JPS61251671A - Production of 5-hydrazinopyrazole-4-carboxylate compound - Google Patents

Abstract

PURPOSE:To obtain the titled substance in high yield, by reacting thiocarbohydrazide with benzaldehyde, etc., reacting the reaction product with ethyl-2-chloroacetoacetate, etc., in the presence of an acid catalyst, and reacting with a nucleophilic reagent. CONSTITUTION:The objective compound of formula IV (R9 and R10 are same as R7 and R8, respectively) can be produced by (1) reacting thiocarbohydrazide with the compound of formula I and/or II (R1 and R2 are H, alkyl, aryl or heterocyclic group; R3 and R4 are same as R1 and R2; R5 and R6 are 1-4C alkyl) at a molar ratio of 1:(0.8-1.2), (2) adding 0.5-5mol of an acid catalyst (preferably hydrochloric acid) to 1mol of the thiocarbohydrazide, (3) reacting with the compound of formula III (R7 and R8 are alkyl, aryl or heterocyclic group; X is halogen, alkylsulfonyloxy, etc.), and (4) treating the reaction product with a nucleophilic reagent (e.g. hydrazine hydrate). USE:Intermediate for photographic coupler.

Description

Detailed Description of the Invention [Technical Field] The present invention relates to a method for producing 5-hydrazinopyrazole-4-carboxylate compounds, and more specifically, the present invention relates to a method for producing 5-hydrazinopyrazole-4-carboxylate compounds, and more specifically, for producing 5-hydrazinopyrazole-4-carboxylate in high yield using thiocarbohydrazide as a starting material. Ginopiracy7. -4-force,.

The present invention relates to a method for producing a boxylate compound.

[Prior art]

5-hydrazinopyrazole-4-carboxylate compounds are useful compounds as intermediates for photographic couplers, particularly magenta couplers. For example, British patent 1,25
No. 2,418, IH-pyrazolo(3,2-c) is prepared by ring-closing a 5-hydrazinopyrazole-4-carboxylate compound in the presence of POC1, in an inert solvent such as benzene. -1,2,4-triazole-7
- A method for producing carboxylate compounds is disclosed. The above-mentioned British patent specification also describes a method other than the above-mentioned method, for example, in which the 5-hydrazinopyrazole-4-carboxylate compound is ring-closed in the presence of bromine and sodium acetate in acetic acid (1). (-Pyrazolo (
A method for producing 3,2c)-1,2,4-triazole-7-carboxylate compounds is disclosed.

Regarding the synthesis of 5-hydrazinopyrazole-4-carboxylate compounds, Hans Φ Bayer (Han.
Berichte (Ber, B-'eyer) et al.
), Vol. 89, p. 2552 (1956), and an almost similar report was made by Joseph Bayley (Jose
Journal of the Chemical Society, Parkin Edition 1 (J, Ch.
em, Soc, *Perkin Trans, I
), pp. 2047-2052 (1977). According to these documents, concentrated hydrochloric acid is added to thiocarbohydrazide dispersed and suspended in refluxing ethanol,
Furthermore, add ethyl-2-chloroacetoacetate,
This mixture is heated to produce ethyl-5-hydrazino-3-methylpyrazole-4-carboxylate.

However, according to the method of this document, the target compound represented by the general formula (+V) can be obtained from the starting material thiocarbohydrazide in a low yield of only 20%.

Further, when R1 in the compound represented by the general formula [I] is a secondary alkyl group, the target product represented by the general formula (ff) can be obtained in a low yield of only a few units in the above method. Furthermore, when 几 is a tertiary alkyl group, only traces of the compound can be obtained.

Attempts have been made to obtain the compound represented by general formula (ff) in high yield by improving synthetic methods.

That is, Japanese Patent Application No. 59-140246 (Examples) describes thiocarbohydrazide and ethyl-2-chloroacetoacetate (a compound of the general formula [seal] as used in the present invention...
... R, = CH3 ... primary alkyl group) under a hydrogen chloride catalyst in a substantially anhydrous state, the desired ethyl-5 was obtained with a yield of 46%. It is disclosed that -hydrazino-3-methylpyrazole-4-carboxylate (compound of general formula (ff) as referred to in the present invention) can be obtained. Although the yield was improved by this method, it was still insufficient, and the R of the compound of general formula [I]
When 1 is a secondary alkyl group, the yield is as low as a dozen or more (the yield in the method according to the report by Berichte is about a few inches, so improvements have been made). Furthermore, when R2 is a tertiary alkyl group, the value decreases to several 1 (only a trace can be obtained by the method according to Berichte's report).

As another improved method, Japanese Patent Application No. 140247/1984 (Example) discloses that after reacting thiocarbohydrazide and benzaldehyde (compound of general formula [■] in the present invention), ethyl-2 - reacting with chloroacetoacetate (compound of general formula [I] in the present invention, described above),
Next, hydrazine hittride (nucleophilic reagent in the present invention)
It is disclosed that by reacting with has been done.

Although this method has improved the yield of the compound represented by the general formula ["ff] compared to the method described in the above-mentioned Japanese Patent Application No. 59-140246, it is still insufficient, and the yield of the compound represented by the general formula [I]
When B of the compound is a secondary alkyl group, 20-odd groups,
In the case of tertiary alkyl groups, there are many problems, and in the case of branched alkyl groups, low yields have not been solved.

It is desired to develop a synthetic method that does not reduce the yield due to a change in the group represented by 几 in the compound of general formula [I] as used in the present invention, that is, a synthetic method that has a wide range of applicability.

[Purpose of the invention]

The present invention has been made in view of the above circumstances, and its purpose is to produce a 5-hydrazinopyrazole-4-carboxylate compound in high yield using thiocarbohydrazide as a starting material. Our goal is to provide the following.

[Summary of the invention]

The above object of the present invention is to react a thiocarbohydrazide with at least one compound represented by the following general formula [I] and/or [shoulder], and then react the following general formula [I] under an acid catalyst.
This is accomplished by a method of producing a 5-hydrazinopyrazole-4-carboxylate compound represented by the general formula (IV) by reacting the compound represented by [I] and then reacting with a nucleophile.

General formula [I] General formula CI+)R4 In the formula, R7 and 几 each represent a hydrogen atom, an alkyl group, an aryl group, or a heterocyclic group. R3 and R4 have the same meaning as the above-mentioned 几 and R2. R5 and R6 each represents an alkyl)Lt group having 1 to 4 carbon atoms.

General Formula [I] % Formula % In the formula, Aya and R6 each represent an alkyl group, an aryl group, or a heterocyclic group, and X represents a halogen atom, an alkylsulfonyloxy group, or an arylsulfonyloxy group.

General formula (ff) In the formula, 89 has the same meaning as R6 and R10 has the same meaning as R8.

[Structure of the invention]

In the present invention, thiocarbohydrazide (NH, NHCNHNH,) used as a starting material is, for example, published in the Journal of Organic Chemistry (J.
Org, Chem, ), 1954, vol. 19, 73
On page 3, L.F. Andries (L, P, And
It can be obtained by reacting hydrazine hydrogen hydride with carbon disulfide as reported by J. Rieth et al.

This compound is a white needle-shaped solid with a melting point of 17
It has a temperature of 2°C to 174°C and is easily available on the market.

This thiocarbohydrazide is used after being dispersed in a dispersion medium during the reaction. Usable dispersion mediums include carbonyl groups such as Kents and aldehydes, and ester bonds such as ethyl acetate. Compounds that do not contain alcohol, such as alcohol, are preferably alcohols and ethers, with alcohols being particularly preferred.

Ketones and aldehydes are not preferred because their carbonyl groups react with the amino groups of thiocarbohydrazide.

Ethyl acetate is also not preferred because the carbonyl group bonds with the amine group of thiocarbohydrazide to form an amide and the alcohol is eliminated, making it impossible to obtain the desired compound.

Alcohols used in the present invention include 1';
Examples include methanol, ethanol, n-propanol, ethylene glycol, and ethylene glycol monomethyl ether.

Furthermore, examples of benzenes include benzene, nitrobenzene, toluene, xylene, and the like. Furthermore, examples of ethers include diethyl ether, ethylene glycol dimethyl ether, carbon tetrachloride, chloroform, bromoform, etc., and examples of amides include formamide, N,N-dimethylformamide, and the like. In addition, dimethyl sulfoxide, acetonitrile, etc. can also be used as a dispersion medium.

This dispersion medium does not necessarily have to be anhydrous.

The thiocarbohydrazide is contained in the dispersion medium in an amount of 1 to 1000 parts by weight, preferably 5 to 100 parts by weight, per 1 part by weight of the dispersion medium.

In the present invention, 几 and 电 in general formula [I] represent a hydrogen atom, an alkyl group, an aryl group, or a heterocyclic group, and among these, a combination of a hydrogen atom and an aryl group or a heterocyclic group is preferred. The alkyl group represented by R1 and R1 includes a methyl group, an ethyl group, an isopropyl group,
Typical examples of the aryl group represented by n-butyl group and R1 include phenyl group and naphthyl group. Zarani Kame and R7
Representative examples of the heterocyclic group represented by the formula include pyridyl group, furyl group, chenyl group, and the like.

几 and R2 may be the same or different,
Preferably, they are different. In order to obtain a high reaction yield, the above R1, R7C and R8 are aryl groups,
Particularly preferred is a phenyl group in which s R2 is a hydrogen atom. These alkyl groups, aryl groups, or heterocyclic groups may have a substituent, and examples of the substituent include a hydroxy group, a halogen atom, a nitro group, and an alkyl group (methyl group, ethyl group).

Next, specific examples of the compound represented by the general formula [I] are shown below, but the present invention is not limited thereto.

1-I HCHO1-2CH3CHO1-3C,H,
CHOI -4C7H, R3 and R4 in the general formula [''] of CHO have the same meaning as R and R2 in the above general formula [1]. R3 and R4 may be the same or different, and preferably the latter. General The alkyl group represented by formula [■] and R6 is a lower alkyl group having 1 to 4 carbon atoms, and specific examples include methyl group, ethyl group, isopropyl group, n-butyl group, etc. .

Next, specific examples of the compound represented by the general formula [O] are shown below, but the present invention is not limited thereto.

The compounds represented by the general formula [I] or [1] may be used alone or both may be used simultaneously. These compounds are used in amounts of 0.5 to 1.5 per mole of thiocarbohydrazide.
It can be used in a molar range, preferably in the range of 0.8 to 1.2 molar.

The compound represented by the general formula [I] or [the seal] may be added at any time before the addition of the compound represented by the general formula [I], and is preferably added dropwise to the dispersion suspension of the thiocarbohydrazide. Add.

Acids used as acid catalysts include hydrohalic acids (e.g. hydrochloric acid, hydrobromic acid, hydriodic acid, etc.), carboxylic acids (e.g. acetic acid, benzoic acid, trifluoroacetic acid, etc.), sulfuric acid, sulfonic acid ( For example, methanesulfonic acid, toluenesulfonic acid, etc.) are typical, and hydrochloric acid, hydrobromic acid, sulfuric acid, and toluenesulfonic acid are preferred, and hydrochloric acid is particularly preferred.

The amount of acid used varies depending on the strength of the acid, but is preferably 0.1 to 10 mol, more preferably 0.5 to 5 mol, per 1 mol of thiocarbohydrazide. The addition time may be any time before adding the compound of general formula [I], or it may be added to the reaction system from the beginning.
and/or may be added after addition of the compound (II).

In the present invention, a compound represented by the following general formula [I] is further used in addition to the above thiocarbohydrazide.

General formula (I) R,, -Co -CH-COOR8 In the formula, R1 and R6 each represent an alkyl group, an aryl group, or a heterocyclic group, and X is a halogen atom, an alkylsulfonyloxy group, or an arylsulfonyloxy group represents.

The alkyl group represented by R6 and R6 is preferably a linear or branched alkyl group having 1 to 30 carbon atoms, such as a methyl group, ethyl group, isopropyl group, t-
Examples include butyl group, octyl group, dodecyl group, eicosyl group, and triacontyl group. This alkyl group can have a substituent, and examples of the substituent include a halogen atom.

Examples of alkyl groups having such substituents include f-(2,4-di-t-amylphenoxy), aryloxy groups, alkylsulfonyl groups, acylamino groups, alkoxy groups, and hydroxy groups. ) propyl group, β-(dodecylsulfonyl)ethyl group, phenoxymethyl group, methoxyethyl group, etc. The above alkyl group also includes a cycloalkyl group.

As the aryl group represented by R2 and R1.

A specific example is a phenyl group. This phenyl group,
may have a substituent, and examples of the substituent include an alkoxy group, a halogen atom, an alkyl group, an amide group, etc. Examples of phenyl groups having such substituents include p-methoxyphenyl group, dodecyloxyphenyl group, p-group, p-)lyl group, mesityl (trimethylphenyl) group, and the like.

Specific examples of the heterocyclic group represented by R1 and R6 include furyl group, pyranyl group, chen'nyl group, pyridyl group, and 2H-pyrrolyl group.

Among the alkyl groups, aryl groups, and heterocyclic groups represented by R1 and R6, alkyl groups are particularly preferred. Among the alkyl groups, methyl groups, ethyl groups, etc. are particularly preferred.

Specific examples of the halogen atom represented by X in general formula [I] include chlorine atom, bromine atom, and iodine atom. The alkylsulfonyloxy group represented by X includes, for example, a methanesulfonyloxy group.

Further, the arylsulfonyloxy group represented by X may specifically include a toluenesulfonyloxy group. Among these, a halogen atom is a clever choice for X in terms of the synthetic route and cost when introducing X, and among the halogen atoms, a chlorine atom is preferable.

Preferable compounds represented by the general formula [I] of the present invention are α-acyl-α-haloacetic alkyl (or aryl) esters, and such compounds are described, for example, in Organic Synthesis, Volume 4. (Org, 5yn
th, Co11. Vol, 4), 592-593
α-acyl alkyl acetate (
Alternatively, it can be obtained by halogenating an aryl) ester at a temperature of 0°C to 5°C. The halogenating reagents used in this reaction include halogen molecules, sulfuryl halide (e.g. sulfuryl chloride), N-
Halogen compounds (e.g. N-bromosuccinimide, N
-chlorosuccinimide, etc.) can be used. This compound is a colorless and transparent toxic liquid at room temperature, and under reduced pressure of 17111Hg, for example, ethyl-2
-Chloroacetoacetate has a boiling point of 85° to 89°C.

Next, typical examples of the compound represented by the general formula [I] are shown below, but the present invention is limited to these.
CH, C0CHCOOC, H1+l 1-2 CH, COC look C00C, H.

*3 CH3COCHC00CHa *4 Ct Hs COCHCOOC! H
al * 5 t C4Ha COCHCOOCt
Ha heat 1 -6 C u H2llcOcHcOOctHs
"B 1-13 (CH3)ICHCOCHCOOC,H
.

I CH, C# The compound represented by the general formula [Seal] used in the present invention C,
The thiocarbohydrazide is added separately to the dispersion medium. The compound represented by the general formula [I] is a compound represented by the general formula [I] and/or
Alternatively, after adding the compound represented by the general formula ["lr], the compound is dissolved in, for example, alcohol, and then added to a dispersion medium (for example, alcohol).

The thiocarbohydrazide used as the starting material of the present invention and the compound represented by the general formula [seal] are l: 0.5 to 1
: used in a molar ratio of 1.5, preferably 1 :
The range is 0.8-1:1.2.

The temperature at which the compound represented by general formula [I] and/or general formula (It) is added dropwise is preferably -20'O to 200°C, particularly θ to 100°C, in order to allow the dehydration reaction to occur relatively smoothly. 'O range is preferred. The above general formula [
After dropping the compound represented by
It is preferable to set it in the range of 00°0, especially 50 to 100
Preferably, the reaction is carried out in the temperature range.

The reason why the reaction temperature after dropping the compound represented by the general formula [I] is set to at least 40°C is to quickly carry out the desulfurization reaction that occurs in this reaction.
The reason why it is set below is that the decomposition force of the product is 5, which lowers the yield.

In addition, in the present invention, the time required for the reaction is not particularly limited, but within the above temperature range, about 5 minutes is sufficient.
Even if it takes more time than this, no inconvenient problems will occur.

Examples of the nucleophilic reagent used in the present invention include those having a lone pair of electrons, preferably compounds having a hydroxyl ion, an alkoxy anion, an aryloxy anion, an amino group, or a hydrazino group.

Alkoxy anions include methoxy anions and ethoxy anions, aryloxy anions include phenoxy anions and chlorophenoxy anions, and compounds with amino groups include hydroxylamine, methylamine, dimethylamine, ethylamine, diethylamine, and propyl. Examples of compounds having 7 hydrazi groups, such as amine, octylamine, aniline, methoxyaniline, aminophenol, and methylaniline, include hydrazine hydrazine, dimethylhydrazine, l
-aminopiperazine, phenylhydrazine, p-hydrazinophenol, isopropylhydrazine and the like. Among these nucleophilic reagents, hydrazine hydride having 7 hydrazi groups is particularly preferred because it is readily available at low cost.

These nucleophiles have the effect of converting by-product sulfur remaining in the reaction system into a water-soluble compound, facilitating purification. The presence of sulfur, even in a trace amount, causes unfavorable results when used as an intermediate for photographic couplers. In addition, when the compound of the general formula (IT) of the present invention is modified to synthesize other compounds, the presence of sulfur, even in a trace amount, shows unfavorable results when a catalytic reduction process is performed. It is necessary to.

This nucleophile is 2 to 1 mole of thiocarbohydrazide.
It can be added in an amount of 100 mol, preferably 3 to 10 mol.

Next, a typical reaction route for producing the 5-hydrazinopyrazole-4-carboxylate compound of the present invention is shown below.

Reaction route-1 Reaction route-2 Bs (Desulfurization reaction) -NH According to the method of the present invention, a compound represented by the following general formula (n) is obtained.

General formula (IT) In the formula, R0 and RIo are the above-mentioned R? and R8.

Next, typical compounds represented by the general formula (ff) are illustrated below, but the present invention is not limited thereto.

Note that all of these compounds can form salts, and the compounds of the present invention include these salts.

IV-117-2 IV-31V-4 ■-517-6 -7N-8 1(-glV-10 IV -11ff -12 ■-13 ■-14 Represented by the general formula (tV) obtained by the method of the present invention The compound is in crystalline form, generally pale yellow plate crystals.This compound can generally be easily separated from alcohols or acetonitrile by a recrystallization method.

This compound is useful as an intermediate for photographic couplers, and is described in the aforementioned British Patent No. 1,252,418 and in the Journal of Chemical Society, edited by Perkin (mentioned above).

1977, pages 2047-2052, an example of producing a photographic coupler using this compound is described [
Specific Examples of the Invention] Specific examples of the present invention will be described below, but the present invention is not limited thereto.

Comparative Example-1 (Berichte, Vol. 89, p. 2552 (195
6 years) Method according to description) 10.6 g of thiocarbohydrazide in 120 J of alcohol
suspend. 30 m of concentrated hydrochloric acid (12N) under reflux and stirring
1 dropwise over 30 minutes. Next, 16.5 g of 1-ethyl-2-chloroacetoacetate was added dropwise over 30 minutes. Then, stir for 30 minutes while refluxing. The reaction solution is ice-cooled, and the precipitated crystals are collected in a furnace and air-dried. The crystals are heated and dissolved in 50% water, filtered to remove insoluble materials, and the aqueous solution (acidic) is neutralized with sodium acetate. The precipitated crystals are collected in a furnace, washed with water,
Air dry. Recrystallize the crystals from methanol to obtain ethyl-5
3.9 g of -hydrazino-3-methylpyrazole-4-carboxylate (exemplified compound IV-2)
3 h) Obtained. Melting point: 177℃ FD mass spectrum: 184
, supporting the above structure.

Elemental analysis value (C, H12N, 0.) Calculated value (CH) C: 45.64 H: 6.57
N: 30.42 Actual value (ch) C: 45.48
H:, 6.51 NS, 30.60 Comparative example-
2 (4! Method described in Application No. 59-140246) 1.8
10.6 g of thiocarbohydrazide are suspended in 120 mA' of alcohol containing mol/l of hydrogen cyclization. A solution of 16.5 g of ethyl-2-chloroacetoacetate diluted with 20 d of alcohol was added dropwise over 20 minutes while keeping the internal temperature at 0.0 (±59° C.). Stir for 1 hour at the same temperature and stir for 1 hour while flowing backward. The reaction solution was treated in exactly the same manner as in Comparative Example-1 to obtain s, 6 g (46.7 g) of exemplified compound ff-2. The structure was supported by elemental analysis and FD mass spectra.

Comparative Example-3 (method described in Japanese Patent Application No. 59-140247)
Thiocarbohydrazide in 100+J alcohol 10.
Suspend 6g. Benzaldehyde 10.
A solution of 6 g diluted with 10*l of alcohol is added dropwise over 30 minutes. 30 minutes after the completion of dripping,
rioo acetoacetate 16.5g alcohol 10-
Add the diluted solution dropwise over 30 minutes. After dripping 3
After 0 minutes, the reaction solution was filtered to remove insoluble matter. - While stirring the solution again, add 100 thihydrazine hydrate 2
Add 5 g dropwise over 90 minutes. Thirty minutes after the completion of the dropwise addition, the alcohol was distilled off from the reaction solution under reduced pressure. Add 50 ml of acetonitrile to the residue, heat, and then allow to cool. The crystals were collected by F, washed with acetonitrile 25+Al, and then washed with 30%
Disperse in J water, wash the crystals again with 30 ml of F water, and air dry. The obtained crystals were recrystallized from methanol to give 10.1 g of ethyl-5-hydrazino-3-methylpyrazole-4-carboxylate (exemplified compound ■-2).
(ss, o%) obtained. Melting point 177°C FD mass spectrum and elemental analysis supported the above structure.

Comparative Example-4 Completely the same operation as Comparative Example-1 except that 19.3 g of ethyl-2-chloroisobutyl acetate was used in place of 16.5 g of ethyl-2-ria-acetoacetate used in Comparative Example-1. I did it.

Target ethyl-5-hydrazino-3-isopropylpyrazole-4-carboxylate (exemplary compound w -
11) Obtained 0.59 g (2.8%). melting point 16
0-161" OFD mass spectrum showed 212, supporting the above structure.

Elemental analysis value (Co HI6 N40!) Calculated value (Chi'
) C: 50.93 H near, 60 N: 26.
40 Actual value (*) c: 50.46 H: 7
．． 54 N: 26.83 Comparative Example-5 Ethyl-2-chloroacetoacetate used in Comparative Example-2
The same operation as in Comparative Example 2 was performed except that 19.3 g of ethyl-2-chloroinbutyl acetate was used instead of 16.5 g of ethyl-2-chloroinbutyl acetate. 2.88 g (13.6 g) of Exemplified Compound 1-11 was obtained. Melting point 160-161' OFD mass spectrum (212) supported the structure.

Comparative Example-6 Comparative Example-3 except that 16.5 g of ethyl-2-chloroacetoacetate used in Comparative Example-3 was replaced with 19.3 g of ethyl-2-chloroisobutylacetate, and recrystallized from toluene. The same operation was performed. Exemplary compound IT
-116.27g (29.7g) was obtained.

Melting point 160-161℃ FD mass spectrum (212)
supported the structure.

Comparative Example-7 20.7 g of ethyl-2-chloropivaloyl acetate was used instead of 16.5 g of ethyl-2-chloroacetoacetate used in Comparative Example-1, and column chromatography was performed instead of recrystallization from methanol. The operation was performed in exactly the same manner as in Comparative Example-1, except that the separation and purification was carried out.

Target ethyl-5-hydrazino-3-t-butylpyrazole-4-carboxylate (exemplary compound ■-5)
was not obtained.

Comparative Example-8 Comparative Example-2 except that 20.7 g of ethyl-2-chloropivaloyl acetate was used in place of 16.5 g of ethyl-2-chloroacetoacetate used in Comparative Example-2, and recrystallization was performed using toluene color. operated in the same way.

26 vxg (0.1%) of exemplary compound ff-5 was obtained. Melting point: 162° C. FD mass spectrum showed 226, supporting the structure.

Elemental analysis value (CiHra N40t) Calculated value (%)
C: 53.08 H: 8.02 N: 2
4.76 actual value (ch) C: 52.89 H near,
96 N: 24.88 Comparative Example-9 Ethyl-2-chloroacetoacetate used in Comparative Example-3
) The same procedure as in Comparative Example 3 was carried out, except that 20.7 g of ethyl-2-chloropivaloyl acetate was used instead of 16.5 g, and recrystallization was performed using toluene color.

Target exemplary compound IT 5 56+ag(0,2
arrogance). Melting point 162-163°C. FD mass spectrum (226) supported the structure.

Example-1 10.6 g of thiocarbohydrazide is suspended in 120+*l of alcohol. 10.6 g of benzaldehyde is added dropwise over 30 minutes while stirring at reflux. After completion of dripping, 30
After refluxing for a minute, it was cooled once and the internal temperature reached 19°C.
8 g of hydrochloric acid gas (hydrogen chloride) is dissolved in the reaction solution.

While stirring under reflux again, 16.5 g of ethyl-2-chloroacetoacetate was added dropwise over 30 minutes. 30 minutes after completion of dripping
After separating, the reaction solution is passed through to remove insoluble matter. While stirring the filtrate and refluxing it again, 35 g of 80'1 hydrazine hydrogen chloride was added dropwise over 90 minutes. After refluxing for 30 minutes, the alcohol was distilled off from the reaction solution under reduced pressure.

50 d of acetonitrile is added to the residue, heated and then allowed to cool. After removing the crystals and washing them with 25 ml of acetonitrile,
Disperse in 50 d of water, remove the crystals again, wash with 50 d of water, and air dry. The obtained crystals were recrystallized from methanol to give ethyl-5-hydrazino-3-methylpyrazole-4.
-16.0 g of carboxylate (exemplified compound ■-2)
(87chi) obtained. Melting point: 177° C. FD mass spectrum showed 184, supporting the above structure.

Example-2 10.6 g of thiocarbohydrazide is suspended in 120 ml of alcohol. 10.6 g of benzaldehyde is added dropwise over 30 minutes while stirring at reflux. After refluxing for 30 minutes, the mixture was cooled and when the internal temperature reached 19°C, 3.7 g of hydrochloric acid gas was dissolved in the reaction mixture. Keep the internal temperature at 50-60°C, 19.
3g of ethyl-2-chloroisobutyl acetate
Drip over several minutes. After stirring at the same temperature for 3 hours, the mixture was heated to reflux. After 30 minutes, the reaction solution was filtered to remove insoluble matter. F
While the liquid was refluxed and stirred again, 35 g of 80 thihydrazine hydrate was added dropwise over 90 minutes. After refluxing for 30 minutes, the alcohol was distilled off from the reaction solution under reduced pressure, and 50 ml of acetonitrile was added to the residue, heated and then allowed to cool. Take the crystal 25
- After washing with acetonitrile, disperse in 50 ml of water,
The crystals were collected again, washed with 50 ttdl of water, and air-dried.

The obtained crystals were recrystallized from toluene, and 16.1 g (76ts
) gain. An 8-point 160-161°C FD mass spectrum (212) supported the structure.

Example-3 120*l! 10.6 g of thiocarbohydrazide are suspended in alcohol. While stirring under reflux, 14.5 g of 2-chlorobenzaldehyde is added dropwise over 30 minutes. After refluxing for 30 minutes, the mixture was cooled and when the internal temperature reached 19° C., 5.5 g of hydrochloric acid gas was dissolved in the reaction mixture. While keeping the internal temperature at 50 to 60°C, 20.7 g of ethyl-2-chloropiparoyl acetate was added dropwise over 3 hours. After stirring at the same temperature for 3 hours, the mixture was heated to reflux. After 30 minutes, the reaction solution was passed through to remove insoluble matter. While stirring the F solution again, 40 g of 80
Add thihydrazine hydrate dropwise over 90 minutes. 30
After refluxing, the alcohol was distilled off under reduced pressure from the reaction solution, and 50 ml of acetonate was added to the residue, heated and allowed to cool. After removing the crystals and washing them with 25 ml of acetonitrile,
Disperse in so ml of water, take 7 crystals again and 50mA! Wash with water and air dry. The obtained crystals were recrystallized from toluene, and ethyl-5-hydrazino-3-t-butylpyrazole-4-carboxylate (exemplified compound 1-5) was dissolved in 1.
22 g (5.4 g) were obtained. Melting point 162-163℃
FD mass spectrum (226) supported the structure.

As is clear from the comparative examples and examples, the manufacturing method of the present invention has been described by Beyer et al.
er,), Vol. 89, p. 2552 (1956), and the synthesis method was of course improved, as well as the patent application filed in 1982.
This method is significantly improved compared to the synthesis methods described in No. 40246 and No. 59-140247, and it is possible to obtain 5-hydrazinopyrazole-4-carboxylate compounds in high yield. Among these, the effect of the invention (improvement in yield) is remarkable when R7 in the compound represented by the general formula [I] represents a secondary alkyl group or a tertiary alkyl group.

Claims (1)

[Scope of Claims] After reacting a thiocarbohydrazide with at least one compound represented by the following general formula [I] and/or [II], a compound represented by the following general formula [III] is reacted with an acid catalyst. A method for producing a 5-hydrazinopyrazole-4-carboxylate compound represented by the general formula [IV], which comprises reacting the compound with a nucleophilic reagent and then reacting with a nucleophilic reagent. General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ General formula [II] ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (In the formula, R_1 and R_2 are each a hydrogen atom, an alkyl group, an aryl group, or a heterocycle. represents a group, R_3 and R
_4 has the same meaning as R_1 and R_2, and R_5 and R_6 each represent an alkyl group having 1 to 4 carbon atoms. ) General formula [III] ▲ Numerical formulas, chemical formulas, tables, etc. are available▼ (In the formula, R_7 and R_8 each represent an alkyl group, an aryl group, or a heterocyclic group, and (Represents an oxy group.) General formula [IV] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_9 has the same meaning as R_7, and R_1_0 has the same meaning as R_6.)