JP2003089698A - Method for producing pyrazolotriazole derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a pyrazolotriazole derivative, by which a 7-monohalogen-substituted-6-ester pyrazolotriazole derivative or a carbamoyl-substituted one useful as a medicine, an agrochemical, especially a cyan coupler for photography is obtained in a high reaction yield at a low side reaction rate and at a low cost. SOLUTION: This method for producing the pyrazolotriazole derivative represented by formula (II) is characterized by using a 1,3-dihalohydrantoin derivative represented by formula (I).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a 7-monohalo-substituted 6-ester or carbamoyl-substituted pyrazolotriazole derivative which is useful as a cyan coupler for pharmaceuticals, agricultural chemicals, and particularly for photography. 1,
Process for producing 7-monohalo-substituted 6-ester or carbamoyl-substituted pyrazolotriazole derivative using 3-dihalohydantoin derivative as halogenating reagent at high reaction yield, low side reaction rate and low cost It is about.

[0002]

BACKGROUND OF THE INVENTION Pyrazoloazole derivatives are useful as pharmaceuticals, agricultural chemicals, photographic couplers and their intermediates. In particular, the 7-position-monohalo-substituted, 6-position-ester or carbamoyl-substituted pyrazolotriazole derivative is highly useful as a cyan coupler for photography.

Various methods are known as methods for introducing a halogen atom into a pyrazoloazole derivative. For example, as disclosed in JP-A-60-55343, a method of reacting chlorine gas or sulfuryl chloride in a halogen-based solvent is widely known. However, the above method has problems such as toxicity of chlorine gas, emission of sulfurous acid gas or hydrogen chloride gas generated by the reaction to the atmosphere, generation of side reaction products caused by acidification of the reaction system, and corrosion of the reaction vessel. Was holding.

As a halogenating reagent for solving these problems, JP-A-60-98434 discloses an example in which N-chlorosuccinimide is used as a chlorinating reagent for a photographic color coupler. In this case, the generation of sulfurous acid gas or hydrogen chloride gas, which was a problem with sulfuryl chloride, was suppressed, but it was necessary to remove the succinimide generated after the reaction of N-chlorosuccinimide, and the price of the reagent. There was a problem that was high.

The above-mentioned known examples are all examples of pyrazolotriazole derivatives having an alkyl group, an aryl group or the like at the 6-position, and these are pyrazolo groups having an ester group or a carbamoyl group at the 6-position. When it is applied to the production of a triazole derivative (pyrazolotriazole-based cyan coupler), there is a problem in that the selectivity of the reaction for the target monochloro compound is poor and the reaction yield is significantly deteriorated.

[0006]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a 7-monohalo-substituted 6-position which is useful as a cyan coupler for pharmaceuticals, agricultural chemicals, especially for photography. An object of the present invention is to provide a method for producing a position-ester or carbamoyl-substituted pyrazolotriazole derivative with a high reaction yield, a low side reaction rate, and a low price.

[0007]

The above object of the present invention can be achieved by the following constitutions.

1. 1,3-represented by the general formula (I)
A method for producing a pyrazolotriazole derivative represented by the general formula (II), which comprises using a dihalohydantoin derivative.

2. 1,3-represented by the general formula (I)
A method for producing a pyrazolotriazole derivative represented by the above general formula (II), which comprises reacting a dihalohydantoin derivative with the pyrazolotriazole derivative represented by the above general formula (III).

3. A method for producing a pyrazolotriazole derivative represented by the general formula (II), which comprises reducing the pyrazolotriazole derivative represented by the general formula (IV).

4. The compound represented by the general formula (V) is halogenated with the 1,3-dihalohydantoin derivative represented by the general formula (I), and subsequently reduced, and the general formula ( A method for producing a pyrazolotriazole derivative represented by VI).

The present invention will be described in detail below. The 1,3-dihalohydantoin derivative according to the present invention is the 1,3-dihalohydantoin derivative represented by the general formula (I).

In the general formula (I), R ₁ and R ₂
Each represents a hydrogen atom, an alkyl group, a cycloalkyl group or an aryl group, R ₁ and R ₂ may be the same or different, and each of these groups includes those having a substituent. Examples of the alkyl group represented by R ₁ and R ₂ include:
Examples thereof include a methyl group, an ethyl group and a propyl group. Examples of the cycloalkyl group include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group and the like. Examples of the aryl group include a phenyl group, a 4-methylphenyl group, a 4-t-butylphenyl group and the like. R ₁ and R ₂ are preferably a hydrogen atom and an alkyl group having 1 to 6 carbon atoms, and more preferably a methyl group.

Each X represents a chlorine atom or a bromine atom, and two Xs are atoms of the same kind, preferably X is a chlorine atom.

The general formula (I) used in the present invention is described below.
Specific examples of the 1,3-dihalohydantoin derivative represented by are shown below, but the present invention is not limited thereto.

[0016]

[Chemical 6]

Next, the pyrazolotriazole derivative represented by the general formula (II) will be described.

In the general formula (II), X represents a bromine atom or a chlorine atom, and preferably X is a chlorine atom.

R ₃ represents -OR ₄ or -NR ₅ R ₆ , preferably R ₃ is -NR ₅ R ₆ . R ₄ , R ₅ and R ₆ each represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group or a heteroaryl group, and examples of the alkyl group include, for example, a straight chain having 1 to 32 carbon atoms, or Examples of the branched chain alkyl group include, for example, methyl group, ethyl group, propyl group, isopropyl group, t-butyl group, tridecyl group, 2-methanesulfonylethyl group,
A 3- (3-pentadecylphenoxy) propyl group and the like can be mentioned. Examples of the cycloalkyl group include a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, a 1-adamantyl group and the like. Examples of the aryl group include, for example, phenyl group, 4-t-butylphenyl group, 2,4-di-t-amylphenyl group, 2,4.
6-trimethylphenyl group, 3-tridecanamide-
2,4,6-trimethylphenyl group, 4-tetradecanamidophenyl group and the like can be mentioned. Examples of the heteroaryl group include, for example, a 2-furyl group, a 2-thienyl group,
Examples include 2-pyrimidinyl group and 2-benzothiazolyl group. These may be further substituted with a substituent, for example, a halogen atom, a hydroxyl group, a carboxy group, a nitro group, a cyano group, an amino group, an amide group, a carbamoyl group, an alkylsulfonyl group, an arylsulfonyl group, a sulfonamide group, It may have a sulfamoyl group, an acyl group, an acyloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group or the like.

R ₆ is preferably an alkyl group, an aryl group or a heteroaryl group, more preferably an aryl group.

Z ₁ and Z ₂ are each = C (R ₇ )-
Or = N-, and Z ₁ and Z ₂ are simultaneously = C (R ₇ )-
Or, it cannot be = N-. Preferably Z ₁ = N
- and, Z ₂ is = C (R ₇₎ - is.

R ₇ represents a hydrogen atom or a monovalent substituent. Examples of the monovalent substituents include alkyl groups, aryl groups, anilino groups, acylamino groups, sulfonamide groups, alkylthio groups, arylthio groups, alkenyl groups,
Examples of each group such as cycloalkyl, halogen atom, cycloalkenyl group, alkynyl group, heteroaryl group, sulfonyl group, sulfinyl group, phosphonyl group, acyl group, carbamoyl group, sulfamoyl group,
Cyano group, alkoxy group, aryloxy group, heteroaryloxy group, siloxy group, acyloxy group, carbamoyloxy group, amino group, alkylamino group, amide group, ureido group, sulfamoylamino group, alkoxycarbonylamino group, aryl Examples also include an oxycarbonylamino group, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylthio group, a spiro compound residue and a bridged hydrocarbon compound residue. These may be further substituted with a substituent, for example, a halogen atom, a hydroxyl group, a carboxy group, a nitro group, a cyano group,
It may have an amino group, an amide group, a carbamoyl group, an alkylsulfonyl group, an arylsulfonyl group, a sulfonamide group, a sulfamoyl group, an acyl group, an acyloxy group and the like.

Next, the pyrazolotriazole derivatives represented by the general formulas (III) to (VI) will be described.

X in the above general formulas (III) to (VI),
Z ₁ , Z ₂ and R ₃ represent X, Z ₁ and Z _{2 in the} general formula (II).
And R ₃ respectively have the same meanings, and the preferred substituents are also the same as those in formula (II). General formula (V), (VI)
R ₈ has the same meaning as R ₇ in formula (II), and the preferred substituents are also the same as in formula (II).

Below, the general formulas (II) to (I
V) (further, (V) to (VI)) are illustrated as specific compound examples of the pyrazolotriazole derivative, but the present invention is not limited thereto.

[0026]

[Chemical 7]

[0027]

[Chemical 8]

[0028]

[Chemical 9]

[0029]

[Chemical 10]

[0030]

[Chemical 11]

[0031]

[Chemical 12]

[0032]

[Chemical 13]

[0033]

[Chemical 14]

Specific examples of the pyrazolotriazole derivative represented by the general formula (V) include the same compounds as the above exemplified compounds III-7 to III-43, and the general formula (VI) Specific examples of the pyrazolotriazole derivative represented are, for example, the above compound example II-
7 to II-43, but the present invention is not limited thereto.

The 7-monohalo-substituted 6-ester or carbamoyl-substituted pyrazolotriazole derivative of the present invention, that is, the pyrazolotriazole derivative represented by the general formula (II), is more suitable than the following scheme. Can be synthesized.

[0036]

[Chemical 15]

Since the 1,3-dihalohydantoin derivative of the present invention has two halogen atoms of the same type in one molecule, it can be used in an amount of 0.
Monohalogenation is possible by using 5 equivalents. By halogenating with the 1,3-dihalohydantoin derivative of the present invention, the pyrazolotriazole derivative is almost selectively monohalogenated, and the dihalogen corresponding to the excess 1,3-dihalohydantoin derivative is used. The body produces. Therefore, if an equivalent amount of the 1,3-dihalohydantoin derivative is used, only the monohalogenated compound is almost selectively produced. However, considering the reaction time, the 1,3-dihalohydantoin derivative is used in a slightly excessive amount. It is preferable. Specifically, it is preferable to use 0.5 to 1 mol based on the starting material, and 0.55 to 0.
It is more preferable to use 8 mol.

As the reaction solvent, a halogen-based solvent (eg, chloroform, methylene chloride, ethylene chloride, carbon tetrachloride, etc.), an ester-based solvent (eg, ethyl acetate, methyl acetate, butyl acetate, methyl propionate, ethyl propionate) Etc.), aromatic hydrocarbon solvents (eg benzene, toluene, xylene etc.), aliphatic hydrocarbon solvents (eg n-hexane, n-heptane, iso-octane etc.), ether solvents (eg diethyl. Ether, di-iso-propyl ether, tetrahydrofuran, dioxane, etc., ketone type solvent (eg, acetone, methyl ethyl ketone, methyl isobutyl ketone etc.), amide type solvent (eg N, N-dimethylacetamide, N, N-dimethylformamide etc.) ), Nitrile solvents (eg, acetonite) Examples thereof include ester solvents, propionitrile, etc.), alcoholic solvents (eg, methanol, ethanol, n-propanol, iso-propanol, butanol, etc.), but ester-based solvents, aromatic hydrocarbon-based solvents, ketone-based solvents, amides. System solvents are preferred, and particularly preferred solvents are ethyl acetate and toluene.
The reaction temperature is generally 0 ° C to 120 ° C, preferably 10 ° C to 70 ° C.

As the post-treatment after the reaction, the post-treatment which is carried out by a normal organic reaction such as extraction is carried out. However, it is possible to proceed to the reduction reaction by directly adding the reducing agent without performing the post-treatment such as extraction. You can also

The dihalogenated pyrazolotriazole derivative produced by an excess of the 1,3-dihalohydantoin derivative is reduced almost quantitatively to the target monochloropyrazolotriazole derivative. The reducing agent used in the present invention is not particularly limited, but alkaline methanol, hydrazine, hydroxylamine, sodium sulfite, active methylene compound and the like are preferably used. These reducing agents vary depending on the amount of the 1,3-dihalohydantoin derivative used, but are 0.01% to the pyrazolotriazole derivative.
~ 3 equivalents are preferably used, particularly preferably 0.1.
Equivalent to 2 equivalents. The temperature of the reduction reaction is 0 ° C to 70
C. is preferable, and 20.degree. C. to 70.degree. C. is more preferable. The reaction time is preferably 10 minutes to 24 hours, more preferably 30 minutes to 4 hours.

After completion of the reduction reaction, the 7-position monohalo-substituted 6-ester or carbamoyl-substituted pyrazolotriazole derivative which is the target compound produced, that is, the pyrazolotriazole derivative represented by the general formula (II) is It can be appropriately separated and recovered from the reaction solution by a usual method such as extraction or crystallization. In this, a method of crystallization by cooling the reaction solvent after extraction, a method of distilling off a part or all of the reaction solvent to concentrate the reaction solution, and then adding another solvent to crystallize are generally used. However, after extraction, it is also possible to concentrate to dryness and use as it is.

For the detailed synthetic method of the pyrazolotriazole derivative represented by the general formula (III), the method described in JP-A-9-281672 can be referred to.

After synthesizing the pyrazolotriazole derivative represented by the general formula (III), the compound represented by the general formula (I) of the present invention is added to the reaction solution and halogenated without isolation. It is also possible to obtain a pyrazolotriazole derivative represented by the general formula (II) which is the final target compound in a running reaction mode by adding a reducing agent to the reaction solution without isolation even after that. it can.

[0044]

The present invention will be specifically described below with reference to examples, but the embodiments of the present invention are not limited thereto.

Example 1 Synthesis of Exemplified Compound II-8 437 g (1.4 mol) of the following compound (A) was stirred and dispersed in 2 liters of toluene, and 256 g of thionyl chloride was added.
(2.2 mol) is added, and the mixture is reacted at about 70 ° C. for 3 hours. After completion of the reaction, the solvent was recovered under reduced pressure.

To the obtained residue, 2.6 liters of ethyl acetate was added, dispersed by stirring, and 513 g (1.5 mol) of the following compound (B) was added dropwise at room temperature. Then, 1.2 kg (2.9 mol) of 33% aqueous potassium carbonate solution is added dropwise at room temperature, and after completion of the addition, the mixture is stirred and reacted at room temperature for 30 minutes. Then 29
262 ml of% aqueous ammonia is added dropwise, and the mixture is reacted with stirring at room temperature for 2 hours. After completion of the reaction, a dilute sulfuric acid aqueous solution is added for neutralization, the aqueous layer is removed, and then washing with water is carried out three times. The water-washed ethyl acetate solution is azeotropically dehydrated under normal pressure, and after the dehydration, the distilled ethyl acetate is added.

Thereafter, 170 g of the exemplified compound (I-2)
(0.86 mol) is added, and the mixture is stirred and reacted at 60 ° C. for 3 hours.

Thereafter, 181 g of sodium sulfite (1.
4 mol) and 0.9 liter of water are added, and the temperature is further increased to 60 ° C.
And react for 2 hours with stirring.

After completion of the reaction, the aqueous layer was removed and the reaction solution was mixed with 3
Wash with water and concentrate the organic layer. This, heptane 1.8
Recrystallize with l and collect the precipitated crystals by filtration.
After washing with liter, 818 g (yield 92%) of the target Exemplified Compound II-8 was obtained (melting point: 83-88).
C). The structure was confirmed by ¹ H-NMR, IR and Mass spectra.

[0050]

[Chemical 16]

Example 2 Synthesis of Exemplified Compound II-9 585 g (1 mol) of Exemplified Compound (III-9) was dissolved in 1.8 l of toluene to give 108 g of Exemplified Compound (I-2).
(0.55 mol) was added, and the mixture was reacted with stirring at room temperature for 8 hours. After completion of the reaction, 63 g of sodium sulfite and 0.6 of water
1 was added and reacted at 60 ° C. for 2 hours. After completion of the reaction, the aqueous layer is removed, the reaction solution is washed 3 times with water, and the organic layer is concentrated. This is recrystallized with 1.2 l of methanol, and the precipitated crystals are collected by filtration and washed with 0.4 l of methanol,
595 g of target Exemplified Compound II-9 (yield 96%)
Obtained (melting point 97-99 ° C). The structure is ¹ H-NM
It was confirmed by R, IR and Mass spectra.

As a comparative example, N-chlorosuccinimide was used in place of the exemplified compound (I-2) (1,3-dichloro-5,5-dimethylhydantoin), which is the chlorinating agent of Example 2, as exemplified compound III-9. When the chlorination reaction was carried out using 1.1 equivalents to the above, a large amount of dichloro body was produced before the raw material disappeared, and the reaction stopped as a mixture of the raw material, the monochloro body and the dichloro body. In addition, it was found that various kinds of by-products were formed.

[0053]

INDUSTRIAL APPLICABILITY According to the present invention, a 7-position-monohalo-substituted, 6-position-ester or carbamoyl-substituted pyrazolotriazole derivative useful as a photographic cyan coupler,
It is possible to provide a production method that can obtain a high reaction yield, a low side reaction rate, and a low price.

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Claims (4)

[Claims] 1. A method for producing a pyrazolotriazole derivative represented by the following general formula (II), which comprises using a 1,3-dihalohydantoin derivative represented by the following general formula (I). [Chemical 1] (In the formula, R ₁ and R ₂ each represent a hydrogen atom, an alkyl group, a cycloalkyl group or an aryl group, and R ₁ and R ₂ may be the same or different. X represents a bromine atom or a chlorine atom. .) [Chemical 2] (In the formula, X represents a bromine atom or a chlorine atom, and R ₃ represents-.
OR ₄ or —NR ₅ R ₆ is represented, and R ₄ , R ₅ and R ₆ are each a hydrogen atom, an alkyl group, an aryl group or a heteroaryl group. Z ₁ and Z ₂ are each = C
(R ₇ ) -or = N-, and Z ₁ and Z ₂ are simultaneously = C.
It will never be (R ₇ )-or = N-. R ₇ represents a hydrogen atom or a monovalent substituent. ) 2. A 1,3-dihalohydantoin derivative represented by the general formula (I) is reacted with a pyrazolotriazole derivative represented by the following general formula (III). A method for producing a pyrazolotriazole derivative represented by (II). [Chemical 3] (Wherein, Z _1, Z ₂ and R ₃ are, Z ₁ in formula (II),
It has the same meaning as Z ₂ and R ₃ . ) 3. A method for producing a pyrazolotriazole derivative represented by the general formula (II), which comprises reducing the pyrazolotriazole derivative represented by the following general formula (IV). [Chemical 4] (Wherein, X, Z _1, Z ₂ and R ₃ are X in formula (II), and Z _1, Z ₂ and R ₃ respectively the same.) 4. A compound represented by the following general formula (V):
A method for producing a pyrazolotriazole derivative represented by the following general formula (VI), which comprises halogenating the 1,3-dihalohydantoin derivative represented by the general formula (I) and subsequently reducing the halogenated compound. . [Chemical 5] (Formula (V), (VI) in, R ₃ is R ₃ in the general formula (II)
In the above formula, R ₈ represents a hydrogen atom or a monovalent substituent. In general formula (VI), X has the same meaning as X in general formula (II). )