t-Butoxide or PTC-Hydroxide?
I ran my first PTC-NaOH reaction 38 years ago and whenever I have a strong base reaction, I naturally always think of PTC-NaOH first. However, many chemists make their first choice of base to use methoxide, ethoxide, t-butoxide, Na hydride, Na amide, Na metal and other expensive and/or hazardous strong bases. In this patent, the inventors made 2.7 kg of the intermediate shown using t-butoxide. Eventually they decided to try PTC-NaOH and obtained similar results.
Frankly, the phneol is so acidic, they probably could have used potassium carbonate. A strong base is not needed to deprotonate the phenol, but it is important to minimize the presence of species that could solvate the phenoxide (like water or alcohol) that reduce its reactivity for nucleophilic aromatic substitution. I would have used carbonate with PTC for this application. The PTC conditions could very likely be optimized to use less phase-transfer catalyst and greatly reaction time, mostly by controlling hydration better.
Click here for patent using PTC-NaOH instead of K t-butoxide for nucleophilic aromatic etherification.
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!).
