JPH11279427A - Production of heterocyclic azomethine dye - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a compound of a heterocyclic azomethine dye without side reaction in high yield by halogenating a specific group of a specified compound, and condensing the halogenated compound with a specific compound. SOLUTION: (A) Ha and Hb of a compound of formula I or II [Ha and Hb are each H; A is an atomic group required for forming a nitrogen-containing 5-membered ring with a methylene part; X1 and X2 are each O, S or a (non) substituted N; B1 and B2 are each a monovalent substituent] is halogenated, and the halogenated compound is condensed with (B) a compound of the formula H2 N-Z (Z is a group derived from a 5- or 6-membered heterocyclic compound) to provide the objective compound of formulae III or IV in the method for producing the heterocyclic azomethine dye. An imidazole compound, a pyrazolin-5-one derivative, a pyrazolotriazole derivative or the like is preferably used as the compound of formula I. The group derived from a thiophene derivative, a pyridine derivative or the like is preferable as the Z of the component B.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a heterocyclic azomethine dye by dihalogenating a compound having an active methylene group and condensing it with a heterocyclic amine compound.

[0002]

2. Description of the Related Art An azomethine dye (hereinafter, referred to as an azomethine dye) synthesized by condensation of a heterocyclic amine compound and an active methylene compound.
"Heterocyclic azomethine dyes") have excellent color tone and spectral absorption characteristics and high stability in heat, light, moisture, air, and chemicals, and are dyes for thermal transfer recording materials. Widely used in such as.

[0003] In general, heterocyclic azomethine dyes have been synthesized by oxidative coupling of an active methylene compound with a heterocyclic amine compound. However, due to side reactions such as the heterocyclic amine compounds being condensed by the oxidizing agent or the generated heterocyclic azomethine dye compound being decomposed by the oxidizing agent, the yield is low in the conventional method and the production cost is high. Had disadvantages.

As a method for solving the above-mentioned drawbacks, there has been disclosed a method in which active methylene is replaced with a halogen such as chlorine or bromine acting as a leaving group to increase the reactivity of an oxidative coupling reaction. For example, Synthesis 1
A method in which a pyrazolin-5-one derivative described in March 985, p. 299 is once subjected to dichlorination and then converted into a monochloro form by a reduction reaction, or a method disclosed in JP-A-9-59250, which discloses 1,3-dihalo-5. A method of monohalogenation using 5-dimethylhydantoin is disclosed, but in each case, an oxidized product of a phenylenediamine derivative frequently used as a coupler and a developer of a color light-sensitive material, which is often used in the photographic industry, is disclosed. The purpose of this method was to improve the reactivity of the compound, and it was insufficient as a method for synthesizing a heterocyclic azomethine dye.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a heterocyclic amine compound and an active methylene compound capable of isolating a target dye in a high yield without side reactions as in the above-mentioned conventional synthesis method. To provide a production method for synthesizing an azomethine dye (heterocyclic azomethine dye) by condensation with azomethine dye.

[0006]

The above object of the present invention has been attained by the following constitutions.

[0007] 1. After halogenating Ha and Hb of the compound represented by the following general formula (Ia) or (Ib),
A method for producing a compound represented by the following general formula (IIIa) or (IIIb), comprising condensing a compound represented by the following general formula (II).

[0008]

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[In the formula, Ha and Hb represent a hydrogen atom, A represents an atomic group necessary for forming a nitrogen-containing 5-membered ring together with a methylene moiety, and X ₁ and X ₂ represent an oxygen atom and a sulfur atom, respectively. An atom or a substituted or unsubstituted nitrogen atom; B ₁ and B ₂ each represent a monovalent substituent;
Represents a group derived from a 5-membered or 6-membered heterocyclic compound. ] 2. After halogenating Ha of the compound represented by the general formula (Ia), the compound represented by the general formula (II) is condensed, and then the compound represented by the general formula (IIIa) is condensed. Production method.

[0010] 3. Wherein the general formula (Ia) is pyrazoline-5
3. The method for producing a compound according to 2, which is a -one derivative, an imidazole derivative or a pyrazolotriazole derivative.

4. 3. The method for producing a compound according to 2, wherein Z in the general formula (II) is a group derived from a thiophene derivative or a pyridine derivative.

5. After halogenating Hc of the compound represented by the following general formula (IV), the compound represented by the following general formula (V) is condensed with a compound represented by the following general formula (VI). Production method.

[0013]

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[Wherein Hc represents a hydrogen atom, and R ₁ ,
R ₂ , R ₃ and R ₄ each represent a hydrogen atom or a monovalent substituent. a, b, c and d each represent a nitrogen atom or a carbon atom, and at least one of a, b, c and d is a nitrogen atom. 6]. After Ha and Hb of the compound represented by the general formula (Ia) or (Ib) are halogenated, the compound represented by the general formula (II) is condensed without isolating a dihalide. The general formula (IIIa) or (III)
A method for producing the compound represented by b).

[0015] 7. After halogenating Ha of the compound represented by the general formula (Ia), the compound represented by the general formula (II) is condensed without isolating the dihalogen compound, )).

8. Wherein the general formula (Ia) is pyrazoline-5
8. The method for producing a compound according to 7, which is a -one derivative, an imidazole derivative or a pyrazolotriazole derivative.

9. 8. The method for producing a compound according to 7, wherein Z in the general formula (II) is a group derived from a thiophene derivative or a pyridine derivative.

10. After halogenating Hc of the compound represented by the general formula (IV), the compound represented by the general formula (V) is condensed without isolating a dihalide. )).

Hereinafter, the present invention will be described in detail.

The compound represented by formula (Ia) of the present invention will be described in detail.

The compound of the general formula (Ia) is a nitrogen-containing 5-membered ring compound formed by a methylene moiety and A, and specifically, a nitrogen-containing 5-membered ring compound such as pyrrole, imidazole, pyrazole and the like. A nitrogen-containing aromatic 5-5 condensed ring compound such as pyrazoloazole or pyrroloazole is exemplified.

The compound of the general formula (Ia) is preferably an imidazole derivative, a pyrazolin-5-one derivative, a pyrazoloazole derivative or a pyrroloazole derivative.
More preferred in terms of improving the yield, imidazole derivatives,
Pyrazolin-5-one derivatives and pyrazolotriazole derivatives, and those which show a particularly remarkable improvement in yield, are pyrazolin-5-one derivatives represented by the general formula (IV). In the general formula (IV), R ₁ and R ₂ represent a hydrogen atom or a monovalent substituent, and may be the same or different. Specific examples of the monovalent substituent include a halogen atom, a cyano group, a hydroxy group, an alkyl group, an aryl group, a heterocyclic group, a nitro group, a carboxy group, a sulfo group, an amino group, an alkoxy group, an aryloxy group, Acylamino group, alkylamino group, anilino group, ureido group, sulfamoylamino group, alkylthio group, arylthio group, alkoxycarbonylamino group, sulfonamide group, carbamoyl group, sulfamoyl group, sulfonyl group, alkoxycarbonyl group, heterocyclic oxy Group, azo group, acyloxy group, carbonyl group, carbamoyloxy group, silyloxy group, aryloxycarbonylamino group, arylcarbonylamino group, imide group, heterocyclic thio group, sulfinyl group, phosphonyl group, aryloxycarbonyl group,
Examples thereof include an acyl group and a silyl group, which may further have a substituent, and R ₁ and R ₂ may combine to form a ring. Of these substituents, preferred R ₁ and R ₂ are an alkyl group, an aryl group, a heterocyclic group, an acylamino group, an alkoxy group, a carbonyl group, an aryloxy group, an alkylthio group, an ureido group, and a carbamoyl group.

Next, the compound represented by formula (Ib) will be described in detail.

In the general formula (Ib), X ₁ and X ₂ represent an oxygen atom, a sulfur atom or a substituted or unsubstituted nitrogen atom, which may be the same or different. The X
_{When 1} and X ₂ are a nitrogen atom having a substituent, specific examples of the substituent include a hydroxy group, an alkyl group, an aryl group, a heterocyclic group, a carboxy group, an amino group, an alkoxy group, an aryloxy group, and an acylamino group. Group, alkylamino group, anilino group, carbamoyl group, alkoxycarbonyl group, aryloxycarbonylamino group, arylcarbonylamino group, aryloxycarbonyl group, acyl group, silyl group, and the like. You may have. More preferred substituents are an alkyl group and an aryl group.

B ₁ and B ₂ represent a monovalent substituent and may be the same or different. Specific examples of the monovalent substituent include an alkyl group, an aryl group, a heterocyclic group, a carboxy group, an amino group, an alkoxy group, an aryloxy group, an acylamino group, an alkylamino group, an anilino group, a carbonyl group, and an alkylthio group. An arylthio group, a carbamoyl group, an alkoxycarbonyl group, a heterocyclic oxy group, an acyloxy group, an acyl group, a heterocyclic thio group, an aryloxycarbonyl group, an arylcarbonyl group, etc., which further have a substituent. And B ₁ and B ₂ may combine to form a ring. The ring is preferably a 5-membered ring. Preferred B ₁ and B ₂ among these substituents are an alkyl group, an aryl group, a heterocyclic group, an acylamino group, an alkoxy group, an aryloxy group, an alkylthio group, an anilino group and an alkylamino group.

Next, the compound represented by formula (II) will be described.

In the general formula (II), Z represents a group derived from a 5-membered or 6-membered heterocyclic compound. Specific examples of the 5-membered heterocyclic compound include pyrrole derivatives, thiophene derivatives, furan derivatives, thiazole derivatives, oxazole derivatives, imidazole derivatives, pyrazole derivatives, triazole derivatives, tetrazole derivatives, thiadiazole derivatives, oxadiazole derivatives and the like. And each may form a condensed ring. As the 6-membered heterocyclic compound, specifically, a pyridine derivative, a pyridazine derivative, a pyrimidine derivative, a pyrazine derivative,
Examples thereof include a triazine derivative and a pyran derivative, each of which may form a condensed ring. Preferred 5- or 6-membered heterocyclic compounds from which the group represented by Z is derived include pyrrole derivatives, thiophene derivatives, furan derivatives, thiazole derivatives, oxazole derivatives, imidazole derivatives, pyrazole derivatives, triazole derivatives,
Thiadiazole derivatives, oxadiazole derivatives, pyridine derivatives, pyrimidine derivatives, pyrazine derivatives, triazine derivatives, pyran derivatives, and more preferably thiophene derivatives, furan derivatives, thiazole derivatives, oxazole derivatives, imidazole derivatives, pyrazole derivatives, pyridine derivatives The thiophene derivative and the pyridine derivative are more preferable in terms of the effect of improving the yield, and the pyridine derivative is most preferable.

Next, the compound represented by the general formula (IIIa) or (III
The compound represented by b) will be described.

The formula (IIIa) or (III)
A, B ₁ , B ₂ and Z in b) each represent the general formula (I)
a), A in general formula (Ib) and general formula (II),
It is synonymous with B ₁ , B ₂ and Z.

Next, the compound represented by formula (V) will be described.

In the general formula (V), R ₃ and R ₄
Represents a hydrogen atom or a monovalent substituent, and may be the same or different. Specific examples of the monovalent substituent include a hydroxy group, an alkyl group, an aryl group, a heterocyclic group, a carboxy group, a sulfo group, an amino group, an alkoxy group, an aryloxy group, an acylamino group, an alkylamino group, and an anilino group. , Ureido group, sulfamoylamino group, alkoxycarbonylamino group, sulfonamide group, carbonyl group, carbamoyl group, sulfamoyl group, sulfonyl group, alkoxycarbonyl group, silyloxy group, aryloxycarbonylamino group, arylcarbonylamino group, imide Group, a sulfinyl group, a phosphonyl group, an aryloxycarbonyl group, an acyl group, a silyl group, etc., which may further have a substituent.
₃ and R ₄ may combine to form a ring, and a, b, c
And d may combine with any of the above to form a ring. Of these substituents, preferred R ₃ and R ₄ are an alkyl group, an aryl group, a heterocyclic group, an acyl group, and a hydroxy group.

A, b, c and d represent a nitrogen atom or a carbon atom, which may be the same or different, and at least one of a, b, c and d is a nitrogen atom. a,
When any one, two or three of b, c and d is a carbon atom, the carbon atom has a hydrogen atom or a substituent;
When any one, two or three of a, b, c and d is a carbon atom having a substituent, the substituent may be a monovalent substituent, and the substituents are bonded to each other to form a ring. May be formed, or may be combined with R ₃ and R ₄ described above to form a ring. As the monovalent substituent, specifically, a halogen atom, a cyano group, a hydroxy group, an alkyl group, an aryl group, a heterocyclic group, a nitro group, a carboxy group,
Sulfo group, amino group, alkoxy group, aryloxy group, acylamino group, alkylamino group, anilino group,
Ureido group, sulfamoylamino group, alkylthio group, arylthio group, alkoxycarbonylamino group,
Sulfonamide group, carbamoyl group, sulfamoyl group, sulfonyl group, carbonyl group, alkoxycarbonyl group, heterocyclic oxy group, azo group, acyloxy group, carbamoyloxy group, silyloxy group, aryloxycarbonylamino group, arylcarbonylamino group, imide Group, heterocyclic thio group, sulfinyl group, phosphonyl group,
An aryloxycarbonyl group, an acyl group, a silyl group, and the like, which may further have a substituent, more preferably a monovalent substituent, such as an alkylamino group,
Anilino group, amino group, halogen atom, cyano group, hydroxy group, alkyl group, aryl group, heterocyclic group, acylamino group, alkoxy group, aryloxy group, alkylthio group, carbonyl group, and ureido group. Most preferred are a halogen atom, a cyano group, an alkyl group, an aryl group, a heterocyclic group, an acylamino group, an alkoxy group, an aryloxy group, an alkylthio group, and a carbonyl group.

Next, the compound represented by formula (VI) will be described.

In the general formula (VI), R ₁ , R ₂ ,
R ₃ , R ₄ , a, b, c and d are each represented by the general formula (IV):
R ₁ , R ₂ , R ₃ , R ₄ , a, b, c in the general formula (V)
And d are synonymous.

Formula (Ia) or (IV)
Specific examples of the compound represented by are shown below, but the present invention is not limited thereto.

[0036]

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[0037]

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[0038]

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Specific examples of the compound represented by formula (Ib) are shown below, but the present invention is not limited thereto.

[0040]

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Specific examples of the compound represented by formula (II) or (V) are shown below, but the present invention is not limited thereto.

[0042]

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[0043]

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The following formulas (IIIa) and (IIIb)
Alternatively, specific examples of the compound represented by the general formula (VI) are shown, but the present invention is not limited thereto.

[0045]

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[0046]

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[0047]

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Next, formula (Ia), (Ib) or (I
The method for halogenating Ha, Hb, and Hc of the compound represented by V) will be described.

As the halogenation method, any known method may be used, and a method using a halogen molecule itself or a halogenating agent is generally used. As the halogen, chlorine and bromine are preferable. As a method of chlorination, for example,
Synthesis, March 1985, p. 299, using 1,3-dichloro-5,5-dimethylhydantoin as a chlorinating agent, Journal of Am
erican Chemical Society 1
958, Vol. 80, p. 5796, a method using chlorine molecules, Journal of Heterocyclic.
c Chemistry 1982, 19, 138
The method described on page 9 uses sulfuryl chloride as a chlorinating agent, a method using N-chlorosuccinimide (NCS) as a chlorinating agent, and a method using phosphorus pentachloride as a chlorinating agent. By using a compound obtained by replacing a chlorine atom of a chlorinating agent with a bromine atom in the chlorination method, bromination can be performed by the same operation.

Under the halogenation conditions, the halogenating agent is used in an amount of 0.1 to 10 mol based on the number of moles of Ha, Hb, or Hc of the compound represented by formula (Ia), (Ib), or (IV), respectively. Use equivalent. Preferably, the compound represented by the general formula (Ia) or (Ib) or (IV) is 0.3 to the mole number of Ha or Hb or Hc.
5 to 2 molar equivalents.

In the halogenation, a compound represented by the general formula (Ia):
A halogenating agent may be added to a substrate such as the compound represented by (Ib) or (IV), or conversely, the substrate may be added to the halogenating agent. When one is added to the other, the required amount may be added all at once, may be added in several portions, may be added little by little, and an appropriate solvent may be used as needed. Both may be added in several portions or in small amounts, and an appropriate solvent may be used as needed.

The reaction temperature is from -50 ° C to 300 ° C,
Preferably it is from -20 ° C to 200 ° C. Heating and cooling may be performed according to the conditions and progress of the reaction.

Examples of the reaction solvent include halogen solvents (eg, chloroform, carbon tetrachloride, dichloromethane, etc.),
Ester solvents (eg, ethyl acetate (EA), acetic acid-n
-Propyl, isopropyl acetate, methyl acetate, ethyl propionate, etc.), aromatic hydrocarbon solvents (eg, benzene, toluene, xylene, etc.), ketone solvents (eg, acetone, methyl ethyl ketone (MEK), cyclohexanone, etc.), amide solvents (Eg, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAc), etc.), carboxylic acid solvents (eg, acetic acid, propionic acid, etc.), alcoholic solvents (eg, methanol, ethanol, n-propanol, etc.) ), Nitrile solvents (eg, acetonitrile, propionitrile, etc.), water and the like can be arbitrarily selected according to the halogenation method, and can be used as a single solvent or as a mixed solvent. Environmental protection and side reactions From the, ester solvents, aromatic hydrocarbon solvents, ketone solvents, amide solvents, carboxylic acid solvents, alcohol solvents, nitrile solvents preferred. Particularly preferred solvents are ethyl acetate, n-propyl acetate, isopropyl acetate, toluene, acetone, DMA
c, acetic acid, acetonitrile.

The post-treatment after the reaction is carried out by a method carried out by a usual organic reaction. Isolation and purification are carried out by column chromatography, crystallization or extraction, or a combination thereof, depending on the nature of the isolation.

Next, the compound represented by the general formula (Ia), (Ib) or (I
Compounds represented by general formula (II) or (V), wherein Ha, Hb, and Hc of the compound represented by V) are halogenated (hereinafter, also referred to as "halogenated compound of the present invention"). (Hereinafter also referred to as “heterocyclic amine compound of the present invention”). In the condensation reaction, the heterocyclic amine compound of the present invention may be a compound which forms a quaternary salt with an appropriate acid. When a quaternary salt is used, a necessary amount of a base may be added to the reaction system in advance, or may be used after neutralization immediately before use. The acid may be any of known organic acids and inorganic acids capable of forming a quaternary salt, and specifically, hydrochloric acid, sulfuric acid, nitric acid, acetic acid,
and p-toluenesulfonic acid. The amount of the heterocyclic amine compound of the present invention to be used is 0.5 to 5 molar equivalents, preferably 0.7 to 1.5, relative to the halogenated compound of the present invention.
It is a molar equivalent.

The heterocyclic amine compound of the present invention may be added to the halogenated compound of the present invention, and conversely, the halogenated compound of the present invention may be added to the heterocyclic amine compound of the present invention. In either case, the substrate may be used as it is, or an appropriate solvent may be used.

When one is added to the other, the required amount may be added all at once, may be added in several portions, or may be added little by little, and if necessary, an appropriate solvent may be used. good. Also, both may be added in several portions or in small amounts, and an appropriate solvent may be used as necessary.
The reaction temperature is from -50 ° C to 300 ° C, preferably-
20 ° C to 200 ° C. Heating and cooling may be performed according to the conditions and progress of the reaction. The reaction solvent is the same as the above-mentioned halogenation conditions. Hydrogen halide is generated as the condensation reaction proceeds. If necessary, a base for neutralizing the hydrogen halide may be added. The base may be an inorganic base or an organic base, specifically, sodium hydroxide, potassium hydroxide,
Metal hydroxides such as lithium hydroxide, carbonates such as potassium carbonate and sodium hydrogen carbonate, acetates such as sodium acetate, tertiary amines such as N, N-dimethylaniline, triethylamine, and nitrogen-containing aromatic 6-members such as pyridine Ring compounds and the like. More preferred bases are carbonates such as potassium carbonate and sodium hydrogen carbonate. The amount used is 0.1 to 3 equivalents, more preferably 0.4 to 2 equivalents, based on the substrate.

The post-treatment after the reaction is the same as the above-mentioned halogenation conditions.

Next, the compound represented by the general formula (Ia), (Ib) or (I
A method for producing a heterocyclic azomethine dye which is obtained by halogenating Ha, Hb, Hc of the compound represented by V) and then condensing the compound with the heterocyclic amine compound of the present invention without isolating the halide of the present invention will be described in detail. . Specifically, the general formula (I
Ha) of the compound represented by a), (Ib) or (IV),
The reaction system after halogenation of Hb and Hc (hereinafter also referred to as the “reaction system of the present invention”) is directly or optionally subjected to a simple post-treatment such as washing with water, and then the heterocyclic amine compound of the present invention. It is to add the reaction system of the present invention to the heterocyclic amine compound of the present invention after addition or after a simple post-treatment such as washing with water, if necessary. The method of condensation is the same as the above-mentioned method of condensation between the halogenated compound of the present invention and the heterocyclic amine compound of the present invention.

[0060]

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

In the following examples, the conditions for high-performance liquid chromatography were measured using a reversed-phase column. Purity is a simple area percentage comparison of each peak on the recording paper.

Embodiment 1

[0063]

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The halogenation is Synthesis 198
Performed according to the method described in March 1993, page 299. Specifically, exemplified compound a-1 18.83 g (0.1 mol)
Is suspended in 50 ml of acetic acid. To this, 19.7 g (0.1 mol) of 1,3-dichloro-5,5-dimethylhydantoin is added little by little while keeping the internal temperature at 30 ° C. or lower while stirring. Was. After charging the powder, the mixture was stirred for 30 minutes, 150 ml of water was added thereto, and the mixture was stirred for 30 minutes, and the precipitate was collected by filtration. The precipitate was dried and then recrystallized from methanol to obtain a compound (A). Yield 20.6
g (80% yield).

From ¹ H-NMR and mass spectrum measurements, the product was identified as the target compound.

Next, after dissolving 20.6 g of this compound (A) in 20 ml of ethyl acetate and adding a solution of 13.8 g of potassium carbonate in 30 ml of water, the exemplary compound II-1 was heated under reflux. A solution of 3 g (0.08 mol) in 20 ml of ethyl acetate was added dropwise. After the completion of the dropwise addition, the mixture was continuously heated under reflux for 1 hour, allowed to cool to room temperature, and then cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product.
After drying the crude product, the purity was measured by high performance liquid chromatography and found to be 97.5%. The crude product was recrystallized from ethyl acetate to give Exemplified Compound 1. Yield 19.8 g (68% yield).

This indicates that the yield of Exemplified Compound 1 based on Exemplified Compound a-1 is 54.4%.

The product was identified as the target compound by ¹ H-NMR and mass spectrum measurements. The purity was measured by high performance liquid chromatography and found to be 99.0%.

Example 2 18.83 g (0.1 mol) of Exemplified Compound a-1 was suspended in 20 ml of ethyl acetate, and the inner temperature was kept at 30 ° C. or lower, and 1,3-dichloro-5 was stirred. And 19.7 g (0.1 mol) of 5-dimethylhydantoin were added little by little as a powder. After the addition of the powder, the mixture was stirred for 30 minutes. The reaction solution was washed twice with 50 ml of water, and a solution of 13.8 g of potassium carbonate dissolved in 30 ml of water was added.
A solution of 9 g (0.1 mol) of ethyl acetate in 20 ml was added dropwise. After the completion of the dropwise addition, the mixture was continuously heated under reflux for 1 hour, allowed to cool to room temperature, and then cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product. After drying the crude product, the purity was measured by high performance liquid chromatography to find that the purity was 99.0%. The crude product was recrystallized from ethyl acetate to give Exemplified Compound 1. Yield 28.3g
(Yield 78%) (Yield of Exemplified Compound 1 based on Exemplified Compound a-1).

The product was identified as the target product by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography and found to be 99.7%.

Example 3 18.83 g (0.1 mol) of Exemplified Compound a-1 was suspended in 20 ml of ethanol, and the suspension was stirred with 1,3-dichloro-5 and 1,3-dichloro-5 at an internal temperature of 30 ° C. or lower. 19.7 g (0.1 mol) of 5-dimethylhydantoin was added little by little as a powder. After the addition of the powder, the mixture was stirred for 30 minutes. 13.8 potassium carbonate was added to the reaction solution.
g and water (30 ml), and then heated under reflux to give Exemplified Compound II.
-1 17.9 g (0.1 mol) of ethanol 20 m
1 solution was added dropwise. After the completion of the dropwise addition, heat reflux for 1
After continuing for an hour, the mixture was allowed to cool to room temperature, added with 40 ml of water, and cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product. After drying the crude product, the purity was measured by high performance liquid chromatography to find that the purity was 98.9.
%Met. The crude product was recrystallized from ethyl acetate to give Exemplified Compound 1. Yield 26.1 g (72% yield).

The product was identified as the target product by ¹ H-NMR and mass spectrum measurements. The purity was measured by high performance liquid chromatography and found to be 99.7%.

Example 4 18.83 g (0.1 mol) of Exemplified Compound a-1 was suspended in 40 ml of ethyl acetate, and 1,3-dichloro-5 was added thereto while maintaining the internal temperature at 30 ° C. or lower. And 19.7 g (0.1 mol) of 5-dimethylhydantoin were added little by little as a powder. After the addition of the powder, the mixture was stirred for 30 minutes. The reaction solution was washed twice with 50 ml of water, and then an aqueous solution in which 27.2 g of potassium carbonate was dissolved in 60 ml of water, and 25.2 g of dihydrochloride of Exemplified Compound II-1.
(0.1 mol) dissolved in 60 ml of water was simultaneously added dropwise while heating under reflux. After the completion of the dropwise addition, the mixture was continuously heated under reflux for 1 hour, allowed to cool to room temperature, and then cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product. After drying the crude product, the purity was measured by high performance liquid chromatography and found to be 98.8%. The crude product was recrystallized from ethyl acetate to give Exemplified Compound 1.
Yield 29.8 g (82% yield).

The product was identified as the target product by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography and found to be 99.8%.

Example 5 The same experiment as in Example 3 was carried out except that the reaction solvent was changed from ethanol to acetonitrile.
Exemplified compound 1 was obtained at a yield of 74% and a purity of 99.7% by recrystallization from 8.7%.

Example 6 An experiment was carried out in the same manner as in Example 4 except that the reaction solvent was changed from ethyl acetate to isopropyl acetate.
Exemplified compound 1 was obtained at a yield of 82% and a purity of 99.7% by recrystallization from 9.0%.

Example 7 The same experiment as in Example 4 was carried out except that the reaction solvent was changed from ethyl acetate to toluene, and the purity of crude product was 98.4.
%, And was recrystallized to give Exemplified Compound 1 in a yield of 80% and a purity of 99.5%.

Embodiment 8

[0079]

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Exemplified compound a-11 20.1 g (0.1
mol) was suspended in 50 ml of ethyl acetate, and 29.6 g (0.22 mol) of sulfuryl chloride was added thereto.
The mixture was heated and refluxed for 30 minutes. 150 ml of water was added thereto, and after washing with water, the organic layer was distilled off under reduced pressure. After drying, the residue was recrystallized from methanol to obtain a compound (B). Yield 21.9 g (81% yield).

The product was identified as the target product by ¹ H-NMR and mass spectrum measurements.

Next, 21.9 g of this compound (B) was dissolved in 20 ml of ethyl acetate, a solution of 13.8 g of potassium carbonate dissolved in 30 ml of water was added, and 11.5 g of the exemplified compound II-11 was heated under reflux. (0.08 mol) in 20 ml of ethyl acetate was added dropwise. After the completion of the dropwise addition, the mixture was continuously heated under reflux for 1 hour, allowed to cool to room temperature, and then cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product.
After drying the crude product, the purity was measured by high performance liquid chromatography and found to be 97.4%. The crude product was recrystallized from acetonitrile to obtain Exemplified Compound 6. Yield 18.4 g (67% yield).

The yield of Exemplified Compound 6 based on Exemplified Compound a-11 is 54.3%.

The product was identified as the target substance by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography to be 98.9%.

Example 9 20.1 g (0.1 mol) of the exemplified compound a-11 was suspended in 50 ml of ethyl acetate, 29.6 g (0.22 mol) of sulfuryl chloride was added thereto, and the mixture was heated and refluxed for 30 minutes. . To this, 150 ml of water was added, and after washing with water, a solution in which 13.8 g of potassium carbonate was dissolved in 30 ml of water was added.
A solution of 2 g (0.1 mol) of ethyl acetate in 20 ml was added dropwise. After the completion of the dropwise addition, the mixture was continuously heated under reflux for 1 hour, allowed to cool to room temperature, and then cooled with ice water. The precipitate was collected by filtration and sufficiently washed with water to obtain a crude product. After drying the crude product, the purity was measured by high performance liquid chromatography and found to be 98.5%. The crude product was recrystallized from acetonitrile to obtain Exemplified Compound 6. Yield 25.8g
(Yield 76%).

The product was identified as the target product by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography to be 99.5%.

Comparative Example 1

[0088]

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Exemplified Compound a-1 18.83 g (0.1
mol) was suspended in 100 ml of ethyl acetate, and 59.5 g (0.25 mol) of sodium persulfate, 140.0 g of potassium carbonate and 400 ml of water were added thereto.
II-1 21.5 g (0.12 mol) of ethyl acetate 2
A 0 ml solution was added dropwise at room temperature. After the dropping, 1
After continuing stirring for an hour, an organic layer was extracted and washed thoroughly with water. After dehydrating the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain a highly viscous amorphous substance. When the purity of this amorphous substance was measured by high performance liquid chromatography, it was 54%, and many impurity peaks were confirmed. The amorphous substance was recrystallized from ethyl acetate to obtain Exemplified Compound 1. Yield 13.5g (37% yield).

The product was identified as the target substance by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography to be 96.8%.

Comparative Example 2

[0092]

Embedded image

Exemplified compound a-11 20.1 g (0.1
mol) was suspended in 100 ml of ethyl acetate, and 59.5 g (0.25 mol) of sodium persulfate, 140.0 g of potassium carbonate and 400 ml of water were added thereto.
A solution of 17.1 g (0.12 mol) of II-11 in 20 ml of ethyl acetate was added dropwise at room temperature. After completion of the dropping, stirring was continued for 1 hour, and then the organic layer was extracted and sufficiently washed with water. After dehydrating the organic layer with anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain a highly viscous amorphous substance. When the purity of this amorphous substance was measured by high performance liquid chromatography, it was 51%, and a number of impurity peaks were confirmed. The amorphous substance was recrystallized from acetonitrile to obtain Exemplified Compound 6.
Yield 11.9 g (35% yield).

The product was identified as the target substance by ¹ H-NMR and mass spectrum measurement. The purity was measured by high performance liquid chromatography and found to be 95.6%.

As described in detail above, the present invention can provide a method for producing a heterocyclic azomethine dye in high yield.

[0096]

Industrial Applicability According to the present invention, an azomethine dye (heterocyclic azomethine) can be obtained by condensation of a heterocyclic amine compound and an active methylene compound. Dyes) can be provided.

Claims (10)

[Claims] 1. A compound represented by the following general formula (Ia) or (Ib), wherein Ha and Hb are halogenated, and then the compound represented by the following general formula (II) is condensed. A method for producing a compound represented by the general formula (IIIa) or (IIIb). Embedded image [Wherein, Ha and Hb represent a hydrogen atom, A represents an atomic group necessary for forming a nitrogen-containing 5-membered ring together with a methylene moiety, and X ₁ and X ₂ represent an oxygen atom, a sulfur atom, or Represents a substituted or unsubstituted nitrogen atom, B ₁ and B ₂ each represent a monovalent substituent, and Z represents a group derived from a 5-membered or 6-membered heterocyclic compound. ] 2. The compound represented by the general formula (III), which comprises halogenating Ha of the compound represented by the general formula (Ia) and then condensing the compound represented by the general formula (II).
A method for producing the compound represented by a). 3. The method according to claim 1, wherein the formula (Ia) is pyrazoline-5-.
The method for producing a compound according to claim 2, wherein the compound is an on derivative, an imidazole derivative or a pyrazolotriazole derivative. 4. The method according to claim 2, wherein Z in the general formula (II) is a group derived from a thiophene derivative or a pyridine derivative. 5. A compound represented by the following general formula (IV):
A method for producing a compound represented by the following general formula (VI), which comprises condensing a compound represented by the following general formula (V) after halogenating c. Embedded image [In the formula, Hc represents a hydrogen atom, and R ₁ , R ₂ , R ₃ and R ₄ each represent a hydrogen atom or a monovalent substituent.
a, b, c and d each represent a nitrogen atom or a carbon atom, and at least one of a, b, c and d is a nitrogen atom. ] 6. After halogenating Ha and Hb of the compound represented by formula (Ia) or (Ib), condensing the compound represented by formula (II) without isolating a dihalide Wherein said general formula (IIIa)
Or a method for producing the compound represented by (IIIb). 7. The method according to claim 1, wherein after halogenating Ha of the compound represented by the general formula (Ia), the compound represented by the general formula (II) is condensed without isolating a dihalide. A method for producing the compound represented by the general formula (IIIa). 8. The method according to claim 1, wherein the formula (Ia) is pyrazoline-5-.
The method for producing a compound according to claim 7, wherein the compound is an on derivative, an imidazole derivative or a pyrazolotriazole derivative. 9. The method according to claim 7, wherein Z in the general formula (II) is a group derived from a thiophene derivative or a pyridine derivative. 10. The compound represented by the general formula (V) is characterized by condensing the compound represented by the general formula (V) without isolating a dihalide after halogenating Hc of the compound represented by the general formula (IV). A method for producing the compound represented by the general formula (VI).