JPH0466573A - Production of 5-amino-pyrazole compound - Google Patents

Abstract

PURPOSE:To efficiently industrially advantageously obtain the title compound useful as an intermediate of silver halide photosensitive material for color photograph in good yield by reacting a relatively inexpensive and readily available compound with hydrazine. CONSTITUTION:A compound expressed by formula II (R1 is alkyl or aryl; hal is halogen) is reacted with hydrazine to provide the 5-amino-pyrazole expressed by formula I. The compound expressed by formula II is obtained by halogenating a compound expressed by formula III in the presence of a Lewis acid or radical inhibitor. The reaction of the compound expressed by formula II with hydrazine is carried out without using solvent or preferably in a solvent such as water or methanol.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to silver halide color photographic light-sensitive materials,
IH-biracyazole couplers used as dye intermediates for thermal transfer processes, color electrophotography, and printing, such as IH-pyrazolo[1,5-b]-1,2
, 4-) lyazole couplers and IH-pyrazolo[3,2-c]-1,2,4-) lyazole couplers, etc. 5-amino-pyrazole compounds, which are useful synthetic intermediates, Furthermore, the present invention relates to a manufacturing method for manufacturing 5-aminopyrazole compounds, which are synthetic intermediates for synthesizing 7-amino-pyrazolo[1,5-al pyrimidine drugs, etc., easily and at low cost on an industrial scale.

(Prior Art) IH-pyrazoloazole couplers, such as IH-pyrazolo[1,5-b]-1,2,4-1-lyazole and IH-pyrazolo[3,2-c]-1,2, 4-) The lyazole compounds are each disclosed in U.S. Patent No. 4,540,654.
It is a magenta coupler that provides excellent hue as described in the patent specification and US Pat. No. 3,725,067. Furthermore, regarding IH-pyrazolo[1,5-C]-tetrazole coupler, IH-imidazo[1,2-b]pyrazole coupler, and IH-pyrazolo[1°5-d]benzimidazole coupler, each
No. 0-33552, No. 59-162548, and US Pat. No. 3,061,432. Further, IH-pyrazoloazole compounds are known as cyan couplers in JP-A-63-264753.

Methods for synthesizing these pyrazoloazole compounds are disclosed in JP-A-60-190779, JP-A 60-197688, JP-A 60-215687, JP-A 61145163, and JP-A No. 61.
-18780, No. 61-249969, etc.

Various synthetic intermediates have been reported in the synthesis method of these pyrazoloazole compounds, and one of the important ones is 5-amino-I H-pyrazoles.

For example, JP-A-60-197688, JP-A No. 6114516
No. 3 contains IH-pyrazolo[1,5b]-1,2,4-
) 5-amino-1H as starting material leading to lyazole
-Pyrazoles are described, also in JP-A-61-249
No. 969 also includes IH-pyrazolo[3,2-c]-1,2,
5-amino 1 as a starting material leading to 4-1-lyazole
There is a description of H-pyrazoles.

As described above, 5-amino-IH-pyrazoles are very useful synthetic intermediates in the synthesis of pyrazolotriazole compounds, but there are not many examples of methods for their synthesis that have been reported. Especially when considering the application to photographic magenta couplers, 5-amino-IH-
Although pyrazoles are important, the only methods specifically described in the literature for their synthesis are as follows.

<Method for synthesizing 5-amino-IH-bisol having an alkyl group at the 3-position> (Problems to be solved by the invention) Among these, the synthetic methods recognized as short and efficient are d) and e. ) and f), but there are problems in that 3-aminocrotononitrile and acylacetonitrile, which are the starting materials for these synthetic methods, are expensive, and are not easy to obtain as they are not readily available materials.

Therefore, there has been a need to develop a new method for synthesizing 5-amino-IH-pyrazoles substituted with an alkyl group at the 3-position, which does not require the use of such starting materials.

(Means for Solving the Problems) As a result of extensive studies to meet these demands, the present inventors have developed a method of halogenating a,β-unsaturated nitriles, which are relatively inexpensive and easily available. By reacting this with hydrazine as a starting material, not only 3-alkyl-5-amino-IH-pyrazoles but also 3-aryl-
It was discovered that 5-amino-LH-pyrazoles can be synthesized, and the present invention was completed based on this knowledge.

That is, the present invention is characterized in that (1) a compound represented by the following general formula (n) is reacted with hydrazine,
A method for producing a 5-amino-virazole compound represented by the following general formula (I), general formula (I) (wherein, R represents an alkyl group or an aryl group), general formula (II) (wherein, R , has the same meaning as above, and haj2 represents a halogen atom.) (2) The compound represented by the general formula (II) is obtained by halogenating the compound represented by the following general formula (I[[). A method for producing a 5-amino-pyrazole compound according to the above (1), characterized in that the compound has the general formula (m) R, -CH2CH-CN (wherein Ro has the same meaning as above) (3 ) Provides a method for producing a 5-amino-pyrazole compound according to the above (1), characterized in that the compound represented by the general formula (ITJ) is norogenated in the presence of a Lewis acid or a radical inhibitor. It is.

Next, the present invention will be explained in detail.

The reaction of the present invention can be represented by the scheme shown below.

Scheme (1) (II) (I) In the above scheme, the reaction for producing compound (II) by halogenation of the acrylonitrile represented by the general formula (TU) may be carried out by dissolving or dispersing it in an appropriate solvent. , may be carried out without solvent. Typical solvents that can be used include halogenated hydrocarbon solvents such as dichloroethane, but preferably the reaction is carried out without a solvent. The compound represented by the general formula (1'l?) and haρ2 (chlorine or bromine) are preferably used in a molar ratio of 1:0.5 to 1:1.
5, more preferably in a molar ratio of 0.8 to 1:1.2. Further, the Lewis acid or radical inhibitor used in this step is preferably 0.01 mol to 1 mol per mol of the compound represented by formula (III)-1.
0 mol is used, more preferably 0.1 mol to 0.5 mol. The reaction temperature can be carried out at 10°C to 150°C, preferably 50°C to 120°C, and particularly preferably 60°C to 100°C. When the reaction temperature is 10°C to 150°C, a reaction time of 10 minutes to 20 hours is sufficient.

Next, a process for obtaining a 5-aminopyrazole compound represented by the general formula (I) by subjecting the compound represented by the general formula (TI) to a cyclization reaction with hydrazine will be explained. This reaction may be carried out without a solvent, or may be carried out using an appropriate solvent. Typical solvents used in this reaction include water, alcohols such as methanol, ethanol, and isopropanol, dimethylacetamide, dimethylimidazolitone, acetonitrile, tetrahydrofuran, dioxane,
Or toluene etc. are mentioned. In particular, water or alcohol solvents are preferred, and these solvents may be used alone or in combination of two or more. The amount of solvent used is 0.1 part by weight of the compound represented by the general formula (■).
It is used in a proportion of ~1000 parts by weight, preferably 0.65 to 20 parts by weight.

The hydrazine used in the present invention may be hydrated or anhydrous. The compound of general formula (II) and hydrazine are preferably used in a molar ratio of 1:50, more preferably in a molar ratio of 1:5. Although a base may or may not be used in this step, typical bases that can be used include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate, or pyridine. , dimethylaminopyridine, triethylamine, DB1no, DABCO
Organic bases such as These bases have the general formula (
The compound represented by II) is used in a molar ratio of 1 to 1:5, preferably 1:1 to 1:1.5. The reaction temperature in this step can be carried out at -20 to 100°C, preferably -20 to 50°C, and -10 to 30°C.
C is particularly preferred. The reaction time is 120°C to 120°C.
In the case of 00°C, the reaction is completed in 30 minutes to 15 hours.

Next, in the production method of the present invention, the compound represented by general formula (II) is used in the next step without being isolated, and the desired compound represented by general formula (I) is synthesized in a high yield. Is possible.

Furthermore, to explain the reaction components of the present invention, the general formula (
II) Furthermore, R1 in the compound represented by (m) represents an alkyl group or an aryl group. More specifically, an alkyl group refers to a linear or branched substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, and examples of substituents for a substituted alkyl group include a halogen atom (for example, a fluorine atom,
chlorine atom), cyano group, nitro group, alkoxy group (e.g. methoxy, ethoxy, hexyloxy), aryloxy group (e.g. phenoxy, 3-nitrophenoxy,
2,4-di-t-amylphenoxy, 3-pentadecylphenoxy), aryl groups (e.g. phenyl, 4-nitrophenyl), alkylsulfonyl groups (e.g. 2-hexyldecanesulfonyl), arylsulfonyl groups (e.g. 2- 5-t-octylphenylsulfonyl), imide groups (eg, phthalimide), amino groups (eg, dibutylamino), and the like. Representative examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, butyl, pentyl, heptyl, nonyl, cyclohexyl, t-butyl, phenylethyl, ethoxymethyl, phenoxymethyl, dibutylaminomethyl, etc. .

Aryl group represents a substituted or unsubstituted aryl group,
Examples of substituents for substituted aryl groups include halogen atoms (
fluorine, chlorine, bromine), nitro groups, cyano groups, hydroxyl groups, carboxylic acid groups, sulfonic acid groups, alkyl groups (e.g. methyl, ethyl, isopropyl, t-butyl), aryl groups (e.g. phenyl), alkoxy groups (e.g. methoxy, ethoxy, butoxy, isopropyloxy, dodecyloxy), aryloxy groups (e.g. phenoxy,
naphthyloxy), alkylthio groups (e.g. methylthio, ethylthio, butylthio, octylthio, 2-ethylhexylthio, 1-ethoxycarbonyldodecylthio)
, arylthio groups (e.g. phenylthio, 4-hydroxyphenylthio, 2-nitrophenylthio), amino groups (e.g. dimethylamino, diethylamino, diisopropylamino), anilino groups, acylamino groups (e.g. acetylamino, hexadecanoylamino), ureido groups (e.g. dimethylureido, diethylureido), urethane groups (e.g. methylurethane, ethylurethane), alkoxycarbonyl groups (e.g. methoxycarbonyl, ethoxycarbonyl, dodecyloxycarbonyl), sulfonamide groups (e.g. methanesulfonamide, butanesulfonamide) , sulfamoyl group (e.g. N,N-dimethylsulfamoyl, N,N-dibutylsulfamoyl, N-butylsulfamoyl, N-cyclohexylsulfamoyl, N-dodecylsulfamoyl), sulfonyl group ( For example, methylsulfonyl, ethylsulfonyl,
butylsulfonyl, phenylsulfonyl), etc.
It may have two or more substituents. When it has two or more substituents, those substituents may be the same or different. Representative examples of aryl groups include phenyl, naphthyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-methoxyphenyl, 2-nitrophenyl,
．． Examples include 4-methoxyphenyl, 4-methylsulfonylphenyl, 2°4.6-)lichlorophenyl, and the like.

The compound represented by general formula (III) may be in the cis or trans form. Many of the available compounds are trans isomers.

Haff in the compound represented by the general formula (II) represents a halogen atom (eg, a chlorine atom, a bromine atom, a fluorine atom, an iodine atom).

The substituent R of the compound represented by the general formula (I) corresponds to the substituent of the starting material and has the same meaning as R1 explained for the general formulas (Il) and (m) above.

Next, the Lewis acid or radical inhibitor used in the halogenation step of the present invention will be explained.

The Lewis acid used in the present invention is zinc chloride (ZnCj2
2), zinc bromide (ZnBr2), aluminum chloride (
A42 Cj2. ), aluminum bromide (+1lB
r3), iron chloride (Fe(J2-), iron bromide (FeBr-
), tin tetrachloride (SnCj2, ), tin tetrabromide (S
nBr4), titanium tetrachloride (Ticρ4), lithium chloride (LiCρ), boron trichloride (Bl3), boron tribromide (BBril, etc.).In addition, radical inhibitors include nitrobenzenes (e.g. nitrobenzene, dinitrobenzene, etc.). ), hindered phenols (e.g. 2,6-di-t-butylphenol, 4-chloro-2,
6-di-t-butylphenol, 4-bromo-2゜6-
di-t-butylphenol), etc.

Next, typical examples of 5-aminopyrazoles represented by the general formula (1) obtained by the method of the present invention are shown below, but the present invention is not limited thereto.

(I-1) (Example) Next, the present invention will be explained in more detail based on Examples.
This does not limit the invention.

Example 1 Br Br (III() (I-1) 11.3 g (0.05 mol) of zinc bromide was added to 33.5 (0.5 mol) of crotononitrile (m-1) and heated to 85°C. 80 g (0.5 mol) of bromine was added dropwise to this solution, and the internal temperature was kept at 90 ± 2°C. After the dropwise addition of bromine, the internal temperature was kept at 80 to 85°C, and stirring was continued for about 45 seconds. continued.

After the reaction was completed, the reaction solution was cooled to room temperature and extracted with 200 ml of methylene chloride and 300 ml of water. This methylene chloride solution was washed with water, dried over anhydrous calcium chloride, and then methylene chloride was distilled off under reduced pressure. The obtained residue was distilled under a reduced pressure of 15 mmHg, and 83,8
g (73.5%) (7) (II-1) was obtained. Boiling point 105-110°C/15mmHg.

A solution of 50 g of hydrazine hydrate (80% aqueous solution) diluted with 200 ml of isopropanol was cooled to -5°C and stirred. (II-1) 45 obtained by the above method was added to this solution.
．． 2 g (0.2 mol) was added dropwise. -1 layer after dropping ℃
After stirring for 1 hour at ~-5°C, an additional 4 hours at 20-25°C
Stirring was continued for an hour. After the reaction is complete, the reaction solution is diluted with ethyl acetate.
Extraction was performed 4 times with 00ml. After concentrating this ethyl acetate solution under reduced pressure, further vacuum distillation was performed to obtain 33.2g
(68,4%) of 5-amino-3-methylpyrazole (
I-1) was obtained. Boiling point 135-140℃/1, OmmH
g.

H: NMR (δ: ppm) CDCf1 s6.2~
5.4 (2-3H, br), 5.35 (LH,
s), 2.13(3H,S) Example 2 Crotononitrile 67. 12.5 g of nitrobenzene was added to Ig (1.0 mol), and the mixture was heated and stirred at 80°C. 160 g (1.0 mol) of bromine are added dropwise to this solution. After the dropwise addition was completed, heating and stirring were continued for 10 minutes. After the reaction was completed, the mixture was cooled to room temperature, and then 500 d of water was added, stirred, and left to stand. The mixture was separated into two layers. The lower organic layer was separated to obtain compound (II-1) as a crude product.

250 g of hydrazine hydrate and 250 g of isopropanol
The mixture was diluted with ml and stirred while cooling to -5°C. The above organic layer was added dropwise to this solution. After stirring for 1 hour at -5~O℃, 2
Stirring was continued for an additional 4 hours at 0-25°C. After the reaction is complete,
The reaction solution was extracted four times with ethyl acetate, and the ethyl acetate solution was concentrated under reduced pressure. The residue was distilled under reduced pressure79
．． 2 g (81.5%) of 5-amino-3-methylpyrazole (I-1) was obtained. The boiling point and NMR spectrum were consistent with those obtained in Example 1 above.

Example 3 Synthesis of Exemplified Compound (I-5) 10 g of nitrobenzene was added to 64.6 g (0.5 mol) of cinnamonitrile (m-5), and the mixture was heated and stirred at 80°C. Bromine at 80° C. (0.5 mol) was added dropwise to this solution. 85~ after completion of dripping
After stirring at 90° C. for 15 minutes, the mixture was cooled to room temperature. To this reaction solution, 20 ml of methylene chloride and 500 ml of water were added, stirred for a while, and then allowed to stand. The lower layer separated into two layers was collected to obtain Compound (II-5) as a crude product.

62.5 g of hydrazine hydrate and 10 g of isopropanol
The diluted solution was cooled to -10°C and stirred. Compound (II-5) obtained by the above method was added dropwise to this solution. After completing the dropwise addition, stir at 0°C to 5°C for 1 hour, and then
Stirring was continued for an additional 4 hours at 5-30°C. After the reaction is complete,
The reaction solution was extracted three times with ethyl acetate. This ethyl acetate solution was concentrated under reduced pressure, and acetonitrile was added to the residue to precipitate crystals, which were collected by filtration and dried. 51.3g (64,
4%) of Exemplary Compound (I-5) was obtained.

HNMR (δ; ppm) CHCJ2 x7.6-7
．． 3 (5H, rn), 5.42 (IH, s),
5.7-4.7 (2H, br) Example 4 Synthesis of Exemplary Compound (I-6) m-Nitrosinnamonitrile (III-6) 87.1 g (0.5 mol)
and 11.3 g of zinc bromide were added, and the mixture was heated to 80°C and stirred. 80 g (0.5 mol) of bromine were added dropwise to this solution. The internal temperature was maintained at 90°C and 2°C. After the dropwise addition of bromine was completed, stirring was continued for 30 minutes while keeping the internal temperature at 80 to 85°C. After the reaction is completed, the reaction solution is cooled to room temperature, and then diluted with methylene chloride 4
00 ml and 400 ml of water were added for extraction. This methylene chloride solution was washed with water, dried over anhydrous calcium chloride, and then the methylene chloride was distilled off under reduced pressure to obtain the crude product compound (
II-6) was obtained.

62.5 g of hydrazine hydrate and 15 g of isopropanol
The solution diluted with 0ml was cooled to -10°C and stirred. Compound (II-6) obtained by the above method was added dropwise to this solution. After completing the dropwise addition, stir at 0 to 5°C for 1 hour, and then stir at 25°C.
Stirring was continued for an additional 4 hours at ~30°C. After the reaction was completed, the reaction solution was poured into water at 3°C to precipitate crystals. The crystals were collected by filtration, washed with water, and then recrystallized with a mixed solvent of acetonitrile/water to yield 65.0 g (63.7%) of the exemplified compound (
I-6) was obtained.

HNMR (δ; ppm) DMSOdall, 8(I
H,br), 8.48(IH,s), L2~8.0
5 (2Hd), 7.8-7.6 (IH, t), 5.
8 (IH, br), 5.15 (2H, br) (Effect of the invention) IH- useful as a color photographic coupler according to the present invention
Pyrazoloazole compounds, such as IH-pyrazolo[1,
5-amino-1-dan-pyrazoles, which are important synthetic intermediates of 5-bl-1,2,4-1-riazole and 1-pyrazolo[5,1-dan]-1°2,4-triazole can be synthesized efficiently and in good yields. Furthermore, the method of the present invention can synthesize a wide range of 5-amino-IH-pyrazoles using relatively inexpensive and easily available materials as starting materials, and can be used as an intermediate for the synthesis of pyrazolotriazole as a photographic coupler. It has great industrial value as a manufacturing method.

Patent applicant Fuji Photo Film Co., Ltd. Agent Patent attorney Ii 1) Toshi Corne 6゛ゝ

Claims (2)

[Claims] (1) The following general formula (I) is characterized by reacting a compound represented by the following general formula (II) with hydrazine.
A method for producing a 5-amino-pyrazole compound represented by General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 represents an alkyl group or aryl group.) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 has the same meaning as above, and hal represents a halogen atom.) (2) Production of a 5-amino-pyrazole compound according to claim (1), wherein the compound represented by the general formula (II) is obtained by halogenating a compound represented by the following general formula (III). Method. General formula (III) R_1-CH=CH-CN (In the formula, R_1 has the same meaning as above.) (3) The compound represented by the general formula (III) is halogenated using a Lewis acid or a radical inhibitor. The method for producing a 5-amino-pyrazole compound according to claim 1, which is carried out in the presence of a 5-amino-pyrazole compound.