TECHNICAL FIELD
[0001] The present invention relates to a process for industrially producing
halogenated α-fluoroethers which are important as an intermediate of
medicines or agrichemicals or as a flon alternative compound
BACKGROUND OF THE INVENTION
[0002] Halogenated α-fluoroethers, the object of the present invention,
serve as an important intermediate of medicines or agrichemicals or as an
important flon alternative compound Particularly, a,6,6,6-tetrafluoroethers
are utilized as a useful intermediate for a volatile anaesthetic ' desflurane" As
conventional techniques for such α-fluoroethers, relating to the present
invention,, the following two techniques are exemplified
[0003] Theie have been disclosed a process for reacting fluoial hemiacetals
with the Yarovenko's leagent (Patent Publication l)» and a process consisting
of two process steps in which fluoral hemiacetals are converted into
corresponding p toluenesulfonic acid esters and then these are leacted with
Fluoride anion (F) (Patent Publication 2)
REFERENCES ABOUT PRIOR ART
Patent Publication
[0004] Patent Publication 1 Japanese Patent Application Publication No
50-76007
Patent Publication 2 Japanese Patent Application Publication No
2-104545
SUMMARY OF THE INVENTION
[0005] An object of the present invention is to provide a process for
industrial production of halogenated α-fluoroethers
[0006] Patent Publication 1 in which the Yarovenko's reagent is used as a

dehydroxyfluormation agent requires previously preparing the reagent from
chlorotrifluoroethylene and diethylamine Furthermore, a fluorine-containing
organic waste is stoichiometrically formed as a by-product, so that an
industrial execution thereof had been difficult
[0007] In Patent Publication 2 where the reaction is achieved with two
process steps, the operations including a post-treatment are so complicated
that a high productivity cannot be expected Additionally, the total yield is
also not satisfying
[0008] Thus, there has been intensely desired a production process which
can be readily and industrially accomplished and provide halogenated
α-fluoroethers with high productivity and yield
[0009] As a result of eager studies the present inventors have made in
view of the above, they have newly found it possible to produce halogenated
α-fluoroethers represented by the general foimula [2] by reacting halogenated
hemiacetals represented by the general formula [1] with sulfuryl fluoride in
the presence of an organic base Furthermore, there has been also newly
found that the present reaction can be applied to bis-derivatives formed
through alkylene group (, in which halogenated α-fluoroether bis derivatives
represented by the general formula [2a] are obtained as the objective by using
halogenated hemiacetal bis-derivatives represented by the general formula
[la] as the starting substrate)
[0010] Incidentally, the present applicant has found a
dehydroxyfluormation reaction of alcohols by combination of sulfuryl fluoride
(SO2F2) and the organic base and has already filed an application therefor
[International Publication 2006/098444 Pamphlet (Japanese Patent
Application Publication No 2006-290870)] On the other hand, the raw
materials of the present invention are relatively unstable "halogenated
hemiacetals" or bis-derivatives thereof These can be said to be "an equivalent
cf a compound having a carbon with which two hydroxyl groups are

concurrently bonded" The present inventors have made it clear that these
raw material compounds are reacted with sulfuryl fluoride (SO2F2) in the
presence of the organic base thereby selectively subjecting "free hydroxyl
group" alone to fluorine substitution, and that, as opposed to this, -OR2 group,
[-0-(CH2)n-0-] -group and haloalkyl group are inducted into the halogenated
α-fluoroethers represented by the general formula [2] or the halogenated
α-fluoroether bis-derivatives represented by the general formula [2a] with
high yield without being subjected to any change
[0011] Moreover, the present invention allows the reaction to be conducted
with one process step as a one-pot reaction, in which fluorosulfuric
acid-esterification of the starting substrate halogenated hemiacetals (or the
bis-derivatives thereof) and a succeeding fluorine substitution proceed
continuously In fluorine substitution, "a salt or complex of an organic base
with hydrogen fluoride" formed as a byproduct in the reaction system by the
fluorosulfuric acid-esterification is usefully utilized as a Fluoride anion source
(see Scheme 1 showing an example where the halogenated hemiacetals
represented by the general formula [l] are used as the starting substrate )
[0012] [Chemical Formula 1]

[0013] In the present invention, it has also been made clear that the
succeeding fluorine substitution enormously excellently proceeds by
conducting the reaction in the additional presence of "a salt or complex of an
organic base with hydrogen fluoride" in the "system (see Scheme 2 showing an
example where the halogenated hemiacetals represented by the general

formula [1] are used as the starting substrate) The fluorosulfuric
acid-esterification of the relatively unstable halogenated hemiacetals proceeds
excellently even in the presence of "a salt or complex of an organic base with
hydrogen fluoride", which is a new finding
[0014] [Chemical Formula 2]

AN EXAMPLE OF A CASE WHERE TRIETHYLAMINE (1 EQUIVALENT) IS USED AS AN
ORGANIC BASE WHILE TRIETHYLAMINE TRIS(HYDROGEN FLUORIDE) COMPLEX (1
EQUIVALENT) IS USED AS "A SALT OR COMPLEX OF AN ORGANIC BASE WITH HYDROGEN
FLUORIDE"
[0015] Furthermore, the present invention have newly made it clear that
hemiacetals of fluoral (corresponding to halogenated hemiacetals represented
by the general formula [3]) or hemiacetals of 3,3,3-trifluoropyruvic acid esters
(corresponding to halogenated hemiacetals represented by the general
formula [5]) are extremely preferable starting substrates When using such
starting substrates, the desired reaction can excellently pioceed under mild
conditions and the objective halogenated α-fluoroethers are obtained with
high selectivity and yield These starting substrates can be readily prepared
from fluoral or 3,3,3 trifluoropyruvic acid esters (either of which is readily
available in large-scale) so as to be suitable also from the viewpoint of a
starting substrate for an industrial production process Particularly,
a,6,8,6-tetrafluoioethylmetriylether obtained from fluoral methyl hemiacetal
are useful as an intermediate for a volatile anaesthetic "desflurane", so as to
be particularly preferable
[0016] Thus, an extremely useful process has been found as a process for
industrially producing the halogenated α-flubroethers, thereby achieving the
present invention

[0017] More specifically, the present invention includes the following 1st
process to 7th process and provides an industrial .production process of the
halogenated α-fluoroethers
[0018] According. to the present invention, there as provided a process for
producing halogenated α-fluoroethers represented by the general formula [2]
[Chemical Formula 4]

by reacting halogenated hemiacetals represented by the general formula [l]
[Chemical Formula 3]

with sulfuryl fluoride (SO2F2) in the presence of an organic base (a 1st process)
[In the formulas haloR represents haloalkyl group, R1
represents hydrogen atom, alkyl gioup, substituted alkyl group,
alkoxycarbonyl group or substituted alkoxycaibonyl group, and R2 represents
alkyl group or substituted alkyl group ]
[0019] According to the presentanvention, there is further provided a process
for producing halogenated α-fluoroether bis-denvatives represented by the
general formula [2a]
[Chemical Formula 6]

by reacting halogenated hemiacetal bis-derivatives represented by the general

formula [la]
[Chemical Formula 5]

with sulfuryl fluoride (SO2F2) in the presence of an organic base (a 2nd
process)
[In ,the formulas haloR mutually ^independently -represents a
haloalkyl group; R1 mutually independently represents a hydrogen atom, an
alkyl group, a substituted alkyl group, an alkoxycarbonyl group or a
substituted alkoxycarbonyl gro„up> and n represents an integer of from 2 to
18]
[0020] The 1st or 2nd process may be a process for producing halogenated
α-fluoroethers or halogenated α-fluoroether bis-derivatives, the process being
characterized in that the reaction is conducted in the additional presence of "a
salt or complex of an organic base with hydrogen fluoride" in a system (a 3ld
process)
[0021] According to the present invention, there is further provided a
process for producing halogenated α-fluoroethers represented by the geneial
formula [4]
[Chemical Formula 8]

by leactmg halogenated hemiacetals represented by the general formula [3]

[Chemical Formula 7]

with sulfuryl fluoride (SO2F2) in the presence of an organic base (a 4th
process)
- [In the formulas, R2 represents an alkyl group or a substituted alkyl
group ]
[0022] The 4th process may be a process for producing halogenated
α-fluoroetheis, the process being characterized in that £he reaction is
conducted in the additional presence of "a salt or complex of an organic base
with hydrogen fluoride" in a system (a 5th process)
[0023] According to the present invention, there is further "provided a
process for producing halogenated α-fluoroethers represented by the general
formula [6]
[Chemical Formula 10]

by reacting halogenated hemiacetals represented by the general formula [5]
[Chemical Formula 9]

with sulfuryl -fluoride (SO2F2) in the presence of an organic-base (a 6th
process)
'[In the formulas, R2-and R3 mutually independently represent an alkyl

group or a substituted alkyl group ]
[0024] The 6th rprocess may be a process for producing halogenated
a fluoroethers, the process being characterized in that the reaction is
conducted in the additional presence of "a salt or complex of an organic base
with hydrogen fluoride" in a system (a 7th process)
DETAILED DESCRIPTION
[0025] Advantageous points of the present invention over conventional
techniques will be discussed below
[0026] As compared to Patent Publication 1, a dehydroxyfluormation agent
used in the present invention is suitable for large-scale production Sulfuryl
fluoride is widely utilized as a fumigant and industrially available at low cost
Additionally, wastes made in the use of sulfuryl fluoride can be conveniently
-treated into inorganic salts such-as fluorite (CaFa), calcium sulfate, etc , which
reduce the "load to the environment
[0027] As compared to Patent Publication 2, the reaction can be conducted
with one process step (in which fluorosulfunc acid-estenfication and a
succeeding fluorine substitution proceed continuously as a one-pot reaction)
with extremely high productivity and in high yield
[0028] Furthermore, impurities serving as by-products difficult to be
separated off are hardly provided in the .present invention, so that the
objective product can be obtained at a high chemical purity
[0029] Thus, the present invention is a production process which can solve
all problems the conventional techniques had carried and can be industrially
flower alkyl ammo
-group* such as "dimethylammo group, diethylamino _group, dipropylamino
group, etc , -lower alkylthio group such as methylthio group, ethylthio group,
propylthio group, etc , cyano group, ilower alkoxycarbonyl group such as
methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, etc ,
aminocarbonyl group (CONH2), lower alkylaminocarbonyl group such as
dimethylaminocarbonyl group, diethylammocarbonyl group,
dipropylammocarbonyl group, etc , unsaturated group such as alkenyl group,
alkynyl group, etc , aromatic cyclic group such as phenyl group, naphthyl
group, pyrrolyl group, furyl group, thienyl group, etc , aromatic cyclic oxy
group such as phenoxy group, naphthoxy group, pyrrolyloxy group, furyloxy
group, thienyloxy group, etc > aliphatic heterocyclic group such as pipendyl
group, piperidino group, morpholmyl group, etc , protected hydroxyl group,
protected amino group (including amino acid and peptide residue), protected
thiol group, piotected aldehyde group, protected carboxyl group, etc
[0035] Incidentally, in the present specification, each of the following terms
is used as having the following meaning "Lower" means a lineai, branched or
cyclic (with a carbon number of not smaller than 3) chain having a carbon
number of fiom 1 to 6 In the case that "unsaturated group" is the double bond
(alkenyl group), it may be in the form of E configuration, Z configuration or a
mixture of these -As "protecting groups of hydroxyl group, -amino group
(including amino acid and peptide residue), thiol group, aldehyde group and
carboxyl group", at is possible to use protecting groups and the like described
in Protective Groups in Organic Synthesis, Third Edition, 1999, John Wiley-&
Sons, Inc (,, in which not less than two functional groups may be protected
with one protecting group) More'over, "unsaturated group", "aromatic cyclic
group", "aromatic cyclic oxy group" and "aliphatic heterocyclic group" may be

subjected to substitution with halogen atom, azide group, nitro group, lower
alkyl group, lower "haloalkyl group, lower alkoxy group, lower haloalkoxy
group, lower alkyl amino group, lower alkylthio group, cyano group, lower
alkoxycarbonyl group, aminocarbonyl,group, lower alkylammocarbonyl group,
protected hydroxyl. group, protected ammo group (including amino .acid and
peptide residue), protected thiol group, protected aldehyde group, protected
carboxyl group or the like
[0036] Among these, hydrogen atom, alkoxycarbonyl group and substituted
alkoxycarbonyl group are preferable Particularly, hydrogen atom and
alkoxycarbonyl group are morej preferable
[0037] R2 of the halogenated hemiacetals represented by the general
formula [l] denotes alkyl group or substituted alkyl group
[0038] The alkyl group and the substituted alkyl group are the same as the
alkyl group and the substituted alkyl group as had been discussed as R1 of the
halogenated>hemiacetals represented by the general formula [l], and can be
selected independently of R1
[0039] HaloR and R1 of the halogenated hemiacetal bis-denvatives
represented by the general formula [la] are the same as haloR and R1 as had
been discussed on the halogenated hemiacetals represented by the general
formula [l] n represents an integer of from 2 to 18 Among these, with regard
to ,n, an integer of from 2 to 12 is preferable and that of from 2 to 6 in
particular is more preferable Two haloR included in the halogenated
hemiacetal bis-denvatives represented by the general formula [la] are
mutually independently selected from the above substituents However, it is
preferable to select the same substituent for the two haloR if taking the
preparation of the starting substrate into account Additionally, the same
thing can be said for two R1 of the halogenated hemiacetal bis-denvatives
represented by the general formula [*la]

- [0040] Stereochemistry of the halogenated hemiacetals represented by the
general formula [l] will be discussed In the halogenated hemiacetals, a
carbon atom with which hydroxyl group forms a covalent bond is an
asyminetric carbon atom with the exception of the case where haloR and R1
jadopt the same substituent In the case where the starting substrate has the
asyminetric carbon atom, it is not only allowed.to use a racemic form (it will be
^understood that the racemic form can be used) but also allowed to use an
optically active form (R configuration or S configuration), and its optical
purity is not limited A dehydroxyfluormation reaction of the present
invention proceeds together with stereochemical reversal, stereochemical
maintenance or racemization This stereoselectivity differs according to the
combination of the starting substrate and the organic base and to the adopted
reaction conditions, so that the starting substrate, the organic base and the
reaction conditions may be suitably selected according to the desired
stereochemistry (R configuiation, S configuration or racemic form) of the
objective halogenated α-fluoroethers represented by
their fluorine atom economy, waste treatment (by which a fluorine containing
organic waste is stoichiometrically formed as a by-product), etc
[0044] Examples of the organic base for the present invention are
trimethylamine, dimethylethylamine, diethylmethylamine, triethylamine,
di- ir propylmethylamine, dimethylcyclohexylamine, dnsopropylethylamine,
tri-72-propylamane, diisopropyhsobutylamine, dimethyl-ij-nonylamine,
trrirbutylamine, drzrhexylmethylamine, dimethyl'/rdodecylamine,
tri-72-pentylamine, l,4-diazabicyclo[2 2 2]octane (DABCO),
dimethylaminopyndine (DMAP), l,5-diazabicyclo[4 3 0]non-5-ene (DBN),
l,8"diazabicyclo[5 4 0]undec"7-ene (DBU), pyridine, 2,3-lutidine, 2,4-lutidine,
2,5-lutidine, 2,6'lutidme, 3,4-lutidine, 3,5-lutidme, 2,3,4-colhdine,
2,4,5-collidine, 2,5,6-collidme, 2,4,6-collidme, 3,4,5-colhdine, 3,5,6-colhdine,
etc
[0045] Among these, the preferable are triethylamine,
dimethylcycldhexylamine, dnsopropylethylamine, trrirpropylamine,
trr/rbutylamine, pyridine, 2,3-lutidme, 2,4-lutidine, 2,6'lutidine, 3,4-lutidine,
3,5-lutidme, 2,4,6-collidme and 3,5,6-colhdme The more preferable .are

trie thy lamine, diisopropylethylamine, tri- ir propylamine, trr/rbutylamine,
pyridine, 2,4-lutidme, 2,6-lutidme, 3,5-lutidme and 2,4,6-collidme, in particular These organic bases may be used singly or in combination
Additionally, an- organic base Jiavmg a carbon number of not less than 8 is
high in fat"solubility so as to be readily recovered at a post-treatment using
water, thereby being reused without*bemg lowered in reactivity Accordingly,
such an organic base is suitable -for an industrial production process In the
present specification, "carbon number" means the total number of carbon
atoms contained in an organic base
[0046] The amount of the used.organic base is required only to be not lower
than 0 7 mole, preferably from 0 8 to 15 moles in general, more-preferably
from 0 9 to 10 moles in particular, relative to 1 mole of the halogenated
hemiacetals represented by the general formula [l] In the case of'using the
halogenated hemiacetal bis-derivatives represented by the general formula
[la] as the starting substrate, it is required only to use it in the same manner
in an amount two times that of the halogenated hemiacetals represented by
the general formula [l]
[0047] Then, "a salt or complex of an organic base with hydrogen fluoride"
to be used in the 3rd process, the 5th process and the 7th process will be
discussed in detail
[0048] Examples of the organic base of "a salt or complex of an organic base
with hydrogen fluoride" include trimethylamine, dimethylethylamine,
diethylmethylamine, triethylamine, dr/rpropylmethylamine,
dimethylcyclohexylamine, diisopropylethylamine, trrirpropylamine,
dnsopropylisobutylamine, dimethyl'Trnonylamine, tri-zrbutylamine,
di n-hexylmethylamine, dimethyl-irdodecylamine, tri-yrpentylamine,
l,4-diazabicyclo[2 2 2]octane (DABCO), dimethylammopyndine (DMAP),
l,5'diazabicyclo[4 3 0]non-5-ene (DBN), t;8-diazabicyclo[5 4 0]undec-7-ene
(DBU), pyridine, 2,3-lutidme, 2,4-lutidine, 2,5-lutidme, 2,6-lutidine,

3,4-lutidme, 3,5-lutidine, 2,3,4-collidme, 2,4,5-collidme, 2,5,6-collidme,
2,4,6-collidme, 3,4,5-collidine, 3,5,6-collidine, etc
*[0049] Among these, the preferable are triethylamine,
dimethylcyclohexylamine, -diisopropylethylamine, tri-zrpropylamine,
trrTrbutylamine, pyridine, 2,3"lutidme, 2,4-lutidine, 2,6-lutidme, 3,4-lutidme,
3,5-lutidme, 2,4,6-collidme and 3,5,6-collidine The more preferable' are
triethylamine, dnsopropylethylamine, trr;r propylamine, trrjrbutylamine,
pyridine, 2,4-lutidme, 2,6-lutidme, 3,5-lutidine and 2,4,6-collidme in
particular
[0050] The mole ratio of the organic base of "a salt or complex of an organic
base with hydrogen fluoride" to hydrogen fluoride is within a range of from
100 1 to 1 100, preferably within a range of from 50 1 to 1 50 in general, and
more preferably within a range of from 25 1 to 1 25 in particular Furthermore,
it is convenient to use "a complex comprising 1 mole of triethylamine and 3
•moles of hydrogen fluoride" and "a complex comprising up to 30% (up to 10
'mol%) of pyridine and up to 70% (up to 90 mol%) of hydrogen fluoride", both of
which are placed on sale from Aldrich (Aldrich, 2007-2008 Comprehensive
Catalogue)
[0051] The amount of "a salt or complex of an organic base with hydrogen
fluoride" to be used is required only to be not less than 0 3 mole as Fluoride
anion (F), preferably within a range of from 0 5 to 50 moles in general and
more preferably within a range of from 0 7 to 25 moles in particular, relative
to 1 mole of the halogenated hemiacetals represented by the general formula
[l] When using the halogenated hemiacetal bis-denvatives represented by
the general formula [la] as the starting'Substrate, it is required only to use it
in the same manner in an amount two times that of the halogenated
hemiacetals represented by the general formula [l]
[0052] Examples of a reaction solvent are aliphatic hydrocarbons such as
zrhexane, cyclohexane, vrheptane, etc» aromatic hydrocarbons such as

benzene, toluene, ethylbenzene, xylene, mesityleme, etc, lialogenated
hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc,
ethers such as diethyl ether, tetrahydrofuran,« dusopropyl ether, tertrbutyl
methyl ether, etc, esters such as ethyl acetate, wbutyl acetate, -etc, amides
such as iYAMimethylformamide, 'A^A^dimethylacetamide,
A^-methylpyrrolidone, --l,3-dimethyl-2-imidazolidmone, etc, nitriles such as
acetonitrile, propionitrile, etc, and dimethylsulfoxide, etc
[0053] Among these, *the preferable are /2-hexane, irheptane, toluene,
xylene, mesitylene, methylene chloride, tetrahydrofuran, dusopropyl ether,
tertrbutyl methyl ether, ethyl acetate, A^A^dimethylformamide,
A^A^-dimethylacetamide, acetonitrile, propionitrile and dimethylsulfoxide
Particularly, the ^more preferable are toluene, xylene, methylene chloride,
tetrahydiofuran, dusopropyl ether, ethyl acetate, A^A^-dimethylformamide
and acetonitrile It is possible to use these reaction solvents singly or in
combination Furthermore, the present invention may be performed without
the solvent
[0054] In the case of using the reaction solvent, the amount thereof is
required-only to be not less than 0 l'L (liter), preferably within a lange of from
0 2 to 10 L in general, and more preferably withm arrange of from 0 3 to 5 L in
particular, relative to 1 mole of the halogenated liemiacetals lepiesented by
the general formula [l] (or the halogenated hemiacetal bis-denvatives
represented by the general formula [la])
[0055] The temperature condition is required only to be conducted within a
range of from -100 to +100 °C, preferably withm a range of from -60 to +60 °C
in general, more preferably withm a range of from -50 to +50 °C in particular
In the case of conducting the reaction under a temperature condition of not
lower than the boiling point of sulfuryl fluoride (-49 7 °C), it is possible to use
a pressure-proof reaction vessel
[0056] The pressure condition is required only to be conducted withm a

,range of from atmospheric pressure*to 2- MPa, preferably within a range of
from atmospheric pressure to*l 5 MPa in general, more preferably withm a
range of from atmospheric pressure-rto l.MPa in particular Therefore,*it is
"preferable to conduct the reaction in the use of a pressure-proof reaction
vessel made of a material such as stainless steel (SU-S) or glass (gla'ss lining)
Furthermore, for infusion of sulfuryl fluoride 'in large-scale, the effective is a
process for causing a negative pressure in a pressure-proof reaction vessel
first of all, and then introducing gaseous 01 liquid sulfuryl fluoride into
therein while recovering the pressure under a reduced pressure
[0057] The reaction time is*within 72 hours, however, it differs according to
the combination of the starting substrate and the organic -base and to the
adopted reaction conditions It is therefore preferable to determine a temporal
point at which the starting substrate is geneially completely consumed as the
endpomt of the reaction, upon tracking the-progress of the reaction by an
analytical means such as gas chromatography, thin layer chromatography,
liquid chromatography, nuclear magnetic resonance (NMR), etc The objective
halogenated α-fluoroethers represented by the general .formula [2] (or the
halogenated α-fluoroether bis'derivatives represented by the general formula
.[2a]) can be obtained by conducting an usual operation on a
-reactioivteimmated liquid as a post-treatment The objective product can be
purified at a high chemical punty by activated carbon treatment, distillation,
recrystallization, column chromatography oi the like as necessary
[0058] Such an operation as to directly distill the reaction-terminated
liquid is ^particularly effective By conducting such a post-treatment
(defluorination, fractional distillation or the like, as necessary), it becomes
possible to obtain a product of quality sufficient either for an intermediate of
medicines or agrichemicals qr for a flon alternative compound
[0059] In the present invention, the halogenated hemiacetals represented
by the general formula [l] (or the halogenated hemiacetal bis-denvatives

represented by the general formula [la]) are reacted with sulfuryl fluoride in
the presence of the organic base, thereby producing the halogenated
α-fluoroethers represented by the general formula [2] (or the halogenated
α-fluoroether bis-derivatives represented by the general formula [2a])
[0060] It is.preferable to conduct the reaction in the presence of "a salt or
complex of an organic-base with hydrogen fluoride", by which the objective
dehydroxyfluormation reaction can proceed extremely favorably
[0061] It is more preferable to use, as the starting substrate, halogenated
hemiacetals represented by the general formula [3] or the general formula [5]
and able to be prepared from fluoral or 3,3,3-trifluoropyruvic acid esters With
this, the industrially important halogenated α-fluoroethers can be industrially
produced with high yield and selectivity
[0062] [Examples]
Embodiments of the present invention are specifically explained bj?
examples The present invention is, however, not limited to these examples
Incidentally, omission marks discussed in the examples are as follows
Et, Ethyl group
Me, Methyl group
[0063] [Example l]
A pressure-proof reaction vessel made of stainless steel (SUS) was
charged with 500 mg (3 47 mmol, 1 00 eq) of halogenated hemiacetals
represented by the following formula
[Chemical Formula ll]

, 3 5 mL-ef acetonitrile, 1 756 mg"(l7 35 mmol, 5 00 eq) of triethylamine and
839 mg (5 20 mmol, 1 50 eq) of triethylamine tris(hydrogen fluoride) complex,

followed by iminersing it in a coolant bath of -78 °C Then, 708 mg (6 94 mmol,
2 00 eq) of sulfuryl fluoride (SO2F2) was blown thereinto by using a bomb,
followed by stirring at room temperature throughout the night The
reaction-terminated liquid was confirmed by ^-NMR and 19F-NMR to have a
conversion rate and a selectivity of 100 % and not less than 70 %,-respectively
By directly distilling the reaction-terminated liquid (at normal pressure),
halogenated α-fluoroethers represented by the following formula
[Chemical Formula 12]

can be obtained as a mixture of triethylamine and acetonitrile The yield was
confirmed by the conversion rate and the selectivity of the
reaction-terminated liquid to be not less than 70 % A molecular weight of 147
(M+l) was observed by GOMS (CI method) *H-NMR and ^F-NMR will be
discussed below
[0064] iH-NMR [Standard substance, (CHs^Si, Deuteration solvent,
CD'Cy. 8 ppm/1 34 (t, 7 0Hz, 3H), 3 86 (m, 1H), 4 03 (m, 1H), 5 41 (dq, 61 9Hz,
3 0Hz, 1H)
19F NMR [Standard substance, C6FG, Deuteration solvent, CDCI3L 8
ppm/19 60 (dq, 61 9Hz, 6 4Hz, IF), 78 03 (dd, 6 4Hz, 3 0Hz, 3F)
[0065] [Example 2]
In conformity with YUKIGOSEIKYOKAISHI (Japan), 1999, Vol 57,
No 10, p 102-103, fluoral (gas) was generated from an excessive amount of
fluoral monohydrate, followed by blowing it into allyl-alcohol Stirring was
conducted for 2 hours at room temperature, thereby obtaining'halogenated
hemiacetals represented by the following formula

[Chemical Formula 13]

at a quantitative yield
[0066] A pressure-proof reaction vessel made of stainless steel (SUS) was
charged -with 1 56 g (9 99 mmol, 1 00 eq) of halogenated hemiacetals
represented by the above formula, 10 mL of acetomtrile, 4 05 g (40 02 mmol,
4 Ol^eq) of triethylamine and 161 g (9 99 mmol, 1 00 eq) of triethylamine
tris(hydrogen fluoride) complex, followed by iminersing it in a coolant bath of
-78 °C Then, 2 04 g (19 99 mmol, 2 00 eq) of sulfuryl fluoride (SO2F2) was
blown thereinto by using a bomb, followed by stirring at room temperature
throughout the night The reaction-terminated liquid was confirmed by
iH-NMR and 19F-NMR to have a conversion late and a selectivity of 100 %
and not less than 70 %, respectively The reaction-terminated liquid was
directly distilled (at normal pressure) thereby obtaining halogenated
α-fluoroethers represented by the following formula
[Chemical Formula -14]

as a mixture of triethylamine and acetohitrile The yield was confirmed by the
conversion rate and the selectivity of the reaction-terminated liquid to be not
less than 70 % iH-NMR and 19F-NMR will be discussed below
[0067] !H-NMR [Standard substance, (CHa^Si, Deuteration solvent,
CDCI3], 8 ppm/4 30 (dd, 13 2Hz, 6 0Hz, 1H), 4 47 (dd, 13 2Hz, 4 2Hz, 1H), 5 36
(dd/16 8Hz, 0 4Hz, 1H), 5 40 (dd, 16 8Hz, 1 2Hz, 1H), 5 42 (dq, 60 7Hz, 3 2Hz,
ffl), 5 92 (m, 1H)
19F-NMR [Standard substance, CGFG,"Deuteration solvent, CDCI3], 8
ppm/17"95 (dq, 60 7Hz, 6 0Hz, IF), 78 29 (dd, 6 0Hz, 3 2Hz, 3F)

[0068] [Example 3]
An excessively small-a mount of methanol was added to ethyl
3,3,3-trifluoropyruvate and then-*stir-red at room temperature throughout the
night, thereby obtaining halogenated hemiacetals represented by the
following formula
[Chemical Formula 15]

at a quantitative yield
[0069] A pressure-proof reaction vessel made of stainless steel (SUS) was
charged with 500 mg (2 47 mmol, '1 00 eq) of halogenated hemiacetals
represented by the above formula, 2 5 mL of acetonitrile, 1 000 mg (9 88 mmol,
4 00 eq) of .triethylamine and 399 mg- (2 47 mmol, 1 00 eq) of triethylamine
tris(hydrogen fluoride) complex, followed by iminersing it in a coolant bath of
-78 °C Then, 505 mg (4 95 mmol, 2 00 eq).of sulfuryl fluoride (SO2F2) was
blown thereinto by using a bomb, followed by stirring at room temperature
throughout the night The reaction-terminated liquid was confirmed by
iH-NMR and 19F"NMR to shave a conversion-rate and a selectivity of 100 %
and not less than 70 %, respectively The reaction-terminated liquid was
directly distilled (at from normal pressure to 23 kPa) thereby obtaining
halogenated criluoroethers represented by the following formula
[Chemical Formula 16]

as a mixture of triethylamine and acetonit-nle The yield was confirmed by the
conversion rate and the selectivity of the- reaction-terminated liquid to be not

less than 70 % iH-NMR and iqF-NMR will be discussed below
[0070] !H-NMR [Standard substance, (CHs^Si, Deuteration solvent,
tCDCls], 6 ppm/I 38 (t, 712Hz, 3H), 3 59 (s, 3H), 4 41 (q, 7 2Hz, 2H)
19F-NMR [Standard substance, CGF6, Deuteration solvent, CDCI3L 6
ppm/26 70 (s, IF), 80 51 (s, 3F)

WE CLAIM
1 A process for producing a halogenated α-fluoroether represented by a
general formula [2]

by reacting a halogenated hemiacetal represented by a general formula [l]

with sulfuryl fluoride (SO2F2) in the presence of an organic base
wherein haloR represents fluoroalkyl group, R1 represents
one of hydrogen atom, and R2 represents one of alkyl group and substituted
alkyl group
2 A process for producing one of a halogenated α-fluoroether and a
halogenated α-fluoroether bis-derivative, as claimed in Claim 1, wherein
the reaction is conducted in the additional presence of "one of a salt and a
complex of an organic base with hydrogen fluoride" in a system

3 A process as claimed in claim 1, wherein the halogenated
α-fluoroether is represented by a general formula [4]

and the halogenated hemiacetal is represented by a general formula [3]

wherein, R2 represents one of an alkyl group and a substituted
alkyl group
4 A process for producing a halogenated α-fluoroether as claimed in
Claim 3, wherein a reaction of Claim 3 is conducted in the presence of "one
of a salt and a complex, of an organic base with hydrogen fluoride" in a
system
5 A process as claimed in claim 1, wherein the halogenated
α-fluoroether is represented by a general formula [6]

and the halogenated hemiacetal is represented by a general formula [5]


wherein R2 and R3 mutually independently represent one of
an alkyl group and a substituted alkyl group
6 A process for producing a halogenated α-fluoroether as claimed in
Claim 5, wherein a reaction of Claim 5 is conducted in the additional
presence of "one of a salt and a complex, of an organic base with hydrogen
fluoride" in a system

ABSTRACT

TITLE Process For Production Of Halogenated a -Fluoroethers
Halogenated α-fluoroethers (or bis-derivatives thereof) can be produced by reacting a halogenated hemiacetal (or bis-derivative thereof) with
sulfuryl fluoride (SO2F2) in the presence of an organic base. The reaction is
conducted preferably in the presence of "a salt or complex of an organic base
with hydrogen fluoride", whereby the objective dehydroxyfluorination can
proceed -extremely favorably It is still preferable to use as the starting
substrate a halogenated hemiacetal prepared -from fluoral or
3,3,3-tiffluoropyruvic acid ester Thus, industrially important halogenated
α-fluoroethers can be industrially produced with high selectivity and in high
yield