DE1244152B - Process for the preparation of 3, 4, 5-tribromosalicylanilide - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

IntCl .: C 07 c 2 ^ % \ AQ

German class: 12 ο -16

Number: 1 244 152

File number: D 45375 IV b / 12 ο

Filing date: September 9, 1964

Opened on: July 13, 1967

The invention relates to a process for the preparation of 3,4 ', 5-tribromosalicylanilide, which only has a low Has content of 4 ', 5-dibromosalicylanilide.

4 ', 5-dibromosalicylanilide appears to face the skin Sensitive to ultraviolet light. When, as a result, brominated salicylanilides on the skin be brought on, e.g. B. in bacteriostatic agents, it is desirable that the content of 4 ', 5-dibromosalicylanilide is limited to a minimum, advantageously to no more than 1 percent by weight, based on tribromosalicylanilide.

After none of the previously known processes for the bromination of salicylanilide can a product can be obtained which has a sufficiently low content of 4 ', 5-dibromosalicylanilide.

The object of the present invention is to provide a process for the preparation of 3,4 ', 5-tribromosalicylanilide to develop in which less than 1 percent by weight of 4 ', 5-dibromosalicylanilide is formed.

The process of the invention for the preparation of 3,4 ', 5-tribromosalicylanilide by reacting salicylanilide with bromine at elevated temperature in the presence of an aqueous organic reagent and removing the brominated salicylanilide from the reaction mixture is that the bromination in a slurry of the salicylanilide in a mixture of 35 to 80 weight percent p-dioxane and 65 performs to 20 weight percent water at a Tempeiatur 35-85 ⁰ C.

The temperature is kept at the same level throughout the reaction. Mostly receives complete reaction after a reaction time of one hour or less to about 4 hours. It is particularly useful if the reaction mixture is heated at room temperature before it is heated about leaves. Towards the end of the reaction, the mixture is cooled and the brominated salicylanilides are separated from the reactant by filtration or centrifugation and can then washed and dried.

Method of manufacture
of 3,4 ', 5-tribromosalicylanilide

Applicant:

The Dow Chemical Company,

Midland, me. (V. St. A.)

Representative:

Dipl.-Ing. F. Weickmann,

Dr.-Ing. A. Weickmann,

Dipl.-Ing. H. Weickmann

and Dipl.-Phys. Dr. K. Fincke, patent attorneys,

Munich 27, Möhlstr. 22nd

Named as inventor:
Theodore Eugene Majewski,
Midland, me. (V. St. A.)

The reactants are preferably in a ratio of 2.5 to 3.5 moles of bromine per mole Salicylanilide, with a molar ratio of about 3: 1 being preferred.

The p-dioxane is used as the reactant in an amount sufficient to react with the salicylanilide to form a suspension or slurry. Preferably 1 to 5 volumes of reactant are used used per unit volume of the total starting materials.

The 3,4 ', 5-tribromosalicylanilide obtained by the process of the invention contains less than 1 percent by weight 4 ', 5-dibromosalicylanilide. It is known for its bacteriostatic properties and can z. B. add to soaps or detergents.

The 3,4 ', 5-tribromosalicylanilide can be measured in the infrared, and the by-products present are determined according to the following procedure ".

A sample is adsorbed on the ion exchange resin Dowex 2-x8 in acetate form. By gradient elution with acetic acid-methanol solution salicylinalide, 4'-bromo-, 5'-bromo- and 4 ', 5-dibromosalicylaniüd separated. The concentrations of the substances are determined by ultraviolet spectrophotometry with a Determined accuracy of ± 0.05%.

Determination by thin layer chromatography

A sample of the product was applied to a test plate along with standard samples. After rinsing with a suitable solvent system, the plate was examined in ultraviolet light. The concentration was determined visually by comparing the relative intensities of the Fluorescence of standard samples and test samples. Here are 4 ', 5-dibromo, 3,5-dibromo and 2 ', 3,4', 5-tetrabromosalicylanilide with an accuracy of ± 0.1% at a concentration of 0.1 to 0.5% determined.

Both methods can detect 0.1% of the specified impurities.

The following table shows the values for those prepared according to the examples of US Pat. Nos. 3,064,048 and 3,057,920 listed below

709 610/549

Products compared with the contents of the products obtained according to Examples 1 to 5 of the process of the invention. ^:

example %
yield 3,4 ', 5 Bromine-Substituted Salicylamides,% 2.76 3 5 _{ 2 ', 3.5 - - 2 ', 3,4', 5 O/
/O
Salicylic 4 ', 5 j 3.5 2.79 -. - anilide Method of the invention 97.0 4.91 - - - - 1 96 97.0 0.24 3.88 - - - - - 2A 96.7 94.0 0.21 1.78 - - - - -. 2 B 94.7 96.0 0.09 4.12 - -. - - - 3 92.3 98.0 0.12 - - - - 4th 86.8 95.0 0.22 16.2 - - · 0.7 0.2 ■ - -. 5 95 0.88 14.2 1.2 0.2 - USA.-Patent 3,064,048 ** 66.3 0.2 3.0 1 84.5 67.1 1.6 19.0 0.2 0.65 4.0 11.9 5 81.4 1.3 7.5 0.2 11.8 U.S. Patent 3,057,920 ** 76.66 8.0 0.3 * 0.1 1 94 89.5 1.66 -. - 1.73 2 90 85.87 2.8 - · 4.0 - 3 87 2.0 -

4'-bromosalicylanilide.

The examples have been reworked.

The above data show that significantly better yields of 3,4 ', 5-tribromosalicylanilide and purer products are obtained by the process of the invention. _,. . , "
example 1

A liquid slurry is prepared by mixing 85.4 grams of salicylanilide in a reactant consisting of 400 grams of 50 percent by weight p-dioxane and 50 percent by weight water. At a constant temperature between 40 and 45 ⁰ C 191.8 g of bromine are added. The reaction mixture is then ^{heated to 80 to 85 °} C. and kept at this temperature for about 1 hour. After cooling to 25 ° C., it is filtered in order to separate the reaction product from the reactant. The reaction product is washed twice with 100 ml each of a mixture of equal parts of dioxane and water and twice with 100 ml of water each time. After drying, 172.9 g (96% yield) of brominated salicylanilide are obtained with the following composition:

3,4 ', 5-tribromosalicylanilide 97.0%

3,5-dibromosalicylanilide 2.76%

4 ', 5-dibromosalicylanilide 0.24%

Example 2

If one works as in Example 1, but brominates at different temperatures, one obtains the following results:

Example 3

If you work again as in Example 1, but using a reactant that consists of 60 percent by weight p-dioxane and 40 percent by weight water, and brominates the salicylanilide 80 to 85 ° C., 166.2 g (92.3% yield) of a product with the following composition are obtained :

3,4 ', 5-tribromosalicylanilide 96.0%

3,5-dibromosalicylanilide 3.88%

4 ', 5-dibromosalicylanilide 0.12%

Bromination
temperature the end
prey Reaction product A. 60 to 65 ⁰ C 96.7% 3,4 ', 5-tribromosalicylanilide 97.0% 3,5-dibromosalicylanilide 2.79% 4 ', 5-dibromosalicylanilide 0.21% B. 75 to 8O ⁰ C. 94.7% 3,4 ', 5-tribromosalicylanilide 94.0% 3,5-dibromosalicylanilide 4.91% 4 ', 5-dibromosalicylanilide 0.09%

Example 4

If the procedure is according to Example 1, but with a reaction agent consisting of 75 weight percent p-dioxane and 25 weight percent water is at a temperature of 80 to 85 ⁰ C, is obtained 155.9 g (86.8% yield) of Product with the following composition:

3,4 ', 5-tribromosalicylanilide 98.0%

3,5-dibromosalicylanilide 1.78%

4 ', 5-dibromosalicylanilide 0.22%

Example 5

Is again according to Example 1 with a reactant composed of 40 percent by weight of p-dioxane and 60 percent by weight Water worked, then one receives 171.3 g (95% yield) of a product with the following composition:

3,4 ', 5-tribromosalicylanilide 95.0%

3,5-dibromosalicylanilide 4.12%

4 ', 5-dibromosalicylanilide 0.88%

Comparative examples

Example 1 is repeated with a reactant composed of 30 percent by weight of p-dioxane and 70 percent by weight water or from 85 percent by weight p-dioxane and 15 percent by weight water, this gives the following results:

Reactants Process product 30 percent by weight 3,4 ', 5-tribromosalicylanilide p-dioxane 92.0% 70 percent by weight 3,5-dibromosalicylanilide water 6.56% 4 ', 5-dibromosalicylanilide 1.44 »/. 85 percent by weight 3,4 ', 5-tribromosalicylanilide p-dioxane 98.0% 15 percent by weight 3,5-dibromosalicylanilide water 1% 4 ', 5-dibromosalicylanilide 1.71%

Claims (1)

Claim: Process for the preparation of 3,4 ', 5-tribromosalicylanilide by reacting salicylanilide with bromine at elevated temperature in the presence of an aqueous organic reagent and Removing the brominated salicylanilide from the reaction mixture, characterized in that that the bromination in a ίο slurry of salicylanilide in a mixture from 35 to 80 percent by weight of p-dioxane and 65 to 20 percent by weight of water for one Temperature of 35 to 85 ° C performs. Id considered publications:
U.S. Patent Nos. 3,057,920, 3,064,048. 709 610/549 7.67 © Bundesdruckerei Berlin