JP2547634B2 - Process for producing 2-acyl-2-aryloxy or heterocyclic oxyacetonitriles and aminopyrazoles - Google Patents

Description

The present invention relates to 2-acyl-2, which is a synthetic intermediate of 7-aryloxy-1H-pyrazolotriazoles, which is useful as a coupler for silver halide color photography. -Aryloxy or heterocyclic oxyacetonitriles and aminopyrazoles.

(Prior Art) In US Pat. No. 4,540,654, 1H-pyrazolo [1,5-
It is disclosed that b 1] [1,2,4] triazoles are magenta couplers having excellent hue in silver halide color photography. Further, in U.S. Pat. No. 4,965,652, a 1H-pyrazolo [1,5- b ] [1,2,4] triazole magenta coupler having an aryloxy group as a coupling-off group at the coupling active position is a coupler for improving color development. Is disclosed. In the patent, the following two methods are shown as a method for introducing an aryloxy group at the coupling active position (7-position).

Method (X 'is a halogen atom, M' Is preferably sodium
Represents ions and potassium ions. R₁′, R₂′ Is hydrogen source
Represents a child or a substituent. R₃′ Represents an aryl group
You. ) Method (X ', R₁′, R₂′ And R₃'Is the same as above. M ' Is above
In addition to metal ions, it also represents the conjugate acid of a tertiary amine.
There is no disclosure regarding the method. On the way
According to two synthetic examples presented as a method according to
26% yield of the reaction to convert the hydrogen atom into an aryloxy group
And 45%, this type of magenta coupler
Improving the synthetic yield of this step to make it versatile
Or, it was necessary to develop a new synthetic method. The method is
Aryloxy after forming the azolotriazole skeleton
Although it has introduced a group, from a cost perspective,
It is better to introduce it at an early stage like the law
The yield is assumed, but it seems to be advantageous in this synthesis.
Be done. However, from compound (A) in the method
Conversion to compound (B) is accomplished by converting compounds (A) and (B)
The yield was rather low due to instability.

(Problems to be Solved by the Invention) Since it has been found that the steps subsequent to the compound (B) are not problematic in the method, the present inventor finds a method for synthesizing the compound (B) under mild conditions in good yield. However, it is considered that the practicality of the aryloxy-releasing pyrazolo [1,5- b ] [1,2,4] triazole magenta coupler is improved.
The present invention has been made to solve this problem.

(Means for Solving the Problem) As a result of intensive studies to solve the above problems, the present inventor has obtained halogen acetonitrile and a metal aryl oxide or a metal heterocyclic oxide, which are easily available, in a high yield. It was found that 2-acyl-2-aryloxy or heterocyclic oxyacetonitrile (the compound (B)) can be easily obtained under mild conditions by using 2-aryloxy or heterocyclic oxyacetonitrile. .

That is, the present invention provides 2-acyl-2-aryloxy represented by the following general formula [I ′] or heterocyclic oxyacetonitriles represented by the general formula [II] as a means for solving the above-mentioned problems. The present invention provides a method for production using heterocyclic oxyacetonitriles.

(However, R ₁ is a hydrogen atom, an alkyl group, an aralkyl group,
It represents an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group or a heterocyclic group, and R ₂ represents an aryl group or a heterocyclic group. ) Further, the present invention is represented by the above-mentioned general formula [II] 2
2-acyl represented by the following general formula [I] using aryloxy or heterocyclic oxyacetonitrile
A 2-aryloxy or heterocyclic oxyacetonitrile is produced, and then the 2-acyl-2-aryloxy or heterocyclic oxyacetonitrile is reacted with hydrazine. The present invention provides a method for producing aminopyrazoles.

(In the formula, R ₁ represents a hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group, or a heterocyclic group,
R ₂ represents an aryl group or a heterocyclic group. ) In the present invention, R ₁ and R ₂ in the compounds represented by the general formulas [I], [I '] and [II] will be described in detail below.

R ₁ will be described in detail. The alkyl group has 1 to 1 carbon atoms.
20 represents a linear or branched alkyl group, an aryl group represents a phenyl group or a naphthyl group, and a heterocyclic group represents a 5- to 7-membered aliphatic or aromatic heterocyclic group. These groups may have a substituent, and they are an organic substituent linked by a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or a halogen atom. More specifically, R ₁ is, for example, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, cyclopentyl, cyclohexyl, methoxyethyl, ethoxyethyl, t-butoxyethyl, phenoxyethyl, methanesulfonylethyl, 2-hydroxy. Ethyl, (3-pentadecylphenoxy) propyl, 4,4,4-trifluorobutyl, 3-
An alkyl group such as (2,4-di-t-amylphenoxy) propyl; for example, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,4-dimethylphenyl, 4-tetradecanamidophenyl. , 2-
Aryl groups such as methoxyphenyl, 2-acetamidophenyl, 1-naphthyl, 2-naphthyl; for example, 2-tetrahydrofuranyl, 2-tetrahydrothienyl, 1-
It represents a heterocyclic group such as piperidino, 4-pyridyl, 1-pyrazolyl, 2-furyl, 2-thienyl, 2-pyrimidinyl and 2-benzothiazolyl.

More specifically, the substituents which these groups may further have include, for example, an alkyl group, an aryl group, a heterocyclic group,
Cyano group, acyl group, aryloxycarbonyl group, alkoxycarbonyl group, carbamoyl group, alkoxy group, aryloxy group, heterocyclic oxy group, acyloxy group, carbamoyloxy group, silyloxy group, aryloxycarbonylamino group, acylamino group, anilino Group, ureido group, sulfamoylamino group, alkoxycarbonylamino group, sulfonamide group, aryloxycarbonylamino group, imide group, alkylthio group,
Arylthio group, heterocyclic thio group, sulfamoyl group,
A sulfonyl group, a sulfinyl group, a fluorine atom, a chlorine atom, and a bromine atom.

R ₁ is preferably methyl group, ethyl group, isopropyl group, t-butyl group, phenyl group, 2-methylphenyl group, 2,4-dimethylphenyl group, 4-methylphenyl group, 4-methoxyphenyl group, 3- Chlorophenyl group,
A 2-nitrophenyl group and a 3-nitrophenyl group.

R ₂ represents an aryl group or a heterocyclic group, and specifically, for example, phenyl, 4-alkylphenyl, 4-alkoxycarbonylphenyl, 4-carboxyphenyl, 2-
Or 4-alkoxyphenyl, 2- or 4-alkanamidophenyl, 3-alkylphenyl, 3,4-dialkylphenyl, 4- (N-alkylcarbamoyl) phenyl, 4- (N-alkylsulfamoyl) phenyl, 2
An aryl group such as naphthyl; for example, 2-pyridyl, 3-
Pyridyl, 4-pyridyl, 2-furyl, 2-thienyl,
It is a heterocyclic group such as 2-benzothiazolyl. R ₂ is preferably a phenyl group, a 4-alkylphenyl group, a 4-alkoxycarbonylphenyl group, a 4- (N-alkylcarbamoyl) phenyl group or a 2-pyridyl group, and more preferably a 4-methylphenyl group or a 4-methylphenyl group. It is an ethoxycarbonyl group.

Next, specific examples of the 2-acyl-2-aryloxy or heterocyclic oxyacetonitriles represented by the general formula [I] and the general formula [I ′] which can be synthesized by the method of the present invention are shown, but the invention is not limited thereto. Not a thing.

Next, embodiments of the present invention will be described in detail. The synthetic scheme of the present invention is shown below.

 (However, X₁Represents a halogen atom, M Is alkaline
Represents a metal ion. X₂Is an alkoxy group, aryloxy
Si group, heterocyclic oxy group, acyloxy group or halogen
Represents an atom. R₁, R₂Represents a group having the same meaning as above. ) Starting material1To halogenate acetonitrile
Easily obtained by X₁= All of F, Cl, Br, I
It can be purchased as a reagent. Especially X₁= Cheaper if Cl
It can be purchased as an industrial chemical.

1The nucleophilic substitution reaction for is usually performed in an aprotic polar solvent.
N, N-dimethylacetamide, N, N-dimethyl
Amide solvents such as ruformamide are preferred. R₂O
M How much is used1About 0.9-1.2 molar equivalents are preferred
Yes. The reaction temperature is 0 ° C to 100 ° C, preferably 0 ° C to 3 ° C.
It is 0 ° C. The appropriate reaction time is 30 minutes to 5 hours.
0 minutes to 2 hours is preferable. Raw represented by the general formula [II]
The product is generally distilled, column chromatographed and regenerated.
Purified with crystals.

X ₂ of R ₁ COX ₂ represented by the general formula [III] is an alkoxy group, an aryloxy group, a heterocyclic oxy group, an acyloxy group and a halogen atom, preferably an alkoxy group and an aryloxy group, and more preferably Is an alkoxy group (particularly a lower alkoxy group). Organic bases such as alkali metal amides, alkali metal hydrides, alkali metal alcoholates, and trialkylamines are used as the base, and sodium amide, sodium hydride, potassium t-butoxide, sodium isopropoxide, diisopropylethylamine are preferred. And
More preferred are sodium hydride and potassium t-butoxide. Examples of the solvent include ether solvents such as tetrahydrofuran, hydrocarbon solvents such as benzene and toluene, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and 1,3-dimethyl-2-imidazo. An amide solvent such as ridinone is used. When R ₁ COX ₂ is an ester and does not self-condense with the base used, the ester as a reaction substrate may be used in excess to serve as a solvent. Reaction temperature is -20 ℃ ~ 10
The temperature is 0 ° C, preferably 0 ° C to 50 ° C, more preferably 5 ° C to 30 ° C.

The amount of the solvent used is appropriately 1 to 20 times, preferably 1 to 10 times the weight of the compound of the general formula [II].

The amount of the compound of the general formula [III] used is required to be approximately equimolar or more with respect to the compound of the general formula [II], and preferably 1.
A large excess may be used when the amount is 5 to 5 molar and can also be used as a solvent as described above.

The amount of the base used is about 0.2 with respect to the compound of the general formula [II].
-3 molar equivalents are suitable, preferably 1.5-2.5 molar equivalents.

The reaction time for these is appropriately 30 minutes to 5 hours, preferably 30 minutes to 4 hours.

The reaction product may be precipitated from the reaction solution as an alkali metal enolate, and in that case, the product of high purity can be obtained by neutralizing after filtration. If not, water is added to the reaction solution to remove organic substances insoluble in water with n-hexane, ethyl acetate, benzene, toluene, etc., and the aqueous layer is then acidified (preferably with protic acid water such as hydrochloric acid or sulfuric acid). After adjusting the pH to 2-5), the desired product is obtained by extraction with an organic solvent such as ethyl acetate or dichloromethane. The by-products of this reaction are mainly compounds that are believed to have self-condensed with the nitrile itself.

Since the compound represented by the general formula [I] is generally not so stable, it is preferably used in the next reaction without purification and then purified as aminopyrazole (the following formula).

Next, the present invention will be described in detail based on examples.

Example 1 Synthesis of Exemplified Compound (2) 286 g (2.65 mol) of ice-cooled cresol in methanol (2
To the solution, 530 ml of 28% sodium methoxide methanol solution was added dropwise (about 10 minutes) while stirring. After removing the ice bath and returning to room temperature, methanol was distilled off under reduced pressure using an evaporator and further sufficiently distilled under high vacuum.

To the dimethylacetamide (1) solution of the thus obtained sodium salt of cresol, 257 g (2.9 mole) of chloroacetonitrile was added dropwise under ice cooling. After the dropping, the mixture was returned to room temperature and stirred for about 2 hours, then extracted three times with a mixed solvent of ethyl acetate and n-hexane (1: 1), the extract was washed with water and saturated saline and dried over anhydrous sodium sulfate. After that, it was concentrated under reduced pressure with an evaporator. By distilling the residue under reduced pressure, 2
Of 335 g (110-124 ° C./4 mmHg, yield 86%) could be obtained.

Under ice-cooling potassium t- butoxide 138g to a solution of 2 147 g (1.0 mol) in ethyl acetate 1.5 was added over about 5 minutes. After stirring for about 1 hour, water was added, and n-hexane was further added. After vigorous stirring, the aqueous layer was separated, and concentrated hydrochloric acid was added to adjust the pH.
To about 2 and then extracted three times with ethyl acetate, dried and concentrated to obtain a crude product of Exemplified compound (2) as an oil. By rapidly separating and purifying this by silica gel column chromatography, 89 g (yield 47%) of Exemplified compound (2) could be obtained.

(Example 2) Exemplary Compound (7) 2 Synthesis of methyl propionate 1.5 obtained in Example 1 of 147
To a solution in which g (1.0 mol) was dissolved, 138 g of potassium t-butoxide was added over about 5 minutes under ice cooling. After about 1 hour, the precipitated crystals were suction filtered and washed with ethyl acetate. The obtained crystals were dissolved in water, adjusted to pH 2 with concentrated hydrochloric acid under ice-cooling, extracted 3 times with ethyl acetate, dried and concentrated to give substantially pure 119 g of Exemplified compound (7) (yield 55 %) I was able to get it.

Example 3 Synthesis of Exemplified Compound (8) Exemplified Compound (8) was prepared in substantially the same manner as Example 1 except that methyl isobutyrate was used instead of ethyl acetate.
Could be obtained with a yield of 39%.

Next, from the 2-acyl-2-aryloxynitriles obtained in Examples 1 to 3, 3 (5) -alkyl-5 (3)-
A method for synthesizing amino-4-aryloxypyrazole and a method for synthesizing 7-aryloxy-1H-pyrazolo [1,5- b ] [1,5,4] triazole magenta coupler using the same are shown.

(Example 4) _{R 1 = CH 3 3 = C} 2 H 5 4 = CH (CH 3) 2 5 Exemplified Compound (2) 50g (0.264mol) in ethanol 50ml and 8
Add 18 g (0.288 mol) of 0% hydrazine hydrate, and add about 3
Heated to reflux for hours. After that, the temperature was returned to room temperature, and the crystals were deposited when left overnight. The crystals were filtered and dried to give 3-amino-5-methyl-4- (4-methylphenoxy) pyrazole 3 , 43.5 g (yield 81%, melting point 157-15).
9 ° C) was obtained.

Similarly, 3-amino-5-ethyl-4- (4-methylphenoxy) pyrazole 4 (melting point: 173-175 ° C) was obtained from the exemplified compound (7) at a yield of 85%, and further from the exemplified compound (8) to 3- Amino-5-isopropyl-4- (4-methylphenoxy) pyrazole 5 (melting point 188-190 ° C) yield 84%
I was able to get at.

(Reference example 1) 5 , 53.5g (0.23mol) to dimethylacetamide 500ml
And heated until dissolved. After melting, the mixture was cooled to about 35 ° C., and 86 g (0.30 mol) of methyl 2-methyl-3-phthalimidopropioimidate hydrochloride was added, followed by stirring at room temperature for about 24 hours. An aqueous solution of 32 g (0.46 mol) of hydroxyamine hydrochloride and 19 g (0.23 mol) of sodium acetate was added to the reaction solution, and the mixture was heated to 50 ° C.
Heated to. After heating for about 1 hour and gradually returning to room temperature and stirring for about 10 hours, while stirring, pour into the ice of 2 and separate the precipitated crystals by filtration, wash well with water and dry to obtain 102 g of 6 (Yield 96%) could be obtained. Melting point ~ 186 ° C (decomposition).

6, the 101g (0.219 mol) of dimethylacetamide 300ml
Was added and stirred. Although 6 was not completely dissolved, 43.8 g of paratoluenesulfonyl chloride dissolved in 120 ml of acetonitrile was added dropwise over about 30 minutes while cooling in a water bath. After the dropwise addition, the mixture was stirred for about 1 hour, 18.6 ml of pyridine was added, and the mixture was stirred for about 1 hour except for the water bath. Then, pour the reaction solution into about 2 ice water, remove the aqueous solution by decantation,
Methanol 2 was added to the remaining solid matter, and the mixture was crushed and filtered to obtain a tosylate body of 6 as a colorless powder. This is immediately dispersed in methanol 1.8, and pyridine 1
After adding 8.6 ml, the temperature was raised to a temperature at which the mixture was heated to reflux, and when the tosylate body was dissolved, heating was stopped, and the mixture was stirred while gradually returning to room temperature. After stirring at room temperature for about 2 days, methanol was distilled off under reduced pressure, concentrated to about 500 ml, and then poured into about 2 water. By filtering out the precipitated powder crystals and drying
It was possible to obtain 50.4 g of 7 (52% yield). Melting point ~ 193 ° C
(Decomposition) 7 , 15g (0.034mol) isopropyl alcohol, 150
2.5 g of 80% hydrazine hydrate (0.062mo
l) was added, and the mixture was heated under reflux for about 8 hours. After returning to room temperature, chloroform and saturated saline were added, and the mixture was subjected to suction filtration to remove the precipitated phthalhydrazide. The filtrate was extracted three times with chloroform, the extracts were combined, washed with saturated brine, dried over magnesium sulfate, filtered, and evaporated to obtain an amine compound as crystals. This amine compound was prepared by mixing dimethylacetamide and acetonitrile in a ratio of 1: 1.
The mixture was dissolved in 100 ml of a mixed solvent, 4.7 ml of triethylamine was added, and 14.2 g (0.034 mol) of 2-octyloxy-4-t-octylbenzenesulfonyl chloride dissolved in 40 ml of acetonitrile was added dropwise under ice cooling with stirring. After dropping, the mixture was stirred for about 1 hour, extracted, dried and evaporated to obtain an oily product, which was subjected to silica gel column chromatography (eluent, n-hexane: ethyl acetate = 4: 1).
17 g (yield 72%) of 8 could be obtained by purification with. Melting point 116-117 ° C (recrystallized from acetonitrile).

(Effect of the Invention) 7- which is useful as a color photographic coupler according to the present invention
Aryloxy or heterocycleoxy-1H-pyrazolo [1,
5- b- ] [1,2,4] triacyl 4-aryloxy or heterocyclic oxy-3-aminopyrazole precursor 2-acyl-2-aryloxy or heterocyclic oxyacetonitrile It became easy to supply the kind. As a result, the value of 7-aryloxy or heterocyclic oxy-1H-pyrazolo [1,5- b ] [1,2,4] triazole as a photographic coupler was increased.

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Claims (3)

(57) [Claims] 1. A 2-acyl-2-aryloxy or heterocyclic oxyacetonitrile represented by the following general formula [I '] is used as a 2-aryloxy or heterocyclic oxyacetonitrile represented by the general formula [II]. Manufacturing method. (In the formula, R ₁ represents a hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, or a heterocyclic group, and R ₂ represents an aryl group or a heterocyclic group.) 2. A compound represented by the following general formula [III] is reacted with the 2-aryloxy or heterocyclic oxyacetonitriles represented by the general formula [II] in the presence of a base. The manufacturing method according to claim 1. (In the formula, R ₁ has the same meaning as R ₁ in the general formula [I '], X ₂
Represents an alkoxy group, an aryloxy group, a heterocyclic oxy group, an acyloxy group or a halogen atom. ) 3. A 2-acyl-2-aryloxy or heterocyclic oxy represented by the following general formula [I] using the 2-aryloxy or heterocyclic oxyacetonitrile represented by the above general formula [II]. A method for producing an aminopyrazole represented by the following general formula [IV], which comprises producing acetonitrile and then reacting the 2-acyl-2-aryloxy or heterocyclic oxyacetonitrile with hydrazine. (In the formula, R ₁ represents a hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group, or a heterocyclic group,
R ₂ represents an aryl group or a heterocyclic group. )