We have reported many O-alkylations in the 12+ years of the PTC Tip of the Month, since phase-transfer catalysis is the highest performance technology for Williamson Ether Synthesis.
The etherification reported in this December 2014 patent is interesting for several reasons. First, the alkylating agent is a secondary benzyl bromide. This means that the use of base has the potential for performing not only etherification of the phenoxide but also dehydrobromination that is additionally driven by conjugation to the aromatic ring. We speculate that this may be one reason for not using 50% NaOH which may be too strong to avoid dehydrobromination to the styrene derivative. The inventors used 7.7 M NaOH (roughly 30% NaOH).
Another possible reason for using 7.7 M NaOH may be that the inventors used methylene chloride as the solvent. When using concentrated NaOH with methylene chloride in the presence of a phase-transfer catalyst, formaldehyde is formed but can be minimized by using lower concentration of NaOH.
The choice of methylene chloride as solvent for PTC alkylations should be avoided for another reason which is “methylene bridging”. This happens when methylene chloride serves as an alkylating agent However, in this case, the probability is low that methylene chloride would react on both sides with the secondary alkylating agent to make the corresponding acetal.
If you have questions about achieving low-cost high-performance PTC etherifications, please send your inquiry to Marc Halpern of PTC Organics to explore integrating PTC Organics highly specialized expertise in industrial phase-transfer catalysis to improve process performance and process R&D efficiency.
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!).
