The etherification shown in the diagram is a solid-liquid PTC reaction and was performed on a 1 mole scale. The reaction was successful with o-nitrophenol and p-nitrophenol.
The phase-transfer catalyst was tetrabutylammonium iodide and was used in only 0.25 mole% which is very economical and important since quat iodides are expensive. The role of the iodide is to serve as a co-catalyst to form iodo acetone in-situ from chloroacetone that can be leveraged to reduce the reaction temperature and time.
The use of potassium carbonate as the base that generates the potassium hydrogen carbonate byproduct keeps the reaction mixture quite dry, in contrast to using NaOH as the base that generates an equivalent of water. The presence of even small amounts of water in solid-liquid PTC systems often has significant effect in reducing reactivity due to hydration of the nitrophenoxide anion. In our 2-day course “Industrial Phase-Transfer Catalysis,” we provide data about the effect of water on the nucleophilicity of p-nitrophenoxide under PTC conditions at different levels of hydration.
Activation of the reaction is particularly important since the nitrophenoxide anion has much reduced nucleophilicity relative to most other phenoxides due to the strong electron withdrawing nitro group.
Therefore, the choice of potassium carbonate as the base (KHCO3 byproduct as desiccant) together with using an iodide co-catalyst and the use of a polar ketone solvent, all likely contribute to reducing the energy of activation that in turn reduces the reaction temperature required to achieve high yield in a reasonable reaction time.
This reaction shows that we need only 1 equivalent of potassium carbonate to fully deprotonate and react a phenol and still achieve near quantitative yield. This point was raised in this month’s PTC Catalyst of the Month that used 2.0 equivalents of potassium carbonate for the etherification of a phenol that was surprising since there was the possibility of deprotonating and alkylating a second acidic functional group in that case.
An additional advantage of using a very small excess of base is to avoid possible base-promoted side reactions of the ketone solvent.
Overall, the solid-liquid PTC conditions chosen for this reaction were chosen very well.
