Imagine a systematic method to rapidly develop and optimize process conditions for low-cost high-performance phase-transfer catalysis reactions! Would you use the systematic method? Of course!
That systematic method exists and it’s called the “PTC pKa Guidelines” (Halpern, M.; Ph.D. Thesis, Hebrew University of Jerusalem, 1983). The full details of the PTC pKa Guidelines will be taught at the 2-day course in Cologne, Germany entitled “Industrial Phase-Transfer Catalysis” in less than 2 months on April 21-22, 2015. Now register here for the 2-day PTC course in Germany.
The PTC pKa guidelines direct you to first consider the pKa of the substrate you are reacting. There are 4 categories: pKa < 16, pKa from 16 to 23, pKa from 24 to 38 and pKa > 38.
If the pKa of the conjugate acid of the reacting anion is below 16, such as phenoxide, acetate, cyanide, mercaptide or hundreds of other inorganic and acidic organic nucleophiles, the rate determining step is likely to be the intrinsic reaction occurring in the organic phase (I-Reaction) and you should choose quaternary ammonium phase-transfer catalysts with 16-32 carbons, non-polar solvents and avoid soft leaving groups (unless the nucleophile is organophilic itself). Details of I-Reactions will be taught at the 2-day course “Industrial Phase-Transfer Catalysis” to be conducted in Germany on April 21-22, 2015 or in-house anytime at your company.
If the pKa of the substrate is 16-23, such as phenyl acetonitrile, cyclohexanone, fluorene or hundreds of organic compounds with diactivated methylene groups, then the rate determining step is likely to be the transfer of the hydroxide as base into the organic reaction phase (T-Reaction) and you should choose quaternary ammonium phase-transfer catalysts with a “q-value” between 1.0 and 2.0 (preferably close to 1.75), use polar solvents that are immiscible with water and use efficient agitation. The q-value is taught in the 2-day course “Industrial Phase-Transfer Catalysis” to be conducted in Germany in April 21-22, 2015 or in-house anytime at your company.
PTC I-Reactions rarely need extremely efficient agitation unless exothermic reactions require the agitation for effective heat transfer.
Every PTC reaction needs to be optimized and studied for safety before determining final process conditions for scale up. But the PTC pKa Guidelines will often reduce the development cycle time in the lab by weeks which is crucial if, like most process chemists, you face tight project deadlines. In fact, using the pKa guidelines may be the difference between achieving a profitable process using PTC or compromising with a less profitable process without PTC since you have limited R&D time to complete process development.
If your company wants to benefit from low-cost high-performance green chemistry using phase-transfer catalysis, contact Marc Halpern of PTC Organics to explore the path forward for the most efficient use of your R&D resources to achieve your commercial goals.
Selected slides from the 2-day PTC course, including an overview of the PTC pKa Guidelines, will be presented by Dr. Marc Halpern in a free PTC Webinar on March 12, 2015 at 9:00 am Eastern US time, 3:00 pm Western Europe time. Now register here for the 1-hour free PTC Webinar.
