PTC excels in C-alkylations of substrates with pKa (measured in water) of the C-H group of up to 23. The pKa of of the C-H group in benzyl phenyl sulfone in DMSO is 23, so the pKa in water is much lower and certainly well within the range of easy C-alkylation under PTC-base conditions.
The reaction shown in the diagram used cesium carbonate as the base and DMSO as the solvent. We know from the PTC C-alkylation of other benzyl phenyl sulfones that these reactions are easily performed with either NaOH or potassium carbonate in high yield and using water-immiscible solvents for easy workup.
An early C-alkylation of a benzyl phenyl sulfone that we teach in our 2-day course “Industrial Phase-Transfer Catalysis, uses KOH as the base, methylene chloride as the solvent (that we would not use today), which forms two phases with water that facilitates workup. That C-alkylation also used benzyl triethyl ammonium chloride, that today we would replace with methyl tributyl ammonium chloride if a T-Reaction or possibly even tetrabutyl ammonium bromide if it is an I-Reaction and if we want to separate the catalyst from the product by extraction of the tetrabutylammonium salts into water.
It is possible that the inventors chose cesium carbonate for the reaction in the diagram to avoid dehydrohalogenation of the bromochloropropane of the mono-haloethyl C-alkylated intermediate before ring closure. The choice of DMSO as the solvent is still undesirable due to handling losses and the workup described in this patent involved a water wash.
In the end, phase-transfer catalysis is a good choice for this C-alkylation of the activated C-H group alpha to the sulfone, but we would have chosen more optimal PTC conditions to achieve lower-cost higher-performance green chemistry.
Now contact Marc Halpern of PTC Organics to improve your PTC C-alkylations in commercial development or production.
