Norbert Lui’s group at Bayer Crop Science has been using phase-transfer catalysis for many years. This month they patented a PTC-halex reaction that we find surprising since the tetrabutylammonium quat typically decomposes by Hofmann Elimination in the presence of fluoride (acting as a base) at high temperature.
In this case, the facts speak for themselves. The F/Cl halex reaction shown proceeds to 100% conversion (94.6% isolated yield after vacuum distillation adjusted for purity) in 3 hours at 150 C in DMF using tetrabutyl ammonium hydrogen sulfate as the phase-transfer catalyst. In the absence of PTC, only 55% conversion at 3 hours is observed under the same conditions (93% conversion at 15 hours).
When using only 10 mole% excess of spray dried KF (instead of 20 mole% excess), the reaction proceeds to 99% conversion (90.5% isolated yield after vacuum distillation adjusted for purity) with 3 mole% TBA HSO4 in 3 hours in DMF versus 35% conversion in 3 hours without PTC and only 65% conversion after 15 hours.
Using 3 mole% TBAB and 10 mole% excess KF under the same conditions gave 98% conversion in 3 hours and 89% isolated yield after vacuum distillation (adjusted for purity).
Even though we expect the tetrabutylammonium quat not to be stable enough under these conditions, the fact is that only 3 mole% of TBAHSO4 does catalyze this reaction to completion much faster than without phase-transfer catalyst.
As we teach in our 2-day course “Industrial Phase-Transfer Catalysis,” PTC-Halex F/Cl exchange is often performed using polar aprotic solvents, though usually using more thermally stable phase-transfer catalysts such as tetraphenylphosphonium, phosphazenium salts or other non-ammonium salts.
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!).
