In this patent application published four days ago, four examples use 18-crown-6 to dietherify magnolol with allyl bromide derivatives. The yields are in the tight range of 82.4% to 86.2%.
The inventors used tetrabutylammonium bromide in DMF with allyl chloride in only one example and they obtained a yield of 77.1%. They performed the reaction at 100 deg C which might decompose the quat catalyst. The reaction with TBAB was run for 4 hours and they used the same weight of quat salt as they did crown ether in the other examples, but that was only 8.2 mole% TBAB.
We are surprised that the use of TBAB was an afterthought after using the much more expensive crown ether for this simple straightforward etherification.
These reactions were performed on an 80 gram scale. Why did the inventors choose to use crown ether instead of standard inexpensive PTC quat salts for these routine etherifications? We don’t know.
We are also surprised that water-miscible solvents were used for all five of these etherifications instead of using a non-polar water-immiscible solvent that would simplify workup by water washing instead of filtration and distilling off the solvent. This is especially surprising since the workup after the O-allylation and before the radical addition of thioacetic acetic in the next reaction step, included three water washes followed by extraction with trichloromethane. Wouldn’t it have been easier to use a water-immiscible non-polar solvent?
Had the inventors taken our 2-day course “Industrial Phase-Transfer Catalysis”, they would not have chosen 18-crown-6 as the phase-transfer catalyst and they would have chosen a much better solvent for workup. They didn’t benefit from the PTC course, but you should!
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!).
