The process conditions chosen for the addition reaction shown in the diagram are interesting for the PTC base-catalyzed addition of fluorene to a variety of acrylamide derivatives.
First, the reaction uses catalytic KOH since the base is not consumed.
Before the KOH is added, the fluorene, acrylamide and TBAB phase-transfer catalyst are dissolved in a mixture of DMSO and toluene to form a homogenous solution.
The use of DMSO-toluene mixture as a solvent for PTC reactions is curious since the phase-transfer catalyst can usually transfer into toluene whatever anion needs to be reacted.
For example, the very first reaction that I (Marc Halpern) ever performed was the deuteration of fluorene (June 1976!). I dissolved fluorene in benzene (that was acceptable in those days!), added triethyl benzyl ammonium chloride and 18.3M NaOD in D2O. The reaction mixture was stirred for an hour at room temperature and afforded 100% di-deuteration at the methylene 9-position. I later performed the C-alkylation of fluorene with dimethyl sulfate under similar conditions. In other words, a polar co-solvent was not needed in order to both deprotonate fluorene to form the fluorenyl anion and activate it for nucleophilic attack.
One wonders if the DMSO was used to somehow help the catalytic aqueous KOH be more compatible with the organic reaction phase. Perhaps the DMSO helped with the solubility of the acrylamide derivatives in toluene. If the acrylamide derivatives were even partially soluble in toluene without DMSO, then the phase-transfer catalyst would probably have been sufficient to induce reaction.
The inventors performed the addition reaction under the same conditions for several acrylamide derivatives: acrylamide (88.4% yield) N,N-dimethyl acrylamide (82.4% yield), N,N-diethyl acrylamide (61.4% yield), and N-isopropyl acrylamide (71.4% yield).
In our course “Industrial Phase-Transfer Catalysis” we each that reactions of fluorene (pKa 23) work better with quaternary ammonium phase-transfer catalysts that have a nitrogen atom with higher accessibility (higher “q-value”) than that of tetrabutyl ammonium.
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