Note: Descriptions are shown in the official language in which they were submitted.
1~2~89Z
Process for Adjusting the ~lalogen
Content of Halo~enated Aliphatic Ethers
___ _
_n~roduction
This invention relates to processes for adjustin~, the
halogen content of halogenated aliphatic ethers, by selective
reduction, i..e., replacement of a halide substituent on the
ether with a hydrogen. More specifically, the invention is
concerned with new processes, and with improvements in
existing processes, for the production of certain halogenated
aliphatic ethers that are useful as inhalant anesthetics.
Back~round
The halogenated ether, 1,1,2-trifluoro-2-chloroethyl
difluoromethyl ether, CHF2OCF2CHFCl, is a valuable inhalant
anesthetic, enflurane, made and sold under the trademark
ETHRANE by Airco, Inc., Montvale, New Jersey 07645. It is
referred to hereafter as enflurane.
The presently-employed process :Eor manufacturing this
anesthetic material generates a number o:E by-~roduc-t streams,
each characterized by having more chlorine in the molecule
than does the desired anesthetic product. One such by-
product stream contains the compouncl of C12~-1OCF2CEC12, which
is very difficult to remove from the desired product by
distillation or other separating technique, and of course it
represents a yield loss for the presently-employed process.
Other by-product streams are produced in the presently-
e _ loy process as "bottoms" from the vacuum stills. These
llZ989Z
ottoms contain the following components in varying proportions:
C~12ClOCF2CHFCl
CC130CF2CHFCl
CC12HOCF2CHFCl
CC12HOCF2CFCl2
CClH20CF2CFCl2
CC130CF2CFC12
At the present time, these materials are useless by-products
that reduce the efficiency of the currently-employed process.
Another important halogenated ether anesthetic is
l-chloro-2-trifluoro difluoromethyl ether, CF3CHClOCHF2,
isoflurane, made and sold under the trademark FORANE by
Airco, Inc. It is referred to hereafter as isoflurane. In
the process for manufacturlng this anesthetic, care must
be exercised to avoid by-product formation) and the process
now in use ~chieves low conversions to the desired product.
Represen~ative by-products produced incl~lcle C13CC120CI-IF2,
which has been considered to be useless in the past.
The selective reduction of halogenated aliphatic ethers
is extremely difficult to accomplish because of the diEferent
responses exhibited by ethers of this kind to a given
reactant or to given reactants. Thus, there are three
important reactions that halogenated aliphatic ethers may
undergo in the presence of a base.
First, a hydrolysis or nucleophilic displacement
reaction may occur. This is a reactlon in which the halogen
atom is replaced by OH, OR, or other nucleophilic group, as
represented by the equation:
B + R-O-R'Cl . , RO-R'-B -~ Cl
where B is OH or OR.
~ 9 Z
Second, dehydrohalogenation may occur. In this reaction,
hydrogen and halogen are removed from adjacent carbom atoms to
form a double boncl:
Cl
I I B
RO-C-C-R ~ RO-C=C-R
R R R R
This type o~ reaction is described in U.S. Patent 2,~03,666,
where this reaction occurs:
~0 C
(CC13C~ICl)2 O + C2HsOH + KOll ~ CCl~ = CClOCCl = CC12.
It is also described by Corley et al in 78 JACS 3~9 at 3491
and 3492, as for example ln this preparation:
reflux
22 hrs
Third, selective reduction may talce place, in accordance
with the present invention. In this reaction the halogen is
replaced by hydro~en, as in the examples oE this application.
In order for the reduction reaction to work, the ether
must not undergo a hydrolysis or nucleophilic displacement
reaction or dehydrohalogenation reaction, which is faster -than
the reduction. In addition, any ether formed by the reduction
reaction must not undergo further reactions, especially
dehydrohalogenation.
In order for selective reduction to take place, rather than
hydrolysis or nucleophilic displacement or dehydrohalogenation,
certain conditions must be met. The reactions of the halogenated
ethers have been little explored and have been considered highly
~Z~89~
unpredic~able T~e present ;.nven~ion i.s remarkable in that only
certain halogenated ethers can be selectively reduced, and in
that the reduction is selective.
Summary of the Invention
It has now been discoverecl that selective replacement o~ a
chlorine or bromine substituent on certain halogenated aliphatic
ethers, with hydrogen,-can be accomplishecl by reactin~ one o
the certain substituted ethers with an alkanol and a base,
preferably but not necessarily in the presence of a catalyst.
The halogen replaced may be bonded to a terminal carbon or to an
inner carbon.
The process of the invention can be concisely described as a
process for replacing a halogen substituent with hydrogen in a
halogenated aliphatic ether of the methyl-ethyl or ethyl-
ethyl type, comprising reacting with a primary or secondary
alkanol and an inorganic base a halogenated aliphatic e-ther
of the formula:
a) CX30cY2cz3
where
CX3 is CF3, CH3, CH2F, CF2CL, CF2Br, or CHF2;
and
CZ3CY2 is CF3CCL2, CF3CClBr, CF3CBr2, CFC12CF2,
CFC12CFCl, CFC12CFBr, CFBrClCF2, CFClBrCFCl,
CFBrClCFBr, CC13CF2~ CFBr2CF2, CFBr2CFCl,
CFBr2CFBr, CC12BrCF2, CClBr2CF2 or CBr3CF2
or
b) CX3cY2ocy2cx3
where at least one of the CX3CY2 groups is selected from
the following:
l CF3CC12, CF3CClBr, CF3CBr2, CFcl2c~2~
CFC12CFCl, CFC12CFBr, CFBrClCF2, CFBrClCFCl,
CFBrClCFBr, CC13CF2, CFBr2CF21 CFBr2CFCl,
CFBr2CFBr, CC12BrCF2, CClBr2CF2 or CBr3CF2;
-5-
8~:
and tlle other CX3CY2 group may be the same or rnay be
selected from the following:
CF3CH2, CF3CI-I~, CF3CI-ICl, CF3CHBr, CF3CF2,
CF3CFCl, CF3CF~r, C~3CH2, CHFCH2, CHFzCFz, .
CFClCF2, CF2ClCFCl, CE'2ClCF13r, CF2BrC'~,
CF2BrCFCl, CF2BrCFBr, CHFBrCF2, C'f:lC12CF2,
CHClBrCF2 or C~IBr2CF2
_he Prior Art
. No prior art is known that discloses or suggest the
present process.
In Fluorine Chemistry Reviews, by Metille and Bur-ton,
__
p. 354, the authors describe the dehalogenation of CF3I to
CF3H, using K0ll in a solvent of high dielectric constant,
specifically referring to ethanol. The use of the reaction to
dehalogenate CF3CF2I to CF3CF2H is also discussed.
The source article referred to by Metille and Burton is
Banus et al., J. Chem. Soc. 1951, pp. 60-64. This publication
states that it is known that the C-I bond in CF3I can under~,o
homolytic ~ission but that, a~)art from clecomposition, CF3Cl,
CF2C12 and C~IF2Cl "do not show reactions involving the homo-
lytic or heterolytic fission of the carbon-chlorine bond." The
publication in general stresses that -the iodo compounds are
unique as compared to the corresponding bromo or chloro
compounds. It would not, therefore, suggest the use of the
same type of reaction even for brominated, chlorinated, or
fluorinated alkanes, let alone ethers.
Young, U.S. Patent No. 3, 391,204, in his Example 11,
describes the reaction:
CF2ClCF2Cl + TEA 2 _~ CF2ClCF2H
where TEA represents triethanolamine.
-6-
.
9 ~
j! Examples 12 and 13 describe ~enerally similar dehalogenations.
Yo~mg says ~hat alcohol. may be present, but characterizes the
alcohol as an "inert" solvent, and his reaction did not operate
on ethers, but rather on halogenated alkanes.
In German patent 2,554,88~, partial dechlorination o
F2CHOCFClCF2Cl, an ether, was accomplished by the use oE
hydrogen and a catalyst of either palladium or a complex
metallic hydride.
Some reactions involving halogenated alkanes are to be
found in the literature. U.S. patents 3,527,813 and 3,535,388
i describe the in-troduction of chlorine and of fluorine into
halogenated alkanes.
Detailed Description of the Invention
The present invention invo].ves the discovery that when
a halogenated aliphatic ether initial compo~md, selected from
a limited class of halogenated ethers as defined above, is
reacted with an alkanol and a base, one chlorine or one bromine
is selectively replaced with hydrogen. This is a rather
¦ remarkable reaction because it occurs despite the presence on
¦ the same molecule of -CF3 or -C- or F-C- groups, where X is
chlorine or bron~ine. It is also a vcry va:luable reaction
because it is specific and permits the conversion of previously
useless by-pro(lucts to valuable products, and also offers a new
tool for synthesis.
l'he two primary areas of immediate commercial interest
relate to the preparation of the two inhalant anesthetics
mentioned above, as follows.
Preparation of Enflurane Anesthetic, CHF20CF2CHFCl
, _~
'l'he halogenated ether C~2ll0C1~2CFC12 is a particularly
undesirable by-product of the presently-employed process for
7-
~98g~
the preparation oE enflurane anes~lletic. It is readily
reduced to enElurane in good yield by the process o the
present invention, as follows:
C~F20CF2CFC12 + CH30H ~ NaOH ~D
(I~
C~IF20CF2C~IFCl + NaCl ~ CM20
(enflurane anesthetic)
Using this reaction, a product s-tream from the presently-
employed process for producing enflurane, that contains this
by-product I, can be up~raded by reacting the product
stream itself to convert the by-product I to enflurane, in situ.
The enflurane itself, that is present in the product stream,
is not affected by the reaction.
In addition, the other halogenated e~ther by-products
mentioned above, that are produced as "bottoms," can be further
processed by distillation and chlorination to obtain a mixture
containing a high proportion of the ether CHC120CF2CFC12.
Fluorination of this ether leads to I above, which can then
be reacted in accordance with the invent.ion to produce more
enflurane, thus materially improving overall process yield and
economics.
It should be noted that when the alkanol employed is
methanol, 1.5 moles are required per mole of ether, so that the
equations above and below, that employ methanol, are not
balanced. The reason is that methanol undergoes the Cannizzaro
reaction. When other suitable alkanols are employed which do
not give a Cannizzaro reaction, the reaction requires one ~ole of
-the alkanol to one mole of reactant ether.
Preparation of Isoflurane Anesthetic, CF3CHClOCHF2
In tlle isoflurane manufacturin~ process, C~3C~120CI-IE~2 is
chlorln ted to give CF3CHClOCl~F2, isoflurane. However, the
-8-
~12~89Z
1,
chlorination must be done at low conversions in order to avoid
Eormation of large amounts of the by-procluct CF3CC120CUF2,
However, this by-product can now be reduced to iso~lurane as
follows:
CF3CC120CHF2 -~ NaO~I ~ CH30H ~ CF3 CIIClOCHF2 -
~
NaCl -~ CH20
_ neral
Only a limited number o:E halogenated ethers are
susceptible to selective reduction in accordance with the
invention.
As to those of the fonnula CX30CY2CZ3, as defined above,
those ethers that are suitable for use in the present invention
were selected from a very large number oE halogenated ethers
of the methyl-ethyl type, based upon several rules. These
rules eliminate those halogenated methyl-ethyl type ethers
that would not be suitable by reason of side reactions, either
initially or aEter reduction. These rules are:
1. No OCY2CZ3 group can have the conEiguration O-CH-CX'
where X' is Br or Cl~ since these compounds would
probably eliminate i-lX' to give -O-C=C in the presence
of base. (CF30CHFCF2Br and CF30C~IFCF2Cl may be
exceptions to this rule, but are not within the scope
of the invention).
2. No OCY2CZ3 group shall have more than one hydrogen on
the ~ carbon unless CY2 is CH2 or CF2; i.e. where two
of the Z = H, then CY2 must be CH2 or CF2. Other~ise
the halogenated ether compounds would not only be
unstable to base but some oE them wo~lld decompose
spon tRneOUs ly .
_g_
1~L29~
3. Within the OCY2CZ3 group, there mus~ be either two
chlorines, two bromines, or one bromine and one
chlorine on one of the carbon atoms, otherwise -the
compound will not be reduced.
The first two rules eliminate those halogenated e~hers
that are unstable in the reaction mixture of this invention.
The third rule confines those ethers that have survived the
screening by rules 1 and 2 to those that would be reduced, and
in addition, eliminates reduced compounds tha-t would not be
stable in the presence of the base in t~le reaction mixture.
The application of these rules, of course, severely limits the
-number of halogenated ethers that are available for use in the
selective reduction process of the invention.
The same considerations can be applied in identifying
those halogenated ethers of the ethyl-ethyl type that are
suitable for use in practising the invention.
The alkanol reactant is à primary or secondary alcohol,
preferably a 1 to 4 carbon alkanol (i.e., a lower al.kanol), but
alkanols o~ any known chain length up to abou-t 12 carbons are
useful and can be expected to be effective, although even
higher alcohols are operative. Water soluble alcohols are
preferred. The alkanol may be substituted but preferably is
not, as a matter of economics. While methanol and ethanol
are generally preferred because of availability and cost,
isopropanol and sec-butanol are useful and also are readily
available.
The base may be: an alkali metal dissolved in the alkanol;
an alkali metal or alkaline earth metal hydroxide, dry or in
aqueous or alcoholic solution; or any strongly basic material
that doe not inte fere with che desired react~on. Sodium
-lO-
- ~12~ z
hydroxide, sodium methylate, potassium hydroxide, lithium
hydroxide and calcium hydroxide, are examples of suitable
basic materials. Ammonia and sodium carbonate are useful in
many reactions.
Catalysts are generally not essential but are useful for
many individual reactions in improving reactions rates, yiel~s
or both. The catalyst, in finely divided or other suitable
state, may be a metal-containing (advantageously, in most cases,
a varivalent metal-containing) catalyst, more particular].y, a
copper-containing catalyst such as metallic (elementary)
copper or a copper salt of an inorganic or organic acid, e.g.,
copper chloride, bromide, nitrate, acetate, propionate,
etc.; or corresponding salts of silver, cobalt, tin, man~anese,
nickel, iron, molybdenum, chromium, antimony, vanadium and the
like, or the said varivalent metals in elementary form, or
alloys thereof with each other or with other metals.
Preferably a copper-containing catalyst, speci~ically elementary
copper in powder form, or a copper salt, is employed. In
general, the use oE a cataly~st compri~sing, Eor example, one or
more of the metals identified above, or the inorganic or
organic salts thereof, tends to produce hi~,her conversions,
shorter induction periods, and lower operating temperatures.
PreEerred catalysts include not only the ~inely divided
metals, metal salts, but also the amines, and mixtures thereof
with metal powders and metal salts. The most preferred catalysts
are mixtures of copper chloride with triethanolamine. Other
suitable amines that may be used, depending on the particular
reaction, include:
~2~89;:
Methylamine(monomethylamine) ~lexamethylenetetramine
Dimethylamine ~mmonlum chloride
Diethylamine ~enzyl ~rimethyl ammonium
Triethylamine methoxide
Isopropylamine E~hylene diamine
Di-n-propylamine Triethylene tetramine
Pipericline N,N,N-trimethyl ethylene
Morpholine diamine
Monoethanolamine N,N-diethylene diamine
Diethanolamine 1,2-cyclohe~ylene dinitrilo
Hydrazine acetic acid
Aniline 3-dimethylamino propylamine
Pyridine ~thylenediamine tetraacetic
acid
Diazo bicyclo (2,2,2,) octane
N-(2-amino ethyl morpholine)
_ nditions of Reaction
The alkanol and base should be employed in excess over the
theoretical amount required to effect the desired reduction of
the ether. The alkanol may function both as a.reactant and
solvent and may be present in substantial excess for that
reason. The limits are those established by the practical
considerations of reaction kinetics, ease of recovery of the
product, and conservation of energy. .
The temperature of the reaction is dependent upon the
particular reactants employed and may range, for example, from
about 0C to about 100-120C. or higher and, preferably,
from about 20C to about 80C. The temperature and/or
pressure advantageously are such that the reaction mass is in
a liquid state during the course of the reaction. The reaction
is exothermic, and once initiated, may require cooling,
I depending upon the equipment availab~e and other conditions.
The time of the reaction is not important since one may
prefer to carry ou~ the reaction for a relatively short period
of time with a relatively low conversion rate, ra~her than to
make the reaction go substantially to comple~ion. In general,
the time oE the reaction depends upon the particular reactants
employed, the temperature of the reaction, the efficacy of the
l ~98~Z
catalyst or catalyst system (if employed), and other
influencing factors. Generally, just a ~ew hours up to about
thirty, is adequate to produce a suitable yield.
The pressure used is dependent primarily upon the
particular reactants employed. The reaction may be carried out
at atmospheric pressure. The pressure employed seems to have
no material effect on the course of the reac-tion.
The product may be isolated by any suitable means from the
reaction mass. Ordinarily, the product is insoluble and is
precipitated by a water-wash, which removes any water-soluble
reaction products and by-produc~s.
To explain the invention further, several demonstrations
of it are reported in the following examples. All temperatures
are in C., and all parts and percentages by weight, as is,
unless expressly stated to be otherwise.
Example l
Production of Isoflurane ~n~sthetic
CF3CCl20CHF2 + NaOH + CH30H CuC12~ CF3CtlClOCHF2 (isoflurane
TEA anesthetic)
~ mixture oE CF3CCl20CHCl2 (44 g, 0.2 mole), 50% aqueous
sodium hydroxicle solution (20 g. 0.25 mole), methanol (lOO ml),
CuCl2 (l g), and triethanolamine (l ~), was refluxed for five
hours and poured into water. The water-insoluble layer was
analyzed by gas chromatography and found to contain 16%
unreacted CF3CCl20CHF2, 25% methanol, and 54% CF3CHClOCHF2
~isoflurane anesthetic).
-13-
I llZ5~851Z
Example 2
_ _,
DiEferent Reactant ~ther Wil:h Cata~sts
._ __ ~ _ __
Example 2A
Production of Enflurane
CHF20CF2CFC12(Material 2) -~ NaOg-l + C~30H T~A
CHF~OCF2CHFCl (enflurane anesthetic)
A mixture of C~IF20CF2CHC12 (44.g, ~.2 mole), 50% aqueous
sodium hydroxide (20 g, ~.25 mole) methanol (100 ml), CuC12
(1 g), and triethanolamine (1 g), was refluxed for seven hours
and then poured into water. The water-insoluble product
recovered (34 g) was analyzed by gas chromatography and found
to be 77% unreacted CHF20CF2CFC12 (Material 2) and 18%
CHF20CF2CHFCl (enflurane).
Material 2 can be separated as a "bottom" in a still
from the enflurane product, for recycling through the process.
The enflurane distillate, in puri.ied form, is useful as an
inhalant anesthetic. .
Example 2B
~u ~ a_ion of Enflurane
A reaction product containing enflurane together with
about 5% of Material 2 was purifie~ as follows.
A mixture of CHF20CF2CHFCl (95.6 g) and CHF20CF2CFCl2
(4.4 g), methanol (15 ml), copper (1 g), ethanolamine (6 g), and
sodium hydroxide pellets (8 g),-was .refluxed for five hours and
then washed with water. The water insoluble product (88.9 g)
was shown by gas chromatography to be 99.7% pure CHF20CF2CHFCl,
with no CHF20CF2CFC12 present.
,
-14-
3L12~9Z
E _mple 2C
Enflurane Preparation with a Catalyst System
~ mixture o:E C}IF20CF2CFC12 (22 g, 0.1 mole), methanol
(50 ml), 50% aqueous sodium hydroxide solution (2h g, 0.3 mole),
ethanolamine (6 g), and copper metal (1 g), was refluxed for
24 hours. The reaction mixture was washed with water ~o
give 10.9 g of water insoluble product, which was analyzed by
gas chromatography and shown to be 90% CIIF20C~2CHFCl. There
was no unchanged starting material present.
When this procedure was repeated, but with the use o~ 75 ml.
of methanol rather than 50 ml., the water insoluble product
recovered amoun~ed to 10.6 g, which is considered to be an
insignificant difference.
Example 3
Different Reactant Ether
Example 3A
_mall Scale Preparation
CF2ClOCF2CFC12 + NaOH + CH30H CuC12 ) CF2ClOCF2CHFCl (Product 3)
A mixture of CF2ClOCF2CFC12 (25.3 g, 0.1 mole)~ methanol
(50 ml), 50% aqueous sodium hydroxide solution (16 g, 0.2 mole),
triethanolamine (1 g), and CuC12 (1 g), was refluxed for
nineteen hours. The reaction mixture was poured into water and
19 g of water-insoluble product recovered. This was analyzed by
gas chromatography and shown to be about 91% CF2ClOCF2CH~Cl
(Product 3).
Product 3 is useful as a solvent and degreasing agent.
11~9~9~:
Example 3B
Lar~er Scale Preparation
This reaction was repeated on a larger scaLe, and with a
¦ more detailec1 characterization oE the proc1uc~, as ~ollows:
A mixture o:E CF2ClOCF2CFCl2 (253 g, 1 mole), me-thanol
¦ (750 ml), 50% aqueous sodium hydroxide (120 g, 1.5 mole),
¦ CuCl2 (l0 g), and triethanolzmine (l0 g), was refluxed for
24 hours. At the end of this time, 85% of the sodium hydroxide
had reacted as shown by titration. The reaction mixture was
distilled to recover 280 g of product, b.p. 53-64, which was
washed with water to give 204 g. containing 69% CF2ClOCF2CHFCl
(Product 3) and 27% unreacted CF2ClOCF2CFCl2. This was
redistilled to recover in purified form CF2ClOCF2CHFCl
(Product 3), b.p. 64, which was identified by its NMR
spectrum.
- Example 4
¦ Different Reactant Ether
CF3CCI20CF2Cl -~ NaO1~-~ C113011 CuCl2 ~ CI'3CHClOCF2Cl (Product 4)
A mixture of CF3CCl2OCF2Cl (50 g, 0.2 mole), methanol (100
ml), 50% aqueous sodium hydroxide solution (48 g, 0.6 mole),
CuCl2 (2 g)~ and triethanolamine (2 g), was refluxed for five
hours. The reaction mixture was washed with water to give
34 g. of water-insoluble product material which was analyzed
by gas chromatography and shown to be 7g% CF3CHClOCF2Cl
(Produ t 4), which i5 useful as a so1vent :nd degreasin agent.
-16-
Itl a different run, a reaction mi.xture of tlle same
composition, after refluxing for 63 hours, produced a major
amount of Product 4.
In still another run, a reaction mixture o~ the same
composition except ~or the sodium hydroxide, which was
present in an amount of 24 ~. (0.3 mole), produced after 4
hours of reflux a product containing over 90V/o oE Product 4.
i
_xample 5
Four Carbon Reactant Ether
CF3CC120CHClCF3 ~ NaOH + CH30H CuEA2 ~CF3CHClOCHClCF3 (Product
A mixture of CF3CC12CCHClCF3 (15 g, 0.053 mole), 50%
aqueous sodium hydroxide solution (6.4 g, 0.08 mole), methanol
(SO ml), CuC12 (0.1 g), and triethanolamine (0.1 g), was
reEluxed for four hours and poured into water. The water-
insoluble product (10 g) was analyzed by vapor phase
chromatography and found to contain 48% CF3CHClOCHClCF3
(Product 5), (dl. form), 38% CF3CHClOCi-lClCF3 (meso form), and
8% unreacted starting material.
Product 5 is useful as a solvent and de~,reasing agent.
_xample 6
Criticality of Ether Reactant
__ __ _
A mixture of CF3CHClOCF2Cl (5.4 g, 0.025 mole), methanol
(10 ml.), 50% aqueous sodium hydroxide (4 g., Q.05 mole),
CuC12 (0.25 g), and TEA (0.25 g), was refluxed overnight. The
water-insoluble product (2 g) was subjected to NMR spectroscopy.
The spectrum showed multipet centered (6 peaks) around 5. 8 and
two CH30 singlets. None of the expected triplet for -OCHF2
was present. It is concluded that this starting ether does not
undergo selective reduction in accordance with the invention.
llZ989Z
C~NCLUSION
The invention provides a valuable, specific technique for
selectively modifying the halogenation of a halogenated aliphatic
ether, by a selective reduction process that substitutes a
hydrogen substituent for a particular halogen substituent, The
process thus makes possible the conversion of h:itherto useless
halogenated aliphatic ethers to materials that are either
useful ~ se or that can be converted by further processing
to directly useful materials.
The invention is of particular value in connection with the
production of enflurane anesthetic, since it not only permits
the conversion of a major by-product, C~IF20CF2CFCl2, into the
desired enflurane anesthetic product, as in Example 2, which is
an important advance in the art in and of itself, but it also
eliminates the need that previously existed for separating this
material from the product stream containing the enflurane
(a difficult task because of the many physical and chemical
similarities between the compounds and the closeness of their
boiling points).
Thus, in the conversion of by-products :Erom the manufacture
of enElurane, the "bottoms" are ch].orinated to obtain a mixture
containing a high proportion of the compound, CHCl20CF2CFC12.
Fluorination of this compound produces CF2~10CF2CFC12, which can
be reduced by the process `of the invention to enflurane~ as in
Example 2.
The process of this invention has the advantage of bèing
highly speci~ic, in the sense that few unwasted materials
appear in the reaction mi~ture produced. Product recoveries
and purifications are thus facilitated and made less expensive.
The many useless by-products produced by the presently-employed
process are either avoided completely because of the new syn-
thesis tool that is available, or the quantity and number is
reduced.
-18-
11
~ 9~
The process provides new ways to synthesize valuable
materials and, in addition, provides a way to convert presently
useless or unusual halogenated by-products into valuable
intermediates.
While the invention has been disclosed herein by reference
to the details of preEerred embodiments, it is to be understood
that the disclosure is intended in an illustrative sense, and
it is contemplated that modifications may be made in the
process within the spirit of the invention and the scope of
the appended claims.
