JPH05320136A - Synthesis of 4-hydroxymethylpyrazoles - Google Patents

Abstract

PURPOSE:To easily obtain a 4-hydroxymethylpyrazole compound as a raw material for timing group for photographic coupler or intermediates for various organic syntheses simply by reacting a specific pyrazole derivative with a ketone or an aldehyde in the presence of a base. CONSTITUTION:The 4-hydroxymethylpyrazole compound of formula III (e.g. the compound of formula III wherein R<1> and R<2> are CH3 and R<3> and R<4> are H) can be produced simply by reacting a compound of formula I (R<1> and R<2> are H, alkyl or aryl, preferably <=3C unsubstituted alkyl) with a compound of formula II (R<3> and R<4> are H, alkyl or aryl, especially independently H or methyl, preferably both R<3> and R<4> are H) in the presence of a base (especially preferably NaOH, KOH or Ca(OH)2) at about 30-80 deg.C.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for synthesizing 4-hydroxymethylpyrazoles which are useful as raw materials for useful timing groups of photographic couplers and as intermediates for various organic syntheses.

[0002]

2. Description of the Related Art Japanese Patent Application No. 3-43008 discloses that photographic couplers derived from 4-hydroxymethylpyrazoles such as 3,5-dimethyl-4-hydroxymethylpyrazole exhibit excellent photographic performance. It is written.
However, for example, with respect to 3,5-dimethyl-4-hydroxymethylpyrazole, as a synthetic method thereof, there is a method published by I. Dvoretzky et al. In 1950 (J. Org. Chem., Vol. 15, p. 1285, 1950).
There are two synthetic methods shown there. The first is to reduce the ester with LiAlH ₄ as shown in scheme 1.

[0003]

[Chemical 4]

Since this method uses LiAlH ₄ having a high ignitability, it is extremely dangerous and unsuitable for application to mass synthesis. The other method is to synthesize the N-methylol derivative of pyrazole as shown in Scheme 2, hydroxymethyl the 4-position for another 1 week, and then remove the hydroxymethyl group on N. It is a thing.

[0005]

[Chemical 5]

In this method, there are problems that three steps are required for the synthesis, the reaction takes one week in the second step, and the yield is as low as 24%.

[0007]

An object of the present invention is to propose a simple synthetic method for 4-hydroxymethylpyrazoles.

[0008]

The object of the present invention is represented by the general formula (III) by reacting a compound represented by the general formula (I) with a compound represented by the general formula (II) in the presence of a base. This was accomplished by a method of synthesizing 4-hydroxymethylpyrazoles to synthesize compounds.

[0009]

[Chemical 6]

(In the formula, R ¹ and R ² each independently represent a hydrogen atom, an alkyl group or an aryl group.)

[0011]

[Chemical 7]

(In the formula, R ³ and R ⁴ each independently represent a hydrogen atom, an alkyl group or an aryl group.)

[0013]

[Chemical 8]

(In the formula, R ¹ , R ² , R ³ and R ⁴ have the same meanings as those in the general formulas I and II.)

The compound represented by formula (I) will be described. R ¹ and R ² are each independently a hydrogen atom, a substituted or unsubstituted alkyl group (methyl, ethyl, tert-
Butyl, decyl, benzyl, etc.) or a substituted or unsubstituted aryl group (phenyl, etc.). Examples of the substituent include an alkyl group, an aryl group, a halogen atom, an alkoxy group, an aryloxy group, a carbamoyl group, an acylamino group, an alkylthio group, an arylthio group, a cyano group and a nitro group. R ¹ and R ² are preferably groups other than hydrogen atoms, more preferably alkyl groups having 6 or less carbon atoms or phenyl groups, and particularly preferably unsubstituted alkyl groups having 3 or less carbon atoms. Is the case.

Next, the compound represented by the general formula (II) will be described. R ³ and R ⁴ are each independently a hydrogen atom,
Represents an alkyl group (methyl, ethyl, isobutyl, etc.) or an aryl group (phenyl, etc.). R ³ and R ₄ are preferably a case where at least one of both represents a hydrogen atom, more preferably R ³ or R ⁴ independently represents a hydrogen atom or a methyl group, and particularly preferably R ³ And R ⁴ both represent a hydrogen atom. Tables 1 and 2 show typical examples of the compound represented by the general formula (II).

[0017]

[Table 1]

[0018]

[Table 2]

The base used in the reaction is
Alkali metal or alkaline earth metal hydroxides,
Metal alkoxides such as thorium methoxide,
Liethylamine, 2,6-lutidine, 1,8-diazabi
Organic bases such as cyclo [5,4,0] -7-undecene
Etc. can be used. Of these, preferably
LiOH, NaOH, KOH, Ca (OH)₂, NaOCH₃Or NaOC ₂H_Five
And particularly preferably NaOH, KOH or Ca (OH)₂so
is there.

Regarding the molar ratio of the reaction, the compound represented by the general formula (II) is used in a molar ratio of 0.5 to 10 times that of the compound represented by the general formula (I). Preferably 0.8
To 3.0, more preferably 0.9 to 2.0.
The range is. The molar ratio of the base to the compound represented by the general formula (I) is used in the range of 0.1 to 3.0, preferably 0.5 to 2.0, more preferably 0.8.
The range is from 1.5 to 1.5.

As the reaction solvent, water, alcohol (methanol, ethanol, isopropyl alcohol, etc.), ether (tetrahydrofuran, 1,4-dioxane, etc.), aprotic polar solvent (N, N-dimethylformamide, dimethylsulfoxide, acetonitrile, etc.) ), A halogen-based solvent (1,2-dichloroethane, methylene chloride, chlorobenzene, etc.), a hydrocarbon-based solvent (hexane, benzene, toluene, etc.), and the like can be used. Moreover, you may use these reaction solvents in mixture of 2 or more types.

The reaction is carried out by mixing the compounds represented by the general formulas (I) and (II) in a suitable solvent and heating with stirring. The reaction temperature is generally 0 ° C to 120 ° C, preferably 20 ° C to 100 ° C, more preferably 3 ° C.
It is between 0 ° C and 80 ° C. Reaction time is usually 10 minutes to 1
It is carried out in the range of 0 hours, and particularly in the range of 30 minutes to 5 hours. As the post-treatment of the experiment, it is often the case that the reaction product is cooled after completion of the reaction and the precipitated crystals are collected by filtration to obtain an almost pure target product. In some cases, the target

The desired product may be isolated as crystals by extracting and concentrating and adding a suitable solvent, or when the residue obtained by concentrating is purified by a silica gel or alumina column to isolate the desired product. There is also. It can also be purified by distillation. Specific examples of the compound represented by formula (III) of the present invention are shown below, but the present invention is not limited thereto.

[0024]

[Table 3]

[0025]

[Table 4]

[0026]

[Table 5]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited thereto.

Example 1 Synthesis of Exemplified Compound (III-1)

[0029]

[Chemical 9]

III-1a (100 g) was added to NaOH (48 g)
Was added to an aqueous solution (400 ml). 37% there
Add formalin aqueous solution (112 ml) and heat to 50 ° C. 2
Reacted for hours. Thereafter, the reaction solution was cooled to room temperature, and the precipitated crystals were collected by filtration, washed with isopropyl alcohol, and dried to give 59 g (46 g) of Exemplified Compound (III-1).
% Yield) was obtained. m. p. 177.5-179.0 ° C.

Example 2 Synthesis of Exemplified Compound (III-3) III-3 could be synthesized in the same manner as in Example 1. Yield 36%.

Claims (1)

[Claims] 1. 4-Hydroxymethylpyrazoles for synthesizing a compound represented by the general formula (III) by reacting a compound represented by the general formula (I) with a compound represented by the general formula (II) in the presence of a base. Method of synthesis. [Chemical 1] (In the formula, R ¹ and R ² each independently represent a hydrogen atom, an alkyl group, or an aryl group.) (In the formula, R ³ and R ⁴ each independently represent a hydrogen atom, an alkyl group or an aryl group.) (In the formula, R ¹ , R ² , R ³ and R ⁴ have the same meanings as those in formulas I and II.)