When stoichiometric (or more) TBA HSO4 is used, the question needs to be asked, why? We speculate that iodide poisoning of the phase-transfer catalyst might be at play in the reaction shown in the diagram. Let’s discuss.
As we teach in our 2-day course “Industrial Phase-Transfer Catalysis” (on manual page 76), quaternary ammonium cations have a higher affinity for larger softer polarizable anions with low charge density. Iodide is a rather large soft polarizable anion and is also a very good leaving group.
Quats are soft cations and their affinities for soft anions are higher than for hard anions with high charge density.
For that reason, iodide and even tosylate can sometimes be a catalyst poison for quaternary ammonium phase-transfer catalysts. It depends on the relative affinities toward the quat cation of the competing anions: iodide and the desired nucleophile.
The reaction shown in the diagram was described in a patent that issued a few days ago. The reaction is the O-alkylation of an alcohol that has 12 carbon atoms, one nitrogen and 7 oxygen atoms, so it is not obvious how organophilic the alkoxide might be.
The reason we are discussing catalyst poisoning is that iodide is the leaving group and tetrabutylammonium hydrogen sulfate is used in excess, which is very rare.
We don’t know why the inventors chose to use so much TBA HSO4, but when we are trying to interpret choice of reaction conditions, we must consider the possibility of catalyst poisoning, especially when using iodide as the leaving group.
By the way, the inventors also used PTC for an O-alkylation using propargyl bromide using catalytic tetrabutylammonium iodide, catalytic sodium iodide, THF as the solvent and KOH as the base.
Now contact Marc Halpern of PTC Organics to explore how to leverage PTC Organics’ highly specialized expertise in industrial phase-transfer catalysis to achieve low-cost high-performance green chemistry for your commercial processes and process in development.
