JPS611669A - 5-benzylidenehydantoin - Google Patents

Abstract

PURPOSE:The reaction of benzaldehyde and hydantoin is effected in the presence of an aminoacid other than glycine in an aqueous solution within a specific pH range to enable high-yield production of the titled compound which is used as an intermediate of phenylalanine. CONSTITUTION:5-Benzylidenehydantoin is obtained by reaction between benzaldehyde and hydantoin in the presence of an aminoacid other than glycine, such as glutamic acid, aspartic acid, lysine, arginine or ornithine or their salt (0.1-2, preferably 0.3-1mol per mol of hydantoin) in an aqueous solution of 8-12, preferably 9-10pH. EFFECT:The compound readily crystallizable is obtained in a relatively short reaction time.

Description

[Detailed description of the invention] It is related to the manufacturing method.

5-Benzylidenehydantoin is an important intermediate in the production of phenylalanine.

The reaction for producing 5-substituted hydantoins by condensing aldehydes and hydantoins is carried out by Wheeler-H
It is called offman reaction and is known (J. Am.

Chem. Soc. , 45, 369 (1911)). In this method the reaction is carried out in the presence of acetic acid and thorium acetate anhydride. Further detailed examples of this reaction can also be found in Org. Syn. , Coll , Vol , 5
, 627, the reaction is carried out in anhydrous vinyl. All of these methods use expensive organic solvents and have low yields of about 70', so they are not industrially satisfactory.

The present invention provides an industrially advantageous method for producing 5-penzylidene by reacting benzaldehyde with hydantoin (2,4-imidazolinonedione) in the presence of an amino acid other than glycine or a salt thereof in the pH range of 8 to 12. The present invention provides a method for producing Hidantoishi. According to the present invention, 5-benzylidenehydantoin with good crystallinity can be obtained in a good yield within a relatively short reaction time in an aqueous solvent. Generally, water is used, but not only water but also a mixture of water and a water-soluble organic solvent such as methanol, ethanol, dioxane, etc., can be used if necessary.

The amino acids used are glutamic acid, asnocrachic acid, lysine, arginine, and ornithine.

α-alanine, leucine, inleucine, valine.

β-alanine, phenylalanine, tyrosine, doha,
Phenylglycine, serine, threonine.

Methionine, taurine, S-carboxymethylcysteine, γ-aminobutyric acid, tranegisamic acid, and 3-aminocyclohexanecarboxylic acid can be used alone or in combination. These salts of amino acids, such as alkali metals,
Alkaline earth metal salts, mineral acid salts, etc. 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 the amount is used in large amount, the corresponding effect will not be obtained and it 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 will be obtained, and it is necessary to prepare the reaction solution PI at the above pH.
There are no particular restrictions on the type of alkali used for the preparation, such as sodium hydroxide.

Alkali metal hydroxides such as potassium hydroxide, sodium carbonate, potassium carbonate and their carbonates, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, etc. can be used.

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

Since the reaction product 5-penzylidenehydanyline is sparingly soluble in water, it precipitates as crystals as the reaction progresses, so it can be easily separated and recovered by a method such as centrifugation.

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

Example 1 A three-necked 500" glugable flask equipped with a thermometer, reflux condenser, and stirrer was set in a constant temperature bath.

Water 200", Hip"Toy: 150.5' (=
0.50"").

g mol alanine 22.3 (=0.25), solid caustic soda 5.0 g (=0.125 "")',
Penzalde at human 53.0' (=0.50) was added, the temperature was raised,
The mixture was stirred at 80°C for 2 hours. During this time, the voice of the reaction liquid was 9.8
It was ~9.6. After cooling to room temperature, the reaction solution was centrifuged to remove 5-penzylidene hydantoy787,0'.
I got it. The yield was 92.6% based on hydantoin.

Example 2 Adding L-glutamino to the alanine base of Example 1
g
moA acid mulberry, -water salt 4
6.8 (=0.25) and reacted in the same manner. During this time, the pH of the reaction solution was 9.8 to 9.5. Yield of 5-benzylidenehydantoin: 82.5.

The yield was 87.8% based on hydantoin.

Example 3 L-lysine salt 9 was added to the alanine base of Example 1.
Using mob acid salt 45.7 (=0.25), the pH was adjusted with caustic potash and the reaction was carried out in the same manner. During this time, the pH of the reaction solution was 96 to 9.3. Yield of 5-benzylidenehydantoin 86.6', relative to hydantoin;
The yield was 92.1 h.

Example 4 Instead of alanine in Example 1, β-alanine g
mat 13.3 (-0,15) was used, the voice was adjusted with calcium hydroxide, and the reaction was carried out in the same manner. During this time, the pH of the reaction solution
was 9.9 to 9.7. Yield of 5-benzyribenhydantoin: 79.5. 84.6′ for hydantoin
The yield was lb.

Example 5 41.3 g (=0.25) of L-phenylol alanine was used in the alanine base of Example 1, and the mixture was reacted in the same manner for 10 hours. During this time, the pH of the reaction solution was 97.
It was ~94. Yield of 5-benzylidenehydantoin: 77.0 g. The yield was 81.9 qb based on hydantoin.

Example 6 L-serine 42.1'o instead of alanine in Example 1
7 (=0.40) and reacted in the same manner.

During this time, the pH of the reaction solution was 9.1 to 8.9. 5-
The yield of benzylidenehydantoin is 75.41! , the yield was 80.2'' based on hydantoin.

Example 7 Taurine 31.3”ot instead of alanine in Example 1 (=0.25) and reacted in the same manner.

During this time, the voice of the reaction solution was 9.5 to 9.3. Yield of 5-benzylidenehydantoin 82.7. The yield was 88.0'' based on hydantoin.

Comparative Example 1 In Example 1, the weight was 32.09 (=0.
A similar reaction was carried out using 10 ml of 80 rr. During this time,
- of the reaction solution was 12.5 to 12.0. The yield of 5-benzylidenehydantoin was 54.0'' for 52.6'o hydantoin. (At this time, HD had disappeared.) Comparative Example 2 t-0.7g (=0.
018""), and the reaction was similarly carried out for 7 hours. During this time, - of the reaction solution was 8.0 to 7.5. Yield of 5-benzylidenehydantoin: 69.7. The yield was 74.1% based on hydantoin.

Comparative Example 3 Alanine 8.9'(=0.10") in Example 1
Ichigo.

-h using Sei Soda 1.0II (=0.05”L) [
Similarly, the reaction was continued for 9 hours. During this time, H in the reaction solution was 8.1
It was ~7.5. Yield of 5-benzylidenehydantoin: 72.1. The yield was 76.7' based on hydantoin.

Application Suspect

Claims (1)

[Claims] Benzaldehyde as an amino acid (excluding glycine)
A method for producing 5-benzylidenehydantoin, which comprises reacting it with hydantoin in an aqueous solution at pH 8 to 12 in the presence of 5-benzylidenehydantoin or a salt thereof.