DE1693032C - Process for the preparation of 1,2-disubstituted adamantane compounds - Google Patents

Description

(D

NXR ₅

in which R, R ₁ , R ₂ and R _3, which can be identical or different, represent a hydrogen atom or a lower alkyl group, R _{5 represents} a lower alkyl group and X represents a chlorine atom; Means bromine or iodine atom, characterized in that a compound of the general formula II

20th

is photochemically irradiated.

The lower alkyl group in the above formulas I and II is an alkyl group with 1 to 8 carbon atoms, especially a methyl or ethyl group.

The preparation of the starting compound of the formula II and its conversion into a compound of Formula I explains the reaction scheme shown below, for example:

NXR ₅

(H)

30th

35

is photochemically irradiated.

2. The method according to claim 1, characterized in that that the compound of formula II is irradiated in an aqueous mixture of acetic acid and sulfuric acid.

40

45

The invention relates to a process for the preparation of 1,2-disubstituted adamantane derivatives of the general Formula I.

CH • CH ₃
CH ₂ NClCH ₃

55

(D

in which R, R ₁ , R ₂ and R ₃ , which can be the same or different, each represent a hydrogen atom or a lower alkyl group, R _{5 is} a lower alkyl group and X is a chlorine. Means bromine or iodine atom.

Compounds derived from adamantane have been pulling in the pharmaceutical field in recent years considerable interest. The invention creates a new synthetic route for the preparation of compounds which are derived from adamantane as they may be a starting point for the manufacture of provides useful 1,2-disubstituted adamantane compounds.

The compounds obtainable according to the process according to the invention show a depressor effect on the central nervous system of warm-blooded animals.

3 4

Example 5 parts of adamantan-1-yl-aoston (V), 97 parts of a

^ Methylamino-Hr-cMoradamantan-l-yl). «J * g £ gjg X ^ Se ^ McÄ

_{After cooling} , 0.25 TeUe Adams-

The salt prepared according to this example is added to the catalyst and the mixture for 4 hours

Hydrochloride of the compounds I of the above reac- at room temperature using a shaker

functional schemes. The example shows how the reaction autoclave was hydrogenated at 4.2 atm. The catalyst was

scheme is practically carried out. filtered off, the filtrate with dilute acid

A. Elevation d. Auseawoduk.es “ t?! £ tf ££? * 1 £? £ fiS. £ 60 parts Adamant-1-yl-acetic acid (III) and 120 parts of aqueous phase was basified and then again with thionyl chloride were 2 hours extracted with each other to the ether Removal of the ether and reflux the removal of excess distillation of the residue gave 4 parts of thionyl chloride at normal pressure and distillation of the desired amine 2-methylamino-l- (adamantane residue under reduced pressure provided 61 parts of 15 Γ-ylJ-propane (VI) in the form of a colorless oil of adamantan-l-yl-acetyl chloride (IV) of bp 84 to bp 82 to 84 ° C at 0.55 mm Hg.
88 ° C at 0.5 mm Hg. 10 parts of 2 - methylamino - 1 - (adamantan-l'-yl) -10.5 parts of magnesium and 12 parts of anhydrous propane (VI) were in 150 parts of dichloromethane in a with ethanol Reflux condenser, dissolved in drops, and the solution mixed for 2 hours with two separate funnels and round-bottom flasks equipped with magnetic stirrers for 20 th portions of 150 parts each of sodium hypochlorite. A few drops of carbon tetrachloride solution were stirred. After separation, the mixture was added, and after 5 minutes, 40 parts of the organic layer were washed with water and added over ether, and anhydrous magnesium sulfate was dried at the temperature with stirring. The rate increased until a steady reflux was obtained. Removal of the solvent yielded 11 parts of N-chlorine. 68.6 parts of diethyl malonate, 39 parts of 25 2-methylamino-l- (adamantan-l'-yl) propane (Ha) in ethanol and 51 parts of ether were made from the drop form of a light yellow oil.
funnel slowly added and the reflux maintained- _ "
received until all the magnesium had reacted, which ^B · Implementation according to the invention
I ^1/2 hours approximately required. A solution of 11.7 parts of N-chloro-2-methylamino-1- (adamantan-80 parts of adamantan-l-yl-acetyl chloride (IV) in 30 l'-yi) propane (IIa) were in 400 parts of 5N- Sulfur 160 parts of ether were slowly added, whereupon fecic acid solution was dissolved in glacial acetic acid. The solution was solidified, the mixture was left to stand for 2 hours using a 11 Hanovia photochemical. The solid was acid treated with a dilute sulfur reactor with a straight arc lamp and the mixture was irradiated with ether for extra Ϋ / ₂ hours, whereupon a test sample was here. The organic phase was treated with water and there was no more reaction to N-chloramine during treatment and the ether was distilled off. The residue gave with potassium iodide solution. The mixture was made basic glacial acetic acid, 30 parts of sulfuric acid and 100 parts with 20% sodium hydroxide solution and extracted with ether for 16 hours with a mixture of 220 parts. The ether extract is heated to reflux. After cooling, it was washed with water, the solution was dried over anhydrous with 20% sodium hydroxide-magnesium sulfate, and the ether solution was made basic and extracted with ether. The withdrawn up to a residue volume of about ether layer was washed with water, over 150 ml. Then dry hydrogen chloride was dried in anhydrous magnesium sulfate and the solution passed in, and the precipitated amine-ether stripped off leaving a colored hydrochloride was filtered off and from ether / Ethanol of loose oil. The distillation under reduced pressure 45 recrystallized, 10.9 parts of 2-methylamino yielding 57.4 parts of adamanlan-1-yl-acetone (V) vom l- (2'-chloradammtan-r-yl) propane hydrochloride (Ia) bp. 82 to 86 ⁰ C at 0.5 to 0.6 mm Hg. From the F. 213 ^C C were obtained.

Claims (1)

Patent claims: 1. Process for the preparation of 1,2-disubstituted Adamantane derivatives of the general formula I According to the invention, the above-described adamantane compound is produced by a Compound of formula II