DE1079066B - Process for the preparation of substituted coumarones - Google Patents

Description

GERMAN

The invention relates to a process for the preparation of substituted coumarones in general formula

OH

in which R is a hydrogen atom or the ethyl group and Y is one or more halogen atoms.

It was found that those represented by the above general formula were substituted Coumarones are pronounced spasmolytics and are in some cases also suitable as coronary vasodilators.

Thus, the new compounds prepared according to the invention are most effective against one of the most effective known spasmolytic remedies, namely 5,8 - dimethoxy - 2 - methylf urano- (4 ', 5': 6,7) -chromon, the following effects:

Spasmolytic "effects when triggered by histamine Cramps compared to 5,8-dimethoxy-2-methylfurano- (4 ', 5': 6.7) -chromon

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Rabbits 1 1 l, 25 times *) 18x 16x 16x 43-fold 25 times 66x

5,8-D imethoxy-2-methy 1-furano- (4 ', 5': 6.7) -chromon

2- (4'-Oxy-3'-chloro-benzoyl) coumarone

2- (4'-oxy-3 ^/ , 5'-diiodo-

benzoyl) coumarone

3-ethyl-2- (4'-oxy-3 ', 5'-dibromobenzoyl) coumarone ....

2- (4 ^/ -oxy-3 ', 5'-diiodo-

benzoyl) -3-ethylcoumarone ..

*) No attempt carried out.

As can be seen from the above values, the new substituted coumarones are many times more effective as spasmolytics than 5,8-dimethoxy-2-methylfurano- (4 ', 5': 6.7) -chromone, so that these compounds are valuable Represent enrichment of remedies. Their usefulness is further improved by the fact that their toxicity is very low and the LD ₅₀ , determined by intraperitoneal administration in mice, is only between 100 and 200 mg / kg.

The inventive method for the preparation of the new substituted coumarones of the above all methods of preparation
of substituted coumarones

Applicant:

Societe des Laboratories LABAZ _r Brussels

Representative: Dr. W. Schalk, Dipl.-Ing. P. Wirth,
Dipl.-Ing. GEM Dannenberg

and Dr. V. Schmied-Kowarzik, patent attorneys,
Frankfurt / M., Große Eschenheimer Str. 39

_L _ Claimed priority:

Belgium 21 December 1956

Buu Hoi, Paris,

and Camille Beaudet, Brussels,

have been named as inventors

common formula is characterized in that one coumarones of the general formula

OH

in which R has the above meaning, halogenated in a manner known per se.

The starting materials can be prepared by methods known per se (cf. e.g. Journal of the Chemical Society [London], 1955, pp. 3693 to 3695).

The process according to the invention is illustrated in more detail by the following examples.

example 1

Production of 2- (4'-oxy-3 ', 5'-diiodobenzoyl) -

3-ethyl coumarone

^J

8.05 g of 3-ethyl-2-p-oxybenzoylcoumarone (temperature = 167 to 168 ° C.) are dissolved in a very small excess of S ^ oiger sodium hydroxide solution. This solution is then gradually added a slight excess of iodine, which has been dissolved in a 25 ^fl / o aqueous solution of potassium iodide. The solution obtained is acidified with a 20% solution of sodium bisulfite, centrifuged, the residue washed with water and then subjected to reduced pressure.

-. 909 769/551

dries. The product is then recrystallized from acetic acid, yielding 13.6 g of 2- (4'-oxy-3 ', 5'-diiodobenzoyl) -3-ethyl coumarone can be obtained (m.p. = 176 ° C).

Example 2

Production of. 2- (4'-Oxy-3 ', 5'-dibromobenzoyl) -3-ethyl coumarone

A solution of 10 g of 3-ethyl-2-p-oxybenzoylcoumarone in acetic acid is treated with 12 g of bromine and heated slowly under reflux until no more gaseous hydrogen bromide is given off. After concentrating, washing several times with water, neutralizing with soda and recrystallizing from cyclohexane, 12 g of the halogenated ketone are obtained in the form of yellowish prisms. F. = 147 ° C.

Example 3
Preparation of 2- (4'-Oxy-3'-chlorobenzoyl) -coumarone

0.1 mol (23.8 g) of 2-p-oxybenzoyl coumarone (temperature = 192 to 193 ° C.) are dissolved in 200 ecm of glacial acetic acid and 100 ecm of chloroform. To this solution, 0.1 mol (13.5 g) of sulfuryl chloride is added at normal temperature, and the mixture is allowed to stand for 15 hours at normal temperature. After evaporation of the chloroform and subsequent partial evaporation of the glacial acetic acid, 21 g of crystalline 2- (4'-oxy-3'-chlorobenzoyl) coumarone are obtained, which are washed with water and recrystallized from acetic acid. F. = 190 ° C.

Claims (1)

Claim ·. Process for the preparation of substituted coumarones of the general formula OH where R is a hydrogen atom or the ethyl group ao and Y is one or more halogen atoms, characterized in that the corresponding halogen-free coumarones are known per se Way halogenated. © 909 769/551 3.6tt