CS197133B1 - Process for preparing adamantylamides of faffy acids - Google Patents

Description

The present invention relates to a process for the preparation of fatty acid adamantylamides of the formula I

wherein R is alkyl or alkenyl of 1 to 18 carbon atoms.

Lower fatty acid Adamantylamides are intermediates for the production of aminoadamantane, which is used as a medicine against influenza and against Parkinsonism. Lower fatty acid adamides can also serve as intermediates for the preparation of plastic processing aids. Higher fatty acid Adamantylamides have caroinostatic effects and have been suggested as anti-sclerosis drugs.

These compounds have so far been prepared by essentially three methods. The first was the reaction of 1-aminoadamantane with fatty acid halides or anhydrides (Angew.Chem. 81, 1001, 1969). The disadvantage of this process is that aminoadamantane, which is The second method is the Ritter reaction, that is, the reaction of hydroxy or haloadamantane or adamantanecarboxylic acid with acid nitriles in the presence of sulfuric acid (see Ber. 92, 1629, 1959, Ber. 96, 3359, 1963, Ber. 98, 338, 1965 »Syntesis 1977, 632). A disadvantage of this method is in particular the work with highly toxic nitriles. The third method, so far most preferred, consists in reacting bromadamantane with acid amides in the presence of silver, copper or mercury compounds (Iharmao 30, 571, 1975) 155, 573). The disadvantage of this procedure is the necessity of use

197 133

197 133 catalyst.

This disadvantage is overcome by the process according to the invention for the preparation of fatty acid adamantylamides of the formula I / K 2 Z-NH-CO-R (I), wherein R is alkyl or alkenyl of 1 to 18 carbon atoms, by treatment with fatty acid amides of the formula II

R-CO-NH ₂ (II) to 1-chloro-adamantane or 1-bromo-adamantane.

Its essence is that the action is carried out at a temperature of 110 to 250 ° C, preferably 170 to 220 ° C, and a molar ratio of fatty acid amide of 1-chloro-adamantane and 1-bromo-adamantane, respectively, of greater than 0.3, preferably 0, 6 to 8.

The basic effect of the process for the production of adamantylamides of fatty acids over the known processes consists in using more readily available adamantane derivatives (chloradamantane, bromadamantane), avoiding work with toxic raw materials and avoiding work with catalyst. The acid is heated to the reaction temperature and maintained at this temperature for 10 to 200 minutes, depending on the reaction temperature and the nature of the reaction components.

The molar ratio of chloradamantane and bromadamantane, respectively, is chosen according to the fatty acid amide structure, particularly in terms of reaction mixture processing and product isolation. In the preparation of lower fatty acid adamantylamides, a higher molar ratio is preferable. The water-soluble fatty acid is then readily separated from the desired product by pouring the reaction product into water and filtering off the precipitated fatty acid adamantylamide with a suitable organic solvent.

High fatty acid amides are poorly soluble or completely insoluble in water and difficult to separate from adamantylamides of the respective fatty acid. Therefore, it is preferable to choose a lower molar ratio of the fatty acid amide haloadamantane so that all the fatty acid amide reacts. Unreacted haloadamantane is then removed from the reaction mixture by crystallization from a suitable organic solvent to give pure adamantylamide of the fatty acid.

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

Example 1

To the reaction vessel were added 8.6 g (0.04 mol) of 1-bromadamantane and 19 g (0.32 mol) of azetamide, the mixture was stirred, melted and heated to 220 ° C under reflux for 15 minutes. The reaction vessels are poured into water, the precipitated product is filtered off with suction, washed with water and dried. After that, it is dissolved in alcohol, carboraffin is added and the solution is boiled for 10 minutes.After cooling, carboraffin is filtered off with suction and distilled off. .

197 133

Example 2

8.6 g (0.04 mol) of 1-bromadamantane and 9.4 g (0.16 mol) of acetamide are used for the reaction. After stirring, the mixture is heated at 170 ° C for 30 minutes. After cooling, the mixture is poured into water and extracted with ether, the ether extract is dried, washed with water, sodium or potassium bicarbonate solution and decolorized with carboraffin. After ether is distilled off, 6.2 g of 1-adamantylacetamide is obtained.

Example 3

8.6 g (0.04 mol) of 1-bromadamantane and 7.0 g (0.12 mol) of acetamide were used in the reaction, and the mixture was heated at 170 ° C for 30 minutes and then worked up as in Example 2. It was obtained 5.7 g of 1-adamantylaoetamide.

Example 4

6.8 g (0.04 mol) of 1-chloro-adamantane and 19 g (0.32 mol) of acetamide are used for the reaction. The SS5 is heated at 190 ° C for 100 minutes and then worked up as in Example 2. This gives

5.6 g of 1-adamantylaoetamide.

Example 5

A mixture of 6.5 g (0.03 mol) of 1-bromo adamantane and 13.0 g (0.15 mol) of butyric acid amide was refluxed for 30 minutes. The reaction mixture was worked up in the same manner as in Example 1. 4 3 g of butyric acid 1-adamantylamide.

Example 6

A mixture of 6.5 g (0.03 mol) of 1-bromadamantane and 15.2 g (0.15 mol) of isovaleric amide was heated to reflux at 220 ° C for 30 minutes. The reaction mixture was ee treated as in Example 1. 4.3 g of 1-adamantylamide of isovaleric acid are obtained.

Example 7

A mixture of 6.5 g (0.03 mol) of 1-bromoadamantane and 14.9 g (0.15 mol) of allylacetic acid amide was heated to 220 ° C under reflux. The reaction mixture was worked up in the same manner as in Example 1. 3.5 g of allylacetic acid 1-adamantylamide were attracted.

Example 8

6.5 g (0.03 mol) of 1-bromadamantane and 6.0 g (0.03 mol) of lauric amide were used for the reaction. The mixture was heated at 220 ° C for 20 minutes. The reaction mixture was poured into water and extracted. ether.

of

The extract was washed with water, sodium or potassium bicarbonate solution, decolorized with carboraffin and the ether was distilled off. The residue was recrystallized from methanol to give 7.2 g of lauric acid 1-adamantylamide.

Claims (1)

SUBJECT OF THE INVENTION Process for the preparation of fatty acid adamantylamides of the formula I NH-CO-R (I) wherein R is alkyl or alkenyl of 1 to 18 carbon atoms by treatment with fatty acid amides of formula II R-CO-NHg (II) to 1-bromo-adamantane or 1-chloro-adamantane, characterized in that the treatment is carried out at a temperature of 110 to 250 ° C, preferably 170 to 220 ° C and a molar ratio of fatty acid amide to bromadamantane or chloradamantane greater than 0.3, preferably 0.6 to 8.