Phase-transfer catalysis excels in performing esterifications by nucleophilic substitution that need to proceed to completion without worrying about reversible dehydration. The esterification shown in the diagram is for producing a pheromone and uses a mesylate leaving group. When performing nucleophilic substitutions with sulfonate leaving groups, it is usually best to choose mesylate as the leaving group and not tosylate since the more lipophilic tosylate can preferably associate with the phase-transfer catalyst and act as a catalyst poison. Phase-transfer catalyst poisoning is less of a concern when the nucleophile is organophilic, as is the case in this reaction. The carboxylate anion transferred and reacted in this reaction has five carbon atoms (called “senecionate”) which is organophilic enough.
The inventors chose tetrabutyl ammonium chloride, TBAC, as the phase-transfer catalyst. TBAC is more expensive than TBAB (bromide) since [1] one cannot form TBAC from tributylamine and butyl chloride due to dehydrochlorination and [2] the ion exchange from bromide to chloride is uphill thermodynamically. When we see people choosing TBAC as the phase-transfer catalyst, it usually means that they don’t know how to choose the optimal phase-transfer catalyst. However, in this case, it is possible that the bromide of TBAB would react with the mesylate to form the alkyl bromide which might be less reactive than the mesylate. So, it is possible that TBAC was chosen properly in this case. We would need to see the results with TBAB to confirm this speculation.
The amount of carbonate used was less than 1 equivalent until you realize that the pKa of the carboxylic acid is about 4.5 and the pKb of the bicarbonate formed by the first deprotonation is about 6. Thus, the base was sufficient.
The focus of the examples in this patent was transesterification of methyl senecionate with an alcohol. The inventors screened a variety of transesterification catalysts. It is ironic that they knew about PTC for the nucleophilic esterification reaction, but didn’t know that PTC could be used for the transesterification reaction.
Now contact Marc Halpern of PTC Organics to benefit from highly specialized expertise in industrial phase-transfer catalysis for esterification and transesterification and achieve low-cost high performance green chemistry.
