DE1643992A1 - Fluorinated ethers and process for their preparation - Google Patents

Description

FARBWERKE HOECHST AG., Formerly Meister Lucius & Brüning File number: - HOE 67 / F 21 k

Date: Mar 9, 1970 - Dr. HG / kä

Fluorinated ethers and process n to your r

A number of fluorinated compounds have already become known which have found considerable interest as narcotics. These mainly include dam 2.2.2-trifluoro-l-chloro-l-broni-Hthan (CF CHClBr), the 1.1-difluoro-2,2-dichloro-Kthyl-tnethyl-athor ₂

O-CH) and the 2.2.2-trifluoroethyl-vinyl-ether (CF, -CH_-O-CH * CK ij *

Ea has now been found that unilaterally perfluorinated athor of the general formula J;

ROR ¹

where typically a fluorinated alkyl group of 1 to 3 carbon monomers tind II a dichloromethyl or chlorobromomethyl group mean, highly effective © represent inhalation anesthetics.

The invention therefore relates to such Xther as well

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ι BATH

16A3992

Process for their manufacture.

The radicals R include: trifluoromethyl, pentafluoroethyl or heptafluoroisopropyl.

The production of chlorinated perfluoroalkyl methyl ethers takes place by direct chlorination of the corresponding perfluoroalkyl methyl ether. The conditions under which The halogenation is carried out are generally known and belong to the state of the art. One can, for example, proceed in such a way that the calculated amount of chlorine is below Exposure initiates. And the resulting hydrogen chloride is discharged via a suitable cooler. The reaction temperatures can be varied within wide limits, but are preferably between -30 ° and 4100 ° C. Isolation and cleaning the "inventionagmofißen connections takes place in known ft Way, for example by neutral washing, drying and fractional distillation of the reaction product. Are you Zweekeüfilgt a € fat »r« chufl to apply chlorine and after one distillation There is no separation of the “chlorination factors” to subject unset starting material to chlorination again. If necessary «can without interruption of the Chlorination reaction, part of the reaction mixture is continuously separated off by fractional distillation and the unreacted starting material, through fresh Starting material supplemented, fed back into the process

The production of the perfluoroalkyl chlorobromomethyl ether

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can be carried out, for example, by reacting the corresponding perfluoroalkyl dichloromethyl ether with a suitable brominating agent, for example an alkali bromide, eg LithTUäliro ^ jjlα f'otT an alkaline earth bromide such as calcium bromide, or with hydrogen bromide.

η., τ, ^ mi-t- ^ Alltali or alkaline earth bromides

The reaction is ^ in the presence of a solvent vde di-, Tri- or tetraethylene glycol dimethyl ether, dimethylformamide odor Mothanol carried out. The reaction temperatures are preferably in the range of * K) - 150 °. The work-up will carried out according to the usual methods. When using High-boiling solvents can cause the reaction product and unconverted starting material depending on.B. from the reaction * gcmisch abdostilliart and by repeated peindootillation can be separated by suitable methods Also design pi-o »ess continuously ·. ·

UrasetKunf with hydrogen bromide takes place in the gas phase «

The most inventive silic ethers are colorless, mobile Liquids. The boiling points are, in spite of the sometimes high molecular weights due to the lowering of the steam pressure Perfluorftlkylgruppe 'in the range of about 30 to 75 ° and allow thus an excellent dosage (admixture) to mix with anesthetic.

The new connections are great under normal conditions stable and, above all, do not form any disruptive acidic cleavage products. This must be done especially with the chlorine-containing compounds be regarded as surprising, since, for example, 1.l-difluoric-2.2-dichloro-ethyl-methyl-ether is known hydrogen halide even at room temperature splits off. They are also heavy or overheated non-flammable. Their special properties as inhalation « narcotics should be described in more detail in the following exi:

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In contrast to the known fluorine-containing, chlorinated ones and / or brominated anesthetics or from diethyltither the new products according to the invention by a pleasant Smell off. It is particularly noticeable that the new connections are afflicted with only minor side effects in the pharmacological test. Relatively little excitation and quick Waking up the animals is paramount.

For pharmacological testing on mice, the new, according to the invention ether in various amounts in a closed bell jar of 26 liters of eel for. Brought to evaporation, the gas mixture was swirled around in the bell from time to time. Served for comparison Diethyl ether and Penthrane® (1.1-Difluoro-2-chloroethyl methyl ether) as standard substances. The animals were each 10 minutes in the Gasrauni. The advance was checked the anesthesia as well as the awakening of the animals.

The table below shows the time T until the onset of anesthesia stage III (tolerance stage) and time A until waking up (recovery time) in mice depending on the concentration of the anesthetic agent (ml evaporated Liquid per 26 liters of air).

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. ¹ p.

TABEL

2.0 ml / 26 1

2.5 uil / 26 1 3.0 ml / 26 1

Substana T Λ T A T Λ - not CF ₃ -CF ₂ -O-CHCl ₂ - - Γ
- ί
ι «* Mm - CF-O-CHCl ₀ - - Ί
τ - 3 'ίο ·· CF -O-CHClBr I.
.1
ntfcht
Ί
ι checked I ¹ OK " - friethyl ether - I.
- i - CH ₃ -O-CF ₂ -CHCl ₂ - -. 1
• ι
3 ¹ yo " 9 * 20 " -

T - Time to _Z "m entry dme stage III dor Narkoe (tolerance stage!). A "time bi" to wake up after 10 minutes (in stage III anesthesia

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BAD ORiGINAL

fl 6 A 3992

k, 0 ml / 26 l

35 "

checked

5, O m 1/26 1 10 .0 ml / 26 1 .. T A. T A. 3 ^f 10 " 1" 2 «! 5 " j ι / _i5 «

1'20 "l ^f 30" 50 "

4 * 50 "3» 2'50 "5'3O"

ORIGINAL

From the findings it can be seen that the procedural Compounds obtained are distinguished from the comparison substances in particular by a more favorable, shorter recovery time. The danger of side effects caused by the anoxia of the heart muscle in particular and the parenchymal organs, especially the liver, is caused is largely reduced. The new fluoroethers according to the invention are therefore excellent as anesthetics in closed, semi-closed, semi-open and because of their not inflaWable properties also in the open system. - ·

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-V-

example 1 Pentaf luorothyl dichlorocycthyl ether

800 g (5.3 mol) of pentafluoroethyl-ethyl ether are placed in a round-bottomed flask equipped with a thermometer, gas inlet roller and cold condenser, then a dry chlorine atom is introduced under exposure to a UV-Larapo. The escaping hydrogen chloride is drained off via the cooler kept at -? 8. In the course of about. 750 g (10.5 mol) of chlorine are consumed in 6 hours | the temperature of the reaction mixture rises from + 5 ° to 4 °. After completion of the chlorine feed »Reaktionsgemiseh with Natrlurahydrogensulfit- and sodium bicarbonate solution is then thoroughly shaken, separated from the aqueous phase, dried with some powdered calcium chloride fractionated and ·" a packed column. You orhält 22k g forward, mainly composed Pentafluorathyl * chlorraethyl ether (Kp h3 ). The forerun can be reused in the following batches. The main line consists of 67Og pentafluoro-ethyl-dichloromethyl-ether, bp 53 ° · In the same way, 655 g (6.55 * fol) · Trifluoromethyl- Biethyl ether and 925 g (13 | 0 mol) of chlorine, 350 g of trifluoromethyldichloromethyl ether, b.p. 33 ° and from 753 g (3 «76 mol) of heptafluorieopropyl methyl ether and 535 g (7.54 mol) of chlorine ^ 35 g Heptafluoroisopropyl dichloromethyl ether of bp 72 obtained.

Example 2

In a five-phase steam sterilizer with a magnetic stirrer, there are 170 S (6.93 moles) of trifluoromethyl dichloromethyl ether, 100 g (10.0 moles) of dry powdered sodium bromide and 2000% of dimethylformamide. The mixture is heated to 100 ° for one hour. The volatile components are then driven out of the autoclave by applying a "vacuum" into a cold trap.

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BATH ORIGMAL

bia vigorously solvent passes. The condensate is shaken out with water, separated from the aqueous phase and dried with a little powdered calcium chloride. By fractional distillation, in addition to 1027 g of unconverted starting material, 85 g of trifluoromethylchlorobronunethyl ether, ^K P · 53-535 ° »are obtained.

According to the same manner 71 ° were prepared from 800 g (3.65 mol) Pentaf luorathyl dichloromethyl ether and 5OO g (5.75 mol) of lithium bromide in 2000 ml of diethylene glycol dimethyl ether 90 g Pentefluoräthyl chloro-bromo-ether, bp. Obtained.

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Claims (1)

JO l) Fluorinated ethers of the formula ROR ¹ R is a perfluoroalkyl group with 1-3 carbon atoms eii
mean. and R is a dichloromethyl or chlorobromaethyl group 2) Process for the production of fluorinated Xethers of Formally ROR ¹ , wherein R is a perfluoroalkyl group having 1-3 carbon atoms and R is a dichloromethyl or chloroboramethyl group, characterized in that corresponding Porfluoroalkyl methyl ether ^ chlorinated and preserved Products treated with a suitable brorizing agent if necessary k) Use of fluorinated ethers of the formula ROR ¹ , where R is a perfluoroalkyl group with 1-3 carbon atoms and R ^{1 is} a dichlorotnothyl or chlorobromomethyl group, ale Inhitlationamorkotika, 5) A method of anesthesia, characterized in that nan al · inhalation anesthetic is a perfluoroalkyl ether of the formula ROR ¹ , wherein R is a perfluoroalkyl group having 1-3 carbon atoms and R is a dichloromethyl or chlorobronnothyl group, applies. 109824 / 2U1 BAD ORiGiNAL