Process design

Summary and further reading

There are a range of different techniques that can be employed for reaction work-up and product, each with their own associated advantages and disadvantages.  In this module we have seen evidence to demonstrate that it is important to think holistically about a process as a whole and ensure that the impact of work-up/down stream processing is not ignored. 

Recommended reading:

N. G. Anderson, Practical Process Research and Development: a guide for Organic Chemists, Academic Press, 2nd edn., 2012.

N. G. Anderson, Assessing the Benefits of Direct Isolation Processes, Org. Process Res. Dev., 2004, 8, 260-265.

L. Delhaye, A. Ceccato, P. Jacobs, C. Köttgen and A. Merschaert, Removal of Reaction Solvent by Extractive Workup:  Survey of Water and Solvent Co-extraction in Various Systems, Org. Process Res. Dev., 2007, 11, 160-164.

C. - K. Chen and A. K. Singh, A “Bottom-Up” Approach to Process Development:  Application of Physicochemical Properties of Reaction Products toward the Development of Direct-Drop Processes, Org. Process Res. Dev., 2001, 5, 508-513.

Solvent Miscibility table (Last accessed: ).

Liquid-liquid extraction (Last accessed: ).

D. Ormerod, N. Lefevre, I. Dorbec Matthieu and Eyskens, P. Vloemans, K. Duyssens, V. Diez de la Torre, N. Kaval, S. Merkul Eugen and Sergeyev and B. U. W. Maes, Potential of Homogeneous Pd Catalyst Separation by Ceramic Membranes. Application to Downstream and Continuous Flow Processes, Org. Process Res. Dev., 2016, 20, 911–920.

H. P. Dijkstra, G. P. M. van Klink and G. van Koten, The use of ultra- and nanofiltration techniques in homogeneous catalyst recycling, Acc. Chem. Res., 2002, 35, 798-810.

D. Nair, H. - T. Wong, S. Han, I. F. J. Vankelecom, L. S. White, A. G. Livingston and A. T. Boam, Extending Ru-BINAP Catalyst Life and Separating Products from Catalyst Using Membrane Recycling, Org. Process Res. Dev., 2009, 13, 863-869.

D. Ormerod, B. Noten, M. Dorbec, L. Andersson, A. Buekenhoudt and L. Goetelen, Cyclic Peptide Formation in Reduced Solvent Volumes via In-Line Solvent Recycling by Organic Solvent Nanofiltration, Org. Process Res. Dev., 2015, 19, 841-848.

Implications of Continuous Manufacturing and Crystallisation (Last accessed: ).

From Pharmaceutical Substance to Product – An Industrial Perspective on Continuous Processing (Last accessed: ).

G. Allison, Y. Tan Cain, C. Cooney, T. Garcia, T. Gooen Bizjak, O. Holte, N. Jagota, B. Komas, E. Korakianiti, D. Kourti, R. Madurawe, E. Morefield, F. Montgomery, M. Nasr, W. Randolph, J. - L. Robert, D. Rudd and D. Zezza, Regulatory and Quality Considerations for Continuous Manufacturing. May 20–21, 2014 Continuous Manufacturing Symposium, J. Pharm. Sci., 2015, 104, 803-812.

I. R. Baxendale, R. D. Braatz, B. K. Hodnett, K. F. Jensen, M. D. Johnson, P. Sharratt, J. - P. Sherlock and A. J. Florence, Achieving Continuous Manufacturing: Technologies and Approaches for Synthesis, Workup, and Isolation of Drug Substance. May 20–21, 2014 Continuous Manufacturing Symposium, J. Pharm. Sci., 2015, 104, 781-791.

T. McGlone, N. E. B. Briggs, C. A. Clark, C. J. Brown, J. Sefcik and A. J. Florence, Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization, Org. Process Res. Dev., 2015, 19, 1186-1202.

P. Plouffe, A. Macchi and D. M. Roberge, From Batch to Continuous Chemical Synthesis—A Toolbox Approach, Org. Process Res. Dev., 2014, 18, 1286-1294.