DE2010221A1 - - Google Patents

Description

FARMEX S a r 1, 7, Rue Anquetil, 94 Nogent s / Marne

France

Nitro derivatives of salicylamide or 2-hydroxy-benzamide and methods of making them

The invention relates to new nitro derivatives of salicylamide or 2-hydroxy-benzamide of the formulas

I.

.CONH

CONH.

and a method for producing these compounds.

The compounds of the formulas given above have an analgesic, anti-inflammatory and antifungal activity. Pharmaceutical comparative experiments with salicylamide as Comparative substances have shown that the compounds of the invention have an improved anti-inflammatory and analytical properties Effect, in particular on the sole edema caused by dextran and histamine in the rat, on that with Eiftlbuain evoked »atopic odors and in the Koster test (peritoneal inflammation with acetic acid). You can therefore used as an active ingredient in pharmaceuticals.

009838 / $ 225

The process of the invention for the preparation of nitro derivatives of salicylamide or 2-hydroxy-benzamide, in particular of 3-nitro-2-hydroxy-benzamide and 5-nitro-2-hydroxy-benzamide of the formulas I and II given above is characterized in that by nitrating salicylamide with concentrated nitrating acid (sulfuric acid-nitric acid mixture) at a temperature below 27 ⁰ C, a mixture of the corresponding nitro derivatives of the formulas I and II given above is prepared, after washing the compounds formed with water, they are recrystallized from normal Butanol separates from one another due to their shift in solubility, the nitro derivative of the formula II being less soluble in normal butanol than the nitro derivative of the formula I.

The following example is intended to illustrate the invention. Bo is obi

a) Preparation of the mixture from the 3-nitro and 5-nitro derivative of salicylamide

137.0 g (1 mol) of salicylamide were slowly added to 300 ml of concentrated sulfuric acid (d * 1.83), the mixture being cooled so that the temperature did not exceed ^{28 ° C.} Then allowed to cool the mixture to room temperature, was then slowly 74 ml about 60tige nitric acid (d »1.38) are added, while the temperature was kept below 27 ⁰ C" One lieft the mixture stand for 30 minutes long, it poured then 1.2 liters of ice water. It was then filtered, and the filtrate was filtered off with suction and washed twice with 250 ml of cold water and then carefully

009838/2253

sucked off. A slightly yellow colored in water was obtained insoluble fraction, which is a mixture of the 3-nitro and 5-nitro derivatives Contained from salicylamide.

b) Production of 5-nitro-2-hydroxy-benzamide

The water-insoluble fraction prepared in step a) was dissolved in 2 liters of normal butanol while boiling under reflux. The boiling solution was filtered and then left to stand for 24 hours. After filtration and vacuum to give 105 g (0.577 mol) of S-nitro-2-hydroxy-benzamide in the form of fine yellow crystals which schmorzen at 227-229 ⁰ C. The yield was -56V, -

c) Preparation of 3-nitro-2-hydroxy-benzamide

The mother liquor obtained in stage b) was concentrated with boiling until crystallization began. It was then left to stand for 24 hours, then filtered, filtered off with suction and the resulting chestnut-brown mass was dried. This mass was taken up in boiling water in the presence of activated charcoal, then the boiling solution was filtered and left to stand for 24 hours. After filtration and suction, 45 g (0.278 mol) of 3-nitro "2-hydroxy-benzamide" were obtained in the form of fine golden yellow crystals which ^{melted at 145 °} C. "The yield was 251"

Phftxmacological properties

An examination of the pharmacological properties showed that the acute toxicity and the DL ₅₀ determined in mice were about 0.5 g / kg for 3-nitro-2-hydroxy-benzamide and about 1 for 5-nitro-2-hydroxy-benzamide g / kg.

009836/2253

Claims (1)

Claims 1, nitro derivatives of salicylamide or 2-hydroxy-beazamide, ge « characterized by the formulas ("Ο CONH. and CONH, A process for the preparation of the nitro derivatives of salicylamide or 2-hydroxy-benzamide according to claim 1, characterized in that by nitration of SalicyMid or 2-hydroxy-benzamide with concentrated nitrating acid at a temperature below 27 ⁰ C a mixture of the corresponding nitro derivatives of claim 1 and the formulas I and II given in 1 are produced by recrystallization from normal butanol separating these nitro derivatives from one another, the nitro derivative of the formula II being less soluble in normal butanol than the nitro derivative of the formula I. 009838 / 225S