Phase-transfer catalysis is very often used to achieve the advantages of high yield, short cycle time and easy workup while avoiding the disadvantages of separating polar aprotic solvents from the product such as handling losses, high boiling points, need to dry the solvent before reuse, etc.
However, this month two patents were issued that report the use of PTC with the high boiling polar aprotic solvents NMP and DMSO. In one patent (US 9,139,869), the inventors surprisingly perform three C-alkylations of dibromofluorene in DMSO (using TBAB as the phase-transfer catalyst) with yields of 70, 75, and 79%. This is surprising because in our 2-day industrial PTC course we teach the same PTC-alkylation of dibromofluorene in 96% yield using toluene as the solvent. Fortunately, in the same patent, the inventors used PTC with toluene for a Michael addition to an acrylate ester that is the subject of the PTC Reaction of the Month.
In another patent (US 9,126,975) shown in the diagram, NMP is used as the solvent for a PTC S-alkylation of mercapto benzothiazole. In that case, the use of NMP is less surprising since the polar reactant may require a very polar solvent for dissolution. It still may be possible to perform this PTC S-alkylation with a less polar solvent and allow the organophilic quat transfer the mercaptide anon into the organic phase, but sometimes stirring of the slurry is difficult, especially when sodium bicarbonate is the base. In addition the mercapto benzothiazole is used in 20 mole% excess, so a polar solvent may be needed to recover that material. Since one of the inventors is a long time subscriber to the PTC Tip of the Month, we may be able to get a comment on that if not restricted by confidentiality.
In most cases, we can replace high boiling polar aprotic solvents with much easier to recover lower boiling common solvents like toluene.
If your company can benefit from replacing high boiling hard-to-recover solvents with solvents like toluene that are easier to recover, now contact Marc Halpern of PTC Organics to integrate highly specialized expertise in industrial phase-transfer catalysis with your process development programs to improve your process performance, process R&D efficiency and profit.
