PTC is known to perform di-C-alkylation of fluorene in high yield. The reaction shown in the diagram is very interesting due to the relative pKa’s of the methylene group of the substituted fluorene and the OH of the bromopropanol.
As we teach in our 2-day course “Industrial Phase-Transfer Catalysis”, in PTC systems we usually observe alkylation at the lower pKa site first. In this case, we expect the pKa of the OH of bromopropanol to be about 17. We expect the pKa of the bromo iodo fluorene to be a bit below 23. That means that in most PTC systems in the presence of 50% NaOH, the bromopropanol would be deprotonated first to form the alkoxide that would be expected to react with another molecule of bromopropanol and form the bromo hydroxy dipropyl ether.
This is likely the reason that the inventors added the bromopropanol slowly. In this way, the diluted bromopropanol avoided colliding with a bromo propoxide anion. The alkoxide would also pair with the quat cation and serve as a base to deprotonate the fluorene. Then the competition for alkylation of the bromopropanol is between the nucleophilic fluorenyl anion and the bromo propoxide anion.
The inventors used only 2.5 equiv brompropanol when they needed 2 equiv. This means that they did not lose a lot of bromopropanol to self-etherification or to dehydrobromination to allyl alcohol.
It is also possible that the choice of DMSO changed the relative pKa’s of the alcohol and the fluorene. There are many reports of the PTC C-alkylation of fluorene using non-polar solvents such as toluene without having to resort to DMSO. In fact, I personally performed C-alkylation of fluorene in the 1970’s during my Ph.D. thesis work on PTC-NaOH reactions.
Now contact Marc Halpern of PTC Organics to optimize your PTC strong base reactions to integrate more than 40 years of experience in developing high performance PTC-NaOH reactions to improve your company’s profit and R&D efficiency.
