JPH0413346B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Field of Application) The present invention relates to an improved method for producing unsaturated hydantoins. Since the use of 5-(substituted arylidene) hydantoin, an unsaturated hydantoin, as an antiviral agent was disclosed (Japanese Unexamined Patent Application Publication No. 1986-54369), it has been widely used in agricultural medicine,
It has been used as an intermediate raw material for food additives, etc.
In addition, substituted pyruvic acid obtained by alkaline hydrolysis of unsaturated hydantoin is useful as a raw material for amino acids due to rapid advances in biotechnology in recent years. (Prior Art) Several methods for producing unsaturated hydantoin have been reported. Among them, USP-2861079 describes a method in which a condensation reaction of a hydantoin and a substituted aromatic aldehyde or the like is carried out in water or a mixed solvent of water and a lower alcohol in the presence of a monoalkanolamine. (Problems to be Solved by the Invention) In this method, the amount of monoalkanolamine used is 0.2 to 10 times the amount of hydantoin, preferably 0.6 to 1.5 times the amount of hydantoin. After the reaction, 5-(substituted arylidene)hydantoin crystals are obtained in a yield of 85 to 90% by neutralization with a large amount of mineral acid. (2) When a large amount of monoalkanolamine is used, the crystal yield of unsaturated hydantoin is low unless it is neutralized; On the other hand, if a small amount of monoalkanolamine is used, unreacted aldehyde will adhere to the crystals, reducing the purity of the unsaturated hydantoin obtained. (3) If the reaction solution is recycled, the unsaturated hydantoin will increase over time. There are disadvantages such as a decrease in reaction yield. The purpose of the present invention is to correct the problems seen in the prior art and obtain high yield and high purity unsaturated hydantoin (means for solving the problems). Therefore, the present inventors conducted extensive studies. As a result, by using a mixed catalyst of monoalkanolamine and alkali metal hydroxide, the amount of monoalkanolamine used can be drastically reduced, and highly pure unsaturated hydantoin can be obtained without mineral acid treatment. They discovered this and arrived at the present invention. That is, the present invention is based on the general formula () (In the formula, R represents a linear or branched aliphatic hydrocarbon group or an aromatic hydrocarbon group having 1 to 20 carbon atoms. Also, some of the hydrogen atoms contained in R are nitro groups, hydroxyl groups, / or may be substituted with a halogen atom) and an aldehyde represented by the general formula () R・CHO () (wherein R is the same as in the general formula ()). Cutting of unsaturated hydantoin characterized by reacting it in the presence of 0.01 to 0.5 mole of monoalkanolamine and 0.005 to 0.5 mole of alkali metal hydroxide relative to hydantoin when produced by condensation reaction. It is the law. Hydantoins used in the method of the present invention are not particularly limited, but include, for example:
As described in Special Publication No. 39-24807
Use a product with a purity of 99.5% or higher, obtained by reacting glycolonitrile with ammonium carbonate by the Bucherer-Bergs method and then recrystallizing the resultant product by treating it with a mineral acid such as sulfuric acid. be able to. The aldehydes used in the method of the present invention are aliphatic aldehydes and aromatic aldehydes, such as acetaldehyde, isobutyraldehyde, isovaleraldehyde, capronaldehyde, capryaldehyde, glycolaldehyde, chloroacetaldehyde, crotonaldehyde, pelargonaldehyde, perilaldehyde,
Aliphatic aldehydes such as dichloroacetaldehyde, tetrolaldehyde, trichlorobutyraldehyde, propionaldehyde, glyoxylic acid, and, for example, benzaldehyde, anisaldehyde, salicylaldehyde, p-hydroxybenzaldehyde, tolualdehyde, vanillin, piperonal, benzoinacetaldehyde, o-isopropylbenzaldehyde, m-isopropylbenzaldehyde, p-isopropylbenzaldehyde, o-chlorobenzaldehyde, m-chlorobenzaldehyde, p-chlorobenzaldehyde, 2,4-dioxybenzaldehyde, 1-naphthaldehyde, 2-naphthaldehyde, o- There are aromatic aldehydes such as nitrobenzaldehyde, m-nitrobenzaldehyde, and p-nitrobenzaldehyde. These aldehydes are different from hydantoin.
It is preferable to use it in a range of 0.9 to 1.5 times by mole, preferably 0.9 to 1.1 times by mole. In the method of the present invention, monoalkanolamines used as catalysts include monoethanolamine, monoisopropanolamine, monobutanolamine, and the like. Among them, monoethanolamine is preferably used as it is the cheapest and most economical. The alkali metal hydroxides used in the method of the present invention are sodium hydroxide, potassium hydroxide,
Lithium hydroxide and the like have exactly the same effect as a catalyst, but sodium hydroxide is preferred as it is the cheapest and most economical. The amounts of monoalkanolamine and alkali metal hydroxide used as catalysts in the method of the present invention are as follows. That is, the monoalkanolamine is used in an amount of 0.01 to 0.5 times, preferably 0.05 to 0.2 times, the amount of hydantoin. If it is less than 0.01 mol, a large amount of unreacted hydantoin remains, while if it exceeds 0.5 mol, the target unsaturated hydantoin will be decomposed and the yield will decrease. In addition, the alkali metal hydroxide is in a range of 0.005 to 0.5 times the mole of hydantoin, preferably 0.02 to 0.5 times by mole.
The range is 0.2 times the mole. Furthermore, the preferred ratio of alkali metal hydroxide to monoalkanolamine is in the range of 0.1 to 4 times the mole. In the method of the present invention, the reaction is usually carried out in a water solvent or a mixed solvent system of water and lower alcohols, and the concentration of the raw material hydantoin is in the range of 1 to 20% by weight, preferably 5 to 15% by weight. It is. The reaction temperature is generally 60~100℃, preferably 80~
90℃ is good. If it is lower than 60°C, unreacted raw materials will remain even if the reaction is carried out for a long time, while if it exceeds 100°C, the unsaturated hydantoin produced will decompose and the yield will decrease. Further, the reaction pressure may be normal pressure or elevated pressure. It is usually carried out under atmospheric pressure using a normal pressure container, but
The reaction may be carried out under pressure using a pressure-resistant container such as an autoclave. The reaction time varies depending on the reaction temperature and other conditions, but when the reaction temperature is 80 to 90°C, 4 to 6 hours is usually required. After the reaction is completed, the reaction product liquid is cooled to precipitate the target product, and the unsaturated hydantoin crystals can be obtained separately. (Function and Effect) When producing unsaturated hydantoin by condensing hydantoin and aldehydes in the presence of monoalkanolamine, the amount of monoalkanolamine used can be reduced by allowing an alkali metal hydroxide to coexist. Moreover, the condensation reaction is carried out at a sufficiently high reaction rate, and highly pure unsaturated hydantoin is produced in high yield. Moreover, even if the reaction solution is used repeatedly, the unsaturated hydantoin obtained is a highly pure crystal. Therefore, the crystals of the unsaturated hydantoin obtained by the method of the present invention can be directly subjected to alkaline hydrolysis to produce substituted pyruvic acid in high yield. The method of the present invention has problems such as high unit consumption of the monoalkanolamine catalyst, low crystal yield when not neutralized with mineral acid, and when recycling the reaction solution under conditions where the molar ratio of monoalkanolamine to hydantoin is small. The disadvantages of low yield and large amount of impurities in the crystalline product can be solved all at once. According to the method of the present invention, it is possible to industrially produce unsaturated hydantoin with such high purity that substituted pyruvic acid can be produced in high yield by directly subjecting the crystals to alkaline hydrolysis. (Example) Hereinafter, the present invention will be specifically explained with reference to Examples. Example 1 Hydantoin 32.0g (0.32mol), benzaldehyde 34.6g (0.32mol), monoethanolamine 3.9g
(0.064 mol), sodium hydroxide 0.7g (0.016 mol)
Furthermore, 249.5 g of water was charged into a glass reactor equipped with a stirring rod and a thermometer, and the temperature was raised to 90°C. The reaction was carried out at 90° C. for 5 hours with stirring. Thereafter, the mixture was cooled to 15° C., and the precipitated 5-(benzylidene)hydantoin was separated using a centrifuge to obtain 65.4 g of crystals. The crystals were dried under a reduced pressure of 10 mmHg in a vacuum dryer.
It was dried at 90°C for 5 hours. The yield of the obtained 5-(benzylidene)hydantoin was 57.3 g, purity 99.8%.
The yield was 95.1%. Examples 2-3 A reaction was carried out in the same manner as in Example 1, except that the amounts of monoethanolamine and sodium hydroxide were changed to those shown in Table 1. The results are shown in Table-1. Comparative Example 1 A reaction was carried out in the same manner as in Example 1, except that the amounts of monoethanol and sodium hydroxide used were changed to those shown in Table 1. The results are shown in Table-1. Comparative Examples 2 to 4 In Example 1, the reaction was carried out in the same manner as in Example 1, except that sodium hydroxide was not added and the amount of monoethanolamine was changed. The results are shown in Table-1. Example 4 The liquid obtained in Example 1 was charged into the reactor again, 0.64 g (0.016 mol) of sodium hydroxide was added thereto (same amount each time thereafter), and further hydantoin,
Benzaldehyde was added in the same amount as in Example 1, reacted in the same manner, and a liquid recycling test was conducted three times. The results are shown in Table-2. Comparative Example 5 The liquid obtained in Comparative Example 1 was charged into the reactor again, hydantoin and benzaldehyde were added thereto in the same amounts as in Comparative Example 1, the reaction was carried out in the same manner, and a liquid recycling test was conducted three times. The results are shown in Table-2. Examples 5 to 9 In Example 1, benzaldehyde is shown in Table-5.
The corresponding unsaturated hydantoin was obtained by carrying out the reaction in the same manner using all the same ingredients except for changing the aldehyde listed above to 0.32 mol. The results are shown in Table-3. Examples 10-11 In Example 1, monoethanolamine
A similar reaction was carried out using exactly the same ingredients except that 0.064 mol was changed to 0.064 mol of monoisopropanolamine or 0.064 mol of butanolamine to obtain 5-(benzylidene)hydantoin.
The results are shown in Table 4.

[Table] Example 4

Claims (1)

[Claims] 1 General formula () (In the formula, R represents a linear or branched aliphatic hydrocarbon group having 1 to 20 carbon atoms, or an aromatic hydrocarbon group. Also, some of the hydrogen atoms contained in R are a nitro group, An unsaturated hydantoin represented by a hydantoin (which may be substituted with a hydroxyl group and/or a halogen atom) is combined with an aldehyde represented by a general formula () RCHO () (wherein R is the same as in the general formula ()). A method for producing unsaturated hydantoin, which comprises reacting hydantoin by a condensation reaction in the presence of a monoalkanolamine in an amount of 0.01 to 0.5 times the mole and an alkali metal hydroxide in an amount of 0.005 to 0.5 times the mole. .