This patent describes the fluoride-chloride exchange at the activated ortho and para chlorine atoms of pentachlorobenzonitrile. There are several interesting aspects of the reaction procedure.
First, the reaction is performed without any added solvent other than the product which is a liquid at the reaction temperature. Usually in solvent-free PTC systems, a liquid starting material is used as the solvent, but as we teach in our 2-day course “Industrial Phase-Transfer Catalysis,” the product can be used as the solvent at the outset of the reaction if it is a liquid at the reaction temperature. This obviously avoids the need for a separate solvent. For reasons that are not clear, the inventors used quite a lot of product as solvent, between 2X and 14X of the weight of the starting material.
We do not learn about the effect of PTC on the reaction because the yields for all seven PTC fluorinations and the two control reactions performed in the absence of the phase-transfer catalyst, were all between 98% and 99% of the trifluoro product. Strangely (mistakenly?), the inventors reported a yield of 98.3% in one case that used only 2.2 equiv KF, when it needed at least 3.0 equiv KF for complete reaction.
We do not expect some of the quaternary ammonium salts to survive the high temperature conditions, such as tetrabutylammonium chloride. Again, it is possible that PTC is not needed for this reaction which is why we can’t learn too much from the reaction that uses only 3 mole% of tetraphenyl phosphonium bromide (TPPB). Usually TPPB serves well in the role of thermally stable phase-transfer catalyst, but it is hard to differentiate between the results with and without catalyst with the possible exception that the fluorination was performed at a somewhat lower temperature than the reactions with phase-transfer catalyst.
It is also interesting that sodium fluoride gave high yield without using potassium fluoride that is the much more common fluorination reagent. The inventors used a higher excess of fluoride when using the sodium salt than the potassium salt but a comprehensive study was not reported to make valid comparisons.
In fact, the inventors did not describe the physical form of the fluoride salt, its moisture content nor how it was prepared. These are usually very important factors for the success of fluoride-Halex reactions.
One confusing aspect in this patent is the description of the workup that was based on distilling the product that is also the solvent, to recover the product. The inventors report distilling the reaction mixture to dryness but somehow report the amount a mass of what appears to be the product produced from the starting material, even though the product and solvent are one and the same.
While there are some aspects of the report in this patent that are not totally clear, these procedures do demonstrate that a pseudo-solvent-free fluorination of pentachlorobenzonitrile to 2,4,6-trifluoro-3,5-dichlorobenzonitrile, can be performed in high yield, including with sodium fluoride. There is learning value in that aspect of the reported procedures and results.
PTC fluoride-halex reactions are important and are covered in our 2-day course “Industrial Phase-Transfer Catalysis.” Now click here to inquire about conducting this valuable PTC course in-house at your company (by live Zoom video conference or in person when travel is feasible).
