JP3010383B2 - Method for synthesizing 3-carboxy-5-acyloxypyrazole - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for synthesizing 3-carboxy-5-acyloxypyrazoles. The present invention relates to a synthesis method for obtaining -5-acyloxypyrazole with high yield and high quality.

[0002]

2. Description of the Related Art Pyrazole derivatives are known as photographic couplers,
It is a compound useful as a skeleton of photographic dyes, medicines and agricultural chemicals. Among photographic dyes, a pyrazolone oxonol dye having a water solubility such as a carboxyl group or a sulfo group is a compound particularly useful as an irradiation preventing dye for improving the sharpness of a photographic image.

[0003] Among the water-soluble pyrazolone oxonol dyes, a substituted carbamoyl group having a water-soluble group at the 3-position of the pyrazole nucleus, such as a (MO ₃ S) nQ-NHCO group (Q
Represents an aliphatic group or an aromatic group, M represents a cation, and n represents an integer of 1 or 2. ) Are described in JP-A-59-111641 as particularly effective dyes.

The publication also discloses a method for synthesizing a 3-substituted carbamoylpyrazole derivative having a water-soluble group, which is an intermediate of the dye.

[0005]

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According to this method, the compound (3) is unstable, and the compound (4) has low reaction activity, so that a competitive reaction between the decomposition of (3) and the formation of (5) occurs. ,
For this reason, there is a disadvantage that the yield is low.

As a method for overcoming this drawback, there is a method in which the 5-position of 3-carboxy-5-pyrazolone is blocked (protected), the 3-position is converted to an acid halide, and then reacted with a substituted amine having a water-soluble group. It is described in JP-A-2-93973. According to this method, a 3-substituted carbamoylpyrazole derivative having a water-soluble group and a 3-carboxy-5-pyrazolone blocked at the 5-position, for example, 3-carboxy-5-acyloxypyrazole can be obtained in high yield. As a matter of fact, no method has yet been found that can synthesize with satisfactory yield and quality.

[0008] Japanese Patent Application Laid-Open No. 2-93973, page 9 and 2-
On page 9 of the specification of 193974, 3-carboxy-5-pyrazolone and an acid halide represented by the above general formula [II] can be prepared in an aprotic polar solvent such as acetonitrile in the presence of an organic base such as triethylamine. React, 3-carboxy
A method for synthesizing -5-acyloxypyrazoles is described.

According to this method, the reactant does not dissolve all the time, the reaction proceeds in a heterogeneous system, and the product has the general formula [IV]
Is by-produced, and it is difficult to remove the compound by repeating the purification operation.

[0010]

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[0011] In the general formula [IV], R ₁ and R ₂ have the same meanings as R _1, R ₂ described in the general formula (I) and (II).

When 3-carboxy-5-acyloxypyrazole contains a compound represented by the general formula [IV], 3
Water-soluble group by a method of reacting with a substituted amine having a water-soluble group after the formation of an acid halide or a condensing agent such as N, N'-dicyclohexylcarbodiimide. It is impossible to produce a 3-substituted carbamoyl-5-acyloxypyrazole having the following formulas with high purity and yield.

[0013]

As described above, 3-carboxy-5, which is an intermediate of a 3-substituted carbamoyl-5-acyloxypyrazole having a water-soluble group, has been described.
A satisfactory synthesis of acyloxypyrazoles has not yet been established.

Accordingly, an object of the present invention is to provide a photographic coupler,
Useful as raw materials and intermediates for photographic dyes, pharmaceuticals, pesticides, etc.
An object of the present invention is to provide a synthesis method for obtaining 3-carboxy-5-acyloxypyrazole with high yield and high quality.

[0015]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that the object of the present invention is achieved as follows, and have made the present invention.

That is, an object of the present invention is to provide a compound represented by the general formula [I] and a compound represented by the general formula [II]:
It has been achieved by a method for synthesizing 3-carboxy-5-acyloxypyrazole represented by the general formula [III], characterized in that the reaction is carried out in a hydrous aprotic polar solvent.

[0017]

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In the general formulas (I), (II) and (III),
R ₁ represents a hydrogen atom, an alkyl group, an aralkyl group, or an aryl group, and R ₂ represents an alkyl group or an aryl group. X represents a halogen atom.

Hereinafter, the present invention will be described more specifically.

Examples of the alkyl group represented by R ₁ include groups such as methyl, ethyl, propyl, i-propyl, t-butyl, pentyl, 2-ethylhexyl, cyclopentyl and cyclohexyl.

The alkyl group may have a substituent. Examples of the substituent include a cyano group and a hydroxyl group. Examples of the substituted alkyl group include a 2-cyanoethyl group,
And a 2-hydroxyethyl group.

Examples of the aralkyl group include a benzyl group,
A 2-sulfophenylmethyl group is exemplified. As the aryl group, a phenyl group is preferable, and the phenyl group may have a substituent.

As the substituent, sulfo, carboxyl,
Each group such as alkoxy, nitro, cyano and the like, and a halogen atom and the like are preferable.

Examples of the substituted phenyl group include 2-sulfophenyl, 3-sulfophenyl, 4-sulfophenyl, 2,4-disulfophenyl, 2,5-disulfophenyl, 2-carboxyphenyl, and 4-carboxyphenyl. Phenyl, 4-methoxyphenyl, 4-nitrophenyl, 2,5-dichlorophenyl, 2,4,6-
Examples include groups such as trichlorophenyl and 2-cyanophenyl.

Examples of the alkyl group represented by R ₂ include methyl, ethyl, propyl, i-propyl and the like, preferably methyl, ethyl and propyl, and the aryl is preferably phenyl. .

X is a halogen atom, for example, chlorine, bromine, iodine, fluorine, etc., preferably chlorine, bromine,
More preferably, it is chlorine.

The aprotic polar solvent used in the present invention includes acetone, acetonitrile, dioxane, N,
N-dimethylformamide, N, N-dimethylacetamide,
Dimethyl sulfoxide, tetrahydrofuran and the like can be mentioned, but acetone or acetonitrile is preferred.

It should be noted that an alcohol solvent cannot be used in the present invention because it reacts with the compound represented by the general formula [II].

The aprotic polar solvent is used in the reaction as a water-containing solvent, and has a water content of 10 to 80%, preferably 30 to 80%.
70%.

The compound represented by the general formula [I] and the compound represented by the general formula [I
When reacting with the compound represented by the formula (I), if the above-mentioned hydrated aprotic polar solvent is used as a reaction solvent, the reaction can be performed in a uniform solution state throughout, and the compound represented by the general formula (IV) The desired 3-carboxy-5-acyloxypyrazole was obtained in high yield and quality with no by-product. This is a surprising result that the present inventors could not have expected at all.

The amount of the water-containing solvent used is preferably 3 to 10 times the amount of 3-carboxy-5-pyrazolone.

The organic base used in the present invention includes triethylamine, pyridine, piperidine, morpholine, dimethylaniline and the like, and triethylamine is preferred.

The amount of the base used is the amount of 3 represented by the general formula [I].
The amount is 0.1 to 10 mol, preferably 1.0 to 1.5 mol, per 1 mol of -carboxy-5-pyrazolone.

The amount of the acid halide represented by the general formula [II] is from 1.0 to 0.4 to 1 mol of 3-carboxy-5-pyrazolone.
Although it is used in a range of 0 mol, it is preferably in a range of 1.0 to 1.3 mol.

The reaction can be carried out at -20 to 100 ° C.
The time required for the reaction is not particularly limited, but is preferably 15 minutes to 2 hours.

Next, the compounds represented by the general formulas [I], [II] and [III] are exemplified, but the present invention is not limited thereto.

[0037]

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[0038]

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The compound represented by the general formula [I] is, for example,
J, Am, Chem, Soc., 71, 983 (1949), Chem, Ber., 109, 253 (1
976), and can be easily synthesized by the method described in JP-A-63-185964.

[0040]

EXAMPLES Specific examples of the present invention will be described below, but the present invention is not limited to these examples.

Example 1 (Synthesis of Exemplified Compound III-NO.6)
56.8 g of 1-methyl-3-carboxy-5-pyrazolone was added to a mixture of 168 ml of acetone and 112 ml of water in a 500 ml beaker, and 40.4 g of triethylamine was added with stirring. A uniform solution was obtained in about 5 minutes. While stirring, it took about 15 minutes at an internal temperature of 20 to 30 ° C., and 56.2 g of benzoyl chloride was added dropwise. Crystals were deposited as the solution was dropped. After completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour, then the reaction product was transferred to a 1-liter beaker, 336 ml of water was added over about 5 minutes, and the mixture was further stirred for 1 hour while cooling with water. The precipitate was collected by filtration and dried, and then recrystallized from 300 ml of acetonitrile containing 15% of water. 91.1 g (91.5% yield) m.p1
The compound corresponding to the general formula [IV] at a temperature of 56 to 159 ° C and an HPLC purity of 99.0% was 0.5%.

FIG. 1 shows an IR spectrum chart.

Ester carbonyl at 1750 cm ^-1 , 1680 cm
Carbonyl carboxyl ^-1, the absorption of the benzene ring is observed at 1550 cm ^-1.

Example 2 (Synthesis of Exemplified Compound III-NO.6)
Using 56.8 g of 1-methyl-3-carboxy-5-pyrazolone, 40.4 g of triethylamine and 56.2 g of benzoyl chloride, acetone-water used in Example 1 as a reaction solvent was replaced with acetonitrile.
The synthesis was performed in the same manner as in Example 1 except that the reaction temperature, time, treatment of the reaction product, and operation were changed to 92 ml and 138 ml of water.

88.1 g (89.5% yield), m.p.
The compound corresponding to the general formula [IV] having a HPLC purity of 99.3%
0.2%.

Example 3 (Synthesis of Exemplified Compound III-NO.11)
81.9 g of 1- (2,5-disulfophenyl) -3-carboxy-5-pyrazolone disodium salt was added to acetonitrile 134 ml and water 19
Add to 5 ml of the mixture and triethylamine 20.
Addition of 2 g resulted in a homogeneous solution. About 15 at internal temperature of 20-30 ° C
With some time, 28.1 g of benzoyl chloride was added dropwise. 1 at room temperature
After stirring for 1 hour, the mixture was added to 1 liter of acetone, and the precipitated solid was collected by filtration and dried. It was dissolved in water and salted out with common salt to obtain the desired product. The yield was 87.5 g (yield 85.4%). The decomposition point was 300 ° C or higher, the HPLC purity was 99.2%, and the compound corresponding to the general formula [IV] was 0.2%.

FIG. 2 shows an IR spectrum chart.

The ester carbonyl at 1770 cm ^-1 , 1700 cm
Carbonyl carboxyl ^-1, the absorption of the benzene ring is observed at 1540 cm ^-1.

The compound represented by the general formula [II
The 3-carboxy-5-acyloxypyrazole represented by the formula (I) is extremely useful as an intermediate of the photographic dye represented by the formula (VIII).

The synthesis route of the dye is illustrated below.

[0051]

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In each structural formula, R ₁ represents a hydrogen atom, an alkyl group, an aralkyl group, or an aryl group, and R ₂ represents an alkyl group or an aryl group. X represents a halogen atom,
Q is an aliphatic group, an aromatic group, M is a cation, and m is 0 or 1.
And n represents an integer of 1 or 2.

Comparative Example (Synthesis of Exemplified Compound III-NO.6)
56.8 g of methyl-3-carboxy-5-pyrazolone was added to 200 ml of acetonitrile in a 500 ml beaker, and 40.5 g of triethylamine was added with stirring. The reaction was not dissolved but was in suspension. 47.8 g of benzoyl chloride was added dropwise over about 10 minutes, and the mixture was stirred at room temperature for 3 hours. The reaction product was added to 2 l of water, and the precipitated solid was collected by filtration, dried and recrystallized from acetonitrile. Yield 84.8 g (861,1% yield) m.p.
HPLC purity was 82.3%, which corresponds to compound 12.4 corresponding to general formula (IV).
% Was found.

From the examples and comparative examples, the compound represented by the general formula [I] is reacted with the compound represented by the general formula [II] to give 3-carboxy-5 represented by the general formula [III]. It can be seen that the yield and quality of the synthesis method of the present invention using a water-containing aprotic polar solvent when synthesizing an acylpyrazole are much better than the synthesis method using an aprotic polar solvent.

[0055]

According to the synthesis method of the present invention, 3-carboxy-5-acyloxypyrazole useful as a raw material for photographic couplers, photographic dyes, medicines, agricultural chemicals and the like, and an intermediate can be obtained in high yield and high quality. Can be synthesized.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an IR spectrum chart of Exemplified Compound III-No. FIG. 2 is an IR spectrum chart of Exemplified Compound III-No.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07D 231/18-231/52 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A compound represented by the general formula [III] characterized by reacting a compound represented by the general formula [I] with a compound represented by the general formula [II] in a hydrated aprotic polar solvent. A method for synthesizing 3-carboxy-5-acyloxypyrazole represented by the formula: Embedded image Wherein R ₁ is a hydrogen atom, an alkyl group, an aralkyl group,
Represents an aryl group, and R ₂ represents an alkyl group or an aryl group. X represents a halogen atom. ]