Reactive Crystallization of Paracetamol in a Continuous Oscillatory Baffled Reactor

Meifen Jiang, Xiong-Wei Ni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
442 Downloads (Pure)


In this article, we report, for the first time, a reactive seeded cooling crystallization of paracetamol successfully performed in a continuous oscillatory baffled reactor (COBR). The synthesis of acetaminophen took place in the first part of the COBR and generated the solvent for crystallization via a specific ratio of starting materials. Seeded cooling crystallization was immediately commenced after the completion of the reaction in the second part of the COBR. We investigated the seeding strategy of three seed masses (10, 15, and 20 w/w%) at a fixed size in this work, enabling smooth and encrustation-free runs. We also estimated agglomeration by comparing the ideal to actual normalized product/seed sizes, which was confirmed by SEM images. The effect of mixing intensity on crystal properties was reported. Samples at two ports a known distance apart along the COBR enabled the study of steady states of the paracetamol concentration and crystal mean size in both temporal and spatial domains as well as the determination of the local and overall growth rates. Form I paracetamol particles were consistently produced with an average purity of 99.96%.

Original languageEnglish
Pages (from-to)882-890
Number of pages9
JournalOrganic Process Research and Development
Issue number5
Early online date8 Mar 2019
Publication statusPublished - 17 May 2019


  • continuous reactive crystallization
  • crystal growth rate
  • mixing intensity
  • seeding load
  • steady state of concentration
  • steady state of crystal size

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry


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