Organic compounds -- part of the class 532-570 series – Organic compounds – Halogen containing
Reexamination Certificate
1999-03-25
2001-03-06
Siegel, Alan (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Halogen containing
Reexamination Certificate
active
06198011
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the fluorination of organic compounds.
BACKGROUND OF THE INVENTION
Considerable problems can arise with the use of conventional solvents in many types of chemical reactions including fluorination reactions. One problem often encountered is that of solvent recovery, which can often prove difficult and lead to solvent disposal problems. In addition, solvent consumption itself may be undesirably large and the solvent may present an explosion hazard. Thus, there exists a need to reduce the amount of solvent used in many reactions.
Surprisingly and beneficially, we have found that fluorination reactions carried out in the presence of a perfluorocarbon (PFC) fluid can require less solvent than would otherwise, i.e. conventionally, be used for the reaction to proceed efficiently.
Perfluorocarbons are largely chemically inert, and are generally regarded as largely immiscible with most organic solvents, although published data is sparse. Miscibility with CFCl
2
CF
2
Cl and some low molecular-weight hydrocarbons has been recorded, together with the fascinating solubility of gases such as oxygen, carbon dioxide and chlorine. Saturated perfluorocarbons (PFCs), e.g. perfluoroperhydrophenanthrene 1 shown in
FIG. 1
, are now industrially available over a wide boiling-point range.
STATEMENT OF THE INVENTION
According to the present invention, there is provided a method of fluorinating an organic compound, comprising reacting an organic compound with a fluorinating agent characterised in that a perfluorocarbon compound is present in the reaction medium.
The PFC may replace up to 100% of a solvent which would otherwise be required for the reaction to proceed efficiently.
Preferably, there is added to the reaction medium an amount of an additive which enables the amount of solvent to be reduced without substantial loss of fluorinating efficiency.
In addition to reducing the amount of solvent required, the use of PFCs according to the present method may also provide the following advantages.
The PFCs may be recovered simply by separation (possibly with cooling) and recycled without purification at the end of the reaction.
The use of PFC leads to reduced explosion hazards.
We have found that PFCs may be used effectively in the so-called ‘Halex’ process for exchange of chlorine by fluorine, using alkali-metal fluorides. This process is operated on the industrial scale for a number of products and solvent recovery can pose waste disposal problems. Furthermore, established procedures have proven hazardous (A. T. Cates,
J. Hazard. Mater.,
1992, 1). The compounds 2H-heptafluorobut-2-ene 2 and hexafluorobut-2-yne 3, shown in
FIG. 2
, may be formed by the Halex process, a synthesis of 2 having been described by Maynard (J. T. Maynard,
J. Am. Chem. Soc.,
1963, 28, 112). Overall, the reaction involves exchange of chlorine in hexachlorobutadiene 4 by fluorine,
FIG. 2
Scheme 1, using potassium fluoride in an aprotic solvent. Typically, sulpholane, i.e. tetrahydrothiophene 1, 1-dioxide (THTD) may be used as the solvent, and it is curious that the proton in 2 most likely originates from the solvent in the final step of the process 3 to 2, via 5, although previously, the mechanism of formation of 2 had not been firmly established.
Surprisingly and beneficially, we have found that by using the method according to the present invention, a proportion of the THTD in the above Halex reaction may be replaced by a PFC. Preferably, perfluoroperhydrophenanthrene 1, bp 215° C., is used as the solvent replacement because of its high boiling point.
Typically, up to 90% v/v of the THTD solvent normally required (Maynard) may be replaced by an equivalent volume of 1.
Preferably, up to 75% v/v of the solvent normally required may be replaced by the equivalent volume of 1.
When replacing up to 75% of the normal THTD charge, reactions may be carried out efficiently using either a Carius tube, or atmospheric pressure conditions on a larger scale. Surprisingly, using the present method, the observed product contains ca. 75% of hexafluorobut-2-yne 3 and 25% of 2. We are unaware of any previous report of the direct synthesis of 3 from 4 and thus these observations, coupled with the recent finding that dehydrofluorination of 2 to the butyne 3 occurs on standing the former over molecular sieve (R. D. Chambers and A. J. Roche,
J. Fluorine Chem.,
1996, 79, 121), provide a simple and novel laboratory synthesis of 3. We find that the 2H-heptafluorobut-2-ene 2, present in the product mixture, is converted quantitatively to 3 when the mixture of 3 and 2 is allowed to stand, in a sealed system, over 4 Å molecular sieve for 25 days. The alternative synthesis of 3 from 4 involves the use of antimony fluorides and/or hydrogen fluoride (A. L. Henne and W. G. Finnegan,
J. Am. Chem. Soc.,
1949, 71, 298).
A reasonable explanation for the unique formation of 3 in the system containing the PFC 1, is that 3 is rapidly transferred to the perfluorocarbon layer and hence removed from access to the fluoride ion source, which otherwise promotes the conversion of 3 to 2, Scheme 1. This explanation is offered merely as a rationalisation of the results and does not limit the invention in any way.
The present method may be applied to the reaction of octachlorocyclopentene with potassium fluoride to form octafluorocyclopentene 6, shown in Table 1 below, and we find that, using the present method, only 25% of the normal THTD charge leads, in this case, to high conversions to 6 either using a Carius tube or atmospheric pressure conditions on a larger scale.
Similarly, we find that the present method can be equally applied to the synthesis of commercial products such as chlorofluoro-pyridines and -pyrimidines, and also to the synthesis of chlorofluorobenzene derivatives; these results are summarised in Table 1 below.
It is believed that the present method will be of benefit to workers who operate the above and like systems on a larger scale, and it is envisaged that the application of PFCs to systems with serious solvent recovery problems or systems with potentially serious heat-transfer problems will be particularly beneficial.
Preferably, an amount of an additive is added to the reaction medium which enables the solvent content to be reduced still further.
Using additives, essentially ‘solventless’ systems may be formed, wherein the PFC acts as a suspension medium. The additive may co-ordinate to the potassium, thereby making the fluoride available.
Suitable additives may include tetrabutylammonium bromide or 18-crown-6 7, shown in
FIG. 3.
18-crown-6 7 is preferred. No fluorination is observed using either water or tetraglyme. Addition of 7 is found to be effective down to levels as low as 1% molar ratio, in relation to the chlorinated reactant, thus demonstrating the concept of potentially ‘solventless’ systems. However, the reactions proceed relatively slowly at these concentrations and therefore, to effect shorter reaction times, it is desirable to employ systems containing 10% molar equivalents of 7.
The PFC may be recovered essentially quantitatively by simple filtration from the residue. The polyether 7 may be mixed with the residual metal salts in the filtrate at this stage but can be easily removed by extraction with acetone. The recovered materials, without further purification but with addition of fresh potassium fluoride, may be used in a second cycle of reaction with octachlorocyclopentene. However, the second cycle of reaction is generally of reduced efficiency compared to the first and some further purification of the recovered 7 is desirable to maintain high efficiency in re-use. Examples of the application of PFCs containing additives to the synthesis of fluorinated aromatic compounds are shown in Table 2 below.
In the reactions with hexachlorobutadiene 4, the products from this reactant and the system containing 18-crown-6 7, remarkably, depends on the ratio of 7 used. When a molar ratio of 50% of 7 with 4 is used, the sole product is 2H-heptafluorobut-2-ene 2; a ratio
Chambers Richard D.
Edwards Andrew R.
F2 Chemicals Ltd.
Nixon & Vanderhye
Siegel Alan
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