CS218283B1 - Method of preparation of the n-acyl-1-amino-tricyclo/3,3,1,13,7/decans - Google Patents

Abstract

N-acyl-1-amino-tricyclo (3,3,1,137) by deans they are promising compounds for preparation drugs. Derivative of this substance - N- (1- -adamantyl acetamide - is a precursor for · Preparation of 1-amlnoadamantane hydrochloride which has antiviral effects. His way The preparation according to the invention consists in that the tricyclo (3,3,1,13 7) dean or his homologues of formula (II) is treated with a mixture nitric acid, hydrogen bromide and / or alkaline acid bromide and an aliphatic acid nitrile the number of carbon atoms in the aliphatic from 1 to 18 at 0 to 100 ° C after for 1 to 100 hours. The product is isolated by extraction ethanol or propanol and precipitates with the addition of water.

Description

The invention relates to a process for preparing N-acyl-1-amino-tricyclo (3.3.1.1 & ³⁷⁾ decane of the formula (I)

wherein Rt denotes an alkyl group having a number of carbon atoms of 1 to 17 by oxidation of the tricyclo (3.3,1.1 ^3,7 ) decane of formula (II)

N-acyl-1-amino-tricyclo (3,3,1,1 ^3,7 ) deans are promising compounds for drug preparation. The tricyclo (3,3,1,1 ^3,7 ) decane derivative, adamantane, N- (1-adamantyl) acetamide is a precursor for the preparation of 1-aminoadamantane hydrochloride - a compound with antiviral effects.

Higher fatty acid N- (1-adamantyl) amides are proposed as anti-sclerotic drugs. Generally, N- (1-adamantyl) acyl amides can be prepared from adamantane by electrooxidation of adamantane on a platinum electrode in the presence of an aliphatic acid nitrile (Koch VR, Miller L. L: Tetrahedron Lett. 1973, No. 9, 693) or by oxidation with bromine in the presence of concentrated sulfuric acid. aliphatic acid nitrile (Ohsugi M., et al .: Synthesis 1977, 632).

This process requires at least a 5 molar excess of bromine to be successful and the reaction time is 8 days. Further, N- (1-adamantyl) acylamide can be prepared by Ritter reaction of adamantane, 1-haloadamantane, 1-hydroxyadamantane or 1-carboxyadamantane with an aliphatic acid nitrile in excess of concentrated sulfuric acid. Adamantane yields are low, while other adamantane derivatives use yields ranging from 60 to 90 why. (Stetter, H. et al., Ber. 92, 226, 1960).

Preferably, N- (1-adamantyl) acylamide can be prepared by oxidation of adamantane in the presence of bromine, aliphatic acid nitrile and nitric acid (Kysilka V., Macoun P., A. O. 209 142). The reaction yields a product of high purity and high yield, but the bromine used in the reaction is an expensive import raw material.

Disadvantages of the above methods substantially eliminates process for preparing N-acyl-L-amino-tricyclo (3,3, l, l ³⁷⁾ decane ohecného formula (I) by oxidation of tricyclo (3.3.1.1 & ^3.7) decane formula (II) according to the invention whose principle consists in that the tricyclo (3,3, l, l ³⁷⁾ decane of the formula (II) is applied simultaneously mixture of nitric acid, hydrogen bromide and / or alkali metal bromide and the fatty acid nitrile the number of carbon atoms in the aliphatic chain 1 to 18.

The reaction is carried out at 0 to 100 ° C for 1 to 100 hours. After completion of the reaction, the mixture is degassed, for example by blowing with an inert gas, neutralized, and the product is separated from the reaction mixture by, for example, extraction with ethanol or propanol, and then precipitated with water. With high demands on the purity of the product, the ethanol solution is refined prior to precipitation, for example using activated carbon. Instead of expensive bromine, the reaction uses inexpensive hydrogen bromide or alkaline bromide, which is easy to handle on a commercial scale. The bromine is generated directly in the reaction and can be captured during and after the reaction in a suitable freezer as a by-product of the reaction.

As bromine precursors, for example, azeotropic hydrobromic acid or solutions of alkali metal bromides, which are omitted from industrial bromination reactions, can be used.

The process for preparing N-acyl-L-amino-tricyclo (3.3.1.1 & ³⁷⁾ decane is cheap, simple and the product is produced in good yields, the present method is further explained in the following examples of its embodiment.

Example 1

To 4.2 g of adamantane (0.03 mol) were added 15 ml of 65% ¹ nitric acid (0.21 mol), 10 ml of 48% hydrobromic acid (0.09 mol) and 2.5 g of acetonitrile (0.06 mol) mol). The mixture was stirred at room temperature for 12 hours and then refluxed for 6 hours. The bromine residue was blown out of the solution hot with nitrogen, then neutralized with a 40% sodium hydroxide solution and the product extracted with 15 ml of ethanol. The organic phase was refined with activated carbon and the product precipitated by the addition of 60 ml of water. 5.0 g of N- (1-adamantyl) acetamide was obtained, containing 5% by-products of the reaction. 70% of the theoretical amount of bromine was collected in the freezer.

Example 2

To 4.2 g of adamantane (0.03 mol) were added 15 ml of 65% nitric acid (0.21 mol), 9.3 g of sodium bromide (0.09 mol) and 2.5 g of acetonitrile (0.06 mol) ). The mixture was stirred at room temperature for 12 hours and then refluxed for 6 hours. Further treated in the same manner as in Example 1. 5.2 g of N- (1218283) were obtained

-adamantyl acetamide which contains 2% by-products of the reaction.

Example 3

15 ml of 65% nitric acid (0.21 mol), 10 ml of 48% hydrobromic acid (0.09 mol) and 3.5 g of propionitrile (0.064 mol) were added to 4.2 4 adamantane (0.03 mol). The mixture was stirred at room temperature for 12 hours and then at 80 ° C for 12 hours

1. 5.5 g of N- (1-adamantyl) amino propionic acid were obtained, containing 5% by-products of the reaction;

Example 4

15 ml of 65% nitric acid (0.21 mol), 10 ml of 48% hydrobromic acid and 8 g (0.03 mol) of octadecanenitrile were added to 4.2 g of adamantane (0.03 mol). The mixture was stirred at 50 ° C for 24 hours and then refluxed for 6 hours. Further processed in the same manner as in Example 1. 8.75 g of N- (1-adamantyl) stearic acid amide was obtained.

Subject

1. A process for preparing N-acyl-L-amino-tricyclo (3,3, l, l ^3-7) decane of the formula (I)

where R | denotes an alkyl group of carbon number 1-17, oxidation tricyclo (3,3, l, l ^3-7) decane of the formula (II)

Claims (4)

wherein the tricyclo (3,3,1, l ^{3 '7)} decane of the formula (II) is applied simultaneously mixture of nitric acid, hromovodíku and / or alkali metal bromide, and fatty acid nitrile of the number of carbon atoms in the aliphatic chain from 1 to 18 at 0 to 100 ° C for 1 to 100 hours. 2. A process according to claim 1 wherein the product is isolated from the reaction mixture by extraction with ethanol or propanol, and then precipitated by the addition of water. 3. Process according to claim 1, characterized in that the reaction is carried out using azeotropic hydrobromic acid and / or an alkali bromide or an aqueous solution thereof. 4. A process according to claim 1 wherein the bromine is removed from the reaction mixture by blowing with an inert gas or by distillation with an inert solvent and collected in a freezing apparatus.