Merial is a company that specializes in veterinary compounds. This October 2019 patent describes the chiral addition of hydroxylamine to alkenes to form chiral isoxazolines. The inventors screened 16 chiral phase-transfer catalysts and they found that for this reaction, quinine derivatized with tribenzyloxybenzyl chloride provided higher enantiomeric excess (99.1% S) than other chiral quats, including trialkoxybenzyl quininium quats (89.0% S for triethoxybenzyl and 86.4% S for trimethoxybenzyl).
One of the poor performing chiral quats was anthracenylmethyl quininium chloride (only 62% S: 38% R). More importantly, when the chiral hydroxyl was capped with an allyl group, the product was racemic! These results are in contrast to other chiral PTC reactions in which anthracenylmethyl cinchona alkaloids work well and O-allyl chiral quats work well.
The procedure for preparing the chiral quat was described on a scale using 1.5 kg quinine. The quininium quat was prepared in toluene as the solvent at 60-65 deg C and 12 hours reaction time.
This patent illustrates the need to screen a variety of chiral quats to best match the specific 3 points of chiral recognition for each different substrate.
If you want to achieve high-performance low-cost PTC processes with efficient utilization of constrained R&D resources, now contact Marc Halpern of PTC Organics to integrate the highly specialized expertise of PTC Organics in industrial phase-transfer catalysis with your company’s commercial goals.
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!).
