CS254726B1 - A method for preparing geminal dihalogen derivatives of diamantane - Google Patents

Abstract

The solution relates to a method for preparing geminal dihalogen derivatives of diamantane. These compounds can serve as intermediates for the preparation of industrially usable diamantane derivatives. The method of preparation consists in the action of thionyl chloride or thionyl bromide on diamantanone derivatives, optionally with 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 derivatives of diamantane.

Recently, it has been found that some diamantane derivatives are physiologically active and may be of use in the pharmaceutical or other industries. The reactive intermediates for the preparation of some diamantane derivatives are the geminal diamantane derivatives of diamantane. Geminal dihalogenated derivatives of hydrocarbons are prepared by reacting aldehydes or ketones with phosphorus pentahalides. A disadvantage of this process for the preparation of diamantane dihalogenates is that the reagents are generally solids which need to be thoroughly mixed to avoid local overheating of the reaction mixture. The reaction with larger amounts of reagents is difficult to handle and it is necessary to use solvents, mostly phosphorus trihalo derivatives. A further disadvantage of this process is that the reaction produces a phosphorus oxyhalide which, like phosphorus trihalo derivatives, is difficult to remove from the reaction mixture.

These drawbacks are overcome by the process for the preparation of the geminal diamantane dihalogenates of the invention. It is based on the action of thionyl chloride or thionyl bromide on diamantane derivatives at a temperature of 0 to 120 ° C. The molar ratio of thionyl chloride or thionyl bromide to diamantanone derivative used is 1 to 100 to one. The reaction rate is increased by adding hydrogen halides to the reaction mixture. Hydrogen halides can be prepared directly in the reaction mixture by the addition of substances which react with thionyl chloride, respectively. thionyl bromide to form hydrogen halides. Such substances are, for example, water, mineral or organic acids or their aqueous solutions or alcohols. The molar ratio of the abovementioned additives to the diamantanone 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 and the reaction is easily manageable even with large quantities of reagents. A further advantage is that by-products are gaseous substances that leave the reaction mixture during the reaction and unreacted thionyl halides can be easily removed by distillation under normal or reduced pressure, which greatly simplifies the isolation of the products.

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

Example 1

A solution of 10.1 g (50 mmol) of diamantanone in 80 g (672 mmol) of thionyl chloride is refluxed for 8 h. Excess thionyl chloride is distilled off, the residues are stripped off in vacuo. 12.2 g of 3,3-diohlordiamantane are obtained.

Example 2

To 5 g (25 mmol) of diamantanone was added 10.5 g (50.5 mmol) of thionyl bromide and the mixture was allowed to stand at room temperature for 1 h. Excess thionyl bromide was distilled off in vacuo. The residue was dissolved in hexane. The hexane solution was washed with water, dried and the hexane was distilled off.

8.3 g of 3,3-dibromodiamantane are obtained.

Example 3

To 2.2 g (10 mmol) ^and 5-hydroxy-3-diamantanonu 35 g (294 mmol) of thionyl chloride and the mixture was refluxed for 40 h. Excess thionyl chloride was distilled off and the residues are stripped off under vacuum. Elution chromatography of the product on silica gel gave 1.2 g of 3,3,5 -trichlordiamantanu ^e and 1.4 ^e mixture of 5-chloro ^and 5-chloro-3-diamantanonu.

Example4

To a solution of 11.1-chloro-3-diamantanone (2.4 g, 10 mmol) in thionyl chloride (35 g, 294 mmol) was added concentrated hydrochloric acid (5 mmol of hydrogen chloride, 9 mmol of water) and the mixture was refluxed. 15 ha are treated in the same way as in Example 1.

2.7 g of 1,5,5-trichlorodiamantane are obtained.

Example 5

To a solution of 2.4 g (10 mmol) of 9-chloro-3-diamantanone in 35 g (294 mmol) of thionyl chloride is added 0/2 g of water (11 mmol), the mixture is refluxed for 15 h and treated in the same manner as in Example 1. 2.8 g of 3,3,9-trichlorodiamantane are obtained.

Example

To a solution of 2.2 g (10 mmol) of 3,5-diamantanedione in 40 g (336 mmol) of thionyl chloride is added 0.25 g (14 mmol) of water and the mixture is refluxed for 60 h. Thionyl chloride is distilled off, pulled under vacuum. Elution chromatography of the product on silica gel gave 1.2 g of 5,5-dichloro-3-diamantanone and 1.2 g of unreacted diamantanedione.

Example 7

To 1.8 g (5 mmol) of 9,11-dibromo-3-diamantanone was added 10.5 g (50 mmol) of thionyl bromide and 0.2 g of concentrated hydrobromic acid (1 mmol of hydrogen bromide, 6.6 mmol of water) and the mixture was heated at 50 ° C for 20 h. Excess thionyl bromide was distilled off in vacuo and the residue dissolved in chloroform. The chloroform solution is washed with water, dried and the chloroform is distilled off. 2.4 g of 3,3,9,11-tetrabromodiamantane are obtained.

Claims (2)

PREFACE OF THE INVENTION A process for preparing geminal diamantane dihalogenates of the general formula I, wherein: 1 2 X denotes a chlorine or bromine atom and R, R denotes a hydrogen atom, an oxo group, a chlorine or bromine atom, characterized in that the diamantanone derivatives of the general formula II, wherein r3 denotes a hydrogen atom, oxo group, hydroxyl, chlorine or bromine atom, with thionyl chloride or thionyl bromide at 0 to 120 ° C, the thionyl chloride or thionyl bromide: II molar ratio being 1 to 100: 1. 2. The process of claim 1 wherein hydrogen halide or a 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.