JP2002161085A - Method for producing 5,5-dimethyloxazolidine-2,4-dione - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially advantageous method for producing 5,5- dimethyloxazolidine-2,4-dione; specifically, to provide an industrially advantageous method for producing 5,5-dimethyloxazolidine-2,4-dione by the use of acetone cyanohydrin as the starting material. SOLUTION: This method for producing 5,5-dimethyloxazolidine-2,4-dione is characterized by comprising a reaction between α-hydroxyisobutyramide, a di-lower alkyl carbonate and an alkali metal alcoholate to form a 5,5- dimethyloxazolidine-2,4-dione alkali metal salt followed by neutralizing it with a mineral acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a 5,5-dimethyloxazolidine-2,4 useful as a photographic drug intermediate.
It relates to a method for producing diones

[0002]

2. Description of the Related Art As a method for producing 2,4-oxazolidinediones, α-hydroxycarboxylic acid esters or α-hydroxycarboxylic acid amides and urea are used in an amount of 100 to 100%.
A method in which the reaction is carried out at a temperature of 250 ° C. (JP-A-09-048)
No. 769) is known.

However, the production of α-hydroxycarboxylic acid esters requires the use of expensive dry hydrochloric acid when using cyanohydrin as a raw material, which is not an industrially advantageous method. In addition, when the corresponding α-hydroxycarboxylic acid amide is used as a raw material, the process becomes longer, which is not an industrially advantageous method. Further, in the reaction of α-hydroxycarboxylic acid amides with urea, the yield of 2,4-oxazolidinediones is extremely low and not at a level that can be industrially carried out.

As another method, a method of reacting an α-hydroxycarboxylic acid ester with an alkali cyanate (Japanese Patent Laid-Open No. 54-130564) is known. When -dimethyloxazolidine-2,4-dione is synthesized, the yield is extremely low and not industrial.

[0005] In addition, a method of reacting an α-hydroxycarboxylic acid ester with a carbonic acid ester (Japanese Patent Application Laid-Open No.
No. 130564), which is an industrially disadvantageous method because an α-hydroxycarboxylic acid ester is used as a raw material as described above.

[0006]

The objects of the present invention are:
It is to produce 5-dimethyloxazolidine-2,4-dione by an industrially advantageous method. Specifically, it is to produce 5,5-dimethyloxazolidine-2,4-dione using acetone cyanohydrin as a starting material by an industrially advantageous method.

[0007]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have developed a novel process for producing 5,5-dimethyloxazolidine-2,4-dione from acetone cyanohydrin. As a result, the present invention has been completed.

That is, the present invention relates to the following items.

(1) Equation (1),

Embedded image Is reacted with α-hydroxyisobutyric acid amide, di-lower alkyl carbonate, and an alcoholate of an alkali metal represented by the formula (2):

Embedded image (Where M represents an alkali metal)
Formula (3), wherein an alkali metal salt of 5-dimethyloxazolidine-2,4-dione is obtained, and then neutralized with a mineral acid.

Embedded image 5,5-dimethyloxazolidine-2,4- represented by
Zion production method.

(2) The 5,5-dimethyloxazolidine- (1) according to (1), wherein the di-lower alkyl carbonate is dimethyl carbonate.
A method for producing 2,4-dione.

(3) The alkali metal alcoholate of (1) or (2), wherein the alkali metal alcoholate is sodium alcoholate.
A method for producing 5-dimethyloxazolidine-2,4-dione.

(4) The sodium alcoholate is sodium methoxide or sodium ethoxide, and the (5) -dimethyloxazolidine-
A method for producing 2,4-dione.

(5) α-hydroxyisobutyric acid amide having a water content of 3% by mass or less is used.
-A process for producing dimethyl oxazolidin-2,4-dione.

(6) α-hydroxyisobutyric acid amide from which the solvent and water have been removed in a molten state at 80 ° C. or higher, using the 5,5-dimethyloxazolidine- (1)-(5).
A method for producing 2,4-dione.

(7) α from which water has been removed by azeotropic distillation
-Use of hydroxyisobutyric acid amide (1) to (6)
For producing 5,5-dimethyloxazolidine-2,4-dione.

(8) The α-hydroxyisobutyramide obtained by hydrating acetone cyanohydrin is used.
A method for producing 2,4-dione.

(9) Manganese dioxide is used as a catalyst for the hydration reaction.
A method for producing 2,4-dione.

(10) The equivalent ratio of α-hydroxyisobutyric acid amide, dialkyl carbonate and alcoholate of alkali metal is 1: 1.1-1.5: 1.1-1.5. 5,5-dimethyloxazolidine-
A method for producing 2,4-dione.

(11) After mixing α-hydroxyisobutyric acid amide and dialkyl carbonate, an alkali metal alcoholate is added and reacted.
0) The method for producing 5,5-dimethyloxazolidine-2,4-dione.

(12) The water content in the raw material solution before the addition of the alkali metal alcoholate is 2% by mass or less.
The method for producing 5,5-dimethyloxazolidine-2,4-dione of 1).

(13) The method for producing 5,5-dimethyloxazolidine-2,4-dione according to any one of (1) to (12), wherein crystallization is performed after neutralization with a mineral acid.

(14) The method according to (13), wherein the crystallization is performed in the presence of an inorganic salt.

(15) 5,5-dimethyloxazolidine-2, which is crystallized in the presence of an inorganic salt.
A method for purifying 4-dione.

[0024]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The details of the present invention will be described below.

The α-hydroxyisobutyric acid amide used as a raw material of the present invention can be produced by a known method, and the production method is not limited. Preferably, it is produced by hydrating acetone cyanohydrin. This hydration reaction proceeds in high yield in the presence of a manganese dioxide catalyst. The amount of water used for the hydration reaction is 2 parts of acetone cyanohydrin.
It is necessary to use at least mass times. More preferably 4
Higher purity α can be achieved by using more than twice the mass of water.
-Hydroxyisobutyric acid amide can be obtained. The upper limit is not particularly limited in terms of the reaction unless the condition is extremely dilute, but it is preferably 6 times or less in view of productivity.

Although the purity of the α-hydroxyisobutyric amide of the present invention may be industrial quality, it is preferable to use one having as low a water content as possible. The water content is desirably 3% by mass or less, more preferably 1% by mass or less. If the water content is high, the yield of 5,5-dimethyloxazolidine-2,4-dione is greatly reduced, which is industrially disadvantageous.

In order to obtain α-hydroxyisobutyric acid amide having a low water content, it is possible to obtain α-hydroxyisobutyric acid amide by wet distillation by crystallization or by crystallization. This is industrially disadvantageous. By heating the aqueous solution of α-hydroxyisobutyric amide obtained by the hydration reaction and evaporating the water, it is possible to industrially advantageously obtain α-hydroxyisobutyric acid amide having a low water content. Heating temperature is over 80 ℃,
Preferably, it is performed at 90 ° C. or higher. When the temperature is lower than 80 ° C., α-hydroxyisobutyric acid amide is solidified, which is a serious problem in the process.

Evaporation efficiency can be improved by evaporating water under reduced pressure. However, care must be taken so that the product temperature is reduced by the reduced pressure and α-hydroxyisobutyric acid amide does not solidify.

The dewatering efficiency can be improved by blowing an inert gas such as nitrogen or air and adding a solvent which forms an azeotrope with water, such as toluene and ethanol.

The equivalent ratio of α-hydroxyisobutyric acid amide, di-lower alkyl carbonate and alkali metal alcoholate is preferably from 1: 1.1 to 1.5: 1.1 to 1.5. If the equivalent ratio of the dialkyl lower carbonate and the alcoholate of the alkali metal is lower than 1.1, the yield of 5,5-dimethyloxazolidine-2,4-dione relative to α-hydroxyisobutyric acid amide decreases, and 1: 1.5. Even with the above, the yield is hardly improved, the raw material cost is increased, and this is industrially disadvantageous.

The α-hydroxyisobutyric acid amide of the present invention,
As a method for charging the di-lower alkyl carbonate and the alcoholate of the alkali metal, it is preferable to mix the α-hydroxyisobutyric acid amide and the di-lower alkyl carbonate and then drop the alcoholate of the alkali metal. Further, it is preferable that the water content of the target liquid to which the alkali metal alcoholate is added is 2% by mass or less. When the water content is 2% by mass or more, the reaction yield decreases, which is industrially disadvantageous.

In the reaction, a solvent can be used. The solvent is not particularly limited, but alcohols such as methanol and ethanol are preferred.

As the alkali metal alcoholate of the present invention, sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like can be used, and sodium methoxide is particularly preferable.

As the di-lower alkyl carbonate of the present invention, dimethyl carbonate, diethyl carbonate, dipropyl carbonate and the like can be used, and dimethyl carbonate is preferred.

The acid used for the neutralization of the present invention is 5,5-dimethyloxazolidine-2,4- obtained by the reaction.
Used to neutralize dione alkali metal salts. There are no particular restrictions on the type of acid, but industrially inexpensive mineral acids such as sulfuric acid, hydrochloric acid, and nitric acid are advantageous. Neutralization is pH 4 or less,
Preferably it is 2-3. When the pH is high, the abundance as an alkali metal salt becomes high, and the pH, 5,5-
Dimethyloxazolidine-2,4-dione recovery rate is reduced. On the other hand, if it is too low, a special material is required, which is industrially disadvantageous.

The 5,5-dimethyloxazolidine-2,4-dione obtained according to the present invention can be purified by distillation, crystallization and the like. Since the boiling point is high, the distillation is preferably performed by distillation under reduced pressure.

In the case of purification by crystallization, after dissolving in a good solvent such as ethyl acetate, hexane or the like, which is a poor solvent, is added, or an aqueous salt solution such as sodium chloride, sodium nitrate or ammonium sulfate is added to the crystallization solvent. It can be implemented by cooling.

[0038]

EXAMPLES Hereinafter, the method of the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples.

In the following examples, the quantification of organic components was performed by liquid chromatography. The conditions are as follows. <Liquid chromatography analysis conditions> Column: Shodex KC-811 (manufactured by Showa Denko KK) Eluent: 0.02 mass% phosphoric acid Flow rate: 1.0 ml Column temperature: 40 ° C

<Example 1> Acetone cyanohydrin 85
g was reacted with water at 5 times the mass of acetone cyanohydrin at 60 ° C. in the presence of a manganese dioxide catalyst. Α in the reaction solution
-Hydroxyisobutyric acid amide was determined.
3 g. This reaction solution was filtered with filter paper (No. 5C) to remove the catalyst. Subsequently, the filtrate was transferred to a four-necked flask, the bath temperature was increased to 130 ° C., and water was evaporated.
When the product temperature rose to 120 ° C., the heating was terminated. When the remaining liquid in the kettle was weighed, it was 90.0 g and the α-hydroxyisobutyric acid amide content was 91% by mass. The water content was measured by the Karl Fischer method and found to be 0.9% by mass. The time required for the water to evaporate was 3 hours.

<Example 2> α obtained in the same manner as in Example 1
-Hydroxyisobutyric acid amide reaction solution is 88 kPaabs
Water evaporation was carried out under the same conditions as in Example 1 except that the pressure was set to. When the remaining liquid in the kettle was weighed, 89.3 g was obtained.
The α-hydroxyisobutyric acid amide content was 92% by mass. The water content was measured by the Karl Fischer method and was found to be 0.7% by mass. The time required for the water to evaporate was 2 hours.

Example 3 α obtained in the same manner as in Example 1
Water was evaporated from the -hydroxyisobutyric acid amide reaction solution under the same conditions as in Example 1. When the product temperature rose to 105 ° C, 15 g of toluene as an azeotropic agent was added, and heating was further continued.
When the product temperature rose to 115 ° C., the heating was terminated. When the remaining liquid in the kettle was weighed, it was 89.5 g and the α-hydroxyisobutyric acid amide content was 92% by mass. The water content was measured by the Karl Fischer method and found to be 0.6% by mass. The time required for the water to evaporate was 2 hours.

Example 4 80 g (0.94 mol) of α-hydroxyisobutyric acid amide of Example 1 was treated with methanol 40
g (1.25 mol) and dissolved.
1.5 g (1.12 mol) were added at room temperature with stirring. At this time, a portion was sampled, and the water content was measured. As a result, it was 0.5% by mass. Subsequently, 235.7 g of a 28% methanol solution of sodium methoxide (1.22 g)
Mol) was added over 30 minutes. Here, the equivalent ratio of charged α-hydroxyisobutyric acid amide to dimethyl carbonate and sodium methoxide is 1: 1.3: 1.3. After the addition,
The mixture was heated until a reflux state was reached, and the reaction was performed for 2 hours. After the reaction, 5,5-dimethyloxazolidine-2,
It was 130.6 g when 4-dione sodium salt was quantified.
(0.86 mol). 5,5-Dimethyloxazolidine-2,4 against α-hydroxyisobutyric acid amide
The reaction yield of -dione sodium salt was 92%.

<Example 5> Using α-hydroxyisobutyric acid amide prepared in Example 2 as a raw material, synthesis of 5,5-dimethyloxazolidine-2,4-dione sodium salt was carried out under the same conditions. The reaction yield of sodium 5,5-dimethyloxazolidine-2,4-dione with respect to hydroxyisobutyric acid amide was 93%.

<Example 6> Using α-hydroxyisobutyric acid amide prepared in Example 3 as a raw material, synthesis of 5,5-dimethyloxazolidine-2,4-dione sodium salt was performed under the same conditions. The reaction yield of 5,5-dimethyloxazolidine-2,4-dione sodium salt with respect to hydroxyisobutyric acid amide was 92%.

Example 7 The reaction solution obtained by the method of Example 4 was transferred to an eggplant-shaped flask, and concentrated at 50 ° C. under reduced pressure using a rotary evaporator until the liquid volume became half. The concentrated solution was adjusted to pH 2.7 with 20% by mass sulfuric acid. This solution was again concentrated by a rotary evaporator until the concentration of the glass nitrate became 21% by mass. Subsequently, water was added so that the concentration of glass nitrate became 12%. After the addition, the mixture was cooled to 23 ° C. with stirring to perform crystallization. When the crystals were separated by centrifugation, 80 g of wet crystals could be obtained. When this crystal was analyzed, the content of 5,5-dimethyloxazolidine-2,4-dione in terms of solid content was 97% by mass.
Met. The yield through neutralization and crystallization was 70%.

Example 8 The reaction solution obtained by the method of Example 5 was transferred to an eggplant-shaped flask, and concentrated at 50 ° C. under reduced pressure using a rotary evaporator until the liquid volume became half. The concentrated solution was adjusted to pH 2.7 with 20% hydrochloric acid. This solution was again rotary-evaporated to a salt concentration of 2
Concentrated to 0%. After concentration, with stirring, 15
After cooling to ℃, crystallization was performed. When the crystals were separated by centrifugation, 91 g of wet crystals could be obtained. When this crystal was analyzed, the 5,5-dimethyloxazolidine-2,4-dione content in terms of solid content was 96.8% by mass.
The yield through neutralization and crystallization was 80%.

Example 9 The reaction solution obtained by the method of Example 4 was transferred to an eggplant-shaped flask, and concentrated at 50 ° C. under reduced pressure using a rotary evaporator until the liquid volume became half. The concentrated solution was adjusted to pH 2.7 with 20% by mass sulfuric acid. This solution was again concentrated by a rotary evaporator until the concentration of oxalate became 21% by mass, and allowed to stand. Then, the solution was separated into two layers. Analysis of both layers indicated that 97% of the 5,5-dimethyloxazolidine-2,4-dione had been distributed to the upper layer. The upper layer was separated by a separating funnel, and a 35% by mass aqueous solution of ammonium sulfate twice as large as the main solution was added. After the addition, the mixture was cooled to 15 ° C. with stirring to perform crystallization. When the crystals were separated by centrifugation, 121 g of wet crystals could be obtained. Analysis of this crystal showed that the content of 5,5-dimethyloxazolidine-2,4-dione was 97% by mass. The yield through neutralization and crystallization was 90%.

Example 10 The reaction solution obtained by the method of Example 6 was transferred to an eggplant-shaped flask, and concentrated at 50 ° C. under reduced pressure using a rotary evaporator until the liquid volume became half. The concentrated solution was adjusted to pH 7.5 with 10% by mass sulfuric acid. This solution was again concentrated using a rotary evaporator until the concentration of the glass nitrate became 10% by mass. Subsequently, water was added so that the glass nitrate concentration was 5.1% by mass. 23 after addition
When 98% sulfuric acid was added to pH 2.8 while maintaining the temperature at 0 ° C and stirring, crystals were precipitated. When the crystals were separated by centrifugation, 81 g of wet crystals could be obtained. Analysis of this crystal revealed that 5,5-dimethyloxazolidine-2,
The 4-dione content was 97.2% by weight. The yield through neutralization and crystallization was 71%.

Example 11 Acetone cyanohydrin 8
5 g was reacted with 5 times the amount of water of acetone cyanohydrin at 60 ° C. in the presence of a manganese dioxide catalyst. Α in the reaction solution
-Hydroxyisobutyric acid amide was determined.
3 g. This reaction solution was filtered with filter paper (No. 5C) to remove the catalyst. Subsequently, the filtrate was transferred to a four-necked flask, the bath temperature was increased to 130 ° C., and water was evaporated.
When the product temperature rose to 110 ° C., the heating was terminated. When the remaining liquid in the kettle was weighed, it was 92.0 g and the α-hydroxyisobutyric acid amide content was 89% by mass. The water content measured by the Karl Fischer method was 3.1% by mass. The time required for the water to evaporate was 2 hours. The reaction was conducted under the same conditions as in Example 4 except that α-hydroxyisobutyric acid amide having a water content of 3.1% by mass was used.
The yield of α-hydroxyisobutyramide of dione sodium salt was 75%.

Example 12 A reaction was carried out under the same conditions as in Example 4 except that the equivalent ratio of α-hydroxyisobutyric acid amide to dimethyl carbonate and sodium methoxide was 1: 1.05: 1.05. However, the yield of α-hydroxyisobutyric acid amide with respect to 5,5-dimethyloxazolidine-2,4-dione sodium salt was 75%.

Example 13 To 80 g (0.94 mol) of α-hydroxyisobutyric acid amide of Example 1 was added methanol 4
0 g (1.25 mol) was added and dissolved.
1.5 g (1.12 mol) were added at room temperature with stirring. At this time, pure water was added so that the water content in the system became 2.5% by mass. Subsequently, sodium methoxide 2
235.7 g (1.22 mol) of an 8% by mass methanol solution
Was added over 30 minutes. After the addition, the mixture was heated to a reflux state and reacted for 2 hours. 5, in the reaction solution
The amount of 5-dimethyloxazolidine-2,4-dione sodium salt was determined to be 112.9 g (0.86 mol). 78% yield of α-hydroxyisobutyric acid amide relative to
Met.

[0053]

Industrial Applicability According to the present invention, 5,5-dimethyloxazolidine is obtained by using acetone cyanohydrin as a starting material.
2,4-dione can be produced industrially advantageously.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Takamitsu Uzukihara 2-3-3 Chidori-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa Prefecture Inside the Showa Denko KK Kawasaki Production and Engineering Division (72) Inventor Shin Saito Kawasaki-shi, Kanagawa 2-3, Chidori-cho, Kawasaki-ku Showa Denko Co., Ltd. Kawasaki Production & Engineering Division F-term (reference) 4C056 AA01 AB01 AC02 AD01 AE03 AF01 BB08 BC01

Claims (15)

[Claims] (1) Formula (1): Is reacted with α-hydroxyisobutyric acid amide, di-lower alkyl carbonate and an alkali metal alcoholate represented by the formula (2), (Where M represents an alkali metal)
Formula (3), wherein an alkali metal salt of 5-dimethyloxazolidine-2,4-dione is obtained and then neutralized with a mineral acid. 5,5-dimethyloxazolidine-2,4- represented by
Zion production method. 2. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to claim 1, wherein the di-lower alkyl carbonate is dimethyl carbonate. 3. The method according to claim 1, wherein the alkali metal alcoholate is sodium alcoholate.
-A process for producing dimethyl oxazolidin-2,4-dione. 4. The method according to claim 1, wherein the sodium alcoholate is sodium methoxide or sodium ethoxide.
4. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to any one of claims 1 to 3. 5. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to claim 1, wherein α-hydroxyisobutyramide having a water content of 3% by mass or less is used. 6. The method according to claim 1, wherein α-hydroxyisobutyric acid amide from which the solvent and water have been removed in a molten state at 80 ° C. or higher is used. Production method. 7. The 5,5-dimethyloxazolidine-2,4 according to claim 1, wherein α-hydroxyisobutyramide from which water has been removed by azeotropic distillation is used.
-A process for the production of Zeon. 8. The method according to claim 1, wherein α-hydroxyisobutyramide obtained by hydrating acetone cyanohydrin is used.
8. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to any one of claims 1 to 7. 9. The 5,5-dimethyloxazolidine- according to claim 8, wherein manganese dioxide is used as a catalyst for the hydration reaction.
A method for producing 2,4-dione. 10. An equivalent ratio of α-hydroxyisobutyric acid amide, dialkyl carbonate and alcoholate of an alkali metal is 1: 1.1 to 1.5: 1.1 to 1.5.
10. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to any one of claims 1 to 9. 11. The method according to claim 1, wherein after mixing the α-hydroxyisobutyric acid amide and the dialkyl carbonate, an alcoholate of an alkali metal is added and reacted. 2,
A method for producing 4-dione. 12. The method for producing 5,5-dimethyloxazolidine-2,4-dione according to claim 11, wherein the water content in the raw material solution before the addition of the alkali metal alcoholate is 2% by mass or less. 13. The method according to claim 1, wherein the crystallization is carried out after neutralization with a mineral acid.
A method for producing dimethyloxazolidine-2,4-dione. 14. The method according to claim 13, wherein the crystallization is performed in the presence of an inorganic salt. 15. A method for purifying 5,5-dimethyloxazolidine-2,4-dione, comprising crystallization in the presence of an inorganic salt.