This C-alkylation is a solid-liquid PTC system that used a small amount of added water (0.77X) to enhance reactivity of the powdered KOH and carbanion nucleophilicity while attempting to maintain stirrability of the thick slurry resulting from the large amount of KBr precipitate. The major side reaction is dehydrobromination to form the alkene impurity shown that further oligomerizes.
Several ideas were tried to optimize the reaction. When the powdered KOH was replaced with 50% NaOH, reactivity decreased significantly (16% conversion instead of complete conversion) and numerous new impurities were observed. So, powdered KOH is the better base in this case. Stirribility was improved only marginally by diluting with double the toluene and water, but that reduced the reflux temperature to 95 deg C (instead of 100-105 deg C) and that greatly reduced reactivity. When the water was distilled out, the reaction temperature was 100 deg C, and that resulted in the reaction going to completion within 1 hour. The yields and purities shown in the diagram are for three runs at scale from 200g to 500 g.
This PTC system is yet another example that demonstrates that careful choice of hydration level is required to achieve the best results.
PTC Organics has experience in increasing selectivity of C-alkylation versus dehydrohalogenation in PTC-OH systems with alkyl halide alkylating agents. Contact Marc Halpern to integrate PTC Organics’ highly specialized expertise in strong base PTC systems with your process development and process optimization programs to achieve low-cost high-performance green chemistry.