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.
About Marc Halpern
Dr. Halpern is founder and president of PTC Organics, Inc., the only company dedicated exclusively to developing low-cost high-performance green chemistry processes for the manufacture of organic chemicals using Phase Transfer Catalysis. Dr. Halpern has innovated PTC breakthroughs for pharmaceuticals, agrochemicals, petrochemicals, monomers, polymers, flavors & fragrances, dyes & pigments and solvents. Dr. Halpern has provided PTC services on-site at more than 260 industrial process R&D departments in 37 countries and has helped chemical companies save > $200 million. Dr. Halpern co-authored five books including the best-selling “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives” and has presented the 2-day course “Practical Phase-Transfer Catalysis” at 50 locations in the US, Europe and Asia.
Dr. Halpern founded the journal “Industrial Phase-Transfer Catalysis” and “The PTC Tip of the Month” enjoyed by 2,100 qualified subscribers, now beyond 130 issues. In 2014, Dr. Halpern is celebrating his 30th year in the chemical industry, including serving as a process chemist at Dow Chemical, a supervisor of process chemistry at ICI, Director of R&D at Sybron Chemicals and founder and president of PTC Organics Inc. (15 years) and PTC Communications Inc. (20 years). Dr. Halpern also co-founded PTC Interface Inc. in 1989 and PTC Value Recovery Inc. in 1999. His academic breakthroughs include the PTC pKa Guidelines, the q-value for quat accessibility and he has achieved industrial PTC breakthroughs for a dozen strong base reactions as well as esterifications, transesterifications, epoxidations and chloromethylations plus contributed to more than 100 other industrial PTC process development projects.
Dr. Halpern has dedicated his adult life to his family and to phase-transfer catalysis (in that order!).
