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WO1994008929A1 - Production of partially fluorinated ethers - Google Patents

Production of partially fluorinated ethers Download PDF

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Publication number
WO1994008929A1
WO1994008929A1 PCT/GB1993/002035 GB9302035W WO9408929A1 WO 1994008929 A1 WO1994008929 A1 WO 1994008929A1 GB 9302035 W GB9302035 W GB 9302035W WO 9408929 A1 WO9408929 A1 WO 9408929A1
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WO
WIPO (PCT)
Prior art keywords
group
hydrogen
fluoroalkyl group
partially fluorinated
transition metal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB1993/002035
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French (fr)
Inventor
Laurent Garnier
James Burdon
Richard Llewellyn Powell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Imperial Chemical Industries Ltd
Original Assignee
Imperial Chemical Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Imperial Chemical Industries Ltd filed Critical Imperial Chemical Industries Ltd
Publication of WO1994008929A1 publication Critical patent/WO1994008929A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
    • C07C43/04—Saturated ethers
    • C07C43/12—Saturated ethers containing halogen
    • C07C43/123—Saturated ethers containing halogen both carbon chains are substituted by halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms

Definitions

  • This invention relates to a process for the production of higher partially fluorinated ethers, in particular
  • 1-difluoromethoxy-1 ,2,2,2-tetrafluoroethane from s lower partially fluorinated ethers, that is a process for the fluorination of partially fluorinated ethers.
  • l-difluoromethoxy-l,2,2,2-tetrafluoroethane commonly known and hereafter referred to as "Desflurane” is known to have valuable anaesthetic properties but processes previously proposed for its production have suffered from various disadvantages relating to the availability and toxicity of starting materials with resulting scale-up problems for the production of commercial quantities.
  • 1-difluoromethoxy-2 ,2,2-trifluoroethane under relatively mild conditions in the vapour phase using a transition metal fluorinating agent, in particular cobalt trifluoride.
  • 1-difluoromethoxy-2 ,2,2-trifluoroethane is itself not readily prepared and the yields of Desflurane obtained by the process are not as high as may be desired, the main by-products being over-fluorinated materials which cannot therefore be further fluorinated to desflurane.
  • 1-difluoromethoxy-2, 2 , 2-trifluoroethane can be fluorinated using a transition metal fluorinating agent to give substantial yields of Desflurane and by-products which may be further fluorinated to Desflurane. Furthermore, such lower fluorinated ethers are much more readily prepared than is 1-difluoromethoxy-2 ,2,2-trifluoroethane.
  • R is a fluoroalkyl group having from 1 to 6 carbon atoms and R 1 is hydrogen, fluorine or a fluoroalkyl group having from 1 to 6 carbon atoms, provided that where R-*- is a fluoroalkyl group, R is not a trifluoromethyl group or a fluoroalkyl group having a difluoromethylene group at the ⁇ -position relative to the oxygen atom, which comprises contacting the fluorinated ether with a transition metal fluorinating agent.
  • the group R comprises a partially fluorinated alkyl group having no more than one fluorine atom attached to the carbon atom at the ⁇ -position relative to the oxygen atom, and more preferably the group R comprises a
  • R 1 is a hydrogen or fluorine atom or a trifluoromethyl group, particularly a hydrogen or fluorine atom.
  • Ve especially prefer that the group R 1 is a fluorine or hydrogen atom and the group R is a 2,2,2-trifluoroethyl or 1 , 2 , 2 , 2-tetrafluoroethyl group, since these compounds readily yield
  • a process for the production of 1-difluoromethoxy-1 ,2,2,2-tetrafluoroethane which comprises contacting a fluorinated ether having the formula
  • each R is independently fluorine or hydrogen, with a transition metal fluoride fluorinating agent.
  • the starting fluorinated ethers of the preferred embodiment of the invention are therefore (i) 1 , 1 , 1-trifluoro-2-methoxyethane , CF3CH2-O-CH3 (ii) 1,1, 1-trifluoro-2-fluoromethoxyethane , CF3CH2-O-CH2F, (iii) l,l,l,2-tetrafluoro-2-methoxyethane, CF3CHF-O-CH3 and
  • (i) may be prepared by the reaction of trifluoroethanol with dimethyl sulphate under basic conditions or by the reaction of methyl iodide with CF3CH2 ⁇ a and (ii) may be prepared by the liquid phase reaction of trifluoroethanol with a mixture of hydrogen fluoride and formaldehyde as described in our published International Patent Application No. WO 93/12057.
  • (iii) and (iv) may be prepared as described in GB Patent No. 1537861, and DT-OS 23 40 560 referred to therein, or by the liquid phase reaction of methanol and fluoral hydrate respectively with a mixture of hydrogen fluoride and formaldehyde, as described in our published International Patent Application No. WO 93/12057.
  • Cobalt trifluoride is the preferred transition metal fluoride fluorinating agent but other transition metal fluoride fluorinating agents which may be employed include, for example, the fluorides of manganese, silver and cerium or alkali metal complexes of the transition metal fluorides, for example potassium tetrafluorocobaltanate , potassium tetrafluoroargentate , and potassium hexafluoronickelate .
  • the temperature at which the process is effected will depend to some extent upon the fluorinating power of the particular fluorinating agent employed although usually the temperature will be in the range from about 150°C to about A50°C. Where the fluorinating agent is cobalt trifluoride, the temperature is preferably in the range from about 180°C to about 280°C, especially from about 200°C to about 260°C.
  • the process is conveniently operated at about atmospheric pressure, although superatmospheric or subatmospheric pressure may be employed if desired.
  • the process of the invention is preferably carried out in the vapour phase.
  • the ether is preferably vaporised over a bed of the transition metal fluorinating agent.
  • a carrier gas may be employed, for example nitrogen.
  • the product ether may be readily purified, for example by fractional distillation.
  • the reactor w s heated to a temperature of 250°C and 50g of 1 , 1 , 1-trifluoro-2-methoxyethane was passed over the catalyst in a stream of nitrogen with a flow rate of 5 litres per hour.
  • the reactor off gases were collected in a Drikold-cooled copper vessel and the organics were separated from hydrogen fluoride by treatment with water at 0°C. 25g of organic product was collected.
  • the organic product was sampled and analysed by gas chromatography.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A process for the fluorination of a partially fluorinated ether having the formula R-O-CH2-R1 wherein R is a fluoroalkyl group having from 1 to 6 carbon atoms and R1 is hydrogen, fluorine or a fluoroalkyl group having from 1 to 6 carbon atoms, provided that where R1 is a fluoroalkyl group, R is not a trifluoromethyl group or a fluoroalkyl group having a difluoromethylene group at the α-position relative to the oxygen atom, which comprises contacting the partially fluorinated ether with a transition metal fluorinating agent, especially cobalt trifluoride. 1-difluoromethoxy-1,2,2,2-tetrafluoroethane may be produced where the fluorinated ether has the formula CF¿3?-CHR-O-CH2R where each R is independently fluorine or hydrogen.

Description

PRODUCTION OF PARTIALLY FLUORINATED ETHERS.
This invention relates to a process for the production of higher partially fluorinated ethers, in particular
1-difluoromethoxy-1 ,2,2,2-tetrafluoroethane, from s lower partially fluorinated ethers, that is a process for the fluorination of partially fluorinated ethers. l-difluoromethoxy-l,2,2,2-tetrafluoroethane, commonly known and hereafter referred to as "Desflurane" is known to have valuable anaesthetic properties but processes previously proposed for its production have suffered from various disadvantages relating to the availability and toxicity of starting materials with resulting scale-up problems for the production of commercial quantities.
It has recently been proposed in European Patent Publication No. 0 A82 936 to produce Desflurane by the fluorination of
1-difluoromethoxy-2 ,2,2-trifluoroethane under relatively mild conditions in the vapour phase using a transition metal fluorinating agent, in particular cobalt trifluoride.
However , 1-difluoromethoxy-2 ,2,2-trifluoroethane is itself not readily prepared and the yields of Desflurane obtained by the process are not as high as may be desired, the main by-products being over-fluorinated materials which cannot therefore be further fluorinated to desflurane.
We have now found that lower fluorinated ethers (lower fluorine content) than
1-difluoromethoxy-2, 2 , 2-trifluoroethane can be fluorinated using a transition metal fluorinating agent to give substantial yields of Desflurane and by-products which may be further fluorinated to Desflurane. Furthermore, such lower fluorinated ethers are much more readily prepared than is 1-difluoromethoxy-2 ,2,2-trifluoroethane.
According to the present invention there is provided a process for the fluorination of a partially fluorinated ether having the formula:
R - 0 - CH2 - 1
wherein R is a fluoroalkyl group having from 1 to 6 carbon atoms and R1 is hydrogen, fluorine or a fluoroalkyl group having from 1 to 6 carbon atoms, provided that where R-*- is a fluoroalkyl group, R is not a trifluoromethyl group or a fluoroalkyl group having a difluoromethylene group at the α-position relative to the oxygen atom, which comprises contacting the fluorinated ether with a transition metal fluorinating agent.
Preferably the group R comprises a partially fluorinated alkyl group having no more than one fluorine atom attached to the carbon atom at the α-position relative to the oxygen atom, and more preferably the group R comprises a
2,2,2-trifluoroethyl or 1 , 2 , 2 , 2-tetrafluoroethyl group. Preferably R1 is a hydrogen or fluorine atom or a trifluoromethyl group, particularly a hydrogen or fluorine atom.
Ve especially prefer that the group R1 is a fluorine or hydrogen atom and the group R is a 2,2,2-trifluoroethyl or 1 , 2 , 2 , 2-tetrafluoroethyl group, since these compounds readily yield
Desflurane .
According to a preferred embodiment of the invention there is provided a process for the production of 1-difluoromethoxy-1 ,2,2,2-tetrafluoroethane which comprises contacting a fluorinated ether having the formula
CF3-CHR-0-CH2R where each R is independently fluorine or hydrogen, with a transition metal fluoride fluorinating agent.
The starting fluorinated ethers of the preferred embodiment of the invention are therefore (i) 1 , 1 , 1-trifluoro-2-methoxyethane , CF3CH2-O-CH3 (ii) 1,1, 1-trifluoro-2-fluoromethoxyethane , CF3CH2-O-CH2F, (iii) l,l,l,2-tetrafluoro-2-methoxyethane, CF3CHF-O-CH3 and
( iv) 1,1,1, 2-tetrafluoro-2-fluoromethoxyethane , CF3CFH-O-CH2F. We have found that Desflurane is produced with greater selectivity from these starting materials than when 1-difluoromethoxy-2 , 2 , 2-trifluoroethane , CF3CH2-O-CF2H is employed as the starting material. The starting materials of the present invention may be readily prepared from commercially available materials. Thus, (i) may be prepared by the reaction of trifluoroethanol with dimethyl sulphate under basic conditions or by the reaction of methyl iodide with CF3CH2θ a and (ii) may be prepared by the liquid phase reaction of trifluoroethanol with a mixture of hydrogen fluoride and formaldehyde as described in our published International Patent Application No. WO 93/12057. (iii) and (iv) may be prepared as described in GB Patent No. 1537861, and DT-OS 23 40 560 referred to therein, or by the liquid phase reaction of methanol and fluoral hydrate respectively with a mixture of hydrogen fluoride and formaldehyde, as described in our published International Patent Application No. WO 93/12057. - A -
Cobalt trifluoride is the preferred transition metal fluoride fluorinating agent but other transition metal fluoride fluorinating agents which may be employed include, for example, the fluorides of manganese, silver and cerium or alkali metal complexes of the transition metal fluorides, for example potassium tetrafluorocobaltanate , potassium tetrafluoroargentate , and potassium hexafluoronickelate .
The temperature at which the process is effected will depend to some extent upon the fluorinating power of the particular fluorinating agent employed although usually the temperature will be in the range from about 150°C to about A50°C. Where the fluorinating agent is cobalt trifluoride, the temperature is preferably in the range from about 180°C to about 280°C, especially from about 200°C to about 260°C.
The process is conveniently operated at about atmospheric pressure, although superatmospheric or subatmospheric pressure may be employed if desired.
The process of the invention is preferably carried out in the vapour phase. The ether is preferably vaporised over a bed of the transition metal fluorinating agent. A carrier gas may be employed, for example nitrogen.
The product ether may be readily purified, for example by fractional distillation.
The invention is illustrated but not limited by the following examples in which all Z are mole Z.
EXAMPLE 1.
6 kilogrammes of cobalt trifluoride were charged to an electrically heated nickel reactor vessel of length 96cm and diameter 16cm and was continually agitated by rotating nickel paddles.
The reactor w s heated to a temperature of 250°C and 50g of 1 , 1 , 1-trifluoro-2-methoxyethane was passed over the catalyst in a stream of nitrogen with a flow rate of 5 litres per hour. The reactor off gases were collected in a Drikold-cooled copper vessel and the organics were separated from hydrogen fluoride by treatment with water at 0°C. 25g of organic product was collected. The organic product was sampled and analysed by gas chromatography. The organic product contained :
60 Z 2-difluoromethoxy-l,2,2,2-tetrafluoroethane, 231 1-difluoromethoxy-2 ,2,2-trifluoroethane, 6Z 1 , 1 , 1 , 2-tetrafluoro-2-fluoromethoxyethane and 6 l-difluoromethoxy-l,l,2,2,2-pentafluoroethane.
EXAMPLE 2.
The procedure of example 1 was repeated except that the reactor was heated to 200°C. The organic product (16g) contained
57Z 2-difluoromethoxy-1 ,2,2,2-tetrafluoroethane , 27Z 1-difluoromethoxy-2 ,2,2-trifluoroethane, 51 1 , 1 , 1 , 2-tetrafluoro-2-fluoromethoxyethane and 31 1-difluoromethoxy-1 , 1 , 2 , 2 , 2-pentafluoroethane .
EXAMPLE 3.
The procedure of example 1 was repeated except that the ether passed over the cobalt trifluoride was lOOg of 1 , 1 , 2, 2-tetrafluoro-1- (2 , 2 ,2-trifluoro- ethoxy ) ethane . The organic product (88g) contained:
CF3CHFOCF2CF2H 662 CF3CH2OCF2CF2H 14Z CF3CH2OCF2CF3 9Z CF3CF2OCF2CF2H 10Z

Claims

CLAIMS .
1. A process for the fluorination of a partially fluorinated ether having the formula:
R - 0 - CH2 - R1
wherein R is a fluoroalkyl group having from 1 to 6 carbon atoms and R1 is hydrogen, fluorine or a fluoroalkyl group having from 1 to 6 carbon atoms, provided that where R1 is a fluoroalkyl group, R is not a trifluoromethyl group or a fluoroalkyl group having a difluoromethylene group at the α-position relative to the oxygen atom, which comprises contacting the partially fluorinated ether with a transition metal fluorinating agent.
2. A process as claimed in claim 1 in which the group R comprises a 1 , 1 , 1-trifluoroethyl or 1 , 1 , 1 , 2-tetrafluoroethyl group.
3. A process as claimed in claim 1 or claim 2 in which R1 is a hydrogen or fluorine atom or a trifluoromethyl group.
A. A process for the production of
2-difluoromethoxy-1 , 1,1,2-tetrafluoroethane which comprises contacting a fluorinated ether having the formula
CF3-CHR-O-CH2R where each R is independently fluorine or hydrogen, with a transition metal fluoride fluorinating agent
5. A process as claimed in any one of claims 1 to A in which the transition metal fluorinating agent is cobalt trifluoride. 6. A process as claimed in any one of claims 1 to 5 in which the temperature is in the range from about 100°C to about A50°C
PCT/GB1993/002035 1992-10-16 1993-09-30 Production of partially fluorinated ethers Ceased WO1994008929A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9221743.9 1992-10-16
GB929221743A GB9221743D0 (en) 1992-10-16 1992-10-16 Production of partially fluorinated ethers

Publications (1)

Publication Number Publication Date
WO1994008929A1 true WO1994008929A1 (en) 1994-04-28

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PCT/GB1993/002035 Ceased WO1994008929A1 (en) 1992-10-16 1993-09-30 Production of partially fluorinated ethers

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WO (1) WO1994008929A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741950A (en) * 1996-12-16 1998-04-21 Minnesota Mining And Manufacturing Company Method of preparing nonafluoroisobutyl methyl ether
US6800786B1 (en) 2002-09-25 2004-10-05 Baxter International, Inc. Preparation of desflurane

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1984002909A1 (en) * 1983-01-20 1984-08-02 Electricity Council Fluorinated ethers
EP0482938A1 (en) * 1990-10-26 1992-04-29 Rhone-Poulenc Chemicals Limited Synthesis of fluorinated ethers

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1984002909A1 (en) * 1983-01-20 1984-08-02 Electricity Council Fluorinated ethers
EP0482938A1 (en) * 1990-10-26 1992-04-29 Rhone-Poulenc Chemicals Limited Synthesis of fluorinated ethers

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741950A (en) * 1996-12-16 1998-04-21 Minnesota Mining And Manufacturing Company Method of preparing nonafluoroisobutyl methyl ether
US6800786B1 (en) 2002-09-25 2004-10-05 Baxter International, Inc. Preparation of desflurane

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Publication number Publication date
GB9221743D0 (en) 1992-12-02

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