This is one of the more interesting PTC reactions we have seen this year, mostly because it requires relatively strong base for deprotonation while at the same requires avoiding hydrolysis of a non-sterically hindered ester of the acrylate Michael substrate.
PTC excels in strong base C-alkylations of substrates up to pKa of about 23 (which is the pKa of fluorene). The reaction described in this patent requires the deprotonation of dibromofluorene that probably has a pKa of about 21 or 22. Solid NaOH or 50% aqueous NaOH is used in PTC C-alkylations of fluorene (I personally performed C-alkylation of fluorene in 1976). The inventors of this patent used 50% NaOH as the base.
Many may find it surprising that it possible to perform the reaction in the presence of concentrated aqueous NaOH and avoid hydrolysis of the ester of methyl acrylate. In this case, toluene was used as the solvent and the sharp phase boundary between the nonpolar toluene and extremely polar 50% NaOH, protects the methyl acrylate that is fully dissolved in the toluene phase. The product is a diester and is likewise protected from the caustic aqueous phase by the phase boundary. In addition, the inventors kept the temperature low (ambient) and that probably contributed to minimizing undesired side reactions.
One difference between Michael addition and C-alkylation is that there is no ionic leaving group in a Michael addition. The reason that is important is that when chloride or bromide salts are generated during a C-alkylation, the high ionic strength of the aqueous phase at the end of the reaction helps minimize hydrolysis by increasing the polarity difference between the polar aqueous phase and the nonpolar organic phase, that results in less hydrolysis of water-sensitive reactants and products.
If your company wants to reduce the cost of strong base reactions such as Michael addition or alkylation, now contact Marc Halpern of PTC Organics to integrate highly specialized expertise in industrial phase-transfer catalyze into your process development and optimization programs.
