CS254725B1 - A method for preparing geminal dihalogen derivatives of adamantane - Google Patents

Abstract

The solution relates to a method for preparing geminal dihalogen derivatives of adamantane. These compounds can serve as intermediates for the preparation of industrially applicable adamantane derivatives. The method of preparation consists in the action of thionyl chloride or thionyl bromide on adamantanone derivatives, possibly in the simultaneous action of hydrogen halides or compounds that, when reacted with thionyl chloride or thionyl bromide, provide hydrogen halides.

Description

The invention relates to a process for the preparation of geminal dihalogenated adamantane derivatives.

A number of adamantane derivatives find use in pharmacy, in the preparation of specialty lubricants and polymers. The reactive intermediates for the preparation of these compounds are the geminal dihalogenated derivatives of adamantane. Geminal dihalogenated hydrocarbons are prepared by reacting carbonyl compounds with phosphorus pentahalides. The application of this reaction to the preparation of geminal dihalogenated adamantane derivatives presents some difficulties. The reagents are mostly solids, they need to be thoroughly mixed, the reaction is subject to local overheating of the reaction mixture, the reaction in large quantities is difficult to handle and solvents need to be used. The by-product is a phosphorus oxyhalide which is difficult to remove from the reaction mixture.

These disadvantages are overcome by the process for preparing the geminal dihalogenated adamantane derivatives according to the invention. It is based on the action of thionyl chloride or thionyl bromide on adamantanone derivatives at 0 to 120 ° C. The molar ratio of thionyl chloride or thionyl bromide to the adamantanone derivative used is 1 to 100: 1. The reaction rate is increased by adding hydrogen halide to the reaction mixture. The addition of substances that react with thionyl chloride and / or thionyl chloride has the same effect. thionyl bromide provides hydrogen halides, for example water, mineral or organic acids, or aqueous solutions or alcohols thereof. The molar ratio of the abovementioned additives to the adamantanone derivative used is less than or equal to 10.

The advantage of the process according to the invention is, in particular, that the reaction takes place in a homogeneous liquid phase, there is no local overheating of the reaction mixture and the reaction is easily manageable even with large quantities of reagents. Another advantage is that the by-products are gaseous and unreacted thionyl halides can easily be distilled off under normal or reduced pressure, which greatly facilitates the isolation of the products.

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

Example 1

To 5 g (33 mmol) of adamantanone was added 10 g (48.1 mmol) of thionyl bromide and the mixture was allowed to stand at room temperature for 1 h. The excess thionyl bromide was then distilled off in vacuo. The residue was dissolved in hexane, the hexane solution was washed with water, dried and the hexane was distilled off. 0.5 g of 2,2-dibromadamantane is obtained.

Example 2

To 3.3 g (19.9 mmol) of 1-hydroxy-4-adamantanone was added 50 g (420 mmol) of thionyl chloride and the mixture was refluxed for 60 h. Excess thionyl chloride was distilled off, the residue was removed in vacuo. 4.4 g of 1,4,4-trichloradamantane are obtained.

Example .1 and d 3

To a solution of 3.5 g (18.9 mmol) of 1-chloro-4-adamantanone in 80 g (672 mmol) of thionyl chloride was added 0.5 g of concentrated hydrochloric acid (5 mmol of hydrogen chloride, 18 mmol of water).

The mixture was refluxed for 60 h and worked up in the same manner as in Example 2. This gave 4.2 g of 1,4,4-trichlotadamantane.

Example 4

To a solution of 4 g (21.7 mmol) of 4 ' -chloro-2-adamantanone in 80 g (672 mmol) of thionyl chloride is added 0.5 g (28 mmol) of water and the mixture is refluxed for 50 h. and the residues are drawn off under vacuum. Product elution chromatography on silica gel to give 2 g of 2,2,4 -trichloradamantanu ^e and 2.3 g of a mixture of isomers of 4-chloro-2-adamantanone.

Example 5

To a solution of 2.2 g (10 mmol) of 6,6-dichloro-2-adamantanone in 33 g (278 mmol) of thionyl chloride is added 0.25 g of concentrated hydrochloric acid (5 mmol of hydrogen chloride, 9 mmol of water) and the mixture is boiled under The excess thionyl chloride was distilled off and the residue was removed in vacuo. 2.6 g of 2,2,6,6-tetrachloradamantane are obtained.

Example6

To a solution of 2,4-adamantanedione (3.2 g, 19.5 mmol) in thionyl chloride (40 g, 336 mmol) was added water (0.25 g, 14 mmol) and refluxed for 60 h. Excess thionyl chloride was distilled off. and the residues are drawn off under vacuum. Elution chromatography of the reaction product on silica gel gave 2.1 g of 4,4-dichloro-2-adamantanone and 1.5 g of reacted 2,4-adamantanedione.

Example 7

A solution of 2 g (12.2 mmol) of 1-methyl-4-adamantanone in 35 g (294 mmol) of thionyl chloride was refluxed for 8 h and the reaction mixture was treated in the same manner as in Example 2. 2.4 g of 1- methyl-4,4-dichloradamantane.

Claims (2)

A process for the preparation of geminal dihalogenated derivatives of adamantane of the general formula I, wherein X denotes a chlorine or bromine atom and R and R denote a hydrogen atom, an alkyl group, an oxo group, a chlorine or bromine atom, characterized in that the adamantane derivative of the general formula II, wherein R and R denote a hydrogen atom, alkyl, oxo group, hydroxyl, chlorine or bromine atom with thionyl chloride or thionyl bromide at 0 to 120 ° C, the thionyl chloride or thionyl bromide: compound II molar ratio being 1 to 100: 1. 2. The process of claim 1, wherein the hydrogen halide or hydrogen halide-providing compound is reacted with thionyl chloride or thionyl bromide, wherein the molar ratio of the compound to the compound of formula II is less than or equal to 10%.