A peer-reviewed paper by Bernard Kaptein and Ben de Lange of InnoSyn BV, published in Chimica Oggi – Chemistry Today (Vol. 39(6), 2021), presents two enabling chiral crystallization technologies — Viedma ripening and Temperature Cycle-Induced Deracemization (TCID) — that allow the complete conversion of a racemic mixture into a single pure enantiomer in virtually quantitative yield, without chiral auxiliaries or catalysts.
Overcoming the Limits of Classical Chiral Resolution
Conventional resolution by crystallization has been the industry standard for over 150 years, yet remains intrinsically limited to 50% yield and requires stoichiometric amounts of chiral resolving agents. Viedma ripening and TCID break through both constraints — enabling full deracemization of conglomerate slurries through either mechanical attrition or programmed temperature cycling, combined with solution-phase racemization.
Key Findings and Technological Advantages
Through extensive laboratory development and scale-up validation, the paper identifies the critical features of both technologies:
- Complete conversion — The solid phase is fully converted to the desired enantiomer; the racemizing mother liquor is recycled, eliminating yield limitations.
- No chiral auxiliaries required — Neither Viedma ripening nor TCID depends on stoichiometric chiral reagents or catalysts.
- Dramatically reduced process times — Optimization with ultrasound or industrial bead mills reduces deracemization from weeks to under one hour at pilot scale.
- Standard equipment for TCID — Temperature cycling runs in any multi-purpose reactor connected to a programmed thermostat, with no specialized hardware needed.
- Broadly described uses — Both technologies have been described to building blocks for pharmaceuticals including Clopidogrel, Prasugrel, Saxagliptin, Praziquantel, and many others.
Industry Impact and Application
These findings provide a practical framework for process chemists working on enantiopure pharmaceutical intermediates, agrochemicals, and food ingredients. With InnoSyn's deep expertise in chiral crystallization and a proven track record of scaling these processes to industrial levels, Viedma ripening and TCID represent sustainable, high-yielding alternatives to classical resolution — available as part of InnoSyn's crystallization technology offering today.
For a deeper dive into the research and its findings, read the full publication.