reaction of the method of the present invention is carried out in the presence of a base,
After reacting a carboxylic acid containing the general formula (I) with phosphorus oxychloride, and then reacting a phenol compound and a base at least 3 times the molar amount of the phosphorus oxychloride, aryl esters containing the general formula (II) are obtained. Will be described in detail by taking as an example the case of manufacturing. The general reaction procedure is
After the base 1 is dropped into the carboxylic acid solution (or dispersion) and the carboxylic acid is sufficiently dissociated, the former stage of the reaction with phosphorus oxychloride and the phenol compound and the base 2 (or a mixture of the phenol compound and the base 2) are successively performed. It consists of a latter-stage reaction in which a desired aryl ester is produced by dropping. Preferred solvents are acetonitrile, ethyl acetate,
Acetone, dichloromethane, chloroform, tetrahydrofuran, toluene, N, N-dimethylacetamide, N, N-
Dimethylacetamide and the like. More preferred are acetonitrile, ethyl acetate, acetone, dichloromethane, tetrahydrofuran, and particularly preferred is acetonitrile. In the first-stage reaction, the base used in the present invention may be an organic or inorganic (for example, K ₂ CO ₃ ) base, and the base 1 is preferably an organic base, such as trimethylamine, triethylamine, N, N-diisopropylethylamine. , 1,8-diazabicyclo [5,4,0]
Undecene (DBU), N, N, N ', N'-tetramethylguanidine and the like.

At this time, the molar ratio of the base 1 to the carboxylic acid is preferably 0.5 to 3.0, more preferably 0.8 to 3.0.
To 1.2, particularly preferably 0.9 to 1.1. When a base having sufficient basicity to dissociate the carboxylic acid is used, it is most preferable to use an equivalent amount of the base to the carboxylic acid. The reaction temperature of the carboxylic acid with the base 1 is preferably from -10 ° C to 100 ° C, more preferably 0 ° C.
C. to 60.degree. C., particularly preferably 10.degree. The reaction time between the carboxylic acid and the base 1 (excluding the dropping time of the base 1) is preferably from 1 minute to 5 hours, more preferably from 5 minutes to 1 hour, particularly preferably from 10 minutes to 1 hour.
30 minutes.

The molar ratio of phosphorus oxychloride to carboxylic acid is preferably from 0.3 to 1.5, more preferably from 0.5 to 1.5.
1.2, particularly preferably 0.9 to 1.1. The reaction temperature between the reaction solution of the carboxylic acid and the base 1 in the first-stage reaction and phosphorus oxychloride is preferably from -20C to 100C, more preferably from -10C to 50C, and particularly preferably from 0C to 3C.
0 ° C. In the first-stage reaction, the reaction time (excluding the dropping time of phosphorus oxychloride) is preferably 1 minute to 5 hours, more preferably 5 minutes to 2 hours, and particularly preferably 10 minutes to 1 hour. .

In the latter reaction, the molar ratio of the phenol compound (ArOH) and the base 2 to phosphorus oxychloride is preferably 3 to 10, more preferably 3 to 10.
To 5, and particularly preferably 3 to 4. Preferred base 2 is the same as described for base 1. Base 2
May be the same as or different from base 1. The order of dropping (or adding) the phenol compound and the base 2 may be arbitrary. That is, the phenol compound may be dropped after the base 2 is dropped (in this case, the base 2 may be dropped before the phosphorus oxychloride is dropped), or the base 2 may be dropped after the phenol compound is dropped. Then, a mixture of phenol and base 2 may be added dropwise. The reaction temperature of the latter reaction is preferably from -20C to 100C, more preferably from -10C to 50C, particularly preferably from 0C to 30C. The latter reaction time is preferably 1 minute to 5 hours, more preferably 5 minutes to 2 hours, and particularly preferably 1 minute to 2 hours.
0 minutes to 1 hour.

When R _{1 in the} compound represented by the general formula (I) represents an acyl group, a sulfonyl group, an alkoxycarbonyl group, or an aryloxycarbonyl group, the number of moles of the phenol compound and the base 2 in the subsequent reaction; By selecting a reaction temperature, a reaction time, and the like, an aryl ester derivative of the compound represented by the general formula (II) wherein R ₁ is a hydrogen atom can be obtained. In particular, when it is desired to selectively obtain an aryl ester derivative in which R ₁ is a hydrogen atom, R ₁
Is preferably an acyl group, an alkoxycarbonyl group, or an aryloxycarbonyl group (more preferably an acyl group, particularly preferably an acetyl group), and the phenol compound and the base 2 are 4 to 5 relative to phosphorus oxychloride.
It is preferable to use twice the molar amount.

Further, R _{1 of the} compound represented by the general formula (I)
When the benzotriazole derivative of a hydrogen atom, that is, the compound represented by the general formula (Ia) is subjected to aryl esterification by the method of the present invention, the -NH- It is preferable that the hydrogen atom is once protected by a protecting group by a conventional method to obtain a compound represented by the general formula (Ib), and then subjected to aryl esterification. In this case, as described above, deprotection can be advanced together with aryl esterification, and the benzotriazole carboxylic acid aryl ester represented by the general formula (IIa) can be easily obtained. If conditions are selected, the production of the benzotriazolecarboxylic acid aryl ester represented by the general formula (IIa) by protection, arylesterification and deprotection of the compound represented by the general formula (Ia) can be performed in one pot. Can be.

The conversion of the compound represented by the general formula (Ia) to the compound represented by the general formula (Ib) (protection of the —NH— group) will be described below. The compound represented by the general formula (Ib) is reacted with the compound represented by the general formula (Ia) and R ₃ COX (X = halogen atom) or (R ₃ CO) ₂ O in the presence of a base or in the absence of a base. Is obtained. More preferably, the compound represented by the general formula (Ia) is reacted with R ₃ COCl in the presence of a base. The compound represented by the general formula (Ia)
The method of reacting R ₃ COCl in the presence of a base will be described in detail. Preferred solvents are acetonitrile, ethyl acetate, acetone, dichloromethane, chloroform, tetrahydrofuran, toluene, N, N-dimethylacetamide,
N, N-dimethylacetamide and the like. More preferred are acetonitrile, ethyl acetate, acetone, dichloromethane, tetrahydrofuran, and particularly preferred is acetonitrile.

Preferred bases are trimethylamine,
Triethylamine, N, N-diisopropylethylamine,
1,8-diazabicyclo [5,4,0] undecene (DBU), N, N,
N ', N'-tetramethylguanidine and the like. The molar ratio of the base to the compound represented by formula (Ia) is preferably 0.5 to 4.0, more preferably 2 to 3. When a base having sufficient basicity to dissociate the carboxylic acid and —NH— of the triazole moiety is used, it is preferable to use twice the amount of the base with respect to the compound represented by the general formula (Ia). Most preferred. The molar ratio of R ₃ COCl to the compound represented by the general formula (Ia) is preferably 0.8 to 1.5.
And more preferably 0.9 to 1.1.

The preferred reaction temperature is preferably between -20 ° C and 5 ° C.
The temperature is 0 ° C, more preferably 0 ° C to 25 ° C. The preferred reaction time (excluding the R ₃ COCl dropping time) is 10 minutes to 5 hours, more preferably 1 hour to 2 hours. The solution of the general formula (Ib) thus obtained is reacted with phosphorus oxychloride and a phenol compound and a base in an amount of 4 to 5 times the amount of phosphorus oxychloride in the same manner as in the above-mentioned method to give a compound of the general formula (Ib). The benzotriazolecarboxylic acid aryl ester represented by (IIa) can be obtained.

[0037]

Next, the present invention will be described in more detail with reference to examples. Example 1 (Synthesis of benzoic acid phenyl ester) Triethylamine (15 ml) was added dropwise to a solution of benzoic acid (12.2 g) in acetonitrile (120 ml) at room temperature, and the mixture was stirred until it became uniform. The solution was cooled to 5 ° C., phosphorus oxychloride (9.3 ml) was added dropwise at 15 ° C. or lower, and the mixture was further stirred at room temperature for 30 minutes. The solution was cooled to 5 ° C and phenol (28.2
g) and triethylamine (41.8 ml) in acetonitrile (20 ml) were added dropwise at 15 ° C. or lower, and the mixture was further stirred at room temperature for 1 hour. (At this time, the production rate of phenyl benzoate by high performance liquid chromatography analysis was 93%.)
Ethyl acetate (400 ml) and 1 mol / l hydrochloric acid aqueous solution (400
ml) was added and the mixture was separated. The organic layer was washed twice with 400 ml of water and then with a saturated saline solution. After concentrating the organic layer, 15.1 g of pure phenyl benzoate was obtained by column chromatography (developing solution: ethyl acetate / hexane = 1/10) and recrystallization (ethyl acetate / hexane) (yield: 76%, melting point: 70- 7
1 ° C.).

Example 2 (Synthesis of 1H-benzotriazole-5 (or 6) -carboxylic acid phenyl ester) 1H-benzotriazole-5 (or 6) -carboxylic acid (50%)
g) and acetonitrile (175 ml) were mixed with triethylamine (65.1 g), stirred at 60 ° C for 30 minutes, and then cooled to 5 ° C. Acetyl chloride (25.3 g) was added dropwise to this solution at 15 ° C. or lower, stirred at 25 ° C. for 1 hour, and then cooled to 5 ° C. Phosphorus oxychloride (49.4 g) was added dropwise to this solution at 15 ° C or less, and 10
After stirring at 1 ° C for 1 hour, the mixture was cooled to 5 ° C. A solution of phenol (115.5 g) in acetonitrile (50 ml) was added dropwise to this solution, and triethylamine (124.8 g) was added dropwise at 10 ° C. or lower, followed by stirring at 25 ° C. for 2 hours. (At this time, the generation rate of 1H-benzotriazole-5 (or 6) -carboxylic acid phenyl ester by high performance liquid chromatography analysis was 95%.) 4.7 mol / l aqueous hydrochloric acid (260 ml) was slowly added to this solution. After that, acetonitrile was distilled off under reduced pressure. 250 ml of water was added dropwise to the concentrated residue while stirring, and further
Stirred at 0 ° C. for 1 hour. The crystals are filtered and washed with water and acetonitrile at 0 ° C. to give 1H-benzotriazole-5 (or 6) -carboxylic acid phenyl ester (6
1.8 g, yield: 84.3%, melting point: 160-162 ° C, HPLC purity: 99.9%).

COMPARATIVE EXAMPLE 3 (1H-benzotriazole-5 (or 1H-benzotriazole-5 by mixed anhydride method using phenyl chlorocarbonate)
6) -Synthesis of carboxylic acid phenyl ester) 1H-benzotriazole-5 (or 6) -carboxylic acid (50
g) and acetonitrile (175 ml) were mixed with triethylamine (65.1 g), stirred at 60 ° C for 30 minutes, and then cooled to 5 ° C. Acetyl chloride (25.3 g) was added dropwise to this solution at 15 ° C. or lower, stirred at 25 ° C. for 1 hour, and then cooled to 5 ° C. To this solution, isobutyl chlorocarbonate (43.5 ml) was added dropwise at 15 ° C or lower, stirred at 10 ° C for 1 hour, and cooled to 5 ° C. To this solution is added dropwise a solution of phenol {72 g (the minimum theoretical amount is 58 g)} in acetonitrile (50 ml), and triethylamine {77.5 g (the minimum theoretical amount is 62 g)} at 10 ° C or less. After the dropwise addition, the mixture was stirred at 25 ° C for 2 hours. At this time, the production rate of 1H-benzotriazole-5 (or 6) -carboxylic acid phenyl ester by high performance liquid chromatography analysis was 79%, which was clearly lower than that of Example 2.

[0040]

According to the production method of the present invention, as described above, phenyl esters can be synthesized in high yield and high purity under mild conditions using inexpensive reagents. Also,
The production method of the present invention can be carried out in one tank from the beginning to the end of the reaction. The present invention is particularly effective for phenylesterification of benzotriazolecarboxylic acids.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 249/18 505 C07D 249/18 505 // C07B 61/00 300 C07B 61/00 300

Claims (4)

[Claims] 1. A reaction between a carboxylic acid and phosphorus oxychloride in the presence of a base, followed by an esterification reaction in the presence of the same or a different base with a phenol compound at least three times the amount of phosphorus oxychloride. A process for producing an aryl ester, characterized by comprising the steps of: 2. After reacting the compound represented by the general formula (I) with phosphorus oxychloride in the presence of a base, the compound is further reacted with phosphorus oxychloride in the presence of the same or a different base.
A method for producing a compound represented by the general formula (II), wherein an esterification reaction is carried out using a phenol compound in an amount of twice or more moles. Embedded image Here, R ₁ is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an acyl group, an alkylsulfonyl group, an arylsulfonyl group, an alkoxycarbonyl group,
Represents an aryloxycarbonyl group, a carbamoyl group, or a sulfamoyl group, R ₂ represents a substituent, m represents an integer of 0 to 3, and Ar represents an aryl group. However, the general formula (I)
When R _{1 in} is a group other than a hydrogen atom, the case where R ₁ in the general formula (II) represents a hydrogen atom is also included. 3. A compound represented by the following general formula (Ia) is converted into a compound represented by the following general formula (Ib), and reacted with phosphorus oxychloride, and further reacted with phosphorus oxychloride in the presence of a base. A method for producing a compound represented by the general formula (IIa), wherein an esterification reaction is carried out using at least three times the molar amount of a phenol compound. Embedded image Here, R ₂ , m and Ar each have the same meaning as above,
₃ represents an alkyl group, an aryl group, an alkoxycarbonyl group and an aryloxycarbonyl group, and M represents a hydrogen atom, an alkali metal or ammonium. 4. After acetylating 1H-benzotriazole-5 or 6-carboxylic acid, it is reacted with phosphorus oxychloride, and a phenol compound is used in the presence of a base in an amount of at least 3 times the molar amount of phosphorus oxychloride. A method for producing 1H-benzotriazole-5 or 6-carboxylic acid phenyl ester, characterized in that the esterification reaction is carried out.