Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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1049048
The pre~ent invention relate~ to a process for the
preparation Or 1-chloro-2,2,2-trifluoroethyldifluoromethyl
ether.
1-Chloro-2,2,2-trifluoroethyl-dirluoromethyl ether !
(CF3C~IClOCHF2) and its use as inhalation anesthetic is known
from German Offenlegungsschrift Dr-OS No 1,814,962 in ~hich
three methods are described for the preparation of this com-
pound. In two of them 2,2,2-trifluoroethyl-difluoromethyl
èther (CF3CH20CHF2) i9 u~ed as intermediate product and i~
then chlorinated in a further step to yield the product
desired. However, the secondary products formed in this
chlorination deteriorate the yield, and furthermore the
formation oP 1-chloro-2,2,2-trif]uoroethyl-difluorochloro-
methyl ether makes the separation so difficult that it is not
possible to prepare the product desired in pure state without
additional and complicated operations (Azeotrop-Destillation
with Aceton, cf. German Ofrenlegungsschrift, DTOS No. 2,234,309).
In the German Offenlegungsschrift mentioned above the
thlrd method described is the c~lorination of 2,2,2-trifluoro-
ethyl-methyl ether wlth elementary chlorine to yield the
1-chloro-2,2,2-trifluoroethyl-dichloromethyl ether which is
converted in a second step into the end product by catalytic
fluorination. In this method, the difficulty lies in the
chlorination which, according to example 2 of the German
Offenlegungsschrift 1,814,962 only yields 34 96 of 1-chloro-
2,2,2-trifluoroethyl-dichloromethyl ether in the crude product
obtained (determined by gas chromatographical analysis) using
2.8 mols of chlorine/mol of trifluoroethyl-methyl ether.
29 In the following working up by fractional distillation this
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portion is reduced to 22.6% of the product which has, however,
only a boiling point of 59 to 64C under 150 mm mercury
~boiling point of the pure product: 650C), that is a difference
of 5C, and thus is still highly contaminated. Such a result
is very unsatisfactory for an industrial process.
The present invention provides a process for the pre-
paration of l-chloro-2,2,2-trifluoroethyl-difluoromethyl ether
which comprises reacting l-chloro-2,2,2-trifluoroethyl-methyl
ether with elementary chlorine to yield the l-chloro-2,2,2-
0 trifluoroethyl-dichloromethyl ether and converting it in a
manner known by itself by fluorination into the l-chloro-2,2,2-tri-
fluoroethyl-difluoromethyl ether.
The starting substance l-chioro-2,2,2-trifluoroethyl-
methyl ether can be obtained according to applicant's copending
application Serial No. 206,866 by chlorinating fluoralmethyl-
semi-acetal.
In this method, the fluoralmethyl-semi-acetal is reacted
with a chlorinating agent, for example, phosphorus penta-
~ chloride, thionyl chloride, optionally in the presence of a
0 tertiary base, for example, triethyl amine or pyridine and/or
an organic solvent in a wide temperature range of from -10C
to +100C or to the boiling point of the reaction mixture.
Suitable solvents for this reaction are methylene chloride,
tetrahydrofurane, diethyl ether, diisopropyl ether, di-n-butyl
ether or di-n-hexyl ether.
This starting substance is chlorinated under the in-
fluence of light in usual manner. It is irradiat:ed with the
usual light sources, such as W lamps ~mercury lamps) or ray
X sources for visible light (bulbs, low pressure discharge tubes)
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if they have a ~ufficient portion of ~hort-wave light. The
irradiation can be effected, for example, by means of an
immersion lamp, or from outside when working in transparent
material. I
S The roaction temperature has only little influence on
the reaction. For general technical reason~, it is, preferably,
within the range of from ^5C to ~50C, especially from +5 C
to +30C.
To avoid chlorination in excess, the amount of chorine
used is below the stoichiometrically required amount, that is
preferably below 1.8 mols, especially below 1.65 mols of
chlorine per mol ether. The lower l~mit is not critical and
i8 only limited by the distillation expenditure and the
losses resulting from distillation. However, for practical
reasons, preferably more than 0.8 mols, especially more than
1.2 mols of chlorine per mol of ether are reacted.
The chlorination can also be effected in two steps.
In the first step a chlorine atom is introduced into the methyl
; group, the resulting 1-chloro-2,2 ~-trifluoroethyl-chloro-
methyl ether i9 isolated by fractional distillation and in the .
second step it is further chlorinated to the 1-chloro-2,2,2-
trifluoroethyl-dichloromethyl ether desired. IA each step,
0.4 to 0.8 mol of chlorine per mol ether are preferably
reacted.
, \ .
25 As the trifluoroethyl-methyl ether very rapidly reacts
with ~he chlorine, the chlorine is advantageously added while
thoroughly mixing the reaction medium. A dilution of the
chlorine stream with inert gases, for example, hydrogen
29 chloride, is possible. In most cases, the reaction vessel
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must be cooled.
The reaction is preferably effected in the absence of a
solvent or diluant, but it can also be carried out in the
presence of SUCIl an inert agent, such as CClt~ or of the per-
chlorinated trifluoroethyl-methyl ether.
Suitable reaction materials are all those generally used
for similar reactions. Those materials are resistant against
chlorine and hydrogen chloride, such as steel, steel alloys,
nickel, nicXel alloys, porcelain ceramics, or glass or
quarzite for irradiation from outside.
The process of the invention leads to considerably
-improved yields of 1-chloro-2,2,2-trifluoroethyl-dichloromethyl
ether as compared to the process described in German Offen-
legungsschrift No. 1,814,962. This result could not be
foreseen.
The yields of the process of the invention are indicated
in ~ in the!following Table according to the analysis by gas
chromatography. It must be taken into account that an amount
of chlorine of 1.6, respectively 1.74 mols of chlorine per mol
of ether corresponds to that of 2.6, respectively 2.74 mols
lndicated in the process described in German Offenlegungsschrlft
No. 1,814,962, as the starting substance of the process of the
invention already contains a chlorine in the place desired.
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T A B L E
Yields in % by weight
Reaction product Molar ratio chlorine : ether
1.6 s 1 1.74 s 1 t
Cl~3CHClOC~12Cl 33.4 20.15
C~3CHClOCHCl2 45.9 52.15
compounds containing
more chlorine atoms 20.7 27.7
.
The 1-chloro-2,2,2-trifluoroethyl-dichloro-methyl ether
desired can be separated from the reaction mixture, in good
yield by fractional distillation optionally after the usual
washing and drying operations. Depending on the effectivity
of the fractionation it can be contaminated by slight amounts
of compounds having a similar boiling point.
The crude 1-chloro-2,2,2-trifluoroethyl-dichloromethyl
eth-r is fluorinated in usual manner, preferably with hydrogen
fluoride in the presence of a fluorination cataly~t, especial-
ly according to one of the known solid bed methods with, for
example aluminum fluoride or, preferably, chromoxy fluoride as
catalyst, or by reacting with a known fluorinating agent, for
example Sb~5. In this process, preferably the Cl-atoms bound
in pairs are exchanged against fluorine, so that the l-chloro-
2,2,2-trifluoroethyl-difluoromethyl ether desired is obtained
in addition to slight amounts of other fluorination products.
The mixture can be separated by fractional distillation which -
yields pure CF3CHClOCHF2.
The following preparation examples illustrate the invention.
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1049048
E X A M P L E 1:
3590 g of CF3CIIClOCH3 (= 24.20 mol~), boiling point: 67 C~
were introduced into a glass flask provided with stirrer,
thermometer, cooler and a gas in~et tube coming up till under
the liquid s~rface. In the course of 26 hours 3003 g = 42.25
mols of chlorine (C12 : ether = 1.74 : 1) were introduced
while stirring and irradiating with a radiation lamp issuing
also near W rays (Ultra-Vitalu ~-Heraeus Hanau), corre~pond-
lng to a speed of 115 g/h = 1.63 mols/h. The temperature in
the reaction vessel was maintained at 14 C to 16C by cooling.
The chlorine was so rapidly absorbed that no yellow coloration
of the reaction solution could be observed. The escaping
hydrogen chloride was led through the cooler and then taken
up in water. 42.22 mols of HCl were obtained. A slight
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amount of accompanying organic substance wa-~ added to the
crude product obtained after separating the hydrochloric acid
formed and drying.
The yield was 4870 g of a mixture which had the following
compo~ition as determined according to gas chromatography.
0.82 % CF3CHClOCH3
25.2 % CF3CHClOCH2Cl
50.5 ~ CF3CHClOCHC12
23.48 ~ compounds containing more chlorine
atoms.
The mixture was subjected to fractional distillation,
which yielded in addition to a slight amount(about 50 ~ of
unreacted starting material 1222 g (= 6.66 mols) of
CF3CHClOCH2C1 (boiling point 92.3C under 758 torr) and
29 2647 g of a fraction which consisted of 90 ~ in CF3CHClOCHC12.
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By a further fine fractionation on a column filled with
nickel spirals this fraction was separated once more and
yielded 2520 g of a fraction boiling at 64.5C~148 torr which
contained 95 - gG % Or CF3CIlClOCHCl2 according to gas
chromatography, corresponding to a yield of CF3CHClOCHCl2
of about 2400 g or 11 mols (= 45.7 ~ of the theory).
The CF3CHClOCH2Cl obtained as intermediate product was
again chlorinated with 0.5 mol Or chlorine per mol of ether
according to example 2 b, whereupon 490 g of CF3CHClOCHCl2
(= 2.24 mols) were obtained once more. So, the total yield .
rose to 13.24 mols (- 54.5 ~ of the theory). It could still
be lncreased by using th- starting material recovered in the
seeond step.
The 1-chloro-2,2,2-trifluoro-dichloromethyl ether of
about 95 ~ so obtained eould now be fluorinated without
, further purifieation.
i E X A M P L E 2t (ehlorination in step~)
a) 1485 g (- 10 molsl of CF3CHClOCH3 were reaeted with 355 g
(- 5 mols) of ehlorine, a~ deseribed in example 1.
1620 g of a mixture were obtained whieh contained 52.5 ~
by weight of CF3CHClOCH3, 46.3 ~ by weight of CF3CHClOCH2Cl
and 0.7 ~ by weight of CF3CHClOCHCl2, as determined by
ga~ chromatography.
By fraetional distillation there were obtained 740 g
25 ~= 5 mols) of unreacted starting material (boiling point:
67C) and 640 g (= 3.5 mols) of CF3CHClOCH2Cl (boiling point:
92.40C).
"~ 2 These amounts corresponded to a yield of 70 ~, caleulated
29 on the unreacted starting material.
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b) 1830 g (_ 10 mols) Or CF3CI~ClOCH2Cl were reacted with
355 g (= 5 mols) Or chlorine, as described in Example 1,
1994 g of a mixture were obtained which contained 49.2
by weight of CF3CHCl~CH2Cl, 42.8 ~ by weight Or
CF3CHClOC~ICl2 and the rest to 100 % by weight of compound~
having more chlorine atoms.
By fractional distillation, there were obtained: 850 g
(= 4.64 mols) of unreacted starting material and 840 g of a
~raction boiling at 63.4C/144 torr which contained about
95 ~ CF3C~ClOCHCl2, corresponding to a yield of 800 g = 3.7
mol~ (= 69 % of the theory) of C~3CHClOCHCl2.
The 1-chloro-2,2,2-trifluoroethyl-dichloromethyl ether
of about 95 ~ so obtained could now be fluorinated without
-further purification.
E X A M P L E ~: (fluorination)
~ 5830 g of a mixture obtained according to Example 1 or
Esample 2 which contained 95 ~ by weight of CF3CHClOCHCl2
corresponding to 5530 g (= 25.4 mols) of C~3CHClOCHCl2 were
; led with a speed of about 400 g/l (= 1.85 molæ/h) together
wlth 140 g/h (= 7.0 mols/h) of hydrogen fluoride at about 120C
to 125C over 0.85 l of a chromoxyfluoride catalyst in a
nickel tube, prepared according to German Patent Specification
No. 1,252,182, example 2. The molar ratio ether s HF was about
1 : 3.8, 96.5 mols of HF were used in total.
The nickel tube used had a diameter of about 50 mm, the
filling height of the catalyst was about 450 mm. The reaction
tube was heated electrically from outside, the temperature was
measured in the interior of the tube.
29 The reaction mixture leaving the reactor was washed with
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watcr and dried over silica gel.
Br fractionation, there were obtained: ~
a main fraction of 3928 g having a boiling poi~t of 48.6C .¦
to 49.4 C which contained 98.6 % of CF3CHC].OCHF2.
By careful fractionation on a column filled with 3 mm
nickel spirals this fraction yielded 2940 g of CF3CHClOCHF2
having a boiling point of 49.1C, corresponding to a yield of
63 ~ of the theory, calculated on the CF3CHClOCHCl2 used.
The product had a purity of 99.8 %. By new fractionation
of the first runnings and second runnings obtained further
pure 1-chloro-2,2,2-trifluoroethyl-difluoromethyl ether was
' obt ~lned.
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