JPH0451551B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 5-arylidenehydantoin.

5-arylidenehydantoin is an important intermediate for producing phenylalanine having a substituent on the aromatic nucleus.

By condensing aldehydes and hydantoins, 5
-The reaction for producing substituted hydantoins is
It is called the Wheeler-Hoffman reaction and is well known.
(J. Am, Chem, Soc., 45, 369 (1911)). In this method the reaction is carried out in the presence of acetic acid and anhydrous sodium acetate. Another detailed example of this reaction is given in Org. Syn., Coll. Vol. 5627, where the reaction is carried out in anhydrous piperazine. All of these methods use expensive organic solvents and yields are as low as about 70%, so they are not industrially satisfactory.

In the present invention, hydantoin (2,4-
The present invention provides an industrially advantageous method for producing 5-arylidenehydantoin by reacting it with 5-arylidenehydantoin (imidazolidinedione). According to the present invention, 5-arylidenehydantoin with good crystallinity can be obtained in a good yield within a relatively short reaction time in an aqueous solvent.

The aryl aldehyde that is the raw material of the present invention includes a halogen atom, a hydroxyl group, a lower alkoxy group,
lower alkylmercapto group, lower alkyl group, lower alkanoyl group, lower alkanoylamino group,
Benzaldehyde substituted with at least one of the following is used. When there are two or more substituents, the substituents may be the same or different, and the two substituents may be bonded to each other to form a ring. Typical examples of these include p-hydroxybenzaldehyde, 3,4-dioxybenzaldehyde, p-methoxybenzaldehyde, p-methylbenzaldehyde, o-hydroxybenzaldehyde, 3,4-methylenedioxybenzaldehyde, p-Ethylbenzaldehyde, p-isopropylbenzaldehyde, p-acetoxybenzaldehyde, p-acetaminobenzaldehyde, p-methylthiobenzaldehyde, p-chlorobenzaldehyde, p-fluorobenzaldehyde, etc. can be used.

Water is generally used as the reaction solvent in the present invention, but not only water but also a mixture of water and a water-soluble organic solvent such as methanol, ethanol, dioxane, etc. may be used if necessary. You can also do that.

Amino acids used include glutamic acid, aspartic acid, lysine, arginine, ornithine, glycine, α-alanine, leucine, isoleucine, valine, β-alanine, phenylalanine, tyrosine, dopa, phenylglycine, serine, threonine, methionine. , taurine, S-carboxymethylcysteine, γ-aminobutyric acid, tranexamic acid, 3-aminocyclohexanecarboxylic acid, etc. can be used alone or in combination. Furthermore, salts of these amino acids, such as alkali metal or alkaline earth metal salts or mineral acid salts, can also be used. The amount of these used is preferably 0.1 to 2 molar ratio, preferably 0.3 to 1 molar ratio to hydantoin. If the amount is too small, the effect will be low, and even if it is used in large amount, the corresponding effect will not be obtained, which is not economical.

The pH during the reaction is preferably 8 to 12, preferably 9 to 10. Even if the amino acid is used in a neutral or acidic state, no effect is obtained, and it is necessary to adjust the pH of the reaction solution to the above-mentioned pH. There are no particular restrictions on the type of alkali used to prepare the PH, and examples include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, and their carbonates, magnesium hydroxide, and water. Alkaline earth metal hydroxides such as calcium oxide can be used.

The reaction temperature and time are not necessarily strictly limited, but are usually 40 to 100°C, preferably 60°C.
~80°C for 1 to 10 hours, preferably 2 to 5 hours.

Since the reaction product 5-arylidenehydantoin is poorly soluble in water, it precipitates as crystals as the reaction progresses, so it can be removed by methods such as centrifugation.
It can be easily separated and recovered.

The method of the present invention will be explained in more detail below with reference to Examples. However, these are merely examples for explanation, and the present invention is not limited to these examples in any way.

Example 1 Three necks equipped with thermometer, reflux condenser and stirrer
A 500ml separable flask was placed in a thermostatic bath.

200ml of water, 50.0g of hydantoin (=0.50mol),
Glycine 18.8g (=0.25mol), solid caustic soda
Add 5.0 g (=0.125 mol) and 61.1 g (=0.50 mol) of p-hydroxybenzaldehyde and raise the temperature to 80
The mixture was stirred at ℃ for 2 hours. During this time, the pH of the reaction solution was 9.8.
It was ~9.6. After cooling to room temperature, 93.0 g of 5-p-hydroxybenzylidenehydantoin was obtained by centrifugation. 91.2 for hydantoin
% yield.

Example 2 In Example 1, the reaction was carried out in the same manner as in Example 1, except that glycine was replaced with 45.7 g (=0.25 mol) of L-lysine hydrochloride and p-hydroxybenzaldehyde was replaced with 69.1 g (=0.50 mol) of 3,4-dihydroxybenzaldehyde.
operated. During this time, the pH of the reaction solution was 9.4 to 9.2. 5-(3,4-dihydroxybenzylidene)-
Yield of hydantoin: 102.5g. For hydatoin,
The yield was 93.2%.

Example 3 In Example 1, glycine was added to 46.8 g (=0.25 mol) of sodium L-glutamate monohydrate and p-
The same reaction and operation were carried out except that 68.1 g (=0.50 mol) of p-methoxybenzaldehyde was used instead of hydroxybenzaldehyde. During this time, the pH of the reaction solution is 9.9~
It was 9.7. 5-(p-methoxybenzylidene)
-Yield of hydantoin 104.5g. The yield was 95.9% based on hydantoin.

Example 4 In Example 1, 31.3g of taurine was substituted for glycine.
(=0.25mol), p-hydroxybenzaldehyde and p-tolualdehyde 60.0g (=0.50mol)
Instead, the reaction and operation were carried out in the same way. During this time, the pH of the reaction solution was 9.8 to 9.6. Yield of 5-(p-methylbenzylidene)-hydantoin: 94.5 g. The yield was 93.6% based on hydantoin.

Example 5 In Example 1, glycine was replaced with β-alanine.
22.2g (=0.25mol) of p-hydroxybenzaldehyde was added to o-hydroxybenzaldehyde.
The amount was changed to 61.1 g (=0.50 mol) and the reaction was carried out in the same manner for 6 hours. During this time, the pH of the reaction solution was 9.6 to 9.2. Yield of 5-(o-hydroxybenzylidene)-hydantoin: 89.3 g. against hydantoin
The yield was 87.5%.

Example 6 In Example 1, the reaction was carried out in the same manner, except that p-hydroxybenzaldehyde was replaced with 75.0 g (=0.50 mol) of 3,4-methylenedioxybenzaldehyde.
operated. During this time, the pH of the reaction solution was 9.8 to 9.6. Yield of 5-(3,4-methylenedioxybenzylidene)-hydantoin: 109.1 g. The yield was 94.1% based on hydantoin.

Claims (1)

[Claims] 1 Arylaldehyde (excluding benzaldehyde) in the presence of an amino acid or its salt at pH 8
1. A method for producing 5-arylidenehydantoins, characterized by reacting them with hydantoin in an aqueous solution in the range of 5-12.