GB2219292A

GB2219292A - Process of preparing 1,2,2,2-tetrafluoroethyl-difluoromethyl ether

Info

Publication number: GB2219292A
Application number: GB8912072A
Authority: GB
Inventors: Toshikazu Kawai
Original assignee: Central Glass Co Ltd
Current assignee: Central Glass Co Ltd
Priority date: 1988-05-31
Filing date: 1989-05-25
Publication date: 1989-12-06
Anticipated expiration: 2009-05-25
Also published as: GB2219292B; GB8912072D0; JPH01301636A

Abstract

CF3CHFOCHF2 useful as an anaesthetic is formed by fluorinating CF3CHXOCHF2, wherein X is a halogen atom other than fluorine atom, by an alkali metal fluoride in an aprotic polar solvent in the presence of a phase-transfer catalyst such as tetramethylammonium chloride or 18-crown-6-ether. The reaction proceeds under mild conditions, and the selectivity to the aimed compound is very high. The aimed compound can easily be separated from unreacted starting compound since the boiling point of the starting compound sufficiently differs from that of the aimed compound.

Description

PROCESS OF PREPARING 1,2,2,2-TETRAFLUOROETHYL- DIFLUOROMETHYL ETHER This invention relates to a process of preparing 1,2,2,2-tetrafluoroethyldifluoromethyl ether which is a compound useful as an anaesthetic.

USP 3,897,502 shows that 1,2,2,2-tetrafluoroethyldifluoromethyl ether is obtained by fluorinating 2,2,2trifluoroethyldifluoromethyl ether by molecular fluorine. From a practical point of view it is inconvenient to use dangerous fluorine gas, and in this fluorination reaction both the conversion of the starting compound and selectivity to the aimed compound are low. Furthermore, it is difficult to purify the reaction product by distillation because the boiling point of the starting compound is close to that of the aimed compound, and hence it is difficult to obtain the aimed compound with sufficiently high purity to use it as an anaesthetic.

DE-A 2,361,508 shows that 1,2,2,2-tetrafluoroethyldifluoromethyl ether is obtained by fluorinating 1,2,2,2-tetrafluoroethyldichloromethyl ether by hydrofluoric acid. In practice, hydrofluoric acid too is a dangerous material. Furthermore, the principal product of this reaction is 1,2,2,2-tetrafluoroethylchlorofluoromethyl ether, and only a small amount of 1,2,2,2-tetrafluoroethyldifluoromethyl ether forms as a by-product. Also in this case it is difficult to obtain 1,2,2,2-tetrafluoroethyldifluoromethyl ether of high purity.

It is an object of the present invention to provide a process of preparing 1,2,2,2-tetrafluoroethyldifluoromethyl ether of high purity at good yield by using a fluorinating agent convenient for practical use.

According to the invention there is provided a process of preparing 1,2,2,2-tetrafluoroethyldifluoro- methyl ether, comprising reacting a compound represented by the general formula CF3CHXOCHF2, wherein X is a halogen atom other than fluorine atom, with an alkali metal fluoride in an aprotic polar solvent in the presence of a phase-transfer catalyst.

The fluorination reaction according to the invention is represented by the following equation.

CF3CHXOCHF2 + MFCF3CHFOCHF2 + MX wherein M represents an alkali metal.

As the starting CF3CHXOCHF2, either 1-chloro-2,2,2trifluoroethyldifluoromethyl ether or 1-bromo-2,2,2trifluoroethyldifluoromethyl ether is preferred.

It is a merit of this invention that an alkali metal fluoride, viz. a compound convenient for handling as an industrial material, is employed as the fluorinating agent. Moreover, the reaction between the starting compound and the fluorinating agent proceeds under mild conditions and forms the aimed compound, 1,2,2,2-tetrafluoroethyldifluoromethyl ether, with very high selectivity and with only very small amounts of byproducts attributed to side reactions, and the aimed compound can easily be purified by distillation of the reaction product containing unreacted starting compound because the boiling point of the starting compound is not close to that of the aimed compound.

In this invention the fluorinating agent is preferably selected from sodium fluoride, potassium fluoride and cesium fluoride. It is necessary to use at least one mol of an alkali metal fluoride per mol of the starting ether, CF3CHXOCHF2.

The fluorination reaction according to the invention is carried out in an aprotic polar solvent.

Good examples of useful solvents are sulfolan, N,Ndimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile and hexamethylphosphoramide.

The rate of the fluorination reaction and the yield of the aimed compound are enhanced by using a phasetransfer catalyst. It is preferred to select the phasetransfer catalyst from tetramethylammonium chloride, tetra-n-butylammonium bromide, benzyltrimethylammonium chloride, benzyltriethylammonium bromide, dodecyltrimethyammonium chloride and crown ethers such as 18crown-6-ether and dibenzo-18-crown-6-ether. A suitable amount of the catalyst ranges from 0.01 to 10 wt% of the starting ether.

It is suitable to carry out the fluorination reaction at a temperature in the range from 30 to 300 C.

When the reaction temperature is below 30 0C the rate of the reaction is very low. When the reaction temperature 0 is above 300 C considerable amounts of by-products are formed besides the aimed compound. The reaction time is variable depending on the reaction temperature and the quantity of the starting compound. In general it takes a few hours to tens of hours to complete the reaction.

Usually the fluorination reaction is performed in an autoclave with continuous stirring.

The reaction according to the invention gives a mixture of the aimed compound, unreacted starting compound, alkali metal halides, inevitable by-products and solvent. It is possible to directly subject this mixture to distillation to thereby obtain CF3CHFOCHF2 of high purity. However, for easily obtaining the aimed compound of high purity usually it is better to take the steps of adding water to the mixture obtained by the reaction and allowing the resultant mixture to separate into aqueous and organic layers and then subjecting only the organic layer to distillation.

The invention is further illustrated by the following nonlimitative examples.

EXAMPLE 1 A 500-ml autoclave was charged with 30-0 g of sulfolan, 110 g of CF3CHClOCHF2, 52 g of potassium fluoride and 2 g of tetramethylammonium chloride, and the mixture was stirred at 2100C for 4 hr to cause the ether to react with potassium fluoride.

After the reaction the mixture containing the reaction product was mixed with 500 g of water, and the resultant mixture was allowed to separate into an organic layer and an aqueous layer. By analysis by gas chromatography, the solute of the organic layer consisted of 64.0% of unreacted CF3CHClOCHF2, 33.9% of CF3CHFOCHF2 and 2.1% of by-produced other compounds.

That is, in the reaction the selectivity to CF3CHFOCHF2 was 94.2%. By distiling this organic mixture 30.7 g of- CF3CHFOCHF2 of 99.9% purity was obtained.

COMPARATIVE EXAMPLE The fluorination reaction of Example 1 was repeated except that the addition of tetramethylammonium chloride was omitted. No alternative catalyst was used.

After the reaction the mixture containing the reaction product was mixed with 500 g of water, and the resultant mixture was allowed to separate into an organic layer and an aqueous layer. By gas chromatography analysis, the solute of the organic layer consisted of 65.5% of unreacted CF3CHClOCHF2, 6.5% of CF3CHFOCHF2 and 28.0% of by-produced other compounds.

That is, in the reaction the selectivity to CF3CHFOCHF2 was 18.8%. This organic mixture was subjected to distillation, but it was impossible to obtain CF3CHFOCHF2 of sufficiently high purity.

EXAMPLE 2 A 1500-ml autoclave was charged with 600 g of N,Ndimethylformamide, 200 g of CF3CHClOCHF2, 104 g of potassium fluoride and 4.0 g of tetramethylammonium chloride, and the mixture was stirred at 220 0C for 4 hr to cause the ether to react with the fluoride.

After the reaction the mixture containing the reaction product was filtered. The filtrate was analyzed by gas chromatography to find that the solute consisted of 55.2% of unreacted CF3CHClOCHF2, 42.3% of CH3CHFOCHF2 and 2.5% of by-produced other compounds.

That is, in the reaction the selectivity to CF3CHFOCHF2 was 94.4%. By distilling the organic mixture 78.2 g of CF3CHFOCHF2 of 99.9% purity was obtained.

EXAMPLE 3 A 100-ml autoclave was charged with 60.0 g of sulfolan, 27.3 g of CF3CHBrOCHF2, 10.0 g of potassium fluoride and 0.5 g of tetra-n-butylammonium bromide, and the mixture was stirred at 210 0C for 4 hr to cause the ether to react with the fluoride.

After the reaction the mixture containing the reaction product was mixed with 100 g of water, and the resultant mixture was allowed to separate -into an organic layer and an aqueous layer. By analysis by gas chromatography the solute of the organic layer consisted of 39.6% of unreacted CF3CHBrOCHF2, 58.6% of CF3CHFOCHF2 - and 1.8% of by-produced other compounds. That is, in the reaction the selectivity to CF3CHFOCHF2 was 97.0%.

The organic mixture was subjected to distillation to obtain 10.1 g of CF3CHFOCHF2 of 99.9% purity.

EXAMPLE 4 A 100-ml autoclave was charged with 60.0 g of sulfolan, 22.0 g of CF3CHClOCHF2, 20.0 g of cesium fluoride and 0.4 g of 18-crown-6-ether, and the mixture was stirred at 1700C for 4 hr to cause the halogenated ether to react with the fluoride.

After the reaction the mixture containing the reaction product was mixed with 80 g of water, and the resultant mixture was allowed to separate into an organic layer and an aqueous layer. By analysi by gas chromatography the solute of the organic layer consisted of 26.3% of unreacted CF3CHClOCHF2, 72.6% of CF3CHFOCHF2 and 1.1% of by-produced other compounds. That is, in the reaction the selectivity to CF3CHFOCHF2 was 98.5%.

The organic mixture was subjected to distillation to obtain 13.0 g of CF3CHFOCHF2 of 99.9% purity.

Claims

1. A process of preparing 1,2,2,2-tetrafluoroethyldifluoromethyl ether, comprising reacting a compound represented by the general formula CF3CHXOCHF2, wherein X is a halogen atom other than fluorine atom, with an alkali metal fluoride in an aprptic polar solvent in the presence of a phase-transfer catalyst.

2. A process according to Claim 1, wherein said compound is selected from 1-chloro-2,2,2trifluoroethyldifluoromethyl ether and 1-bromo-2,2,2trifluoroethyldifluoromethyl ether.

3. A process according to Claim 1 or 2, wherein said alkali metal fluoride is selected from sodium fluoride, potassium fluoride and cesium fluoride.

4. A process according to Claim 1, 2 or 3, wherein said phase-transfer catalyst is selected from tetramethylammonium chloride, tetra-n-butylammonium bromide, benzyltrimethylammonium chloride, benzyltriethylammonium bromide and dodecyltrimethylammonium chloride.

5. A process according to Claim 1, 2 or 3, wherein said phase-transfer catalyst is selected from 18-crown6-ether and dibenzo-18-crown-6-ether.

6. A process according to any of the preceding claims, wherein the reaction is carried out at a temperature in the range from 30 to 3000C.

7. A.process according to any of the preceding claims, wherein said aprotic polar solvent is selected from sulfolan, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and hexamethylphosphoramide.

8. A process of preparing 1,2,2,2-tetrafluoroethyldifluoromethyl ether, substantially as hereinbefore described in any of Examples 1 to 4.