TECHNICAL FIELD
[0001] The present invention relates to a method for purifying difluoroacetic
acid chloride useful as an intermediate for pharmaceuticals and agrochemicals and
an reagent.
BACKGROUND OF THE INVENTION
[0002] As a method for producing difluoroacetic acid chloride, there have been
known: (1) a method of chlorinating difluoroacetic acid with a chlorinating agent
such as phosphorous pentachloride and the like; (2) a method for oxidizing 1,1-
difluoro-2,2-dichloroethane (R-132a) with oxygen under temperatures and pressures
(Patent Publication 1); and (3) a method for causing oxidation by irradiating a
mixture of l,l-difluoro-2, 2-dichloroethane (R-132a), O2 and Cl2 with a high-
pressure mercury lamp (Patent Publication 2).
[0003] Additionally, it has been known that difluoroacetic acid fluoride is
obtained by subjecting l-alkoxy-l,l,2,2-tetrafluoroethane to thermal decomposition
in the presence of a metal oxide catalyst (Patent Publication 3).
[0004] Furthermore, in Patent Publication 4, there is disclosed that
benzofluoride having a fluorine-containing substituent is fluorinated with calcium
chloride thereby being converted into a corresponding benzochloride.
REFERENCES ABOUT PRIOR ART
Patent Publication
[0005] Patent Publication 1: U.S. Patent No. 5905169
Patent Publication 2: Japanese Patent Application Publication No. 8-
53388
Patent Publication 3: Japanese Patent Application Publication No. 8-
92162
Patent Publication 4: European Patent No. 293747

SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
[0006] At the time of producing difiuoroacetic acid chloride by oxidizing 1,1-
difluoro-2,2-dichloroethane according to the method as discussed in Patent
Publication 1 or 2 or the like, by-products such as difiuoroacetic acid fluoride and
difiuoroacetic acid are often formed. Moreover, in a case of converting
difiuoroacetic acid fluoride into difiuoroacetic acid chloride by a halogen-exchange
reaction, a small amount of difiuoroacetic acid fluoride sometimes remains
unreacted. In addition, there are some cases where difiuoroacetic acid chloride is
decomposed during storage to generate hydrogen fluoride and difiuoroacetic acid
fluoride is formed by this action.
[0007] In view of the above, an object of the present invention is to provide a
method for making a difiuoroacetic acid chloride composition product that contains
difiuoroacetic acid fluoride (in the present specification, referred to as "crude
difiuoroacetic acid chloride" or "crude DFAC") into a highly pure difiuoroacetic
acid chloride by a simple device.
Means for Solving the Problems
[0008] The present inventors studied a method for removing difiuoroacetic acid
fluoride that accompanies difiuoroacetic acid chloride in order to solve the above
problems. As a result, it was found that difiuoroacetic acid chloride that does not
substantially contain difiuoroacetic acid fluoride can easily be obtained by bringing
crude difiuoroacetic acid chloride into contact with a heated anhydrous calcium
chloride, with which the present invention had reached completion.
[0009] The present invention is as follows.
[0010] [Invention 1]
A method for purifying difiuoroacetic acid chloride, including the step
of:

bringing a difluoroacetic acid chloride composition that contains at least
difluoroacetic acid fluoride into contact with calcium chloride at a temperature
enabling reaction thereof thereby converting difluoroacetic acid fluoride into
difluoroacetic acid chloride.
[0011] [Invention 2]
A method for purifying difluoroacetic acid chloride, as discussed in
Invention 1, wherein the contact includes the step of causing the difluoroacetic acid
chloride composition to flow through calcium chloride at a temperature enabling
reaction thereof.
EFFECTS OF THE INVENTION
[0012] In the purification method of the present invention, difluoroacetic acid
fluoride contained in a difluoroacetic acid chloride composition is converted into
pure difluoroacetic acid chloride, and fluorine atoms that have undergone exchange
are fixed in the form of calcium fluoride. Therefore, a highly pure product is
obtained without further purification after a treatment conducted according to this
method, and the product may be sent into an arbitrary subsequent reaction step.
MODE(S) FOR CARRYING OUT THE INVENTION
[0013] The present invention is a method for purifying difluoroacetic acid
chloride, including a chlorination step where a difluoroacetic acid chloride
composition that contains at least difluoroacetic acid fluoride is brought into contact
with calcium chloride at a temperature enabling reaction thereof.
[0014] Crude difluoroacetic acid chloride produced or formed by any method is
acceptable. It may be exemplified by difluoroacetic acid chloride obtained by
oxidizing l,l-difluoro-2,2-dichloroethane with oxygen, a mixture into which
difluoroacetic acid fluoride is mixed (Patent Publications 1 and 2) and the like.
[0015] In the purification method of the present invention, crude difluoroacetic
acid chloride is purified in such a manner as to bring it into contact with calcium
chloride at a temperature enabling reaction thereof to convert difluoroacetic acid
fluoride into difluoroacetic acid chloride.

[0016] The reaction relating to the purification method of the present invention
is represented by the following equation.
2CHF2COF + CaCl2 → 2CHF2COC1 +CaF2
As shown in the above equation, difluoroacetic acid fluoride is converted
into pure difluoroacetic acid chloride and therefore a further purification operation is
not necessary, while fluorine atoms removed by halogen-exchange are fixed in the
form of calcium fluoride so that waste treatment and the like can easily be carried
out.
[0018] The content of difluoroacetic acid fluoride contained in crude
difluoroacetic acid chloride is not limited. From a practical standpoint, it is
preferably less than 50 mass%, more preferably less than 20 mass%, much more
preferably less than 10 mass% of the crude difluoroacetic acid chloride.
Additionally, it is further preferable that the content of difluoroacetic acid fluoride is
previously adjusted to be less than 1 mass%.
[0019] Calcium chloride (CaCl2) used in the purification method of the present
invention is preferably anhydride. In particular, calcium chloride products for
general purpose use, which are not required to be high in purity and commercially
available as a reagent, a raw material for chemicals and a drying agent, may be used.
In the case of using calcium chloride having crystalline water, it is preferable that a
pretreatment is conducted, where the crystalline water is removed in advance at
300°C or more under the flow of nitrogen and the like. The form may freely be
selected, but the powder form is preferable when the reaction system is a fluidized
bed type or batch type, while the granular form is preferable when calcium chloride
is used under a flow system. Though the grain size is not particularly limited and
depends on the shape of the reactor or on the tube diameter in particular, it is
preferable to use granular calcium chloride consisting chiefly of grains having a size
of around 1-20 mm at the maximum because it is easy to handle.
[0020] The reaction system may freely be selected and therefore it may be either
the liquid phase or the gas phase, but the reaction is preferably conducted in the gas
phase. Though it is also possible to adopt a batch type or a flow type, the flow type

system is preferable in view of operational convenience. A reaction in the liquid
phase is conducted at low temperatures and high pressures in order to liquefy
difluoroacetic acid fluoride, which is economically disadvantageous. Moreover, in
the case of forming the liquid phase by using a solvent, it is necessary to remove the
solvent after treatment. Therefore, the method of the present invention is preferably
performed in the gas phase continuous style.
[0021] In the flow system, the method of the present invention serves as a
method for flowing crude difluoroacetic acid chloride that contains difluoroacetic
acid fluoride through granular calcium chloride at a temperature sufficient for
difluoroacetic acid fluoride to convert into difluoroacetic acid chloride, i.e., a
temperature enabling the reaction, in which difluoroacetic acid fluoride is converted
into difluoroacetic acid chloride quantitatively. By the way, this reaction is a gas-
solid reaction where a solid usually contributes to the reaction only at its surface and
therefore its inner portion does not contribute to the reaction in most cases; however,
granular calcium chloride used in the present reaction can contribute to the reaction
substantially at all of the portion including the inner portion of a grain of calcium
chloride, and can maintain its original shape without causing a remarkable
powdering.
[0022] The reaction temperature depends on treatment conditions including the
retention time and the like, and it preferably 50 to 250°C and more preferably 100 to
200°C. The retention time depends on the reaction temperature and it preferably 1
to 1000 seconds, more preferably 10 to 700 seconds, much more preferably 50 to
500 seconds. A reaction shorter than 1 second may sometimes not terminate and
therefore not preferable. A reaction over 1000 seconds may proceed but it does not
preferable since the throughput is reduced. Pressure to be applied during the
reaction may freely be determined, but an operation conducted substantially at
atmospheric pressure without increasing or reducing the pressure is preferable.
When a reaction tube is used in the flow system and the content of DFAF is high, a
localized heated state (a heat spot) of 10-30°C occurs in the vicinity of the inlet at
the initial stage of the reaction and then the heat spot gradually shifts toward the

outlet. With this phenomenon, the consumption of calcium chloride is noticed and
the timing of its replacement can be determined thereby. To use an apparatus
relatively large within the scope of a person having ordinary skill in the art is
preferable because the frequency of the replacement of calcium chloride is reduced.
It is preferable that the reaction tube is formed of stainless steel, Monel (registered
trademark), Inconel (registered trademark), Hastelloy (registered trademark),
fluorocarbon polymers or a material obtained by conducting lining on the above
materials. A larger ratio between the tube length and the tube diameter of the
reaction tube is to improve the purification efficiency but the increase of the ratio
accelerates pressure drop, so that the ratio is preferably 5 to 200.
[0023] In the reaction, it is also possible to contain argon, nitrogen, hydrogen
and the like as a carrier gas. The thus obtained difluoroacetic acid chloride can be
provided directly as a product without a further purification, or alternatively, can be
used as a reagent for various reactions without a further purification.
[0024] Calcium fluoride that the reaction forms as a by-product may be used as
a material for producing an optical crystal or hydrogen fluoride.
EXAMPLES
[0025] Hereinafter, the present invention will be explained with reference to
examples; however, the present invention is not limited to these examples. Analysis
of organic substances was performed by gas chromatography (Flame Ionization
Detector) and the composition was expressed in terms of area % (hereinafter
indicated by "%").
[0026] [Example 1]
A reaction tube formed of stainless steel and having an inner diameter of
37 mm and a length of 1000 mm was charged with 150 g of anhydrous calcium
chloride available from JUNSEI CHEMICAL CO., LTD. (grain size: about 2.5-3.5
mm) and heated by a tape heater to 200°C under the flow of nitrogen. After the
temperature was stabilized at 200°C, crude difluoroacetic acid chloride (DFAC, 95.0
% purity) containing 4.8 % of difluoroacetic acid fluoride (DFAF) was started to

flow at a rate of 0.2 g/min, and simultaneously the supply of nitrogen was
suspended. Organic substances (98 g) recovered after the flow of 100 g of the crude
difiuoroacetic acid chloride at a dry ice trap connected to the outlet of the reaction
tube was subjected to analysis by gas chromatography. As a result, the purity of
DFAC was 99.9 % and a trace amount (lower than 0.001 %) of DFAF was
confirmed.
[0027] [Example 2]
(Preparation of DFAC)
A 1000 cc autoclave formed of stainless steel and equipped with a stirrer
was charged with lithium chloride (LiCl, 168.7 g, 4.0 mol) and then the inner section
was decompressed. After cooling the autoclave in an acetone-dry ice bath until the
internal temperature reached -40°C, DFAF (300 g, 3.06 mol) containing a small
amount of monofluoromethane was introduced thereinto with pressure while
stirring. Thereafter, the bath was removed and the autoclave was stirred for 1 hour
at room temperature (about 25°C), followed by taking 1 hour to increase the
temperature to 70°C by a band heater and then letting the autoclave stand for 4
hours. Pressure applied at this time was 0.56 MPaG (gage pressure). After the
reaction had terminated, the content was recovered and subjected to flash
distillation. As a result of conducting analysis by gas chromatography, the content
was found to be DFAC (CHF2COCl) of 98.64 % purity (recovery rate: 96 %). It
was confirmed that impurities consisted chiefly of: 0.36 % of CH3F derived from
impurities contained in the starting material DFAF; 0.15 % of unreacted DFAF; and
0.33 % of difiuoroacetic acid (CHF2COOH).
[0028] (Purification)
By using the thus obtained crude DFAC, the same experiment as in
Example 1 was repeated. More specifically, Organic substances (103 g) recovered
after the flow of 100 g of the crude DFAC at a dry ice trap connected to the outlet of
the reaction tube was subjected to analysis by gas chromatography. As a result, the
purity of DFAC was 99.9 % and a trace amount (lower than 0.001 %) of DFAF was
confirmed.

INDUSTRIAL APPLICABILITY
[0029] The present invention is useful as a method for purifying difluoroacetic
acid chloride useful as an reagent for introducing a difiuoromethyl group.

WE CLAIM:
1. A method for purifying difiuoroacetic acid chloride, including the step of:
bringing a difiuoroacetic acid chloride composition that contains at least
difiuoroacetic acid fluoride into contact with calcium chloride at a temperature
enabling reaction thereof thereby converting difiuoroacetic acid fluoride into
difiuoroacetic acid chloride.
2. A method for purifying difiuoroacetic acid chloride, as claimed in claim 1,
wherein the contact includes the step of causing the difiuoroacetic acid chloride
composition to flow through calcium chloride at a temperature enabling reaction
thereof.
3. A method for purifying difiuoroacetic acid chloride, as claimed in claim 1 or
2, wherein the reaction temperature is 50 to 250°C.
4. A method for purifying difiuoroacetic acid chloride, as claimed in any of
claims 1 to 3, wherein the retention time is 1 to 1000 seconds.
5. A method for purifying difiuoroacetic acid chloride, as claimed in any of
claims 1 to 4, wherein the reaction is conducted in a liquid phase.
6. A method for purifying difiuoroacetic acid chloride, including the step of:
reacting difiuoroacetic acid fluoride with lithium chloride thereby producing a
difiuoroacetic acid chloride composition that contains at least difiuoroacetic acid
fluoride; and
bringing the difiuoroacetic acid chloride composition into contact with
calcium chloride at a temperature enabling reaction thereof thereby converting
difiuoroacetic acid fluoride into difiuoroacetic acid chloride.

7. A method for purifying difluoroacetic acid chloride, as claimed in claim 6,
wherein the contact includes the step of causing the difluoroacetic acid chloride
composition to flow through calcium chloride at a temperature enabling reaction
thereof.
8. A method for purifying difluoroacetic acid chloride, as claimed in claim 6 or
7, wherein the reaction temperature is 50 to 250°C.
9. A method for purifying difluoroacetic acid chloride, as claimed in any of
claims 6 to 8, wherein the retention time is 1 to 1000 seconds.
10. A method for purifying difluoroacetic acid chloride, as claimed in any of
claims 6 to 9, wherein the reaction is conducted in a liquid phase.