JPH05306276A - Production of ketopantolactone - Google Patents

Abstract

PURPOSE:To easily and safely obtain a ketopantolactone in high yield from a raw material easily available at a low cost. CONSTITUTION:A ketopantolactone is produced by oxidizing DL-pantolactone with dimethyl sulfoxide.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing dihydro-4,4-dimethyl-2,3-furanodione (hereinafter referred to as ketopantolactone). More details, D
L-dihydro-3-hydroxy-4,4-dimethyl-2
The present invention relates to a method for producing ketopantolactone by oxidizing (3H) -furanone (hereinafter referred to as DL-pantolactone) with dimethyl sulfoxide.

[0002]

D-pantolactone is an important precursor substance for pharmaceuticals such as calcium pantothenate. D-pantolactone can be obtained by optical resolution of DL-pantolactone, but this method is technically difficult and economically disadvantageous. On the other hand, there are many techniques for selectively synthesizing D-pantolactone by asymmetric hydrogenation of ketopantolactone (JP-A-54-70257 and JP-A-57-18109).
No. 3, etc.). Therefore, D-pantolactone can be easily obtained by oxidizing DL-pantolactone, converting it to ketopantolactone, and then performing asymmetric reduction. From the above viewpoint, it can be said that the technology for producing ketopantolactone by oxidizing DL-pantolactone has a very important industrial significance.

As a method for producing ketopantolactone by oxidizing DL-pantolactone, a method of oxidizing with halogen such as chlorine or bromine (JP-A-59-10).
6479), oxygen oxidation using Ru and Pd as catalysts (JP-A-58-126880) and electrode oxidation (JP-A-1-208488),
A method of oxidizing microorganisms (Japanese Patent Laid-Open No. 187426/1987) can be used.

However, there are the following problems. That is, in the method of 1, halogen is highly toxic and poses a safety problem. The method (1) is economically disadvantageous because the catalyst used is expensive. Further, especially in the case of oxygen oxidation, it is necessary to blow oxygen at a high temperature, which is a safety problem. With this method, scale-up is difficult and is industrially disadvantageous.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have used dimethyl sulfoxide, which is inexpensive and easily available, at room temperature or below,
It was found that by oxidizing DL-pantolactone, ketopantolactone can be obtained safely and conveniently in high yield.

[0006]

The method of the present invention is a DL-
This is a process for obtaining ketopantolactone by oxidizing pantolactone with dimethyl sulfoxide.

In the method of the present invention, as an activator of dimethyl sulfoxide, oxalyl chloride, acetic anhydride, trifluoroacetic anhydride, dicyclohexylcarbodiimide, diphosphorus pentoxide, sulfur trioxide-pyridine complex, chlorine, halogenated organic acid, It is preferable to oxidize in the presence of halogenated sulfonic acid, thionyl chloride, phosphorus trioxide, oxophosphorus trichloride, uranul chloride, etc. The amount used varies depending on the kind of the activator, but 1 to 20 equivalents are appropriate ..

In the method of the present invention, a base is used as a deoxidizing agent, and a tertiary amine having a large steric hindrance is particularly suitable, and triethylamine, isopropylethylamine, pyridine or the like can be used. The amount used is appropriately 1 to 5 equivalents.

In the method of the present invention, an auxiliary solvent may or may not be used, but when it is used, dichloromethane, toluene or the like is particularly preferable.

The reaction can be carried out in the range of -78 ° C to 50 ° C, but it is particularly preferably carried out at -50 ° C to room temperature.
The reaction is completed in 30 minutes to 24 hours.

[0011]

EXAMPLES Examples will be shown below. Example 1 In a 50 ml three-necked flask, 1.0 ml of oxalyl chloride (1
15 ml of a dichloromethane solution containing 1 mmol) was added, and -6
Cooled to 0 ° C. Dimethylsulfoxide 1.7 with stirring
5 ml of a dichloromethane solution containing ml (22 mmol) was added dropwise. Then DL-pantolactone 1.30 g (10 mmo
10 ml of a dichloromethane solution containing 1) was added dropwise over 5 minutes, and the mixture was stirred for 15 minutes after the addition. Further, 7.0 ml (50 mmol) of triethylamine was added, and the mixture was stirred for 5 minutes and then heated to room temperature to obtain 96.3% of ketopantolactone (GC analysis value).

Example 2 DL-pantolactone 1.0 was added to a 50 ml three-necked flask.
0 g (7.7 mmol), 10 ml of distilled acetic anhydride (106
mmol) and 15 ml (211 mmol) of dimethyl sulfoxide, and the mixture is stirred at room temperature for 20 hours to give ketopantolactone 8
1.4% (GC analysis value) was obtained.

Example 3 A 50 ml three-necked flask was charged with dimethyl sulfoxide 14.
10 ml of a dichloromethane solution containing 2 ml (200 mmol) was added and cooled to -50 ° C. With stirring, 5 ml of a dichloromethane solution containing 14.1 ml (100 mmol) of trifluoroacetic anhydride was added dropwise over 10 minutes, and after the addition, the mixture was stirred for 10 minutes.
Subsequently, 5 ml of a dichloromethane solution containing 1.30 g (10 mmol) of DL-pantolactone was added dropwise over 10 minutes, and the mixture was stirred for 30 minutes after the addition. Then 4 ml of triethylamine
(30 mmol) was added dropwise over 10 minutes, the temperature was raised to room temperature over 1 hour after the addition, and the mixture was stirred for 1 hour to obtain 82.6% ketopantolactone (GC analysis value).

[0014]

EFFECT OF THE INVENTION According to the method of the present invention, ketopantolactone can be obtained safely and simply in high yield using inexpensive and easily available raw materials.

Claims (2)

[Claims] 1. DL-dihydro-3-hydroxy-4,
Dihydro-4,4, characterized in that 4-dimethyl-2 (3H) -furanone is oxidized with dimethylsulfoxide.
-Method for producing dimethyl-2,3-furanodione. 2. The method according to claim 1, wherein oxalyl chloride, acetic anhydride, or trifluoroacetic anhydride is used as the activator of dimethyl sulfoxide.