Abstract:
The invention provides an improved process for preparing bis(fluoroxy)difluoro-methane (BDM) by continuously reacting F 2  with CO 2  in a reactor containing a fluorination catalyst (e.g., CsF), wherein the process is conducted at a pressure above atmospheric pressure. The process provides BDM of very high purity and very low residual F 2 .

Description:
BACKGROUND OF THE INVENTION  
         [0001]    This invention relates to a continuous process for preparing bis(fluoroxy)-difluoromethane (BDM) in high yields.  
           [0002]    There is a need in the art for scaleable processes which are capable of generating electrophilic fluorination agents (hereinafter referred to as “F + ” agents) with sufficient “F + ” character, or alternatively, “F + ” power, to effect electrophilic fluorination reactions of a wide variety of organic substrates with high selectivity, but yet are safe to produce and use as intended.  
           [0003]    In order to achieve high selectivity in electrophilic fluorination reactions, and hence commercial utility, the desired “F + ” agent must be very low or nearly completely devoid of radical fluorine sources, F · , including F 2 . Thus, the most desirable process must be highly efficient in converting F 2  to the “F + ” agent. An example of a “F + ” agent which possesses sufficient fluorination (“F + ”) power and selectivity in fluorination reactions with organic substrates is bis(fluoroxy)difluoromethane, hereinafter referred to as BDM.  
           [0004]    BDM can be synthesized by a variety of processes. Hohorst et al., “Bis(fluoroxy)difluoromethane, CF 2 (OF) 2   .” Journal of the American Chemical Society  (1967), Vol.89, pages 1809-1810, prepared BDM in 99.7% yield through the static room temperature reaction between CO 2  and a 305% molar excess of F 2  in the presence of a large molar excess of CsF. Cauble et al. “Preparation of Bis(fluoroxy)difluoromethane, CF 2 (OF) 2   .” Journal of the American Chemical Society  (1967), Vol. 89, page 1962, prepared BDM at room temperature in 99.1% yield using a similar procedure and nearly 100% excess F 2 . Cauble et al. “Fluorocarbonyl Hypofluorite.”  Journal of the American Chemical Society  (1967), Vol. 89, pages 5161-5162, prepared BDM by the reaction of fluorocarbonyl hypofluorite with excess F 2  in the presence of CsF. Lustig et al. “The Catalytic Addition of Fluorine to a Carbonyl Group. Preparation of Fluoroxy Compounds.”  Journal of the American Chemical Society  (1967), Vol. 89, pages 2841-2843, prepared BDM in 98.0% yield using a similar procedure with 15.7% excess F 2 . Thompson et al. Thompson, “Preparation and Characterization of Bis(fluoroxy)perfluoroalkanes. II. Bis(fluoroxy)perfluoromethane.”  Journal of the American Chemical Society  (1967), Vol. 89, pages 1811-1813 and U.S. Pat. No. 3,420,866 (Prager et al., 1969), disclosed the preparation of BDM by treating sodium trifluoroacetate, perfluorosuccinic anhydride, or sodium oxalate with diluted F 2  (≦50% v/v) in a flow system, and subsequently trapping all volatile products at −186° C.; however, the yields were poor (e.g., 2% yield when using sodium trifluoroacetate and 1-15% when using sodium oxalate). Mulholland et al., “Facile, Temperature-Dependent Formation of C 1  and C 2  Perfluoroalkyl Hypofluorites. Applications as Electrophilic Fluorinating Agents.”  Journal of Organic Chemistry  (1986), Vol. 51, page 1482, report that BDM was obtained in 5% yield by flowing 10% F 2 /N 2  (v/v) through sodium trifluoroacetate, followed by trapping all volatiles at −196° C. U.S. Pat. No. 3,394,163 (Kroon, 1968) discloses the production of BDM by fluorination of alkali metal oxalates followed by trapping the products at −158° C. and subsequent purification of BDM product by distillation. U.S. Pat No. 4,499,024 (Fifolt, 1985) and Michael J. Fifolt et al., “Fluorination of Aromatic Derivatives with Fluoroxytrifluoro-methane and Bis(fluoroxy)difluoromethane.”  Journal of Organic Chemistry  (1985), Vol. 50, pages 4576-4582 disclose that BDM can be produced in a sequence of steps involving flowing mixtures of F 2  and CO 2  through a bed of activated CsF, collecting the exit gases, and recovering BDM from the collected gases.  
           [0005]    Following are some of the shortcomings found in known processes for producing BDM, such as those discussed here:  
           [0006]    batch (static) processes require subsequent separation of the BDM product from excess F 2 ;  
           [0007]    BDM-containing product gases, produced in a flow system, must be collected (trapped) and separated from residual F 2 ; and  
           [0008]    when BDM is produced in flow systems, the substrate beds are sacrificial and must be replenished, and the BDM product must be subsequently recovered and purified.  
           [0009]    In addition, the above-cited processes which collect BDM product in a low-temperature trap in order to separate it from residual F 2  are quite disadvantageous since: (i) the excess F 2 , which is difficult and expensive to make and handle, is wasted, and moreover, must be disposed of (which is neither trivial nor inexpensive); and (ii) condensation of BDM product in a low-temperature trap is potentially very dangerous due to (a) the uncertainty of co-condensing highly energetic and unstable byproducts of the BDM synthesis reaction, and (b) the potential for spark-initiated explosive decomposition of BDM in the condensed phase (discovered by the inventor).  
           [0010]    Accordingly, it is desired to provide a safe and commercially scaleable process to prepare BDM, which is low in radical fluorine sources or impurities, including F 2 .  
         BRIEF SUMMARY OF THE INVENTION  
         [0011]    The invention provides an improved process for preparing BDM by continuously reacting F 2  with CO 2  at moderate temperature in a reactor containing a fluorination catalyst, wherein the process is conducted at a pressure above atmospheric pressure. The process provides BDM of very high purity and very low residual F 2 , such that the continuous product mixture is useable for fluorination or other applications without collection, isolation, purification or dilution.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWING  
       [0012]    [0012]FIG. 1 shows an embodiment of a BDM generation system of the invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0013]    In the present invention, BDM (i.e., CF 2 (OF) 2 ) is produced in a flow system from the reaction between F 2  and CO 2  in the presence of a fluorination catalyst (e.g., CsF) as depicted in the following equation:  
                         
 
         [0014]    Preferred embodiments of the present invention provide a continuous (flow) process for synthesizing an electrophilic fluorination agent, BDM, with very high purity and very low residual F 2 . BDM yields are preferably at least 90%, more preferably at least 95%, most preferably at least 99% (calculated as (experimental/theoretical)×100).  
         [0015]    The F 2  utilization efficiency of the present process is also excellent, and is significantly greater than that known in the background art cited above. Thus, product mixtures of the invention preferably contain residual F 2  in amounts less than 1%, more preferably less than 0.6%, most preferably undetectable amounts of F 2  (as determined by on-line UV analysis @311 nm).  
         [0016]    Moreover, there is a greater degree of safety inherent in the present invention as compared to the prior art, since in the present case, isolation and purification of the BDM product mixture are not required. Condensation of fluoroxy compounds, including BDM, is quite hazardous since these compounds have the potential to explode violently in concentrated or condensed forms. In fact, the inventor and colleagues have demonstrated that concentrated BDM mixtures will decompose explosively if a spark is introduced to the mixture.  
         [0017]    The reaction of the invention is conducted at super-ambient pressure. Preferably, the reaction pressure is at least about 6 psig (142.7 kPa), more preferably at least 75 psig (618.5 kPa), and even more preferably 75 psig to 320 psig (618.5 kPa to 2307.8 kPa).  
         [0018]    The reaction is preferably conducted at super-ambient temperature, but can also be conducted at ambient or sub-ambient temperature. Preferably, the temperature is about 5° C. to about 51° C.; more preferably, 20° C. to 38° C.  
         [0019]    In preferred embodiments, super-ambient reaction pressures and moderate reaction temperatures of about 20 to 38° C. are used to ensure complete conversion of F 2  and to control or avoid the formation of unwanted byproducts. The resulting product stream is completely, or nearly completely free of residual F 2  and unwanted byproducts and as such, can be used directly for useful purposes, e.g., electrophilic fluorination, oxidation, initiation of radical polymerization processes, and etching, without the need to collect the BDM product and separate it from residual F 2  and unwanted byproducts.  
         [0020]    The molar ratio of carbon dioxide to fluorine can range from 0.5 to 25 Typically it ranges from 2.5 to 10.  
         [0021]    The residence time on the fluorination catalyst is preferably greater than 0.25 minutes, more preferably 0.3 minutes to 1.3 minutes.  
         [0022]    When CsF is used as the catalyst, it should be rigorously dry and totally free of H 2 O and HF. The inventor has found that even minimum exposure of the bulk CsF catalyst bed to either H 2 O or HF results in immediate and non-reversible poisoning of the catalyst bed to the point of not functioning at all as a catalyst. Thus, the catalyst should preferably be activated (i.e., rendered dry and free of H 2 O and HF) prior to use as suggested in the examples, below, or by any other method suitable for the purpose.  
         [0023]    Although CsF has been the typical catalyst used in the process to produce BDM from CO 2  and F 2 , other known fluorination catalysts can be used in this invention.  
         [0024]    The amount of catalyst that is required depends on the intended flow rate of reactant gases, the catalyst bed pressure used, the ratio of CO 2 , F 2 , and other process parameters.  
         [0025]    Referring to FIG. 1, the gas streams are mixed downstream of mass flow controllers  10  and passed through a three-way valve  12  and an on/off valve  14  before entering a catalyst bed  16 . The reaction product mixture exits bed  16  and passes through an on/off valve  18 . The pressure of the flow stream is measured by a pressure indicator  20  downstream of on/off valve  18  and upstream of a back-pressure regulator  22 . The pressure in bed  16  is maintained at the preferred super-ambient operating pressure by means of back pressure regulator  22 . Upon exiting back pressure regulator  22 , the product mixture is passed through an infrared spectrometer  24  for the purpose of monitoring product composition, and through an ultraviolet (UV) spectrometer  26  for the purpose of monitoring for residual F 2 , before being diverted through a three-way valve  28  to the point of end use. Note there is some uncertainty in measuring residual F 2  at very low levels because of the interference due to a “tailing” BDM UV adsorption in the same region of the spectrum.  
         [0026]    The invention will be illustrated in more detail with reference to the following Examples, but it should be understood that the present invention is not deemed to be limited thereto.  
       EXAMPLES  
       [0027]    In all the examples, the product stream was monitored for F 2  by UV spectroscopy (F 2  absorption maximum is 314 nm, CO 2  absorption maximum is less than 120 nm, and BDM adsorption maximum is about 195 nm) and composition by FT-IR (Fourier-transform infrared spectroscopy).  
       Examples 1-5  
       [0028]    These examples demonstrate the effect of CsF catalyst activation using CsF, as well as the effect of using super-ambient catalyst-bed operating pressures, on the rate of BDM formation and F 2  conversion. The CsF catalyst bed temperature for each of Examples 1-5 was 21-23° C. Data are summarized in Table 1. These examples also demonstrate that the BDM product stream can be used directly for selective electrophilic fluorination of an aromatic substrate.  
                                                             TABLE 1                               CO 2     Total   Reactor   F 2             F 2  Flow   Flow   Flow   pressure   Breakthrough       Example   (sccm a )   (sccm)   (sccm)   (psig)   (approx. %) b                                  1*   5   100   125    0   4       2a*   5   100   125    0   4       2b   5   100   125   36   1.9       2c   5   100   125   67   1.4       3a   5   100   125   64   0.97       3b   5   100   125   73   0.90       4a   2    50    60   78   0.31       4b   2    50    60   110    0.26       4c   2    50    60   120    0.15       5   2    50    60   80   0.29                                          
 
       Example 1 (Comparative)  
       [0029]    Referring to Table 1, 362.2 g of CsF was used directly (without activation) from the vendor (99.9% CsF obtained from Aldrich Chemical Company). Using no CsF catalyst bed pressure (0 psig), 25 sccm flow of 20% F 2 /N 2  (v/v) and 100 sccm CO 2  were passed through the catalyst bed and the resulting product mixture was shown to contain a minimal amount of BDM product and about 4% residual F 2 .  
       Example 2a (Comparative)  
       [0030]    Example 1 was repeated with an activated catalyst bed, which had been activated by heating to 165° C. overnight with flowing dry nitrogen. The resulting product mixture was shown to contain a minimal amount of BDM product and about 4% residual F 2 .  
       Example 2b  
       [0031]    Example 2a was repeated with the bed pressure increased from 0 to 36 psig, which resulted in significantly more BDM and less (1.9%) F 2  observed in the product mixture.  
       Example 2c  
       [0032]    Example 2a was repeated with the bed pressure increased to 67 psig, which resulted in more BDM and less (about 1.4%) residual F 2  in the product mixture.  
       Example 3a  
       [0033]    Example 2a was repeated with the bed pressure increased to 64 psig, which resulted in a product mixture containing BDM, CO 2  and residual F 2  (approximately 0.97%).  
       Example 3b  
       [0034]    Example 3a was repeated with the bed pressure increased to 73 psig, which increased the ratio of BDM to CO 2 , relative to that of Example 3a. In addition, less residual F 2  was observed in the product mixture of this example than in Example 3a.  
       Example 4a  
       [0035]    Example 3b was repeated except using flows of 2 sccm F 2  and 50 sccm CO 2  and with the bed pressure increased to 78 psig, which increased the ratio of BDM to CO 2 , relative to that of Example 3b. In addition, less residual F 2  was observed in the product mixture of this example than in Example 3b.  
       Example 4b  
       [0036]    Example 4a was repeated with the bed pressure increased to 110 psig, to yield a product mixture containing good quality BDM, CO 2 , and residual F 2  (approximately 0.26%).  
       Example 4c  
       [0037]    Example 4b was repeated with the bed pressure increased to 120 psig, to yield a product mixture containing good quality BDM and less residual F 2  (approximately 0.15%) than that observed in Example 4b.  
       Example 5  
       [0038]    Example 4a was repeated with the bed pressure adjusted to 80 psig. The BDM product stream (containing approximately 0.29% residual F 2 ) was then used directly for an electrophilic aromatic fluorination reaction. Thus, the BDM product was delivered to a stirred solution at −48° C., which contained an aromatic substrate, 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazolin-5-one (3.0 g, 11.6 mmol) and 2.0 g of nitrobenzene (16.3 mmol) in 220 mL solvent (a 10:1 mixture of CHCl 3 /CF 3 COOH). After the addition of 20 mol % excess BDM was complete, a sample was taken, neutralized, and examined by GC. The sample showed 99.5% conversion with 90% selectivity to the desired product, 1-(4-chloro-2-fluorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazolin-5-one.  
       Examples 6-33  
       [0039]    These examples demonstrate how BDM production and F 2  conversion efficiencies are affected by varying certain reaction parameters, such as catalyst bed temperature, pressure, F 2 :CO 2  ratio, and residence time. In each of Examples 6-33, the product stream composition was monitored continuously by on-line UV (at 311 nm) and IR. Note that there is a great amount uncertainty associated with F 2  concentration measurements of ≦0.5% by UV; these measurements can be assumed to be dominated by interference due to BDM adsorption at 311 nm.  
         [0040]    A BDM generation system was assembled according to FIG. 1. The CsF catalyst bed consisting of a 316-SS cylinder was loaded with 3325.1 g of CsF powder, which had previously been activated by melting, cooling in a dry inert atmosphere, and grinding to a uniform fine consistency.  
       Example 6  
       [0041]    In this example 1 slpm CO 2  and 1 slpm 20% F 2 /N 2  were flowed through the CsF catalyst bed. The bed pressure and temperature were 51 psig and 21° C., respectively Residual F 2  breakthrough was less than 0.2% (not corrected for BDM adsorption or background).  
       Example 7  
       [0042]    Up to 7 slpm CO 2  and 7 slpm 20% F 2 /N 2  were flowed through the CsF catalyst bed. The bed pressure and temperature were up to 230 psig and 28° C., respectively. Residual F 2  breakthrough was less than 0.9% (not corrected for BDM adsorption or background) even at the highest flow rate.  
       Example 8  
       [0043]    Up to 5 slpm CO 2  and 5 slpm 20% F 2 /N 2  were flowed through the CsF catalyst bed. The bed pressure and temperature were up to 207 psig and 51° C., respectively. Residual F 2  breakthrough was less than 0.6% (not corrected for BDM adsorption or background) even at the highest flow rate.  
       Examples 9-33  
       [0044]    In Examples 9-33, the effects of varying the reaction parameters: CsF catalyst bed temperature and pressure, CO 2 /F 2  mol ratio, and residence time, on BDM production efficiency (calculated as BDM observed versus BDM expected) and residual F 2  breakthrough were assessed. The results are summarized in Table 2.  
                                                                                     TABLE 2                           Bed   Bed   CO 2 /F 2     Res.               20% F 2             Temp a     Pressure   mol   Time   BDM   F 2  Break-   CO 2  flow   flow       Ex.   (° C.)   (psig)   ratio   (min)   efficiency   through b     (slpm c )   (slpm)                                 9   29/20   204   5.0   0.65   97.4%   0.3%   2.02   2.02       10   22/15   207   5.0   0.65   97.5%   0.3%   2.02   2.02       11   24/16   208   5.0   0.65   96.1%   0.4%   2.02   2.02       12   27/19   102   5.0   0.65   96.0%   0.4%   2.02   2.02       13   20/14   309   5.0   0.65   95.8%   0.4%   2.02   2.02       14   23/22   205   2.5   0.65   94.8%   0.2%   1.02   2.02       15   20/16   208   10.0   0.65   97.6%   0.2%   4.04   2.02       16   22/18   205   5.0   1.28   96.2%   0.4%   1.03   1.02       17   20/19   205   5.0   1.28   97.4%   0.3%   1.02   1.02       18   26/19   205   5.0   0.32   97.0%   0.3%   4.05   4.04       19   11/11   204   5.0   0.65   96.4%   0.4%   2.03   2.02       20   11/12   102   2.5   1.28   94.7%   0.7%   0.52   1.02       21   10/9    104   2.5   0.32   87.9%   1.6%   2.02   4.04       22   12/12   105   9.9   1.28   93.7%   0.4%   2.02   1.02       23   9/9   104   10.0   0.32   76.8%   1.6%   8.07   4.04       24   10/12   305   2.6   1.29   94.6%   0.7%   0.52   1.01       25   32/22   205   5.0   0.65   97.5%   0.3%   2.03   2.02       26   35/23   103   2.5   1.29   96.0%   0.5%   0.51   1.01       27   35/25   104   2.5   0.32   93.1%   0.9%   2.03   4.03       28   32/22   104   10.0   1.28   99.6%   0.0%   2.03   1.02       29   35/33   104   10.0   0.33   91.9%   0.5%   8.02   4.02       30   30/29   103   10.0   0.32   89.5%   0.7%   8.07   4.04       31   33/27   309   2.5   1.28   83.5%   2.2%   0.51   1.02       32   36/35   207   10.0   0.32   &gt;99.9%   0.0%   8.07   4.04       33   25/23   208   10.0   0.32   &gt;99.9%   0.0%   8.07   4.04                                  
 
         [0045]    The data in Table 2 show that BDM production is efficient at a variety of reaction parameters, as long as the pressure is above atmospheric.  
       Example 34  
       [0046]    Approximately 360 g of CsF recovered from a previously used catalyst bed was combined with 300 g of fresh CsF from Aldrich and was activated by melting in a Pt crucible, quickly transferring the crucible and melt to the dry atmosphere of a glove box, and following cooling, was ground to a very fine consistency using a grinder. The resulting CsF powder weighing 537 g was transferred under these anhydrous conditions to the BDM reactor and then evaluated for its catalytic activity using a variety of flow and bed pressure settings. The results are summarized in Table 3.  
                                             TABLE 3                           Fluorination of CO 2  with F 2  Over Activated CsF            20% F 2     CO 2     Total   Molar   CsF Bed   Vol % BDM           Flow   Flow   Flow   Ratio   Pressure   Concentration   % F 2         (sccm)   (sccm)   (sccm)   F 2 :CO 2     (psig)   at Outlet   Breakthrough               10   50    60   0.04   9   1.7   0.0       20   50    70   0.08   7   3.0   0.0       30   50    80   0.12   7   4.1   00       40   50    90   0.16   7   4.9   0.0       50   50   100   0.20   8   5.6   0.0       60   50   110   0.24   6   6.1   0.0       70   50   120   0.28   6   6.6   0.0       80   50   130   0.32   6   7.0   0.0       90   50   140   0.36   6   7.4   0.0       100    50   150   0.40   6   7.7   0.0                  
 
         [0047]    The data in Table 3 show that at pressures as low as 6 psig, there is no fluorine breakthrough, indicating the effectiveness of even a very low pressure for complete conversion of fluorine and carbon dioxide to BDM.  
         [0048]    While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.