CA2118828A1 - Vapor phase chlorination of difluoromethyl methyl ether - Google Patents

Abstract

ABSTRACT
The synthesis of fluorinated dimethyl ethers of the formula CF2HOCClxFyH3-(x+y) wherein x is 0, 1 or 2; y is 1, 2 or 3; and wherein (x+y) is 1, 2 or 3. The process involves chlorination of methyl difluoromethyl ether in the presence of oxygen to form a chlorinated reaction product of the formula CF2HOCH3-zClz wherein z is 1 or 2, and wherein the formation of CF2HOCCl3 is inhibited. The resulting compound(s) is then fluorinated with HF before or after separation, to give a fluorinated reaction product including the aforementioned fluorinated dimethyl ethers.

Description

VAPOR PHASE CHLORINATION OF DIFLUOROMETHYL MEl~IYL ETHER
BACKGROUND OF l~E INVENTION
This invention relates in general to fluorinated dimethyl ethers and specifically to methyl difluoromethyl ether as a starting material for the synthesis of fluorinated dimethyl ethers. Such fluorinated dimethyl ethers, including bis(difluoromethyl)ether (CHF20CHF2), have u~lity has CFC alternatives, particularly for use as refrigerants, blowing agents, etc.
Bis(difluoromethyl)ether has been prepared previously by chlorination of dimethyl ether followed by isolation and fluorination of bis(dichloromethyl)ether. The chlorination step resulted in a complex mixture of chlorinated dimethyl ethers, some of which were unstable, e.g. to distillation, from which bis(dichloromethy1~ether was separated. Moreover, chloromethyl methyl ether and bis(chloromethyl)ether are produced by this reaction, and are carcinogens.
Another approach to the synthesis of methyl difluoromethyl ether is disclosedby Hine and Porter in Methvlene derivatives as int_rmediates in polar reaction VIII. Difluoromethvlene in the Reaction of Chlorodifluoromethane with Sodium Methoxide, published in the Journal of the American Chemical Society 79, 5493~ (1957). This article describes a reaction mechanism wherein the desired difluoromethyl-methyl-ether is synthesized in a batch reaction in a fixed ratio with the by-product trimethyl-orthoformate, while continuously refluxing the unreacted feed.
However, not only does this reaction produce large amounts of trimethylorthoformate, but also the product itself breaks down to trimethylorthoformate, resulting in less than advantageous yields of the desired difluoromethyl methyl ether.
U.S. Patent No. 5,185,474, the disclosure of which is hereby incorporated by reference, discloses avoiding the production of such carcinogens and unstable compounds by using methyl difluoromethyl ether as a starting material. The methyl difluoromethyl ether is chlorinated to produce a reaction mixture including at least one compound of the formula CF2HOCH3.zClz, wherein z is 1, 2, or 3. The mixture can then be fluorinated, or any one of the chlorination - ~ 2 ~ 2 ~

compounds first separated from the mixture and separately fluorinated. ~;
However, during the chlorination of CF2HOCH3, it is difficult to control the distribution of products. Although manipulation of the molar flow rates of Cl2 and CF2HOCH3 can give a ~ ~ ;
slight predominance of CF2HOCH2CI or CF2HOCHCI2, a sigmficant arnount of CF2HOCCI3 is formed. If the desired product to be subsequently fluorinated is either CF2HOCH2CI or CF2HOCHCI2, the formation of CF2HOCCI3 causes a considerable reduction in the efficiency of the process.
Accordingly, it is an object of the present invention to provide an improved process for the production of bis(difluoromethyl) ether.
It is an further object of the present invention to provide an improved process for the production of bis(difluoromethyl) ether wherein the various required separations may be effected by distillation without loss of yield and danger of explosion ~ue to marked instability of the various intermediates.
It is a still further object of the present invention to provide a process for efficiently producing difluoromethyl methyl ether.

SU~ARY OF THE INVENTION
The problems of the prwr art have been overcome by the present invention, which provides a process for the production of difluoromethyl methyl ether. More specifically, the process of the present invention includes means for preferentially inhibiting the formation of CF2HOCCl3, and which does not produce carcinogens as intermediates.
The unstable complex mixture of chlorinated ethers, some of which are carcinogens, in accordance with the prior art, is avoided in the present invention by employing methyl difluoromethyl ether as a starting material. The methyl difluoromethyl ether ischlorinated to give a chlorinated reaction mixture including at least one compound of the formula CF2HOCH3 zClz, -.: . , : . ~-:
:. .

,-: - . -~:, ' ' ' ' ' ': -; - .
... .

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wherein z is 1, 2 or 3, which compound can be readily separated from the chlorinated reaction mixture. The chlorination of metbyldifluoromethyl ether would generally form only tbree derivatives, i.e., z--l, z=2 and z=3. The dichloromethyl difluoromethyl ether (z=2) can be readily separated from the chlorinated reaction mixture and is then fluorinated, with or without such separation, to form the bis(difluorome&yl)ether. The production of CF2HOCC13 (z=3) can be inhibited, and any produced also may be separated from the chlorination reaction product and fluorinated. Alternatively, the chlorination reaction product itself may be fluorinated (without prior separation) as follows:

CF2HOCH2CI ~ CF2HOCH2F (I) ~_, CF2HOCHCIF
CF2HOCHCk ~
--' CF2HOCHF2 (II) CF2HOCCkF
CF2HOCCI3 - ~ CF2HOCCIF2 -- CF2HOCF3 (m) All of the above would find utility as refrigerants, especially (I) monofluoromethyl difluoromethyl ether and aI) bis(difluoromethyl)ether, which are considered to be substitutes for R-l 1 and R-l 14 refrigerants, respectively.

DETAILED DESCR~IION OF TEIE lNVENTION
The methyl difluoromethyl e~her which is regarded as the starting material for the process of the present invention is a known compound which may be prepared in the manner reported by . ` 2 ~

Hine and Porter in their aforementioned article published in the Journal of the American Chemical Societv. Specifically, difluoromethyl methyl ether is produced by reaction of sodium methoxide (NaOMe) with chloro~difluoromethane (CF2HCl), which reaction may be represented as follows~
.. ~ .
CF2HCl + CH30Na~ CF2HOCH3 + NaCI

Briefly, the method involves forming an alcohol solution of sodium methoxide and bubbling the chlorodifluoromethane slowly into the reaction mixture to obtain the methyldifluoromethyl ether as a residue in the reaction mix~ure. Some product is entrained with unreacted CF2HCI and can be separated from it in a distillation operation.
The starting ether, CHF20CH3, also might be prepared by first reacting NaOH with CH30H, in effect rnaking CH30Na, and then reacting it with CF2HCI. However, water is also formed in the NaOH/CH30H reaction. The effect water has on the subsequent reaction to form CHF20CH3 is to reduce the yield of CHF20CH3.
The chlorination and fluorination steps of this invention can be represented as follows:

zCl2 CHF20CH3 ~> CF2HOCH3~zClz + zHCI (where~n z = 1, 2, or 3) F
CF2HOCH3 zClz ~----> CF2HOCH3~Clz yFy (whe~ein z = 1, 2, or 3 y= 1,2,or3 y S z) The inventors of the present invention have found that the formation of CF2HOCH3 zClz wherein z = 3 in the above reaction scheme can be inhibited or even eliminated upon the addition of an oxygen source, preferably air, to the vapor phase reacdon medium. Rather than inhibiting the three chlorination products equally, the addition of oxygen surprisingly preferentially inhibits . . ... ".,.. ~,, -., . , :; . , , , . :
.

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the formation of CF2HOCC13. Although the inventors of the present invention are not to be limited by any mechanism theory, it is believed that the inhibition is caused as a result of oxygen forming a complex w,lth the activated chlorine molecule, with the kinetics of the reaction being such that the trichloro derivative is preferentially inhibited. Any oxygen source not deleterious to the production of the desired compounds could be used, including oxygen-containing compounds which liberate oxygen in si~u.
The oxygen should be present in an amount effective for the desired inhibition. In the case of air, preferably tbe air is added in an amount from about 1.5 to about 5.5% of the total gas flow. Those skilled in the art will recognize that where pure oxygen is used, the amounts will be about 1/5 that of air. Preferably the oxygen source is added to the reaction medium for as long æ the chlorine gæ is flowing.
It hæ been found tbat CHF20CH3 may be suitably chlorinated by liquefying the CHF20CH3 and reacting it with chlorine gas while irradiating with a source of visible light.
Alternatively, one may use other light sources such as ultraviolet light or heat, a catalyst or a free radical initiator to aid in the reaction. The chlorirlation products of CHF20CH3 can be readily separated prior to fluorination or the reaction mixture can be fluorinated without separation to give an admixture of CF2HOCCI2F, CF2HOCF2CI, CF2HOCH2F, CF2HOCFHCI, CF2HOCF2H. All separations may be effected by fractional distillation.
A preferred method of chlorinating the CHF20CH3 is to maintain &e CHF20CH3 in a vapor phæe and react it with chlorine gæ while subjecting the chlorination reaction to a source of light, preferably visible orultraviolèt light. Alternatively, other reaction aids such as a catalyst, heat or a free radical initiator rnay be used instead of light in the chlorination reaction.
In t&e preferred fluorination procedure, the chlorinated reaction product is reacted with anhydrous hydrogen fluoride (HP), which reaction may be represented as follows:

2CF2HOCCI3 + 3HF~--> CF2HOCFCl2 + CF2HOCF2CI + 3HCI

~' ~

Utilizing the above reaction with hydrogen fluoride t'ne inventor has obtained a yield as high as 78% CF2HOCF2Cl with a small amount of CF2HOCFC12. This was an unexpected result since HF by itself does not normally replace a halogen such as chlorine, except perhaps at very high temperatures, but instead fluorinates by continuous regeneration of a fluorinating agent such as SbCI5qFy7 such as SbF3, or SbF3C12. Apparently, the difluoromethoxy group activates the chlorine on the alpha-carbon atom, aDowing it to react readily with HF.
Alternatively, the HF may be diluted with an organic solvent, preferably a dipolar aprotic solvent such as metbyl pyrrolidone, in order to reduce fragmentation of the fluorinated material, resulting in higher yields of desired product with less by-product generation. Other sources of fluorine for the fluorination step include metal fluorides that can form salts of the HF2e anion, such as KHF2, NaHF2, LiHF2, NH4HF2, etc., and pyridine salts of HF and NaF and KF in suitable solvents.
The resultant fluorinated products may be separated by distiDation or by the process as taught in U.S. Patent 4,025,567 or U.S. Patent 3,887,439 which are incorporated herein by reference in their entirety.
The present invention will now be further iDustrated by the foDowing examples.

a) Preparation of CF2HOCH3 A 25 wt ~ solution of sodium methoxide in methanol (1533. lg) containing 7.1 moles of sodium methoxide was placed in a 4 liter jacketed autoclave fitted with a temperature sensor, a pressure gauge and a dipleg. The vessel was cooled to 0 to 5C and chlorodifluoromethane (318.2g, 3.70 moles) added over a period of 2.5 hours with agitation. When the addition of gas had been completed, the autoclave was s1Owly warmed to about 60C while venting gaseous products through the water-cooled condenser into a coDection trap cooled to about -70C.

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When all volatile material had been collected unreacted CHF2CI was removed at ^20C
and the remaining CF2HOCH3 transferred to a metal cylinder. The recovered difluoromethyl methyl ether (150 0g, 1.83 moles) represented a yield of 49.4% based on CF2HCI.
b) Chlorination of CF2HOCH3 Chlorine and CF2HOCH3 in a gaseous phase are passed through separate condensers cooled to 0C and then the gas strearns combine and pass into one arm of a U-shaped reactor, irradiated with visible light or W. Both anns of the reactor are jacketed and cooled with water.
There is an outlet at the bottom of the U to which is attached a product collection flask.
A Dewar-type condenser cooled to -50C is attached to the outlet of the second arm of the U-tube and, in turn, it is connected in series wi& a cold trap to collect unreacted chlorine and an NaOH
scrubber to remove HCI. The reaction is normally carried out at atmospheric pressure, but higher or lower pressure can be used. Temperature should not be allowed to rise much above 50C in the reactor to avoid attack on the glass.
In practice, the apparatus is flushed with nitrogen and then chlorine and CHF2OCH3 are fed to the reactor at rates such that the ratio of the flow of chlorine to that of the ether is maintained at about 2.5:1 for optimum results, i.e., yield of CF2HOCHCI2. A predorninant amount of any one of the three products can be obtained by changing t~e ratio of the gas flows.
After the passage of 2.3 moles of chlorine and 0.9 moles of CHF2OCH3, 136.6g of product were recovered. GC analysis of the product n~ixture showed CF2HOCH2Cl 10.0%, CF2HOCHCl2 62.4%, and CF2HOCCI3 22.2%.
c) Fluorination of CHF2OCHCl2 with HF
The chlorinated CHF2OCH3 (40.0g) containing 46.1% CF2HOCHCl2 in a stainless steel cylinder was then cooled in ice before adding anhydrous HF (30.0g). The cylinder was closed with a valve and pressure gauge and then was placed in a water bath at 60C for 3 hours. The cylinder was then vented through a NaOH scrubber and volatile products collected in a trap cooled ~ ~ , , ................. . .. .. . . .. - .

...

2 ~ ? r~
at -70C. The weight of product recovered from the trap was 16.8g. It contained 71.8%
CF2HOCF2H by GC analysis, corresponding to a yield of 83.8% of CF2HOCF2H.
When conducted on a larger scale (e.g., 5 gallons), almost quantitative yields of CF2HOCF2H (based on CF2HOCHCI2) were obtained.

A sample of chlorinated difluoromethyl ether rLuxture (25g) containing 50% CF2HOCCI3, was placed in a polyethylene flask fitted with an inlet tube for nitrogen as carrier gas, an outlet tube leading to a secondpolyethylene flæk containing NaOH solution (10%), followed by a drying tube and a trap cooled in Dry Ice/MeOH.
An excess of anhydrous hydrogen fluoride was added to the chlorinated ether and the mixture stirred with a magnetic stirrer. Heat was not applied, the temperature remaining at about 20C. More hydrogen fluoride was added to the mixture as needed until all the organic material had reacted. The weight of material collected from the cold trap was 9.5g.
Analysis of the recovered product by GC showed it to consist of 84.3 % CF2HOCF2CI, a yield of 78% bæed on the CF2OCCI3 content of the chlorinated mixture. A small amount of CFzHOCFCl2 wæ also present.

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The chlorination apparatus consisted of two vertical lengths of jacketed glass tubing, 4 feet long by 2 inches I.D., connected at the lower ends in a U-tube fæhion by a short length of unjacketed 2 inch I.D. tubing. A drain tube led from the lowest point of the U-tube arrangement so that product could be collected as it forrned and removed continuously from the apparatus or alternatively allowed to accumulate in a receher. Three 150 watt incandescent flood lamps were arranged along the length of each tube.

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The gases were fed into the upper end of one arm of the U-tube arrangement. Flow rates were measured by calibrated mass flowmeters. A low temperature condenser on the ou~det of the second arm of the U-tube returned unreacted E-152a and chlorine to &e illuminated reaction zone.
Hydrogen chloride by-product and air passed through the condenser into a water scrubber where the hydrogen chloride was removed.
A mixture of methanol and water, cooled to O to 5C was circulated &rough &e cooling jackets of &e apparatus.
In a typical run, coolant at a temperature of O to 5C is circulated through &e cooling jackets, &e flood lamps were turned on and dry ice placed in the low ternperature condenser.
Chlorine was introduced into the apparatus first, followed by difluorome&yl ether and air in the desired ratios. Product was removed at illtervals from &e receiver and washed with saturated NaHC()3 solution to remove HCl. Since the reaction was continuous, it could proceed for any length of time desired. At the end of the reaction, gas flows were stopped and product allowed to drain froIn &e vertical reactor tubes into the receiver.
The results are tabulated in Table 1 below. Examples 6-29-1 to 6-29-7 show ~he distn~ution of products normally obtained without the addition of air to &e gas stream. Examples 7-7-3 through 7-8~ show the effect of the addition of air in dirninishing arnounts, in accordance wi& the presentinvention.

--Flow Rates-- hod=l --P~oduct Distributioo----Moles-- Mob Ratio m T:ral Air m E1DIYQ C80 ~ 152a A~ ~Y~ ~SQ~Q r~ Tn S~2 E~2a C~2oe~2~ Ch5~0w S~lQi (mlshDiD) (gms) (%) (%) (%) ~0) (%) 6-29-1 500 273 _ 69.6 6.0 42.5 33.60.0203 0.0111 1.83 .
6-29-2 500 280 _ 95.6 8.2 42.5 30.40.0203 0.0114 1.~8 .
6-29-6 510 270 - 81.4 22.5 38.5 33.70.0207 0.0110 1.88 .
6-29-7 500 280 - 79.1 23.2 42.3 37.20.0203 0.0114 1.~8 _ 7-7-3 870 380 6~ 69.3 55.0 32.9 2.80.0353 0.0154 2.29 5.4 7.~
4 850 440 65 96.8 56.8 37.0 3.50.0345 0.01~9 1.93 5.1 ~.6 ~-~-5 900 405 63 119.3 48.3 42.4 5.20.0365 0.0164 2.23 4.8 7.0 ~ 900 405 60 116.0 54.3 39.8 4.50.0365 0.0164 2.23 4.6 6.~
7-~-8 930 405 62 111.5 52.5 36.2 3.30.0378 0.0164 2.30 4.6 6.7 ~-8-2 1430 600 55 198.6 43.0 45.2 ~.20 0581 0 0244 2 38 2.~ 3.8 ~-8-3 1850 ~50 54 202.4 42.8 46.5 5.00 0~51 0 0305 2 46 2 1 2 9 7-8-6 2200 1030 51 213 0 33.6 56.9 7 ~0.0893 0.0418 2.14 1 3 Z-3 ", '~

Claims (11)

1. A process for the preparation of fluorinated dimethyl ethers of the formula CF2HOCClxFyH3-(x+y), wherein x is 0, 1 or 2 and y is 1, 2 or 3 and wherein the total of x + y is 1, 2, or 3, said process comprising:
chlorinating CHF2OCH3 by reacting said CHF2OCH3 with chlorine in the presence of oxygen to form a chlorinated admixture containing at least one compound of the formula CF2HOCH3-zClZ, wherein z is 1 or 2, and inhibiting the formation of CF2HOCCl3; and fluorinating said at least one compound of the formula CF2HOCH3-zClz with a fluorine source selected from the group consisting of hydrogen fluoride, anhydrous hydrogen fluoride, metal salts of HF2?M NaF, KF and pyridine salts of HF, in the absence of a catalyst to obtain a fluorinated admixture containing at least one compound of formula CF2HOCH3-zClz

2. A process in accordance with claim 1 wherein said chlorination step occurs in either a vapor or liquid phase and the chlorine is in the form of a liquid or a gas.

3. A process in accordance with claim 1 wherein said chlorination step is in the vapor phase and the chlorine is in the form of a gas.

4. A process in accordance with claim 1 wherein the hydrogen fluoride is selected from the group consisting of anhydrous hydrogen fluoride and hydrogen fluoride in an organic solvent.

5. A process in accordance with claim 1 wherein said at least one compound of the formula CF2HOCH3-zClz is CF2HOCHCl2 and said fluorinated reaction product includes CF2HOCF2H and CF2HOCHFCl.

6. A process in accordance with claim 1 wherein said at least one compound of the formula CF2HOCH3-zClz is CF2HOCHCl2 and said at least one compound of the formula CF2HOCClxFyH3-(x+y) is CF2HOCF2H, and further comprising separating and recovering said CF2HOCF2H from said fluorinated admixture.

7. A process in accordance to claim 1 wherein said chlorination is conducted at a temperature and pressure sufficient to maintain said CF2HOCH3 in a gaseous state.

8. A process in accordance with claim 1 further comprising reacting CHF2Cl with an alkali metal methoxide in solvent solution to form said CHF2OCH3.

9. A process in accordance with claim 1, wherein air is the source of said oxygen.

10. In a process for the preparation of fluorinated dimethyl ethers of the formula CF2HOCCLxFyH3-(x+y), wherein x is 0, 1 or 2 and y is 1, 2 or 3 and wherein the total of x + y is 1, 2, or 3, wherein CHF2OCH3 is chlorinated by reacting said CHF2OCH3 with chlorine to form a chlorinated admixture containing at least one compound of the formula CF2HOCH3-zClz, wherein z is 1 or 2, and said at least one compound of the formula CF2HOCH3-zClz is fluorinated with a fluorine source selected from the group consisting of hydrogen fluoride, anhydrous hydrogen fluoride, metal salts of HF2-, NaF, KF and pyridine salts of HF, in the absence of a catalyst to obtain a fluorinated admixture containing at least one compound of formula CF2HOCH3-zFyClz-y, means for inhibiting the formation of CF2HOCCl3 by conducting said chlorination step in the presence of oxygen.

11. The process of claim 10 wherein air is the source of said oxygen.