A very simple procedure was reported this month for the etherification of the phenolic O-H of vanillin with epichlorohydrin without using base.
The reaction was performed using excess epichlorohydrin as the solvent that apparently could be recovered by distillation during work up.
The reaction appears to start as a homogeneous solution in which vanillin, excess epichlorohydrin and 10 mole% tetrabutylammonium bromide are mixed and dissolved.
The etherification is initiated by bromide that is solubilized in the reaction medium by the TBAB. The bromide attacks the epoxide to open the ring and presumably forms the bromohydrin which reacts with the phenolic O-H of vanillin, liberating the bromide for another catalytic cycle.
TBAB is not acting as a phase-transfer catalyst, it is simply a source of organic-soluble bromide catalyst.
The reaction generates chloride leaving group that apparently forms HCl. So, no salt byproduct is generated.
The reaction takes only about an hour at 90 deg C.
Workup is easy by dilution with ethyl acetate and washing with brine followed by washing with distilled water and drying. The organic phase is distilled to produce an oil that is triturated with cold isopropyl alcohol that causes rapid crystallization of the product.
The yield is 85% after crystallization with purity “greater than 90%.”
The results show that there is no need to neutralize the phenol with base that would produce salt as waste and could result in several potential undesired side reactions.
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!).
