This PTC reaction has two very interesting aspects.
First, it is not widely recognized that phase-transfer catalysis enhances the addition of nitromethane to alkenes. This should not be overly surprising since the pKa of nitromethane is 10, so it should be easily deprotonated by common inorganic bases used in PTC systems. In fact, potassium carbonate has a pKb of 10 and was used to induce this reaction in high yield.
Secondly, the inventor wanted chiral addition to the double bond that is not constrained in a ring. This is not easy. The chiral phase-transfer catalyst used, in only 2 mole%, was N-(4,5-dimethoxybenzyl-2-nitrobenzyl)quinidinium bromide, the synthesis of which was noted in this month’s PTC Catalyst of the Month.
Such chiral PTC reactions are usually enhanced by non-polar solvents to push the reactants together in close proximity to the chiral centers of the phase-transfer catalyst. The inventor chose toluene and worked at 0 C to improve enantiomeric excess. The crude product had 76% ee which was increased to 99%+ after recrystallization.
Now contact Marc Halpern of PTC Organics to improve your process performance and profit for base-induced phase-transfer catalysis 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!).
