CS228793B1 - Process for refining (2-chloro-1,1,2-trifluoroethyl) difluoromethyl ether - Google Patents

Abstract

The essence of the invention consists in treating the above-mentioned crude ether of formula I, containing /2,2-dichloro-1,1,2-trifluoroethyl/difluoromethyl ether II,8/ or chloroform with powdered metals in protic solvents, and/or in water, and/or in the presence of surfactants, preferably zinc in water and in the presence of a solvent. Ether II is converted by reduction of the carbon-chlorine bond in the dichloromethyl group with a metal to ether I, and chloroform is converted by analogous reduction of the carbon-chlorine bond to low-boiling chloroform or methyl chloride, which is removed during rectification.

Description

The invention relates to a process for the refining of crude (2-chloro-1,1,2-trifluoroethyl) difluoromethyl ether of the formula

HCFC1-CF ₂ -O-CHF ₂ (I) containing (2,2-dichloro-1,1,2-trifluoroethyl) difluoromethyl ether of formula

CFC ₁₂ -CF ₂ -O-CHF ₂ (XI), and / or chloroform.

The ether of formula I is a modern inhalation anesthetic, the synthesis of which does not completely prevent the formation of an ether of formula II which is not removed from the ether of formula I by rectification and which, in addition to anesthetic effects, also causes muscle cramps. The content of ether II in ether I intended for pharmaceutical purposes is minimized in the synthesis process with the chlorination of (2-chloro-1,1,2-trifluoroethyl) methyl ether of the formula)

HCFC1-CF ₂ -O-CH ₃ (iii) by Se chlorece ether III to perform only power from 1.25 to 1.40 moles of chlorine per mole of ether III. Under these conditions, the (2-chloro-1,1,2-trifluoroethyl) dichloromethyl ether of formula is obtained

HCFC1-CF ₂ -O-CHC1 ₂ (IV), who ^ y is the starting material for the preparation of ether and removable fluorinating β containing a minimum amount / 2,2-dichloro-1,2-trifluoroethyl / dichlormetyléteru cfci formula -CF _{2 2} -O-I ₂ (V), which produces an undesirable fluorination ether II / RC Terrell, Summit NJ, US patent 3,469,011 / 1969 /} Brit. U.S. Patent 1,138,406 (1969); J. Med. Chem. 14, 517 (1971)].

However, this process does not completely prevent the formation of ether V and thus the presence of the undesirable ether II in ether I in relative proportions of tens of ppm.

Chloroform is formed by fluorination of ether IV to ether I. Both substances, chloroform and ether II, are very difficult to remove from ether I by rectification. According to literature, chloroform can be removed by the action of aqueous alkaline hydroxide solutions / Terrell R. C. Ger. Offen.

35 3 330 (1973)

According to the invention, these processes are overcome by a process for the refining of crude (2-chloro-1,1,2-trifluoroethyl) difluoromethyl ether (I) which contains (2,2-dichloro-1,1,2-trifluoroethyl) difluoromethyl ether (II) e. or chloroform. It is based on the fact that an ether of formula I containing an ether of formula II and / or chloroform is treated with metals, preferably zinc, magnesium, iron, cadmium, aluminum, in the presence of protic solvents such as lower alcohols, glycols, glycerol, 2- ethoxyethanol, and / or metals in water, and / or metals in water in the presence of surfactants, for example, mixtures of powdered zinc, water and Slovaviv. '

The refining is carried out by stirring an ether of formula I which contains an ether of formula II and / or a chloroform with a metal powder in a protic solvent solution, e / or an emulsion with water in the presence of a surfactant at normal temperature and / or mixtures. After completion of the reaction, the reaction mixture is worked up by distillation or / or steam distillation, washing with water, drying and rectifying.

The effect of the method according to the invention is that; The process is characterized in that the present ether of formula (II) is converted into an ether of formula (I) by reduction of the carbon-chlorine bond in the dichlorofluoromethyl group with metal.

The process according to the invention is described in the following by means of several exemplary embodiments.

Example 1

100.9 g of the ether of formula 1 containing 0.57% relative ether II and 0.15% chloroform were mixed with 50 ml of 2-ethoxyethanol and 10.0 g of zinc powder. The resulting mixture was heated to reflux (65 ° C) for 8 hours with stirring. The reaction mixture was then worked up by distillation and subsequent rectification yielded 89.5 g of ether I, bp 56.0 to 56.5 ° C, containing less than 1 ppm of ether II and no chloroform (determined by gas chromatography).

EXAMPLE 2 a <205.0 g of ether of formula I, which contained 6.3% relative ether II and 0.2% chloroform, was mixed with 50 ml of ethanol and 15.0 g of zinc powder. The mixture was heated to reflux (85 ° C) for 10 hours with stirring. To the reaction mixture was added

50 ml of water and distilled. The distillate was stripped of ethanol three times with 20 ml of water and 182 g of ether layer was obtained. The crude ether was rectified to give 157.5 g of ether I, bp 56.0 to 56.5 ° C, containing 2 ppm of ether II and no chloroform.

Example 3

516.0 g of ethers I containing 0.080% relative ether II and 0.20% relative chloroform were mixed with 300 ml of water, 60 g of zinc dust and 15 g of Slovaviv.

The mixture was heated to reflux (65 ° C) for 16 hours with stirring. After completion of the reaction, ether I was distilled off with some of the water, and after separation of water, 1,485.0 g of crude ether I were obtained. Subsequent rectification yielded 1,456.0 g of ether I, boiling at 56.0 to 56.5 ° C, containing less than 1 ppm of ether II and no chloroform.

Example

500.0 g of ether I containing 0.26% relative ether II and 0.20% relative chloroform were mixed with 150 ml of water, 50.0 g of hydrochloric acid-activated aluminum and 10.0 g of Slovaviv. The mixture was heated to reflux (65 ° C) for 16 hours with stirring. After completion of the reaction, ether I with water was distilled off and after separation of water 486.0 g of crude ether I were obtained. Subsequent rectification yielded 458.5 g of ether I, boiling at 56.0 to 56.5 ° C, containing 2 ppm of ether II and no chloroform.

Claims (2)

A process for the refining of (2-chloro-1,1,2-trifluoroethyl) difluoromethyl ether of formula hcfci-cf ₂ -o-chf ₂ (I), which comprises (2,2-dichloro-1,1,2-trifluoroethyl) difluoromethyl ether formulas CFC1 ₂ -CF ₂ -O-CHF ₂ (II) and / or chloroform, characterized in that an ether of formula I containing an ether of formula II e / or chloroform is treated with metals (Zn, Fe, Cu, Cd, Mg, Al) in protic solvents, for example in lower alcohols, glycols, glycerol, 2-ethoxyethanol, water and / or water in the presence of surfactants, preferably zinc in water and in the presence of a surfactant. Process according to claim 1, characterized in that the refining is carried out at room temperature and / or at temperatures up to the boiling point of the reaction mixture.