JPH06100543A - Production of 1-benzylhydantoin - Google Patents

Abstract

PURPOSE:To provide a process for producing 1-benzylhydantoin in high yield from a starting compound which is easily producible on an industrial scale. CONSTITUTION:1-Benzylhydantoin of formula II is produced by reacting N- benzylaminoacetonitrile of formula I with an alkali metal cyanate and an acid and heating the obtained reaction mixture in the presence of an acid.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 1-benzylhydantoin which is an intermediate useful for medicines, agricultural chemicals, photographic agents and the like.

[0002]

2. Description of the Related Art Conventionally, as a method for synthesizing 1-benzylhydantoin, an aqueous solution of potassium cyanate was dropped into an aqueous solution of N-benzylglycine hydrochloride, followed by cyclization with concentrated hydrochloric acid.
-Methods for obtaining benzylhydantoin are known.
(Acta Acad. Abo., Math. Phy
s. 27 (6), 18 pp. (1967) (Ge
r))

[0003]

The starting material of the conventional method, benzylglycine hydrochloride, is obtained by reacting benzylamine and glycolonitrile in an aqueous medium to obtain N-benzylaminoacetonitrile. Obtained by hydrolyzing acetonitrile with an alkali metal hydroxide and then reacting with an acid. Thus, benzylglycine hydrochloride is not a readily available compound because it requires a large number of reaction steps to obtain it and a large amount of inorganic salt is produced. Therefore, the conventional method is not an advantageous method as an industrial method. It is an object of the present invention to provide a method for producing 1-benzylhydantoin in high yield using a compound obtained by an industrially simple method as a starting material.

[0004]

The present invention comprises reacting N-benzylaminoacetonitrile represented by the following Chemical Formula 3 with an alkali metal cyanate and an acid (hereinafter referred to as the first step), and then obtaining the obtained reaction. The mixture is heat-treated in the presence of an acid (hereinafter referred to as the second step),
Provided is a method for producing 1-benzylhydantoin represented by Chemical Formula 4 below.

[Chemical 3]

[Chemical 4]

According to the method of the present invention, the starting material, N-
1-Benzylhydantoin can be obtained from benzylaminoacetonitrile in a single pot with high yield and high selectivity, and it can be handled with low-pressure equipment which is inexpensive in terms of equipment. Is the law.

The reaction mechanism of the present invention is to produce isocyanic acid by reacting an alkali metal cyanate with an equivalent amount of an acid,
Formation of N-benzylhydantoinyl nitrile by reaction of isocyanic acid with benzylaminoacetonitrile,
It is presumed to consist of formation of N-benzylhydantoinamide by acid hydrolysis of N-benzylhydantoinyl nitrile and formation of desired 1-benzylhydantoin by cyclization of N-benzylhydantoinamide in the presence of acid. It

Next, the present invention will be described in more detail. The N-benzylaminoacetonitrile of the present invention can be easily synthesized by reacting benzylamine and glycolonitrile in an aqueous medium. As the aqueous medium, it is preferable to use water alone or a mixed solvent of water and alcohol. As alcohol, methanol, ethanol, n-propanol, 2-propanol, n-
Examples include butanol and 2-butanol.

The N-benzylaminoacetonitrile thus obtained can be used for the method of the present invention without isolating the N-benzylaminoacetonitrile from the reaction solution as it is or as a concentrated solution of the reaction solution. When water alone is used as the aqueous medium,
It is also possible to separate the reaction solution and use the oil layer for the method of the present invention. Benzylaminoacetonitrile can also be used as a mineral acid salt such as hydrochloride or sulfate.

Examples of alkali metal cyanates include sodium cyanate and potassium cyanate, which are industrially easily available. Although it is possible to use the powder of the alkali metal cyanate as it is, it is generally industrially easier to handle it as an aqueous solution. Further, there is no problem even if an industrial product having low purity is used. The amount of the alkali metal cyanate used is preferably 0.8 to 1.5 times the molar amount of N-benzylaminoacetonitrile, and 1.0 to 1.2.
A double mole is more preferable.

The reaction temperature is 0 in the first step.
C. to 100.degree. C. is preferable, and 10.degree. C. to 50.degree. C. is more preferable. About 2nd process, about 20 to 120 degreeC is preferable, and 50 to 90 degreeC is more preferable. When the reaction temperature is low, the reaction rate becomes slow, and when the reaction temperature is high, a large amount of by-products are produced, which causes coloring.

As the acid, it is preferable to use a mineral acid such as hydrochloric acid, sulfuric acid or nitric acid. Since 1 equivalent of the acid is required in the first step and 1 equivalent in the second step per mol of N-benzylaminoacetonitrile, the total amount of the acid used is 2 mol per mol of N-benzylaminoacetonitrile.
-5 equivalents are preferable, and 2-3 equivalents are more preferable.

As the reaction method, after suspending an aqueous solution of an alkali metal cyanate in N-benzylaminoacetonitrile, an acid is added dropwise and then the temperature is raised to carry out the second step to obtain the desired 1-benzylhydantoin. There is a way to get it. Further, as another reaction method, a mineral acid is added dropwise to N-benzylaminoacetonitrile to obtain N-benzylaminoacetonitrile salt, then an alkali metal salt of cyanic acid is added dropwise, and then the temperature is raised to carry out the second step. Although there is a method of carrying out, the former reaction method is superior in terms of stirring state and yield.

Next, the former reaction method will be described in detail. The acid dropping time is preferably 1 hour or more. More preferably, about 1 equivalent required for the first step is dropped at a low temperature over 1 to 3 hours, then heated to drop the remaining amount. The treatment in the second step is preferably 2 after the acid addition is completed.
The reaction is completed by stirring for at least the time, more preferably at least 4 hours, at the same temperature as the acid dropping.

[0014]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. Example 1 In a glass four-necked flask having a capacity of 300 ml,
29.2 g (0.2 mol) of N-benzylaminoacetonitrile was added, and 137 g (0.21 mol) of 10% sodium cyanate aqueous solution was added thereto at room temperature. Next, at the same temperature, 10.1 grams of 97% sulfuric acid (0.
1 mol) was added dropwise over 1 hour, and then the temperature was raised to 50 ° C.
20.2 g (0.2 mol) of 7% sulfuric acid was added dropwise over 1 hour, and the mixture was stirred at the same temperature for 4 hours.
After cooling to ℃ and precipitating the precipitated crystals, the crystals were dried under reduced pressure to obtain 32.9 g of 1-benzylhydantoin (yield 86.6%).

Example 2 In a glass four-necked flask having a capacity of 300 ml,
29.2 g (0.1 mol) of 36% sulfuric acid was added dropwise at room temperature over 29.2 g (0.2 mol) of N-benzylaminoacetonitrile for 1 hour to obtain N-benzylaminoacetonitrile sulfate, Next, 10% at the same temperature
After adding 137 g (0.21 mol) of an aqueous solution of sodium cyanate in 2 hours, the mixture was stirred at room temperature for 1 hour, and then 50
20 g (0.2 mol) of 97% sulfuric acid was added dropwise at 0 ° C over 1 hour, and then the mixture was stirred at the same temperature for 4 hours. The resulting reaction solution was cooled to 5 ° C., the precipitated crystals were filtered, and dried under reduced pressure to give 1-benzylhydantoin 22.
9 grams (60.3% yield) were obtained.

Example 3 In a glass four-necked flask having a capacity of 300 ml,
29.2 g (0.2 mol) of N-benzylaminoacetonitrile was added, and 137 g (0.21 mol) of 10% sodium cyanate aqueous solution was added thereto at room temperature. Next, at the same temperature, 20.3 g (0.30%) of 36% hydrochloric acid was added.
(2 mol) was added dropwise over 2 hours, and the mixture was stirred at the same temperature for 1 hour. After adjusting the reaction temperature to 90 ° C., 36% hydrochloric acid was added to 40.
6 g was added dropwise over 1 hour, and the mixture was stirred at the same temperature for 4 hours.
The obtained reaction liquid was cooled to 5 ° C., and the precipitated crystals were filtered and dried under reduced pressure to obtain 28.5 g of 1-benzylhydantoin (yield 75.0%).

[0017]

According to the present invention, a compound obtained by an industrially simple method is used as a starting material, and a high yield is obtained.
1-Benzylhydantoin can be produced.

Claims (3)

[Claims] 1. A method comprising reacting N-benzylaminoacetonitrile represented by the following chemical formula 1, an alkali metal cyanate and an acid, and then heat-treating the obtained reaction mixture in the presence of an acid. 1 shown in Chemical Formula 2 below
Method for producing benzyl hydantoin. [Chemical 1] [Chemical 2] 2. A method of reacting a mixture of N-benzylaminoacetonitrile and an alkali metal cyanate while adding an acid, and then subjecting the obtained reaction mixture to heat treatment in the presence of an acid. Manufacturing method. 3. A mixture of N-benzylaminoacetonitrile and an alkali metal cyanate kept at 10 to 50 ° C. is reacted while adding an acid, and the resulting reaction mixture is then heated at 50 to 90 ° C. in the presence of an acid. The heating method according to claim 2, wherein the heat treatment is carried out.