CS209142B1 - Process for the preparation of N- (1-adamantylacidylidamide) - Google Patents

Abstract

Method for preparing N-(1-adamantyl)acylamides by oxidation of adamantane in the presence of aliphatic acid nitrile. These substances are promising compounds for the preparation of drugs with antiviral and antisclerotic effects. N-(1-adamantyl)acylamides with the number of carbon atoms in the acyl from 1 to 18 are prepared by oxidation of adamantane in the presence of the corresponding aliphatic acid nitrile in such a way that adamantane is reacted with bromine or chlorine, aliphatic acid nitrile and nitric acid. The reaction is carried out at a given temperature.

Description

The invention relates to a process for the preparation of N- (1-adamethyl) acylamides having an acyl carbon number of 1 to 18 by oxidation of adamantane in the presence of an aliphatic acid nitrile,

N- (1-adamantyl) acylamides are promising compounds for the preparation of medicaments. N- (1-adamantyl) acetamide is a precursor for the preparation of 1-aminoadamantane hydrochloride, a compound with antiviral activity. Higher fatty acid N- (1-aminamantyl) amides have been proposed as anti-sclerotic drugs.

In general, N- (1-adamantyl) acylamides can be prepared by electrooxidation of adamantane on a platinum electrode in the presence of an aliphatic acid nitrile (Koch VR, /, Miller LL: Tetrahedron Lett. 1973, No. 9, 693) or bromine oxidation in the presence of concentrated sulfuric acid; aliphatic acid nitrile (Ohsugi M., et al.: Synthesis 1977, (9), 632). However, this process is not very suitable, since a minimum of five molar excess of bromine is required for a successful reaction, the reaction time is 8 days and moreover, we have found that adamantane is lost from the reaction mixture, probably due to carbonization in concentrated sulfuric acid. known fact (Landa S., Macháček V .: Coll. Czech. Chem. Commun. 5, 1 (1933)). Furthermore, N- (1-adamantyl) acylamide can generally be prepared by the Ritter reaction of adamantane

1-haloadamantane, 1-hydroxya'damantane or 1-carboxyadamantane with an aliphatic acid nitrile in the presence of concentrated sulfuric acid. Adamantane yields are low, with other adamantane derivatives and yields ranging from 60 to 90% (Stetter H., et al .: Ber. 92, 1929 (1959); Stetter H., et al .: Ber. 93, 226 (1960)). Furthermore, β- (i-adamantyl) acyl amide can generally be prepared by reacting 1-aminoadamantane with an aliphatic acid chloride or anhydride (Stetter H., et al .: Angew. Chem. 81, 1001 (1969)) or by melting 1-haloadamantane and an aliphatic acid amide with catalysis by copper sulfate or mercuric oxide (Sztariczkai F. et al .: Pharmazie 30, No. 9, 571 (1975)) or by melting 1-haloadamantane with an aliphatic acid amide without catalyst at a temperature of at least 150 ° C with a yield of 65 to 75% (Oanki O., et al .: Author's Certificate No. 197 133). This reaction produces by-products which complicate the refining of the final product.

The disadvantages of all of the above processes are substantially eliminated by the process for the preparation of N- (1-adamantyl) acylamides having a number of carbon atoms in acyl of 1 to 18 by oxidation of adamantane in the presence of a nitrile corresponding to an aliphatic acid of the invention. bromine or chlorine, an aliphatic acid nitrile having a carbon number in the aliphatic chain of 1 to 18, and nitric acid.

The use of nitric acid creates an adamantane-halogen-nitrile of aliphatic acid-nitric acid with completely new properties, characterized by high selectivity of reaction, low, halogen consumption and high reaction rate. Nitric acid is directly involved in the reaction by oxidizing the resulting hydrogen halide back to halogen, thereby substantially reducing the amount of halogen required for the reaction, but only selectively hydrolyzing the reaction intermediates to the end product without undesirable carbonization of the adamantane.

The reaction is carried out at 0 to 100 ° C for 1 to 48 hours. After completion of the reaction, the product is readily isolated, for example by precipitation in an aqueous medium. Halogen residues in the auro2 product are removed by the action of a reducing agent, for example an aqueous sodium bisulfite solution.

This process for preparing N- (1-adamantyl) acylamides is simple, fast and inexpensive. The product is produced in high yields (at least 90%) and in high purity. This method of preparation does not impose great demands on production equipment and is suitable for industrial use.

He did.

1.4 g of adamantane, 1 g of acetonitrile, 5.25 ml of 65% nitric acid and 3.2 g of bromine were stirred at 60 ° C for 1 hour and at 70 ° C for 6 hours. The crude product was precipitated by cooling, filtered and traces of bromine were reduced with aqueous sodium bisulfite solution. Wash the product with a minimum of cold water. Yield: 1.85 g of N- (1-adamantyl) acetamide, 98.7% pure.

Example 2

1.4 g of adamantane, 1.2 g of propionitrile, 5.25 ml of 65% nitric acid and 3.2 g of bromine are stirred under reflux for 1 hour at 60 ° C and 8 hours at 70 ° C. Example 1. Yield: 1.96 g of N- (1-adamantyl) propionic acid amide of purity

97.5%.

Claims (2)

OBJECT OF THE INVENTION A process for the preparation of N- (14-adamantyl) acylamides having an acyl carbon number of 1 to 18 by oxidizing adamantane in the presence of a nitrile of the corresponding aliphatic acid, characterized in that adamantane is reacted with bromine or chlorine, aliphatic acid nitrile and nitric acid. 2. The process according to claim 1, wherein the reaction is carried out at a temperature of 0 to 100 [deg.] C. for 1 to 48 hours.