JPS6115872B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing hydantoin from an inorganic acid salt of glycinonitrile and an alkali metal salt of cyanic acid. Conventionally, various methods for producing hydantoin have been proposed. For example, a method for producing hydantoin by reacting glyoxal and urea according to the following formula [] or [] is known. According to this method, hydantoin can be obtained in a relatively good yield, but it is not an economical method because the raw material glyoxal is expensive, and since a large amount of inorganic acid is used in the production process, its removal is time-consuming. On the other hand, as an economical production method, there is the so-called Bucherer-Bergs method in which formaldehyde and cyanide are reacted according to the following formula. However, this method has a low selectivity for the target product, so methods to improve this include treating the reaction product with an inorganic acid (Japanese Patent Publication No. 39-24807), adding a tertiary amine to the reaction system ( Japanese Patent Application Publication 1973-
92371) have been proposed, but both methods involve more side reactions than the reactions [ ] and [ ] and require purification because the desired product is likely to be colored. Furthermore, as another method for producing hydantoin, a method has been proposed in which glycine and urea are reacted as shown in the following formula []. However, since this method involves a melt reaction, there are many problems from an industrial perspective. There is also a method in which glycine ester and cyanate are reacted as shown in the following formula []. According to this method, a target product of relatively high purity can be obtained in high yield, but the raw material glycine ester is expensive, so it cannot be called an economical method. By the way, methods for producing substituted hydantoins by reacting various aminonitriles (or derivatives thereof) with cyanates have been known, and for example, the following synthetic methods have been attempted. Yield 62% [JACS, 44 , 1746, (1922)] Yield 71% [JACS, 58 , 474 (1936)] Yield 73% [JACS, 70 , 900, (1948)] (d) A solution obtained by mixing KCN, KOCN, and an addition compound of aldehyde and ammonia is gradually reacted with dilute sulfuric acid. [Ann, 169 , 125, (1873)] The present invention essentially utilizes this reaction to produce unsubstituted hydantoin (hydantoin) from glycinonitrile salt and cyanate; No attempt to produce hydantoin has yet been reported. This is probably because glycinonitrile is a particularly unstable compound among aminonitrile and is prone to polymerization.
When using this method, side reactions are likely to occur, and as is well known, hydantoin is more easily hydrolyzed than substituted hydantoins, so even if hydantoin is produced using this method, the yield is high. It is presumed that this is because it is thought that the target product cannot be obtained at this rate. However, the present inventors first reacted glycinonitrile hydrochloride, sulfate, etc. with an alkali metal salt of cyanic acid in an aqueous medium, and then heat-treated the resulting reaction mixture with sulfuric acid, hydrochloric acid, etc. The present inventors have surprisingly discovered that hydantoin can be obtained in high yield and high selectivity, and that hydantoin can be produced using this method in a variety of ways more advantageously than conventional methods, leading to the present invention. That is, the present invention is based on the general formula

[Formula] (wherein, Z represents HCl or H ₂ SO ₄ ) glycinonitrile inorganic acid salt and general formula MeOCN (wherein, Me represents Na or K) alkali cyanate Reacting the metal salt in an aqueous medium at a temperature range of 0 to 20°C,
The gist of the present invention is a method for producing hydantoin, which is characterized in that sulfuric acid or hydrochloric acid is then added to the resulting reaction mixture and heat-treated at a temperature in the range of 70 to 110°C. For example, the advantages of the present invention are as follows. (1) The raw material glycinonitrile inorganic acid salt is a substance that can be easily synthesized from hydrocyanic acid, formalin, and ammonia, and is usually not expensive. According to the present invention, hydantoin can be produced more economically than before. be able to. (2) The reaction selectivity is high, and hydantoin can be obtained with a yield of 80% or more. (3) Especially compared to the Bucherer-Bergs method, there are fewer side reactions that cannot be converted into hydantoin, the product is easy to purify, and the product is significantly less colored. To explain the present invention, the glycinonitrile inorganic acid salt used as a raw material can be easily obtained by neutralizing glycinonitrile with sulfuric acid or hydrochloric acid. The other raw material, an alkali metal salt of cyanic acid, is manufactured industrially and is easily available. The proportions of the inorganic acid salt of glycinonitrile and the alkali metal salt of cyanic acid are usually equimolar, or the cyanate is used in slight excess. In the present invention, water is usually used as a medium in the reaction of the inorganic acid salt of glycinonitrile and the alkali metal salt of cyanic acid, and the amount used is preferably 400 to 1000 ml per mole of the inorganic acid salt of glycinonitrile. As a reaction method, it is preferable to add a cyanate salt little by little to an aqueous solution of an inorganic glycinonitrile salt and cause the reaction to occur. The reaction temperature is usually 0 to 20°C, preferably 0 to 10°C.
It is ℃. If the reaction is carried out at a temperature higher than 20°C, side reactions will increase, which is not preferable. It is generally desirable to complete the addition of cyanate within one hour. After the addition of the cyanate salt is completed, the reaction mixture is aged for 1 to 2 hours while maintaining the reaction temperature to complete the reaction. In the present invention, it is thought that hydantoic acid nitrile is first produced by the reaction between glycinonitrile inorganic acid salt and cyanate, and then this is hydrated to produce hydantoic acid amide. In the course of this reaction, inorganic salts are produced as by-products. After the reaction is completed, sulfuric acid or hydrochloric acid is added to the reaction mixture and heat treated, and hydantoin is produced by this treatment. The amount of sulfuric acid or hydrochloric acid used at this time is 1 to 2 mol per 1 mol of the raw material glycinonitrile inorganic acid salt, and concentrated sulfuric acid or concentrated hydrochloric acid is used, respectively. The temperature of the heat treatment etc. is usually 70 to 110°C, preferably 80 to 100°C. Sulfuric acid or hydrochloric acid is preferably added gradually to the reaction mixture, and the addition time is usually within 1 hour. After adding the acid, the treated material is heated to 1°C while maintaining the treatment temperature.
Aging for ~4 hours to complete hydantoinization. After the treatment, if hydrochloric acid is used, the treatment solution is distilled under reduced pressure to remove as much hydrogen chloride as possible, and then the water is evaporated to dryness. The resulting residue is then extracted with an organic solvent that does not dissolve the by-product inorganic salt but dissolves the hydantoin. At this time, examples of the organic solvent used include diglyme, dimethylformamide, N.N-dimethylacetamide, and N-methylpyrrolidone. On the other hand, when sulfuric acid is used, after the treatment, the treated product is neutralized with a base such as ammonia, soda carbonate, sodium bicarbonate, caustic soda, quicklime, slaked lime, calcium carbonate, etc., and then the water is evaporated to dryness. The resulting residue is then extracted with the same organic solvent as in the case of hydrochloric acid treatment. The extract obtained as described above is concentrated by an appropriate method to obtain the target hydantoin. The present invention is preferably implemented as follows. Glycinonitrile inorganic acid salt is charged into a reactor equipped with a reflux condenser, a stirrer, a thermometer, and a dropping funnel, and a predetermined amount of water is added to dissolve it. Next, the solution is cooled to a temperature below 10°C, and cyanate powder is gradually added thereto for reaction. The reaction was slightly exothermic, and the liquid gradually became cloudy and a precipitate was clearly visible. After the addition of the cyanate salt is completed, the reaction is aged for about 1 hour while maintaining the reaction temperature to complete the reaction. Next, the reaction mixture is heated to a temperature of 90° C., and a predetermined amount of sulfuric acid or hydrochloric acid is added dropwise into the reaction mixture through a dropping funnel for acid treatment. While dropping the acid, adjust the dropping amount so that the temperature of the material to be treated remains between 90 and 100°C. After dropping, the treated material is heated for 2 hours while maintaining the above temperature.
Age for ~4 hours. When sulfuric acid is used for this acid treatment, sodium carbonate is added to the treated material after the treatment to adjust the pH of the treated material to 3 to 5. After neutralization, water is removed from the treated product under reduced pressure and the product is dried. Next, dimethylformamide is added to the obtained residue, and the mixture is heated and stirred at a temperature of about 80°C for 1 to 2 hours to extract the soluble content. The extract is heated to separate by-product inorganic salts. The dimethylformamide solution is concentrated under reduced pressure to obtain the target hydantoin. By such a method, hydantoin with little coloring and high purity can be obtained. Next, the present invention will be explained in more detail with reference to Examples. Example 1 In a 500 ml separable flask equipped with a reflux condenser, stirrer, thermometer, and dropping funnel, 26.25 g (0.25 mol) of industrial glycinonitrile sulfate and 150 ml of water were dissolved. Next, the inside of the flask was cooled to a temperature of 10° C. or less, and 18.08 g (purity: 90% or more) of industrial sodium cyanate powder was added little by little to cause a reaction. A slight exotherm was observed, the solution gradually became cloudy, and a precipitate formed. After the addition of the sodium cyanate was complete, the contents of the flask were heated at 5-10 DEG C. for 1 hour and at room temperature for 1 hour. Next, the inside of the flask was heated to 90°C, and 31.85 g of concentrated sulfuric acid (0.325 mol) was added dropwise. A clear exothermic reaction occurs, but the temperature inside the flask is 90~
Make sure to maintain the temperature at 100℃. After the dropwise addition was completed, the mixture was aged at the above temperature for about 2 hours. Next, after cooling the flask to room temperature, add soda carbonate powder into the flask to adjust the pH of the contents to 3-5.
I made it. After neutralization, water was distilled out from inside the flask under reduced pressure and dried. Next, add 100ml of dimethylformamide to the flask.
was added, stirred at 80°C for about 1 hour, and then filtered. Add 90ml of dimethylformamide from the liquid under reduced pressure.
After distillation, it was left at room temperature. The precipitated crystals were separated and washed with a small amount of dimethylformamide, and the obtained crystals were vacuum dried at 60°C. The amount of crystals obtained was 20.94 g (yield 83.8%), the crystals exhibited a slight yellow color, and the content of hydantoic acid or hydantoic acid amide in the crystals was determined to be less than 2% by colorimetric analysis using Erlich reagent. . In addition, an additional 1.5 g from the crystal separation mother liquor and washing solution
of hydantoin was recovered. Example 2 In a reactor similar to that used in Example 1, 23.13 g (0.25 mol) of industrial glycinonitrile hydrochloride and water were added.
80ml was charged and dissolved. Next, the inside of the flask was cooled to 10° C. or lower, and 22.5 g of potassium cyanate (purity of 95% or more) was added little by little into the flask. As potassium cyanate is added, a slight heat generation occurs inside the flask, and crystals begin to precipitate. After the addition of potassium cyanate was completed, the contents of the flask were aged at 5-10°C for 1 hour and at room temperature for 1 hour. Next, the inside of the flask was heated to 90°C, and 33.85% concentrated sulfuric acid (0.325 mol) was added dropwise. While dropping concentrated sulfuric acid, maintain the temperature inside the flask at 90-100°C. After the dropwise addition was completed, the mixture was aged at the above temperature for about 2 hours. Next, hydrogen chloride and water were evaporated from the inside of the flask under reduced pressure to dryness. Then add dimethylformamide to the flask.
After adding 100 ml and stirring at 80°C for about 1 hour, it was filtered. Add 90ml of dimethylformamide from the liquid under reduced pressure.
After distillation, it was left at room temperature. The precipitated crystals were separated, washed with a small amount of dimethylformamide, and the obtained crystals were vacuum-dried. The amount of crystals obtained was 21.75 g (yield 87%), the crystals exhibited a slight yellow color, and the content of hydantoic acid or hydantoic acid amide in the crystals was determined to be less than 1% by colorimetric analysis using Erlich reagent. . In addition, an additional 1.5 g from the crystal separation mother liquor and washing solution
of hydantoin was recovered. If you want to obtain hydantoin with higher purity, heat-treat the crystals with a small amount of hydrochloric acid (concentration 10-20%), remove hydrogen chloride under reduced pressure, leave to stand, and separate and dry the precipitated crystals. Colorless crystals are then obtained.

Claims (1)

[Claims] 1 Glycinonitrile inorganic acid salt represented by the general formula [formula] (wherein Z represents HCl or H ₂ SO ₄ ) and the general formula
MeOCN (In the formula, Me represents Na or K)
An alkali metal salt of cyanic acid represented by
A method for producing hydantoin, characterized by heat treatment in the range of 70 to 110°C.