CA1075267A - Process for the manufacture of difluoromethyl 1,2,2-trifluoromethyl ether - Google Patents
Process for the manufacture of difluoromethyl 1,2,2-trifluoromethyl etherInfo
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- CA1075267A CA1075267A CA267,244A CA267244A CA1075267A CA 1075267 A CA1075267 A CA 1075267A CA 267244 A CA267244 A CA 267244A CA 1075267 A CA1075267 A CA 1075267A
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- ether
- difluoromethyl
- chlorine
- hydrogen
- chf2
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- 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
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A process for the manufacture of the anaesthetic compound CHF2-O-CHF-CHF2 which comprises the reduction of a mono, di- or tri-chlorinated or brominated derivative of the above compound, or the replacement by fluorine of one or more hydrogen, chlorine or bromine atoms in a less-fluorinated derivative of the above compound.
A process for the manufacture of the anaesthetic compound CHF2-O-CHF-CHF2 which comprises the reduction of a mono, di- or tri-chlorinated or brominated derivative of the above compound, or the replacement by fluorine of one or more hydrogen, chlorine or bromine atoms in a less-fluorinated derivative of the above compound.
Description
10~526~
This invention relates to a chemical process and more particularly it relates to a process for the manufacture of the compound difluoromethyl 1,2,2-trifluoroethyl ether, which has the formula CHF2-0-CHF-CHF2.
This compound has been described as a by-product obtained during the fluorination of 1,4-dioxan over cobalt trifluoride, by Burdon and Parsons in "Tetrahedron" 1971, 27, 4533 to 4551, but the yield (less than 6%) obtained was so small and the separation so complex that this process is impractical for the commercial production of the compound.
' Furthermore a process for the manufacture of the compound bythe fluorination of ethyl methyl ether over cobalt trifluoride has been described by Brandwood et' alia in the Journal of Fluorine Chemistry, 1975, 5, 521 to 535, but the yield is less than 1% and it i8 not practical to separate this amount from the major products of th'is fluorination. A second process described in this latter publication, the further fluorination over cobalt trifluoride of monofluoromethyl 1,2,2-trifluoro-ethyl ether at higher temperature, is also inconvenient for the commercial production of the compound.
We have now found, and herein lies our invention, that difluoromethyl 1,2,2-trifluoroethyl ether may conveniently be obtained in commercially attractive yields from the readily available tetrafluoroethylene by a number of processes.
According to the invention there is provided a process for the manufacture of difluoromethyl 1,2,2-trifluoro-ethyl ether whichcomprises either the reduction of a compound '' .
i - 2 -1(~75267 of the formula:-wherein X is hydrogen, chlorine or bromine, and wherein either Y and Z, which may be the same or different, each is hydrogen, chlorine or bromine, provided that X, Y and Z are not all hydrogen, or wherein Y and Z are joined together to form an olefinic bond between the two carbon atoms;
or the fluorination of a ccmpound of the f~rmula:-CHX2X3_o-cHy2-cHzlz2 wherein X2, X3, zl and z2, which may be the same or different, each is fluorine, chlorine or bromine and wherein B Y ~is hydrogen, fluorine, chlorine or bromine, provided that X , X~, y~, zl and z2 are not all fluorine.
The reduction may b~ carried out by means of hydrogen 15 and a catalyst, for example a palladium catalyst, particularly an 0.5% or 5% palladium-on-charcoal catalyst, and it may be carried out at a temperature appropriate to the reaction to be carried out, for example at a temperature of up to 250~C.
Alternatively, the reduction may be carried out by non-catalytic 20 means, for example by means of hydrogen provided by a dissolving metal, for example by use of sodium or zinc dissolving in an alcohol, for example methanol, ethanol or isopropanol~ or by use of a complex metal hydride, for example ~075Z67 lithium aluminium hydride or sodium borohydride, in an appropriate solvent, for example diglyme.
The various starting materials may ~e obtained, as shown in Figure 1, by a series of reactions starting from methyl 1,2,2-trifluorovinyl ether, which is itself conveniently obtained from tetrafluoroethylene as follows:-
This invention relates to a chemical process and more particularly it relates to a process for the manufacture of the compound difluoromethyl 1,2,2-trifluoroethyl ether, which has the formula CHF2-0-CHF-CHF2.
This compound has been described as a by-product obtained during the fluorination of 1,4-dioxan over cobalt trifluoride, by Burdon and Parsons in "Tetrahedron" 1971, 27, 4533 to 4551, but the yield (less than 6%) obtained was so small and the separation so complex that this process is impractical for the commercial production of the compound.
' Furthermore a process for the manufacture of the compound bythe fluorination of ethyl methyl ether over cobalt trifluoride has been described by Brandwood et' alia in the Journal of Fluorine Chemistry, 1975, 5, 521 to 535, but the yield is less than 1% and it i8 not practical to separate this amount from the major products of th'is fluorination. A second process described in this latter publication, the further fluorination over cobalt trifluoride of monofluoromethyl 1,2,2-trifluoro-ethyl ether at higher temperature, is also inconvenient for the commercial production of the compound.
We have now found, and herein lies our invention, that difluoromethyl 1,2,2-trifluoroethyl ether may conveniently be obtained in commercially attractive yields from the readily available tetrafluoroethylene by a number of processes.
According to the invention there is provided a process for the manufacture of difluoromethyl 1,2,2-trifluoro-ethyl ether whichcomprises either the reduction of a compound '' .
i - 2 -1(~75267 of the formula:-wherein X is hydrogen, chlorine or bromine, and wherein either Y and Z, which may be the same or different, each is hydrogen, chlorine or bromine, provided that X, Y and Z are not all hydrogen, or wherein Y and Z are joined together to form an olefinic bond between the two carbon atoms;
or the fluorination of a ccmpound of the f~rmula:-CHX2X3_o-cHy2-cHzlz2 wherein X2, X3, zl and z2, which may be the same or different, each is fluorine, chlorine or bromine and wherein B Y ~is hydrogen, fluorine, chlorine or bromine, provided that X , X~, y~, zl and z2 are not all fluorine.
The reduction may b~ carried out by means of hydrogen 15 and a catalyst, for example a palladium catalyst, particularly an 0.5% or 5% palladium-on-charcoal catalyst, and it may be carried out at a temperature appropriate to the reaction to be carried out, for example at a temperature of up to 250~C.
Alternatively, the reduction may be carried out by non-catalytic 20 means, for example by means of hydrogen provided by a dissolving metal, for example by use of sodium or zinc dissolving in an alcohol, for example methanol, ethanol or isopropanol~ or by use of a complex metal hydride, for example ~075Z67 lithium aluminium hydride or sodium borohydride, in an appropriate solvent, for example diglyme.
The various starting materials may ~e obtained, as shown in Figure 1, by a series of reactions starting from methyl 1,2,2-trifluorovinyl ether, which is itself conveniently obtained from tetrafluoroethylene as follows:-
2 2 + NaOCH3 > CH~0-CF = CF
It is to be understood that in the scheme shown in Figure 1 two of X, Y and Z may sometimes be the same halogen atom, in which case the same symbol (Xl or yl) is used in both positions.
Some of the intermediate compounds described in Figure 1 are novel compounds. In particular, the compounds ; of the following formulae are novel and are particularly exemplified herein, and these form further features of the invention:-CHC12-0-CFCl-CF2Cl (A) CHF2-0-CFCl-CF2Cl (B) CHF2 - o-cF = cF2 ( C ) CHF2-0-CFCl-CEIF2 (D) CC13-0-CHF-CHF2 (E) t CF2Cl-0-CHF-CHF2 (F) CHC12-0-CFCl-CHF2 (G) and CHC12-0-CHF-CHF2 (H) , , ,~
..' ~:;;
~;~`' ' ~ ~.
,~ -~ ~ X C ~ ~
" ~ .
8~ a ~~ .
h a ~ N ~ ~ d D
~ ~1 ~ 1 t I T ~ ~ ~ ~
.
.~ ~o ^¢ ~ û~
~ ~ ~ x~ O
~.~
v ~" 1075267 The fluorination process of the invention may be carried out using a conventional fluorinating agent.
Thus, for example, a suitable fluorinating agent which may be used to replace a chlorine or bromine atom x2 or X3 by fluorine is, for example, antimony trifluoride.
x2 and X3 are preferably both chlorine atoms. A suitable fluorinating agent which may be used to replace a chlorine ~ or bromine atom y2~ zl or z2 by fluorine i8, for example, ¦ mercuric fluoride. y2~ zl and z2 are preferable all chlorine atoms. A suitable fluorinating agent which may be used to replace the hydrogen atom y2 by fluorine is, ~; for example, chlorine trifluoride or bromine trifluoride.
The starting material of the formula CHF2-0-CHY CHF2 ~: ~ ;. ` 2 t~ ' wherein Y is hydrogen-or chlorine is a known compound ~ ~ .S`
~ f" 'i'~. ~ 15 ~ ournal of Medicinal Chemistry, 1971, 14, 517 to 519).
~c~ ,~
The difluoromethyl 1,2,2-trifluoroethyl ether possesses valuable anaesthetic properties and may be used in the anaesthetic composition described and claimed in our copending Canadian Application Serial No. 250,113.
The invention is illustrated but not limited by the following Examples:-Example 1 A stream of hydrogen is passed at the rate of 7650 ml. per minute through 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether (48 g.) and the gaseous mixture thus obtained is passed through a horizontal tube, 60 cm. long and 7.5 cm. in diameter, which contains a 5% palladium-on-charcoal catalyst (20 g.) heated to a temperature of between 200 and 250C. The process is continued until all of the ether has been carried over the catalyst. The gases leaving the tube are ~ passed into a vessel cooled with solid carbon dioxide in acetone.
; The collected liquid is fractionally distilled and there is thus ob-tained difluoromethyl 1,2,2-tr-fluoroethyl ether (19 g.) b.p. 53-54C.
The 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether used as starting material may be obtained as follows:-Chlorine gas is passed through 1,2-dichloro-1,2,2-tri-fluoroethyl methyl ether (68 g.) which is contained in a 50 ml. radi-ation cell fitted with a condenser and a solid carbon dioxide in acetone trap, and which is irradiated by means of a Hanovia* medium pressure lamp. An exothermic reaction takes place, the internal temperature rising to 50C. When the weight of the reaction mixture has increased to 99 g., * Trademark ~: . ;
~ - .
' - ' ~ ' - , :
, -indicating replacement of two atoms of hydrogen by two atomæ
of chlorine, the reaction i8 stopped and the reaction mixture fractionally distilled. There is thus obtained dichloromethyl 1,2-dichloro-1,2,2-trifluoroethyl ether, b.p. 127C.
The above material (48 g.) is added slowly to antimony trifluoride (35.8 g.) which is stirred at 90C., and the product which distils from the reaction is collected in a vessel cooled by solid carbon dioxide. The product is fractionally distilled and there is thus obtained 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether, b.p. 61-61.5C.
Example 2 A stream of hydrogen is passed at the rate of 750 ml.
per minute over the surface of difluoromethyl 1,2,2-trifluoro-vinyl ether (25.4 g.) and the gaseous mixture thus obtained is passed through a horizontal tube, 50 cm.long and 2.5 cm. in diameter, which contains a 5% palladium-on-charcoal catalyst (40 g.) supported on small porcelain cylinders (100 g.) and ;~ heated to a temperature of 60C. The process is continued until all of the ether has been carried over the catalyst.
The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid (15.6 g.) is fractionally distilled, some starting material (8.5 g.) being recovered and there is thus obtained difluoro-~;¢~0~^0~
D methyl 1,2,2-triflùoromc~hyl ether, b.p. 53-54C., in 40% yield based on the vinyl ether consumed.
The difluoromethyl 1,2,2-trifluorovinyl ether used as starting material may be obtained as follows:-1,2-Dichloro-1,2,2-trifluoroethyl difluoromethyl ether (50 g.) is added dropwise during 30 minutes to a stirred suspension of zinc dust ~25 g.) and zinc chloride (1.65 g.) in dimethylsulphoxide (125 ml.) which is maintained at 110C.
The volatile gases which distil out of the reaction mixture are condensed in a trap cooled with solid carbon dioxide in acetone. The collected liquid is fractionally distilled and there is thus obtained difluoromethyl 1,2,2-trifluorovinyl ether, b.p. 10.5-11C (25.4 g.) Example 3 A stream of hydrogen at the rate of 500-600 ml. per minute is passed over difluoromethyl 1,2,2-trifluorovinyl ether ~50.4 g.) which is cooled to -5C. The gaseous mix-ture thus obtained is passed through a vertical tube, 45 cm.
long and 2.5 cm. in diameter, which contains 80 g. of an 0.5%
palladium-on-charcoal catalyst heated at 153C. The gases leaving the tube are passed into a vessel coolet with solid carbon dioxide in acetone. The collected liquid ~36 g.) is washed with water and then with saturated aqueous sodium bicarbonate solution, dried over magnesium sulphate and then fractionally distilled. There is thus obtained difluoromethyl 1,2,2-trifluoroethyl ether (21.5 g.), b.p. 53-54C.
Example 4 A stream of hydrogen is passed at the rate of 500 ml.
per minute through l-chloro-1,2,2-trifluoroethyl difluoro-methyl ether (5.7 g.) and the gaseous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm.
_g_ .
in diameter, which contains an ().56% palladium-on-charcoal catalyst (80 g.) heated at 240C. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid is poured onto ice-water~
5 separated from the water, dried over magnesium sulphate and fractionally distilled. There is thus obtained difluoromethyl 1,2,2,-trifluoroethyl ether, b.p. 53-54C., in 45% yield.
The l-chloro-1,2,2-trifluoroethyl difluoromethyl ether used as starting material may be obtained as follows:-A stream of hydrogen chloride is passed at the rate of 500 ml. per minute over difluoromethyl 1,2,2-trifluorovinyl ether (53 g.) which is cooled to -6 C., and the gaseous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which 15 contains a catalyst consisting of a 4:1 weight by weight mixture of granular carbon (10-18 mesh) and calcium sulphate (8 mesh) heated at 186 C. The reaction is exothermic and the temperature rises to 229 C. The gases leaving the tube ~re passed into a vessel cooled with solid carbon dioxide 20 in acetone. The collected liquid (42.4 g.) is poured onto ice-water, separated from the water, dried over magnesium sulphate and then fractionally distilled. There is thus obtained l-chloro-1,2,2-trifluoroethyl di~luoromethyl ether (4.5 g., b.p. 56C.), and later fractions of the distillate 25 consist o~ 2-chloro-1,2,2-trifluoroethyl difluoromethyl ether (17.5 g., b.p. 56 C.~ used as starting material in Examples 6, 7 and 8) and 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether (7.9 g., b.p. 61-61.5C.) . , -- ~.0 --.. . . .
1075'~67 Example 5 A mixture of l-chloro-1,2J2-trifluoroethyl difluoro-methyl ether (1.8 g.), zinc (3.5 g.), zinc chloride (0.3 g.) and absolute alcohol (12 ml.) is heated at 150C. in a sealed, shaken vessel for 24 hours. The reaction mixture is fractionally distilled and the distillate boiling within the range 54-77C. (7.0 g.) is collected. This distillate is further fraction-ally distilled and there is thus obtained difluoromethyl 1J2~2-trifluoroethyl ether, b.p. 53-54C., in 40% yield.
Example 6 A mixture of 2-chloro-1,2,2-trifluoroethyl difluoro-methyl ether ~3 g.), zinc powder (6.5 g.), zinc chloride (0.2 g.) and absolute alcohol (10 ml.) is heated at 150C. in a sealed glass tube for 24 hours. The reaction mixture is then fraction-ally distilled using a Vigreux distillation column, and the fraction boiling within the range 42-60C. is collected. This material is further separated into its constitu~nts by gas-liquid chromatography using a 10% Carbowax* column, and there is thus obtainet difluoromethyl 1,2,2-trifluoroethyl ether.
Example 7 Sodium metal (0.46 g.) is gradually added to a stirred mixture of 2-chloro-1,2,2-trifluoroethyl difluoro-methyl ether (1.8 g.) and absolute methanol (1.0 ml.), and after the reaction is complete the mixture is filtered and the filtrate is washed with water and dried over molecular sieve 4A.
The material thus obtained is separated into its constituents by preparati~e gas liquid chromatography using a 20% Carbowax* 20 M
column at 7~C,, and there is thus obtained difluoromethyl 1,2,2-* Trade mark -11-: .
`
trifluoroethyl ether.
Example 8 A solution of sodium borohydride (0.53 g.) in diglyme (7 ml.) i5 added gradually durin~ thirty minutes to a stirred mixture Or 2-chloro-1,2,2-trifluoroethyl difluoromethyl ether (1.85 g.), water (0.9 ml.) and diglyme (4 ml.) which is maintained at 5C. Water is then added to the reaction mixture and the lower organic layer is separated, washed with water and dried over molecular sieve 4A. The material thus obtained is separated into its constituent parts by gas-liquid chromatography, and there is thus obtained di~luoromethyl 1,2,2-trifluoroethyl ether.
Example 9 A stream of hydrogen at the rate of 500-600 ml.
per minute is passed through a mixture of 1-bromo-1,2,2-trifluoroethyl difluoromethyl ether (4.2 g.) and 2-bromo-1,2,2-trifluoroethyl difluoromethyl ether (2.0 g.) and the gaReous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which contains 80 g. of an 0.5% palladium-on-charcoal catalyst heated at 240C. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid is poured onto ice-water and the non-aqueous layer is separated, dried over magnesium sulphate and then fractionally distilled. There is thus obtained difluoromethyl 1,2,2-trifluoroethyl ether, b.p. 53-54~C., in 40% yield.
The mixture Gf di~luoromethyl 1-bromo-1,2,2-trifluoroethyl ether and di~luoromethyl 2-bromo-1,2,2-tri~luoro-ethyl ether used as starting material may be obtained as follows:--- 1~ --.
A stream of hydrogen bromide is passed at a rate of 500 ml. per minute over difluoromethyl 1,2,2-trifluoro-vinyl ether (21.3 g.) which is cooled to -8C., and the gaseous mixture thus obtained passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which contains a catalyst consisting of a 4:1 weight by weight mixture of granular carbon (10-18 mesh) and calcium sulphate (8 mesh) heated at 158C. The reaction is exothermic and the temperature rises to 170C. after the passage of gases has continued for 20 minutes. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid (15 g.) is poured into ice-water and the organic layer is separated, dried over magne~ium sulphate and then fractionally distilled. There is thus obtained a mixture f l-bromo-1,2,2-trifluo~oethyl difluoromethyl ether (7 g.), b.p. 72.5C., and 2-bromo-1,2,2-trifluoroethyl difluoromethyl ether (3.3 g.), b.p. 72.5-73C.
Example 10 Chlorine gas is passed through methyl 1,2,2-tri-fluoroethyl ether (14 g.) which is contained in a glass radiation cell fitted with a condenser and a solid carbon dioxide in acetone trap, and which is cooled in ice-water B ar~d irradiated by means of a Hanovia medium pressure lamp, until 17 g. of chlorine have been absorbed. The reaction mixture is distilled and there is thus obtained a mixture containing as main components dichloromethyl 1,2,2-trifluoro ethyl ether, trichloromethyl 1,2,2-trifluoroethyl ether and dichloromethyl l-chloro-1,2,2-trifluoromethyl ether.
This mixture i5 added dropwise to a stirred mixture of : antimony trifluoride (20 g.) and antimony pentachloride (1 ml.) which is heated at 105C., and the product which distils from the reaction having a boiling point within the range 53 to 66~C. is collected. This product is fractionally distilled and there is thus obtained as second fraction di~luoromethyl 1,2,2-trifluoroethyl ether, b.p. 53-54~., yield 23% based on the methyl trifluoroethyl ether starting material. Another product of the fluorination reaction, which is the rirst fraction in the distillation, is chlorodifluoromethyl 1,2,2-trifluoroethyl ether, b.p. 46C.
(yield 20%).
The methyl 1,2,2-trifluoroethyl ether used as starting material may be obtained as follows:-A stream Or hydrogen is passed for 2 hours at the
It is to be understood that in the scheme shown in Figure 1 two of X, Y and Z may sometimes be the same halogen atom, in which case the same symbol (Xl or yl) is used in both positions.
Some of the intermediate compounds described in Figure 1 are novel compounds. In particular, the compounds ; of the following formulae are novel and are particularly exemplified herein, and these form further features of the invention:-CHC12-0-CFCl-CF2Cl (A) CHF2-0-CFCl-CF2Cl (B) CHF2 - o-cF = cF2 ( C ) CHF2-0-CFCl-CEIF2 (D) CC13-0-CHF-CHF2 (E) t CF2Cl-0-CHF-CHF2 (F) CHC12-0-CFCl-CHF2 (G) and CHC12-0-CHF-CHF2 (H) , , ,~
..' ~:;;
~;~`' ' ~ ~.
,~ -~ ~ X C ~ ~
" ~ .
8~ a ~~ .
h a ~ N ~ ~ d D
~ ~1 ~ 1 t I T ~ ~ ~ ~
.
.~ ~o ^¢ ~ û~
~ ~ ~ x~ O
~.~
v ~" 1075267 The fluorination process of the invention may be carried out using a conventional fluorinating agent.
Thus, for example, a suitable fluorinating agent which may be used to replace a chlorine or bromine atom x2 or X3 by fluorine is, for example, antimony trifluoride.
x2 and X3 are preferably both chlorine atoms. A suitable fluorinating agent which may be used to replace a chlorine ~ or bromine atom y2~ zl or z2 by fluorine i8, for example, ¦ mercuric fluoride. y2~ zl and z2 are preferable all chlorine atoms. A suitable fluorinating agent which may be used to replace the hydrogen atom y2 by fluorine is, ~; for example, chlorine trifluoride or bromine trifluoride.
The starting material of the formula CHF2-0-CHY CHF2 ~: ~ ;. ` 2 t~ ' wherein Y is hydrogen-or chlorine is a known compound ~ ~ .S`
~ f" 'i'~. ~ 15 ~ ournal of Medicinal Chemistry, 1971, 14, 517 to 519).
~c~ ,~
The difluoromethyl 1,2,2-trifluoroethyl ether possesses valuable anaesthetic properties and may be used in the anaesthetic composition described and claimed in our copending Canadian Application Serial No. 250,113.
The invention is illustrated but not limited by the following Examples:-Example 1 A stream of hydrogen is passed at the rate of 7650 ml. per minute through 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether (48 g.) and the gaseous mixture thus obtained is passed through a horizontal tube, 60 cm. long and 7.5 cm. in diameter, which contains a 5% palladium-on-charcoal catalyst (20 g.) heated to a temperature of between 200 and 250C. The process is continued until all of the ether has been carried over the catalyst. The gases leaving the tube are ~ passed into a vessel cooled with solid carbon dioxide in acetone.
; The collected liquid is fractionally distilled and there is thus ob-tained difluoromethyl 1,2,2-tr-fluoroethyl ether (19 g.) b.p. 53-54C.
The 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether used as starting material may be obtained as follows:-Chlorine gas is passed through 1,2-dichloro-1,2,2-tri-fluoroethyl methyl ether (68 g.) which is contained in a 50 ml. radi-ation cell fitted with a condenser and a solid carbon dioxide in acetone trap, and which is irradiated by means of a Hanovia* medium pressure lamp. An exothermic reaction takes place, the internal temperature rising to 50C. When the weight of the reaction mixture has increased to 99 g., * Trademark ~: . ;
~ - .
' - ' ~ ' - , :
, -indicating replacement of two atoms of hydrogen by two atomæ
of chlorine, the reaction i8 stopped and the reaction mixture fractionally distilled. There is thus obtained dichloromethyl 1,2-dichloro-1,2,2-trifluoroethyl ether, b.p. 127C.
The above material (48 g.) is added slowly to antimony trifluoride (35.8 g.) which is stirred at 90C., and the product which distils from the reaction is collected in a vessel cooled by solid carbon dioxide. The product is fractionally distilled and there is thus obtained 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether, b.p. 61-61.5C.
Example 2 A stream of hydrogen is passed at the rate of 750 ml.
per minute over the surface of difluoromethyl 1,2,2-trifluoro-vinyl ether (25.4 g.) and the gaseous mixture thus obtained is passed through a horizontal tube, 50 cm.long and 2.5 cm. in diameter, which contains a 5% palladium-on-charcoal catalyst (40 g.) supported on small porcelain cylinders (100 g.) and ;~ heated to a temperature of 60C. The process is continued until all of the ether has been carried over the catalyst.
The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid (15.6 g.) is fractionally distilled, some starting material (8.5 g.) being recovered and there is thus obtained difluoro-~;¢~0~^0~
D methyl 1,2,2-triflùoromc~hyl ether, b.p. 53-54C., in 40% yield based on the vinyl ether consumed.
The difluoromethyl 1,2,2-trifluorovinyl ether used as starting material may be obtained as follows:-1,2-Dichloro-1,2,2-trifluoroethyl difluoromethyl ether (50 g.) is added dropwise during 30 minutes to a stirred suspension of zinc dust ~25 g.) and zinc chloride (1.65 g.) in dimethylsulphoxide (125 ml.) which is maintained at 110C.
The volatile gases which distil out of the reaction mixture are condensed in a trap cooled with solid carbon dioxide in acetone. The collected liquid is fractionally distilled and there is thus obtained difluoromethyl 1,2,2-trifluorovinyl ether, b.p. 10.5-11C (25.4 g.) Example 3 A stream of hydrogen at the rate of 500-600 ml. per minute is passed over difluoromethyl 1,2,2-trifluorovinyl ether ~50.4 g.) which is cooled to -5C. The gaseous mix-ture thus obtained is passed through a vertical tube, 45 cm.
long and 2.5 cm. in diameter, which contains 80 g. of an 0.5%
palladium-on-charcoal catalyst heated at 153C. The gases leaving the tube are passed into a vessel coolet with solid carbon dioxide in acetone. The collected liquid ~36 g.) is washed with water and then with saturated aqueous sodium bicarbonate solution, dried over magnesium sulphate and then fractionally distilled. There is thus obtained difluoromethyl 1,2,2-trifluoroethyl ether (21.5 g.), b.p. 53-54C.
Example 4 A stream of hydrogen is passed at the rate of 500 ml.
per minute through l-chloro-1,2,2-trifluoroethyl difluoro-methyl ether (5.7 g.) and the gaseous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm.
_g_ .
in diameter, which contains an ().56% palladium-on-charcoal catalyst (80 g.) heated at 240C. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid is poured onto ice-water~
5 separated from the water, dried over magnesium sulphate and fractionally distilled. There is thus obtained difluoromethyl 1,2,2,-trifluoroethyl ether, b.p. 53-54C., in 45% yield.
The l-chloro-1,2,2-trifluoroethyl difluoromethyl ether used as starting material may be obtained as follows:-A stream of hydrogen chloride is passed at the rate of 500 ml. per minute over difluoromethyl 1,2,2-trifluorovinyl ether (53 g.) which is cooled to -6 C., and the gaseous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which 15 contains a catalyst consisting of a 4:1 weight by weight mixture of granular carbon (10-18 mesh) and calcium sulphate (8 mesh) heated at 186 C. The reaction is exothermic and the temperature rises to 229 C. The gases leaving the tube ~re passed into a vessel cooled with solid carbon dioxide 20 in acetone. The collected liquid (42.4 g.) is poured onto ice-water, separated from the water, dried over magnesium sulphate and then fractionally distilled. There is thus obtained l-chloro-1,2,2-trifluoroethyl di~luoromethyl ether (4.5 g., b.p. 56C.), and later fractions of the distillate 25 consist o~ 2-chloro-1,2,2-trifluoroethyl difluoromethyl ether (17.5 g., b.p. 56 C.~ used as starting material in Examples 6, 7 and 8) and 1,2-dichloro-1,2,2-trifluoroethyl difluoromethyl ether (7.9 g., b.p. 61-61.5C.) . , -- ~.0 --.. . . .
1075'~67 Example 5 A mixture of l-chloro-1,2J2-trifluoroethyl difluoro-methyl ether (1.8 g.), zinc (3.5 g.), zinc chloride (0.3 g.) and absolute alcohol (12 ml.) is heated at 150C. in a sealed, shaken vessel for 24 hours. The reaction mixture is fractionally distilled and the distillate boiling within the range 54-77C. (7.0 g.) is collected. This distillate is further fraction-ally distilled and there is thus obtained difluoromethyl 1J2~2-trifluoroethyl ether, b.p. 53-54C., in 40% yield.
Example 6 A mixture of 2-chloro-1,2,2-trifluoroethyl difluoro-methyl ether ~3 g.), zinc powder (6.5 g.), zinc chloride (0.2 g.) and absolute alcohol (10 ml.) is heated at 150C. in a sealed glass tube for 24 hours. The reaction mixture is then fraction-ally distilled using a Vigreux distillation column, and the fraction boiling within the range 42-60C. is collected. This material is further separated into its constitu~nts by gas-liquid chromatography using a 10% Carbowax* column, and there is thus obtainet difluoromethyl 1,2,2-trifluoroethyl ether.
Example 7 Sodium metal (0.46 g.) is gradually added to a stirred mixture of 2-chloro-1,2,2-trifluoroethyl difluoro-methyl ether (1.8 g.) and absolute methanol (1.0 ml.), and after the reaction is complete the mixture is filtered and the filtrate is washed with water and dried over molecular sieve 4A.
The material thus obtained is separated into its constituents by preparati~e gas liquid chromatography using a 20% Carbowax* 20 M
column at 7~C,, and there is thus obtained difluoromethyl 1,2,2-* Trade mark -11-: .
`
trifluoroethyl ether.
Example 8 A solution of sodium borohydride (0.53 g.) in diglyme (7 ml.) i5 added gradually durin~ thirty minutes to a stirred mixture Or 2-chloro-1,2,2-trifluoroethyl difluoromethyl ether (1.85 g.), water (0.9 ml.) and diglyme (4 ml.) which is maintained at 5C. Water is then added to the reaction mixture and the lower organic layer is separated, washed with water and dried over molecular sieve 4A. The material thus obtained is separated into its constituent parts by gas-liquid chromatography, and there is thus obtained di~luoromethyl 1,2,2-trifluoroethyl ether.
Example 9 A stream of hydrogen at the rate of 500-600 ml.
per minute is passed through a mixture of 1-bromo-1,2,2-trifluoroethyl difluoromethyl ether (4.2 g.) and 2-bromo-1,2,2-trifluoroethyl difluoromethyl ether (2.0 g.) and the gaReous mixture thus obtained is passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which contains 80 g. of an 0.5% palladium-on-charcoal catalyst heated at 240C. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid is poured onto ice-water and the non-aqueous layer is separated, dried over magnesium sulphate and then fractionally distilled. There is thus obtained difluoromethyl 1,2,2-trifluoroethyl ether, b.p. 53-54~C., in 40% yield.
The mixture Gf di~luoromethyl 1-bromo-1,2,2-trifluoroethyl ether and di~luoromethyl 2-bromo-1,2,2-tri~luoro-ethyl ether used as starting material may be obtained as follows:--- 1~ --.
A stream of hydrogen bromide is passed at a rate of 500 ml. per minute over difluoromethyl 1,2,2-trifluoro-vinyl ether (21.3 g.) which is cooled to -8C., and the gaseous mixture thus obtained passed through a vertical tube, 45 cm. long and 2.5 cm. in diameter, which contains a catalyst consisting of a 4:1 weight by weight mixture of granular carbon (10-18 mesh) and calcium sulphate (8 mesh) heated at 158C. The reaction is exothermic and the temperature rises to 170C. after the passage of gases has continued for 20 minutes. The gases leaving the tube are passed into a vessel cooled with solid carbon dioxide in acetone. The collected liquid (15 g.) is poured into ice-water and the organic layer is separated, dried over magne~ium sulphate and then fractionally distilled. There is thus obtained a mixture f l-bromo-1,2,2-trifluo~oethyl difluoromethyl ether (7 g.), b.p. 72.5C., and 2-bromo-1,2,2-trifluoroethyl difluoromethyl ether (3.3 g.), b.p. 72.5-73C.
Example 10 Chlorine gas is passed through methyl 1,2,2-tri-fluoroethyl ether (14 g.) which is contained in a glass radiation cell fitted with a condenser and a solid carbon dioxide in acetone trap, and which is cooled in ice-water B ar~d irradiated by means of a Hanovia medium pressure lamp, until 17 g. of chlorine have been absorbed. The reaction mixture is distilled and there is thus obtained a mixture containing as main components dichloromethyl 1,2,2-trifluoro ethyl ether, trichloromethyl 1,2,2-trifluoroethyl ether and dichloromethyl l-chloro-1,2,2-trifluoromethyl ether.
This mixture i5 added dropwise to a stirred mixture of : antimony trifluoride (20 g.) and antimony pentachloride (1 ml.) which is heated at 105C., and the product which distils from the reaction having a boiling point within the range 53 to 66~C. is collected. This product is fractionally distilled and there is thus obtained as second fraction di~luoromethyl 1,2,2-trifluoroethyl ether, b.p. 53-54~., yield 23% based on the methyl trifluoroethyl ether starting material. Another product of the fluorination reaction, which is the rirst fraction in the distillation, is chlorodifluoromethyl 1,2,2-trifluoroethyl ether, b.p. 46C.
(yield 20%).
The methyl 1,2,2-trifluoroethyl ether used as starting material may be obtained as follows:-A stream Or hydrogen is passed for 2 hours at the
3 rate of 750 ml. per minute over methyl 1,2,2-trifluorovinyl ether (22 g.) and the gaseous mixture thus obtained is passed down a column, 16 mm. internal diameter, containing a 1%
palladium on 4-8 mesh granular charcoal catalyst (24 g.).
The gases emerging from the column are condensed in a trap cooled with solid carbon dioxide in acetone. The column is then purged with a stream of nitrogen for 18 hours, and the gases emerging are similarly condensed. The product is distilled and there is thus obtained methyl 1,2,2-trifluoro-ethyl ether, b.p. 55-57C. (yield, 71%).
Example 11 A mixture of l-chloro-2,2-difluoroethyl difluoro-methyl ether (5.0 g.) and mercuric fluoride (3.6 g.) is heated at 115C. in a sealed tube under an atmosphere of nitrogen for 4 hours. The reaction mixture is fractionally distilled and there is thus obtained difluoromethyl 1,2,2-trifluoromethyl ether (1.9 g.), b.p. 53-54C.
palladium on 4-8 mesh granular charcoal catalyst (24 g.).
The gases emerging from the column are condensed in a trap cooled with solid carbon dioxide in acetone. The column is then purged with a stream of nitrogen for 18 hours, and the gases emerging are similarly condensed. The product is distilled and there is thus obtained methyl 1,2,2-trifluoro-ethyl ether, b.p. 55-57C. (yield, 71%).
Example 11 A mixture of l-chloro-2,2-difluoroethyl difluoro-methyl ether (5.0 g.) and mercuric fluoride (3.6 g.) is heated at 115C. in a sealed tube under an atmosphere of nitrogen for 4 hours. The reaction mixture is fractionally distilled and there is thus obtained difluoromethyl 1,2,2-trifluoromethyl ether (1.9 g.), b.p. 53-54C.
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the manufacture of difluoromethyl 1,2,2-trifluoroethyl ether which comprises either the reduction of a compound of the formula:-wherein X is hydrogen, chlorine or bromine, and wherein either Y and Z, which may be the same or different, each is hydrogen, chlorine or bromine, provided that X, Y and Z are not all hydro-gen, or wherein Y and Z are joined together to form an olefinic bond between the two carbon atoms; or the fluorination of a compound of the formula:-wherein X2, X3, Z1 and Z2 which may be the same or different, each is fluorine, chlorine or bromine and wherein Y2 is hydrogen, fluorine, chlorine or bromine, provided that X2, X3, Y2, Z1 and Z2 are not all fluorine.
2. A process as claimed in claim 1 wherein the reduction is carried out by means of hydrogen and a catalyst.
3. A process as claimed in claim 2 wherein the catalyst is a palladium catalyst.
4. A process as claimed in claim 1 wherein the reduction is carried out by means of hydrogen provided by a dissolving metal.
5. A process as claimed in claim 4 which is carried out by use of sodium or zinc dissolving in an alcohol.
6. A process as claimed in claim 1 wherein the reduction is carried out by means of a complex metal hydride in an appropriate solvent.
7. A process as claimed in claim 6 wherein the hydride is lithium aluminium hydride or sodium borohydride.
8. A process for the manufacture of difluoromethyl 1,2,2-tri-fluoroethyl ether which comprises the fluorination of a compound of the formula CHX2X3-O-CHFCHF2, wherein each of X2 and X3, which may be the same or different, is chlorine or bromine, by means of antimony tri-fluoride.
9. A process for the manufacture of difluoromethyl 1,2,2-tri-fluoroethyl ether which comprises the fluorination of a compound of the formula CHF2-O-CHY2-CHF2 or CHF2 or CHF2-O-CHF-CHZ1Z2, wherein each of Y2, Z1 and Z2, which may be the same or different, is chlorine or bromine, by means of mercuric fluoride.
10. A process for the manufacture of difluoromethyl 1,2,2-tri-fluoroethyl ether which comprises the fluorination of a compound of the formula CHF2-O-CHY2-CHF2, wherein Y2 is hydrogen, by means of chlorine trifluoride or bromine trifluoride.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB50040/75A GB1503999A (en) | 1975-12-05 | 1975-12-05 | Preparation of halogenated methyl ethyl ethers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1075267A true CA1075267A (en) | 1980-04-08 |
Family
ID=10454426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA267,244A Expired CA1075267A (en) | 1975-12-05 | 1976-12-06 | Process for the manufacture of difluoromethyl 1,2,2-trifluoromethyl ether |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5271407A (en) |
| CA (1) | CA1075267A (en) |
| DE (1) | DE2655196A1 (en) |
| DK (1) | DK544476A (en) |
| FI (1) | FI763497A (en) |
| FR (2) | FR2357510A1 (en) |
| GB (1) | GB1503999A (en) |
| IN (1) | IN143299B (en) |
| NO (1) | NO764138L (en) |
| SE (1) | SE7613545L (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1129892A (en) * | 1979-03-12 | 1982-08-17 | Ross C. Terrell | Process for adjusting the halogen content of halogenated aliphatic ethers |
| CA1130322A (en) * | 1979-04-25 | 1982-08-24 | Airco, Inc. | Method for the dehalogenation of ethers |
| CN111315715B (en) * | 2017-11-09 | 2022-06-17 | 关东电化工业株式会社 | 1, 2-dichloro-1- (2,2, 2-trifluoroethoxy) ethylene, process for producing the same, and use thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3461213A (en) * | 1966-10-03 | 1969-08-12 | Air Reduction | 1,1 difluoro-2,2-dichloroethyl difluoromethyl ether or an anesthetic agent |
| GB1499818A (en) * | 1974-12-06 | 1978-02-01 | Ici Ltd | Anaesthetic composition |
-
1975
- 1975-12-05 GB GBGB50040/75A patent/GB1503999A/en not_active Expired
-
1976
- 1976-12-02 SE SE7613545A patent/SE7613545L/en unknown
- 1976-12-03 FI FI763497A patent/FI763497A/fi not_active Application Discontinuation
- 1976-12-03 NO NO764138A patent/NO764138L/no unknown
- 1976-12-03 DK DK544476A patent/DK544476A/en not_active Application Discontinuation
- 1976-12-03 FR FR7636614A patent/FR2357510A1/en active Pending
- 1976-12-04 IN IN2158/CAL/76A patent/IN143299B/en unknown
- 1976-12-06 CA CA267,244A patent/CA1075267A/en not_active Expired
- 1976-12-06 JP JP51146436A patent/JPS5271407A/en active Pending
- 1976-12-06 DE DE2655196A patent/DE2655196A1/en not_active Withdrawn
-
1977
- 1977-08-12 FR FR7724929A patent/FR2351933A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5271407A (en) | 1977-06-14 |
| IN143299B (en) | 1977-10-29 |
| DK544476A (en) | 1977-06-06 |
| FI763497A (en) | 1977-06-06 |
| GB1503999A (en) | 1978-03-15 |
| FR2351933B1 (en) | 1981-01-09 |
| FR2357510A1 (en) | 1978-02-03 |
| FR2351933A1 (en) | 1977-12-16 |
| SE7613545L (en) | 1977-06-06 |
| NO764138L (en) | 1977-06-07 |
| DE2655196A1 (en) | 1977-06-16 |
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