Tetrabutylammonium tribromide (TBATB) is used as a source of bromine that is convenient for weighing as a solid instead of liquid bromide that could spill and cause safety and environmental consequences.
The procedure to perform the reaction shown in the diagram is extremely easy and straightforward by just mixing the reactants.
The inventors did not report the selectivity of the bromination site. The downstream isomer products were separated by chromatography after two additional steps of fluoride-bromide exchange and oxidation. Judging by the mass of isolated isomers after two chromatography separations, the ratio of the two products was very roughly 1.5:1 for 7-fluoro-6-methoxy to 5-fluoro-6-methoxy.
The process development group at Ono Pharmaceuticals used TBATB for the ring bromination of 3-ethyl phenol as described in the July 2013 PTC Catalyst of the Month. See http://phasetransfercatalysis.com/ptc_catalyst/tetrabutyl-ammonium-tribromide/
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!).
