KR850000226B1 - Process for preparing 5-(3-chloro-hydroxyphenyl)-3-hydroxymethyl hydantoin - Google Patents

Abstract

5-(3-chloro-hydroxyphenyl)-3-hydroxymethyl hydantoin (I) used as an antibiotic agent against fungi, yeast, or bacteria is prepared from compound (III) by means of a reaction with formaldehyde. (III) is prepared from 5-(4-hydroxyphenyl) hydantoin (II) by means of a reaction with chlorine dissolved in methanol soln. for 1-2 hrs. at 30 (±5)≰C. Main reaction is conducted for 4 hrs. at 70-80≰C and a pH 7- 7.5 maintained by addition of aquueous ammonia.

Description

Method for preparing 5- (3-chloro-4-hydroxyphenyl) 3-hydroxymethyl hydantoin

The present invention relates to a novel compound of the following formula (I) having a strong bacteriostatic power against a wide range of microorganisms such as mold, yeast, bacteria and the like and a method for preparing the same.

The method for preparing the compound of the present invention is as follows.

Next, reacting for 1-2 hours at 30 ° ± 5 ° C while injecting chlorine gas into the solution of 5- (4-hydroxyphenyl) hydantoin of Structural Formula (II) in methanol, and recovering the solvent under reduced pressure. When distilled water is added and precipitated, 5- (3-chloro-4-hydroxyphenyl) hydantoin of formula (III) is obtained.

Then disperse 5- (3-chloro-4-hydroxyphenyl) hydantoin in distilled water, add 35% formaldehyde, add 0.1N ammonia water to pH 7-7.5, and adjust for 4 hours at 70-80 ° C. The reaction yields 5- (3-chloro-4-hydroxyphenyl) -3-hydroxymethylhydantoin of formula (I).

The final product prepared in this way was found to have a strong bacteriostatic action against all microorganisms, such as mold, yeast and bacteria, as a result of experiments on various microorganisms.

First, in order to determine the minimum inhibitory concentration against bacteria, the compound according to the present invention was diluted stepwise in 10 ml of Nutrient broth and filtered through Millipore filter (0.45M) to make it completely sterile.

As such, 10 ml of various concentration dilutions of the compound of the present invention were inoculated one by one with bacteria incubated for 24 hours in neutriant broth (10 ⁶ cells / 10 ml of inoculated bacteria), followed by incubation at 37 ° C for 48 hours to grow bacteria. Whether or not was observed, the results are shown in Table 1. The growth of bacteria is determined by the turbidity of the test tubes.

TABLE 1

Minimum Inhibitory Concentration (B / V) against Bacteria of the Compounds According to the Present Invention

The determination of bacteriostatic effect on molds and yeasts on the compounds of the present invention was carried out uniformly by adding 1 ml of the solution of the present invention to a suitable concentration of Sabouraud Dextrose Agar. After mixing and incubating the spore suspension of each experimental bacteria in stripes and incubated for 5 days at 25 ° C to observe the germination of the table to determine the minimum inhibitory concentrations for mold and yeast, the results are shown in Table 2.

TABLE 2

Minimum Inhibitory Concentration% (W / V) on Mold and Yeast of Compounds According to the Present Invention

EXAMPLE

Chlorine gas generated by adding 53 g of concentrated hydrochloric acid to 15 g of potassium permanganate was slowly washed with water, dried with sulfuric acid, and 30 g of 5- (4-hydroxyphenyl) hydantoin dissolved in 500 ml of methanol through a gas induction pipe. Inject the solution and stir the reaction solution strongly. While maintaining the reaction temperature between 30 ° C ± 5 ° C and reacting by generating chlorine over 2 hours, the temperature of the reaction mixture is gradually raised and stirred for another 30 minutes at 50 ° C. The solvent is recovered under reduced pressure and distilled water 200 ml was added, and the precipitated white precipitate was filtered, washed twice with water, and recrystallized with 50% aqueous methanol solution to obtain 30.8 g of white needle crystal.

From the infrared spectra and nuclear magnetic resonance spectra of this white needle crystal, it was confirmed that the structure of the foreign substance was 5- (3-chloro-4-hydroxyphenyl) hydantoin.

Melting Point (mp): 238-240 ° C

10 g of 5- (3-chloro-4-hydroxyphenyl) hydantoin was dispersed in 100 ml of distilled water, and 3.8 g of 35% formaldehyde aqueous solution was added thereto, 0.1N ammonia water was added to raise the pH of the reaction solution to 7.3. The mixture was stirred for 4 hours at 70-80 ° C. and then distilled under reduced pressure to recrystallize the white material. Thus, 9.1 g of white needles were obtained.

From the infrared spectra and nuclear magnetic resonance spectra of this material, it was confirmed that the structure of this white needle crystal was 5- (3-chloro-4-hydroxyphenyl) -3-hydroxymethylhydantoin.

Yield: 81%, Melting point (mp): 197-199 ° C.

Claims (1)

5- (4-hydroxyphenyl) hydantoin of the following structural formula (II) is reacted with chlorine to prepare a compound of the following structural formula (III), which is reacted with formaldehyde to give 5- (3-chloro of the following structural formula (I) Method for preparing 4-hydroxyphenyl) -3-hydroxymethylhydantoin.