PTC is very effective for the etherification of nitrophenoxide, a weak nucleophile, with chlorodifluoromethane.
The reaction shown in the diagram was performed on a 1 mole scale and gave high yields using an excess of 0.4 to 2.7 equiv of the gaseous chlorodifluoromethane (b.p. = -41 C) as the alkylating agent. The patent does not describe the use of a pressure vessel but it could be assumed. It is also possible that the bromide of the TBAB formed the more reactive bromodifluoromethane (b.p. = -15 C) in-situ.
When using 1.42 equiv of chlorodifluoromethane instead of 3.7 equiv, a yield of 88% was obtained, so the excess alkylating agent does have an effect but one can get reasonably good yield at lower excess reagent.
When using p-nitrophenol as the nucleophile and 1.7 equiv chlorodifluoromethane, with tetrabutylphosphonium bromide as catalyst, a yield of 96.8% was obtained. When using tetrabutylphosphonium as the phase-transfer catalyst, it is important to avoid using a large excess of NaOH a high temperature due to decomposition to phosphine oxide, a mechanism that tetrabutylammonium does not undergo.
If your company needs to achieve low-cost high-performance green chemistry for etherification of phenols or alcohols, now contact Marc Halpern of PTC Organics to explore how to integrate highly specialized expertise in industrial phase-transfer catalysis with your process development goals.
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!).
