Phase-transfer catalysis excels in elimination reactions under basic conditions to form alkenes. The most common PTC-NaOH elimination reaction to form alkenes is dehydrochlorination and proceeds via an E2 mechanism (Halpern, M. Ph.D. Thesis, 1983). The reaction shown in the diagram eliminates phenyl sulfinic acid to form the alpha, beta unsaturated amide.
The choice of dilute aqueous NaOH (18% NaOH diluted from 28% NaOH) for this PTC elimination is a bit surprising since higher NaOH concentration is usually preferred, but the inventors reported that the elimination reaction was complete typically within 2.5 hours at 25-30 deg C . The reaction is activated by the conjugation to the carbonyl which likely added to the driving force for the formation of the alkene. Perhaps the purpose of the extra water was to dissolve the sodium sulfinate salt byproduct after the elimination.
The inventors chose tetrabutylammonium chloride as the catalyst. If the development of this process would proceed to scale up, then a less expensive option of using tetrabutylammonium bromide would likely work and be more cost effective.
The overall isolated yield was 93% for the 3-chemical step process (plus crystallization) from the starting piperazine to the adipate product. In the first step, the piperazine N-H reacted with an anhydride made from 3-(phenylsulfonyl)propionic acid and pivaloyl chloride (formed by reaction of an adduct of pivaloyl chloride activated by N-methylmorpholine) to form the 2-phenylsulfonyl ethyl amide. The PTC elimination of phenyl sulfinic acid was the second step to form the alpha, beta unsaturated amide (and sodium phenyl sulfinate). The third step was a neutralization with adipic acid to form the adipate salt with one of the basic nitrogen atoms in the molecule.
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!).
