If you are using ethanolic borohydride for reductions, like almost everyone does (including me until Y2K), your company is probably wasting a lot of money on excess borohydride. You can often greatly reduce the excess borohydride you are using by using phase-transfer catalysis with aqueous borohydride. There are two reasons for this and you have to get them right. One is that borohydride is more stable in water at the right pH than it is in ethanol. The other is that we don’t need ethanol to co-dissolve the borohydride and the reactant to be reduced. We can use any organic solvent that will dissolve the reactant and use a phase-transfer catalyst to transfer the borohydride into that solvent and activate it for the reduction of the substrate.
The diagram shows a borohydride reduction of terfenadone to terfenadine (the first non-drowsy antihistamine in the market years ago). The patent [Magni, A. (Gruppo Lepetit) 1989 Eur. Pat. EP 0 346 765] states that when using ethanolic borohydride, the inventor needed a 30 mole% excess of borohydride. When switching to using the inexpensive methyl tributyl ammonium chloride phase-transfer catalyst with 1M NaOH in water, the inventor was able to reduce the borohydride excess to just 4 mole% (based on using all 4 hydrides) and still achieve a yield of 97.7%.
Are you still using ethanolic borohydride? If you answered yes, then the time has come to start switching to phase-transfer catalysis and save your company money.
Next month we will highlight another very important aspect of this patent and it relates to choice of solvent in commercial PTC applications.
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!).
