JPH1112216A - Production of beta-hydroxycarbonyl compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound useful as an intermediate for synthesizing physiologically active substances by reacting an aldehyde compound with an enolether compound in the presence of a specific catalyst and a surfactant in water. SOLUTION: This method for producing a beta-hydroxycarbonyl compound comprises reacting 1 mole of an aldehyde of the formula: R<1> -CHO (R<1> is a hydrocarbon, an acyl, a heterocyclic group) with 0.9-1.5 moles of an enolether of the formula (R<2> is H, an alkyl, a cycloalkyl, an aralkyl, an aryl, an alkoxy, an alkylthio; R<3> , R<4> are each H, an alkyl, a cycloalkyl, an aralkyl, an aryl, an alkoxy; R<5> is a trialkylsilyl) in the presence of 0.01-0.2 mole of a scandium catalyst (preferably scandium triflate) and 0.001-0.5 mole of a surfactant (e.g. sodium dodecylsulfonate in water at a temperature of 0-40 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a β-hydroxycarbonyl compound useful as an intermediate for synthesizing a physiologically active substance.

[0002]

2. Description of the Related Art Hitherto, many methods have been reported for obtaining a β-hydroxycarbonyl compound by reacting an aldehyde with an enol ether in the presence of a Lewis acid catalyst. Above all, it is known that when a scandium triflate or lanthanoid triflate catalyst is used, a β-hydroxycarbonyl compound is produced even when water coexists in a water-soluble solvent.

[0003]

However, in the case of many Lewis acid catalysts, strict anhydrous conditions are required, and in the case of scandium catalysts and lanthanoid catalysts, it is necessary to recover and reuse complicated water-soluble solvents. Had a problem. Therefore, if water can be used as a solvent without using an organic solvent in order to enhance volumetric efficiency and prevent environmental pollution, it has great industrial significance.

[0004]

Means for Solving the Problems The present inventors diligently studied a reaction method for synthesizing a β-hydroxycarbonyl compound in an aqueous solvent, and found that a scandium triflate catalyst was used in the presence of a surfactant. As a result, it was found that the desired product could be obtained in good yield, and the present invention was completed.

That is, the present invention provides a compound represented by the general formula (1)

[0006]

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(Wherein R ¹ represents a hydrocarbon group, an acyl group or a heterocyclic group) [hereinafter referred to as aldehyde (1)] and a general formula (2)

[0008]

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(Wherein R ² represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkoxy group, or an alkylthio group, and R ³ and R ⁴ represent a hydrogen atom, an alkyl group, a cycloalkyl group, An aralkyl group, an aryl group, or an alkoxy group, and R ⁵ represents a trialkylsilyl group).
Enol ether (2)] in the presence of a scandium catalyst and a surfactant in water.

[0010]

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(Wherein R ¹ , R ² , R ³ and R ⁴ are as defined above) [hereinafter referred to as β-hydroxycarbonyl compound (3)] It relates to a manufacturing method.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula, examples of the hydrocarbon group represented by R ¹ include an alkyl group, a cycloalkyl group,
Examples thereof include an alkenyl group, an aralkyl group, and an aryl group. Examples of the alkyl group represented by R ¹ , R ² , R ³ and R ⁴ include a methyl group, an ethyl group, a propyl group, a butyl group,
t-butyl group, pentyl group, heptyl group and the like; cycloalkyl group includes cyclopentyl group, cyclohexyl group and cyclooctyl group; and aryl group includes phenyl group, naphthyl group, tetrahydronaphthyl group and the like. These are lower alkyl groups such as methyl group, ethyl group, t-butyl group, methoxy group,
It may be appropriately substituted with a lower alkoxy group such as a propoxy group, a halogen atom such as a fluorine atom, a chlorine atom and a bromine atom, a cyano group, a nitro group and the like. Examples of the aralkyl group include a benzyl group and a phenethyl group.

The alkenyl group represented by R ¹ includes a crotyl group, a prenyl group and a styryl group, and the heterocyclic group includes a furyl group, a thienyl group, a pyridyl group and an indolyl group. Examples of the acyl group include an acetyl group, a propionyl group, a butyryl group, and a benzoyl group.

The alkoxy groups represented by R ² , R ³ and R ⁴ include methoxy, ethoxy, propoxy, t
-Butoxy group and the like, and the alkylthio group represented by R ² includes a methylthio group, an ethylthio group, a t-butylthio group, a phenylthio group and the like.

The trialkylsilyl group represented by R ⁵ includes trimethylsilyl, t-butyldimethylsilyl, triethylsilyl and the like.

Examples of the surfactant include alkali metal salts of organic sulfonic acids such as sodium dodecyl sulfonate and sodium dodecyl benzene sulfonate, and polyethylene glycol 4- (1,1,3,3-tetramethylbutyl) phenyl ether. Are preferred.

As the scandium catalyst, halides, organic sulfonates and the like are used, and scandium triflate is particularly preferred.

The amount of the enol ether (2) used per mole of the aldehyde (1) is preferably from 0.9 to 1.5 moles, and the amount of the surfactant used per mole of the aldehyde (1) is from 0.001 to 0. The scandium catalyst is used in an amount of 0.05 mol per mol of the aldehyde (1).
It is preferably from 0.01 to 0.5 mol, more preferably from 0.01 to 0.2 mol.

Although the reaction is carried out in water, the presence of a small amount of an organic solvent does not affect the reaction.

The reaction is preferably carried out at a temperature in the range from 0 ° C. to 100 ° C., more preferably at a temperature in the range from 0 ° C. to 40 ° C.

The product can be isolated from the reaction solution by adding an ion-exchange resin to the reaction solution to remove the surfactant, and then adding an organic solvent to the reaction solution, extracting the reaction solution by steam distillation, or using a reaction solution. It can be easily carried out by a method in which water is distilled off and an organic solvent is added to the residue to extract the residue. The scandium catalyst recovered in the aqueous layer or as a concentrated residue can be used repeatedly for the reaction.

[0022]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention.

Example 1 0.5 mmol of benzaldehyde, 1-phenyl-1-
0.75 mmol of pullenyloxytrimethylsilane,
29 mg of sodium dodecylsulfonate and 25 mg of scandium triflate were stirred in 3 ml of water for 4 hours. Amberlyst IRA-93ZU [weakly basic anion exchange resin manufactured by Organo Co., Ltd.] was added and stirred for 30 minutes, followed by filtration, 15 ml of water and 15 ml of ethyl acetate.
ml was added for liquid separation. The aqueous layer was extracted with ethyl acetate, the organic layer was dried, concentrated, and then purified by silica gel chromatography to give 1,3-diphenyl-3-.
Hydroxy-2-methyl-1-propanone in 88% yield
I got it. The NMR of the product was consistent with the standard.

Example 2 0.5 mmol of benzaldehyde, 1-phenyl-1-
0.75 mmol of pullenyloxytrimethylsilane,
Polyethylene glycol 4- (1,1,3,3-tetramethylbutyl) phenyl ether 0.1 mmol and scandium triflate 25 mg in 3 ml of water 6
Stirred for 0 hours. 15 ml of ethyl acetate was added thereto to carry out liquid separation. The aqueous layer was extracted with ethyl acetate, the organic layer was dried, concentrated, and then purified by silica gel chromatography to give 1,3-diphenyl-3-hydroxy-2-methyl-1-propanone in a yield of 89%. Obtained. Product N
MR was consistent with the standard.

Examples 3 and 4 Example 1 was repeated except that in place of benzaldehyde, 0.5 mmol of 3-phenylpropionaldehyde or 0.5 mmol of cinnamaldehyde was used.
By carrying out the reaction and the post-treatment in the same manner as described above, 1,5-
Diphenyl-3-hydroxy-2-methyl-1-pentanone and 1,5-diphenyl-3-hydroxy-2-
86% each of methyl-4-penten-1-one, 8
Obtained in 8% yield.

Example 5 1-Phenyl-3 was obtained by performing the same reaction and post-treatment as in Example 1 except that 3 ml of an aqueous formalin solution was used instead of benzaldehyde and 50 mg of scandium triflate was used. -Hydroxy-2-methyl-1-propanone was obtained with a yield of 82%.

Examples 6 and 7 In Example 1, 0.75 mmol of 1-phenyl-1-propenyloxytrimethylsilane was used instead of 0.75 mmol of 1-phenyl-1-propenyloxytrimethylsilane.
1-phenyl-1-hydroxy-2-methyl by performing the reaction and the post-treatment in the same manner as in Example 1 except that 0.75 mmol of 0.7 mmol of 1-ethylthio-2-methyl-1-propenyloxytrimethylsilane was used. −
3-Pentanone and 2,2-dimethyl-3-hydroxy-3-phenylpropionic acid ethyl thiol ester were obtained in 88% and 94% yields, respectively.

Example 8 In Example 1, 0.75 mmol of 1-phenylethenyloxytrimethylsilane was used instead of 0.75 mmol of 1-phenyl-1-purenyloxytrimethylsilane.
1 and using 50 mg of scandium triflate, followed by reaction and post-treatment in the same manner as in Example 1 except that 0.75 mmol of 1-phenyl-1-pulpenyloxytrimethylsilane was further added after 6 hours. 1,3-Diphenyl-3-hydroxy-1-propanone was obtained in a yield of 75%.

Example 9 In Example 1, 0.75 mmol of 1-methoxy-2-methyl-1-propenyloxytrimethylsilane was used in place of 0.75 mmol of 1-phenyl-1-purenyloxytrimethylsilane, and After 6 hours, the reaction and the post-treatment were carried out in the same manner as in Example 1 except that 0.75 mmol of 1-methoxy-2-methyl-1-propenyloxytrimethylsilane was added, whereby 2,2-dimethyl-3-hydroxy- 3-Phenylpropionic acid methyl ester was obtained with a yield of 84%.

Example 10 In Example 1, 0.5 mmol of cinnamaldehyde was used instead of benzaldehyde, and 0.75 mm of 1-phenyl-1-purenyloxytrimethylsilane was used.
Example 1 except that 0.75 mmol of 1-ethyl-1-propenyloxytrimethylsilane was used instead of ol.
1-Phenyl-1-hydroxy-2-methyl-3-pentanone was obtained at a yield of 80% by carrying out the reaction and post-treatment in the same manner as in 1.

The results of Examples 1 to 10 are summarized in Table 1.

[0032]

[Table 1]

[0033]

The present invention provides a method for producing a β-hydroxycarbonyl compound in good yield without using an organic solvent.

Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 49/17 C07C 49/17 E 49/175 49/175 A 49/255 49/255 A 67/347 67/347 67/44 67/44 69/675 69/675 327/28 327/28 C07D 213/30 C07D 213/30 307/12 307/12 333/16 333/16 // C07B 61/00 300 C07B 61/00 300

Claims (1)

[Claims] 1. The following general formula (1): (Wherein, R ¹ represents a hydrocarbon group, an acyl group or a heterocyclic group) and an aldehyde represented by the general formula (2): (Wherein, R ² represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, an aryl group, an alkoxy group, or an alkylthio group, and R ³ and R ⁴ represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, Wherein R ⁵ represents an aryl group or an alkoxy group, and R ⁵ represents a trialkylsilyl group) in water in the presence of a scandium catalyst and a surfactant in the general formula (3). Embedded image (Wherein R ¹ , R ² , R ³ and R ⁴ are as defined above).