JPH02279674A - Production of 5-amino-3-alkyl-4-chloro-1h-pyrazole hydrochloride - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as a raw material for photographic coupler, etc., readily and in high yield by chlorinating a 5-amino-3-alkyl-1 H-pyrazole, etc., as a raw material with inexpensive sulfuryl chloride in a specific solvent at a specific temperature. CONSTITUTION:1mol 5-amino-3-alkyl-1H-pyrazole shown by formula I (R2 is 1 to 4C alkyl; (m2) is 0 or 0.5 to 2.0) or a salt thereof is chlorinated with 1.0 to 2.0mols sulfuryl chloride at <=50 deg.C in an aqueous solution or in a diluted solution of hydrochloric acid in the case that (m2) is 2 to give the objective compound shown by formula II ((m1) is 0.9 to 2.0) having stability to oxidation, high storage stability, crystal form and excellent handleability as a reaction raw material, useful as a synthetic intermediate for 1H-pyrazolo[1,5-b]-1,2,4- triazole-based magenta coupler usable for sensitized material of silver halide color photography, 7-amino-pyrazolo[1,5-a]pyrimidine-based drug, etc.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to I H-pyrazolo (1,5-b'1-1.2.
41 Lyazole machine coupler or l)l
-pyrazolo (3,2-cl) -1,24-triazole magenta coupler and 7-amino birazolo (1,5
-a) 5-amino-3-alkyl-4 to 4-m, which is a useful synthetic intermediate for synthesizing pyrimidine drugs, etc.
+-11-1 It relates to a manufacturing method for producing Viradul hydrochloride easily and at low cost on an industrial scale.

(Prior art) Silver halide color photography (1 Fl-
Pyrazolo ct, 5-b:+-1,2,4-triazole and I H-pyrazolo(3,2-c)-12,4
1 lyazol compounds are disclosed in U.S. Pat. No. 4.540,
It is known from US Pat. No. 654 and US Pat. No. 3,725,067 to be a magenta coupler that provides excellent hue.

Methods for synthesizing these pyrazolotriazole compounds are disclosed in JP-A Nos. 60-190779, 60-197688, 60-215687, 61-145163,
It is described in No. 61-18780, No. 6l-2499F17, etc.

Furthermore, various reports have been made regarding intermediates leading to these pyrazolotriazole compounds, and various reports have also been made regarding 5-amino-IH-pyrazole intermediates.

For example, in JP-A-61-145163, 5-amino-3alkyl-4-halogen-
I H-pyrazole was described in JP-A-62-2527.
No. 73 and JP-A No. 61-249987 disclose 5-amino-3-alkyl-4 as the starting material for IH-pyrazolo[32-c)-1,2,4-1-riazur.
-Chloro-IH-pyrazole is described. Pharmaceutical journal 8
Vol. 4, No. 11, p. 1113 (1964) describes the 5-amino-3-methyl-4-bromo-IH-pyrazole compound, and JP-A-56-15E1768 describes the 5-amino-3-methyl-4-bromo-IH-pyrazole compound.
-amino-3-methyl-4-iodo-IH-pyrazole compound, Li, ebigs A
r+n Chew, 707 141 pages (196
7) reported 5-amino-4-chloro-IH-pyrazole. West German published patent (OLS) 2,305
, 984 and 2.646012, 5-amino-4-halogen IH-pyrazole compounds are also known.

JP-A-63-239272 describes 5-amino 4-chloro-3-methyl-IH-pyrazole hydrochloride.

(Problems to be Solved by the Invention) As a method for synthesizing a 5-amino-4-chloro-3-methyl-IH-pyrazole compound, 5-amino-3-methyl-IH-pyrazole (J, lle terocy
c IChe+m, Volume 11, Page 423, 197
4) with chlorine, sulfuryl chloride or N-chlorosuccinimide compounds. In particular, if N-chlorosuccinimide is used as a chlorinating agent and the reaction is carried out in a halogenated solvent such as methylene chloride, chloroform, or carbon tetrachloride, 5-amino-4-chloro-
It is conceivable that 3-methyl-11■-pyrazole could be formed. However, N-chlorosuccinimide is expensive as an industrial chlorination agent, and requires an operation to remove unnecessary succinimide generated from the reaction system after the chlorination reaction, so it cannot be used on a laboratory scale. Although effective for this purpose, it is unsuitable for chlorination reactions carried out on an industrial scale.

JP-A-63-239272 proposes a method using inexpensive chlorine or sulfuryl chloride as a chlorination agent. As the solvent for this chlorination reaction, halogen solvents such as dichloromethane, dichloroethane, and chloroform, ester solvents such as ethyl acetate and butyl acetate, and organic acids such as acetic acid and propionic acid are described. .

However, the use of these solvents causes a deterioration of the working environment, and furthermore, since they are relatively expensive solvents, they cannot be said to be optimal as solvents for chlorination reactions carried out on an industrial scale.

In JP-A-62-252773, sulfuryl chloride is used as a chlorinating agent, and the temperature is increased to 1° C., preferably from 50°C to 90°C, more preferably from 60°C to 80°C. It has been proposed to react at 65°C to 70°C to 11+j.

However, the specifically described method has a low whistle and on an industrial scale! ! It cannot be said that this is the best method for building.

Therefore, an object of the present invention is to provide a method for producing 5-amino-3-alkyl-4-chlorol H-pyrazole hydrochloride that can be produced on an industrial scale.

(Means for solving the problem) Therefore, as a result of intensive study, the present inventors found the following -m formula (
5-Amino-3-alkyl-4-chloro-I H-pyrazole hydrochloride represented by [) is 5-amino-3-alkyl-11(-pyrazole or its hydrochloride represented by general formula (b)). It has been found that it can be prepared in high yields by chlorination with sulfuryl chloride in aqueous solution or dilute hydrochloric acid solution at temperatures below 50°C.

- Formula (1) General formula (TJ) (wherein, R3 represents an alkyl group having 1 to 4 carbon atoms,
m represents any positive number including a decimal point from 0.9 to 2.0, and mz represents any positive number including 0 or a decimal point from 0.5 to 2.0. , ) General formula (1) and CI will be explained in detail below.

R1 represents an alkyl group having 1 to 4 carbon atoms, and specific examples thereof include methyl group, ethyl group, n-propyl group, j-
Examples include propyl group, n-butyl group, i-butyl group, and t-butyl group. It is particularly preferable from the viewpoint that methyl groups can be obtained in high yield.

m representing the stoichiometry of the above hydrochloride in the present invention,
To explain mz, the hydrochloride of a nitrogen heterocyclic amine compound is usually monohydrochloride, dihydrochloride,
Public opinion on hydrogen chloride is usually thought of as a positive integer. However, as a result of various experiments carried out by the present inventors, we found that the required stoichiometry of hydrogen chloride cannot necessarily be expressed as a positive integer, and varies depending on the method of production, the method of taking out the crystals, and the drying conditions. is 0.9~ including the case of decimal point
It became clear that it was in the range of 2.0. When drying is carried out sufficiently (e.g. under reduced pressure), m is 0.9~
Elemental analysis revealed that it converged to 1.0.

The preferable ml defined in the present invention is any positive number including a decimal point from 0.9 to 1.5. When m is out of the above range, the stability of the compound deteriorates.

+712 represents the stoichiometric value of the hydrochloride of the compound represented by the general formula ([). In this case m2 is 0 or 0.5 ~
It represents the number 2.0, preferably any number including a decimal point between 0°5 and 1.5.

Next, embodiments of the present invention will be described. In the present invention, sulfuryl chloride is used as a chlorinating agent for the compound of general formula (11). The amount of sulfuryl chloride is determined by the general formula ([
1) of the compound 1). O~2.0 times mole, especially 1.3~1
．． 6 times the molar amount is preferred.

Water is used as a solvent for this chlorination reaction.

-M When mz is 0 in formula (n), it is preferable to use hydrochloric acid water.

The amount of hydrochloric acid used is preferably such that mz is 0.5 to 2.0.

The amount of water to be used, including the amount of water in dilute hydrochloric acid, is calculated using the general formula (
It) 1000ml to 3000ml/kg of compound
1, especially 150 (1+ffi to 2000-) is preferred.

The temperature of the chlorination reaction is below 50°C, particularly preferably 40°C to 0°C.

5-Amino-4-chloro-3-methyl-IH pyrazole hydrochloride can be easily crystallized from the reaction solvent and isolated by filtration, but it can be isolated by adding acetone, acetonitrile, isopropanol/n-hexane, etc. It is preferable to filter it after washing. It is particularly preferable to add acetone.

The amount of acetone to be added is 4 times or less, preferably 2 times or less, and most preferably 1 time or less by volume based on the total water used. If crystallization is not performed from the reaction solvent, it is preferable to add the above-mentioned solvent after water is distilled off under reduced pressure and perform crystallization.

In addition, without using 5-amino-3-methyl-11-1-pyrazole or its hydrochloride, 5-aminol 3 -Methyl-1,It-biradur (or its hydrochloride) is produced and chlorinated without isolation to produce 5-amino-4-4-3-methyl-11(-pyrazole hydrochloride), which is also an industrial method. It is useful for this purpose.

The details will be clarified in Example 4.

(Effect of the invention) According to the method of the invention, 5-amino-3-alkyl-I
H-pyrazole is chlorinated using inexpensive sulfuryl chloride in an aqueous solvent in a reaction time comparable to that of conventionally known methods and at a relatively low temperature to produce 5-amino in higher yields. -3-alkyl-4-chloro-I
H-pyrazole hydrochloride can be isolated as crystals. Therefore, it is suitable as a method to be implemented on an industrial scale.

On the other hand, the obtained 5-amino-3-alkyl-4-chloro-IH-pyrazole hydrochloride is extremely stable against oxidation despite being an amino compound, and has high storage stability (, Therefore, it is easy to handle as a reaction raw material and is useful as a raw material for high-purity synthesis of photographic couplers, dye intermediates, etc.

(Examples) Next, the present invention will be described in more detail based on Examples and Comparative Examples.

Example 1 5-amino-3-methyl-t H-pyrazole 194,
3 g (2, Omole) in 12 ml of water) and 172 ml of concentrated hydrochloric acid (36%) were added with stirring. Water-cooled sulfuryl chloride 226 ml! (2,
8 mole) was added dropwise at 10 to 40°C (crystals precipitated during the dropping of surifuryl chloride). After dropping, 0-20℃
The reaction was carried out for 1 hour. Add 200ml of acetone,
After pressing for 1 hour at ~10°C, the crystals were filtered, washed with 100 ml of acetone, and dried.

293.7 g (137.4%) of 5-amino-4-chloro-3-methyl-IH pyrazole hydrochloride was obtained. Melting point: 204°C to 206°C Example 2 5-amino-3-methyl-I H-pyrazole 600
g (6,18 mole) in water (11)) and concentrated hydrochloric acid (36%) I+8 was added dropwise with stirring.

600ml (7,42 mole) of sulfuryl chloride
It was added dropwise at 0 to 40°C. After the dropwise addition, the mixture was reacted at the same temperature for 1 hour, then cooled to 10° C., and the precipitated crystals were filtered. It was washed three times with 350 ml of acetone and dried.

856.7 g (82.5%) of 5-amino-4-chloro-3-methyl-IH pyradul hydrochloride was obtained. Melting point 2
03°C to 206°C Example 3 (5-amino-3-methyl-I 5-amino-4-chloro3-methyl-IH using H-pyrazole hydrochloride
Synthesis of pyrazole hydrochloride) 5-amino-3-methyl-
Dissolve IH Pyrazole 291, 4g (3, Omole) in dichloromethane 3e, and add 164g of hydrogen chloride gas while stirring and keeping the temperature inside the flask at 20-40℃.
was gradually injected. (White crystals precipitated during the process.) The precipitated crystals were collected by filtration and dried. Yield 381g (95%
).

Obtained 5-amino-3-methyl-IH pyrazole hydrochloride 2
67. 3 g (2 mole) was dissolved in 345 d of water. 226 ml of sulfuryl chloride while stirring and cooling with water.
(2,8 mole> was added dropwise at 10-40°C (crystals precipitated during the dropping). After the dropwise addition, the reaction was carried out at 0-20°C for 1 hour. Next, 200#lβ of acetone was added,
After stirring for 1 hour at 10°C, the crystals were filtered and diluted with acetone 1
Washed and dried with 00 cloth.

296.1 g (86, G%) of 5-amino-4-di4-3-methyl-1,tl-pyrazole hydrochloride was obtained. Melting point 203-206'C.

Example 4 <Synthesis of 5-amino-4-chloro-3-methyl-111 pyrazole hydrochloride using 3-71 minocrotononitrile as starting material) 3-aminocrotononitrile 164.2 g (2 mol
e) , 150.0g of 80% foamy hydrazine (24m
ole) for 1 hour at 70°C with stirring, and then at 120°C for 1 hour.
The mixture was heated and reacted at ℃ for 3 hours.

After the reaction, it was cooled to 50°C and 92.8g (1,
6 mole) was added dropwise and reacted at 50'C for 30 minutes.

Next, solvent 8 was distilled off under reduced pressure, and 5-amino 3-methyl-
194 g of I H pyrazole (<100%) was obtained.

After adding 172 mff1 of water to this and dissolving it, 172 mm of concentrated hydrochloric acid (36%) was added dropwise. Under water cooling, sulfuryl chloride 226d (2,8Ilole) was added dropwise with stirring at 10 to 40°C (crystals precipitated during the dropwise addition of sulfuryl chloride), and after the dropwise addition, the mixture was reacted at 0 to 20°C for 1 hour.

After adding 200° of acetone and stirring at 0 to 10°C for 2 hours, the crystals were filtered, washed with 100° of acetone, and dried. 289.0 g (86.0%) of 5-amino 4-chloro-3-methyl-IH-pyrazole hydrochloride was obtained. Melting point: 203°C to 206°C.

Example 5 100 g of 5-amino-3-ethyl-IH-pyrazole
(0.9 mole) was dissolved in water 77- and concentrated hydrochloric acid (36%) 77- was added dropwise.

30 sulfuryl chloride 102d (1,26 mole)
The mixture was added dropwise at a temperature of 40°C to 40°C. After the dropwise addition, the mixture was reacted at the same temperature for 1 hour, and about 40 TR1 of water was distilled off under reduced pressure. Acetone (80°C) was added to the residue, cooled to 0-10°C, and the precipitated crystals were filtered. Acetone 50! Washed and dried with d.

132.7 g (81.0%) of 5-amino-4-chloro-3-ethyl-11-1-pyrazole hydrochloride was obtained.

Comparative Example 1 (method described in JP-A-62-252773) 600 g of 5-amino-3-methyl-IH-pyrazole
(6,18no!,)Wed 11:j? F or L and 1 liter of Soshite Akebono hydrochloric acid (36%) were added dropwise with stirring.

Sulfuryl chloride 600d (7,42no!) at 65℃
It was added dropwise at ~70°C. After the dropwise addition, the mixture was reacted at the same temperature for 1 hour, then cooled to 10° C., and the precipitated crystals were filtered. It was washed three times with 350 ml of acetone and dried.

685.4 g (66%) of 5-amino-4-chloro-3-methyl-IH-pyrazole hydrochloride was obtained. Melting point 203
℃～205℃.

Claims (1)

[Claims] (1) General formula (I
) A method for producing a compound represented by General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R_1 represents an alkyl group having 1 to 4 carbon atoms,
m_1 represents a number from 0.9 to 2.0. General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R_1 represents an alkyl group having 1 to 4 carbon atoms,
m_2 represents 0 or a number from 0.5 to 2.0.