JPS6143168A - Production of hydantoin - Google Patents

Abstract

PURPOSE:To obtain hydantoin useful as an intermediate for synthesizing drugs and agricultural chemicals, by using glycinonitrile as a starting substance, reacting it with an alkali metal bicarbonate or an alkali metal hydroxide and carbon dioxide, or their mixture in an aqueous solvent. CONSTITUTION:For example, glycolonitrile is reacted with ammonia to give glycinonitrile, which is reacted with an alkali metal bicarbonate in an aqueous solution or an aqueous solution containing a hydrophilic solvent at 60 deg.C or at >=60 deg.C to give hydantion, or, in the reaction, CO2 is added to the aqueous solution or the aqueous solution containing a hydrophilic solvent of glycinonitrile and an alkali metal hydroxide, and reaction is carried out at >=60 deg.C. Introduction of CO2 into the system can prevent decomposition of glycinonitrile, coloring is further reduced, and excess CO2 can be easily recovered and reused by using the alkali metal hydroxide.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing hydantoins useful as intermediates in the synthesis of pharmaceuticals and agricultural chemicals.

Conventionally, hydantoin was produced using shea, 7. , #method using salt and the so-called Bu c b e r e r -B
It is based on the ERGS method. However, this method generally has a low yield, and various improved methods have been reported. For example, there is a method in which glycolonitrile and ammonium bicarbonate are reacted under closed pressure and then treated with an acid (Japanese Patent Publication No. 39-24807), or glycolonitrile and ammonium bicarbonate are reacted under normal pressure with a secondary amine or There is a method of reacting in the presence of a tertiary amine (Japanese Patent Application Laid-Open No. 50-671).

However, these methods require that glycolonitrile is particularly unstable and this decomposition causes coloration of the reaction product.
There were operational and equipment problems, such as the need for pressure-resistant equipment in order to carry out the reaction under closed pressure.

As a result of intensive studies to overcome these problems, the present inventors have found that glycinonitrile can be mixed with alkali metal bicarbonate or alkali metal hydroxide and carbon dioxide, or with carbon dioxide in an aqueous solution. The present inventors have discovered that hydantoin can be obtained by reacting with a mixture of the following, and have completed the present invention.

Although the mechanism of action in the present invention is not necessarily clear, the bicarbonate ion produced by glycinonitrile and bicarbonate (
This is thought to be a reaction with HCO3"'), and this was not previously known. In other words, the production of hydantoin was
It is said to be due to carbamic acid (Nl2C00H). (Wangka Ji Dandan, 494 (1964)) Next, the present invention will be explained in more detail.

To carry out the present invention, glycinonitrile and an alkali metal bicarbonate are first reacted in an aqueous solution or an aqueous solution containing a hydrophilic solvent at a temperature of 60° C. or higher. At this time, carbon dioxide may be added to an aqueous solution of glycinonitrile and an alkali metal hydroxide or an aqueous solution containing a hydrophilic i-vehicle and the reaction may be carried out at a temperature of 60° C. or higher.

In the former method, the decomposition of glycinonitrile is prevented by blowing 2rti carbon into the system, and more favorable results such as less coloring can be obtained. In this case, excess carbon dioxide can be easily recovered and reused by using an alkali metal hydroxide.

After the reaction is completed, the reaction product is cooled, and the resulting white crystals are filtered off and recrystallized from water to obtain hydantoin. Alternatively, if an acid is added to the reaction product, heated, and then cooled, the by-produced hydantoic acid is cyclized to hydantoin, and a more preferable result can be obtained.

As the glycinonitrile used in the present invention, for example, a reaction product of glycolonitrile, ammonia, and 8 can be used directly, or a purified product thereof, or an aqueous solution of another product can be used.

Alkali metal bicarbonates include potassium bicarbonate, sodium bicarbonate, and lithium bicarbonate (present only in solution)
etc. can be used.

Further, carbon dioxide may be allowed to act on an aqueous solution of potassium hydroxide, sodium hydroxide, lithium hydroxide, or an aqueous solution containing a hydrophilic solvent.

As the hydrophilic solvent, aqueous alcohol solutions such as methanol, ethanol, ethylene glycol, trimethylene glycol, and dioxane are used as appropriate.

Further, the amount of metal bicarbonate used in the reaction is not necessarily limited, but is generally 2 to 1 c! for 1 mole of glycinonitrile. mol, preferably 3 to 5 mol. When blowing CO2 gas during the reaction, it is generally 0.5 to 5 mol, preferably 0.6 to 2 mol, per 1 mol of glycinonitrile.

There is no strict limit to the reaction temperature, but it is usually 60 to 100"C, more preferably 66 to 80"C.
Next, representative examples of the method of the present invention will be shown and explained in more detail.
These are merely illustrative examples, and the invention is therefore not equally limited by these examples.

28.0 g (0.5 mol) of glycinonitrile and 150 g (1.5 mol) of potassium bicarbonate are added to 400 rxl of water.

When the temperature is raised to 70°C, it becomes uniform. Let it react as it is for about 5 hours. When this aqueous solution was cooled after the reaction, precipitation occurred. Filter the precipitate and recrystallize from water to obtain white crystals 1
4.5g was obtained. This crystal was fixed as hydan-i-in by IR and NMR five-element analysis.

Example 2 25.5 g of glycinonitrile (0.4E1 mol),
24 g (0.60 mol) of sodium hydroxide in 300 g of water
Add to m1. Add 0.5 mol/CO2 gas to this aqueous solution.
75°C while blowing with hr! Raise the temperature and react for 5 hours. Liquid chromatography analysis of the resulting reaction solution confirmed that hydantoin was produced at a yield of 45% based on glycinonitrile. Also, Bucherer
It was also found that hydantoic acid and hydantoic acid amide, which are commonly found in the Bergs method, were hardly produced.

Example 3 50 g (0.80 mol) of heavy carbon sodium was added to 300 g of water.
Add to step 1 and raise the temperature to 80°C. In the resulting aqueous solution,
While blowing CO2 gas at 0.8 mol/hr,
Glycinonitrile was added at 0.2 mol/hr. After 5 hours, the addition of glycolonitrile was stopped, and the mixture was recrystallized by adding water for another 5 hours to obtain 85 g of hydantoin.

Example 4 9.5 g (0.17 mol) of glycinonitrile and 50 g (0.5 mol) of potassium bicarbonate were added to a 300 rn 30% methanol water solution and reacted at 60'C for 7.5 hours.

Liquid chromatography analysis of the reaction solution revealed that hydantoin was produced at a yield of 50%.

Patent applicant Showa Denko Co., Ltd. Procedure amendment (method) Sunset in December 1978

Claims (1)

[Claims] A method for producing hydantoins, which comprises reacting glycinonitrile with an alkali metal bicarbonate or an alkali metal hydroxide and carbon dioxide or a mixture thereof in an aqueous solution.