Wednesday, October 24, 2012

Process Wednesday: the peril of scaling up catalyzed reactions

Kilomentor has a fascinating post on "catastrophic failure" in the plant and goes on this interesting tangent about the dangers of scaling up a catalyzed reaction: 
The probability of catastrophic failure is increased for catalyzed reactions of which, for example, enantioselective reactions are a prominent contemporary class. The special additional risk is that the catalytic system may be more easily shut down by small, even trace, impurities that are difficult to measure much less control. Put another way, a catalyzed reaction is susceptible to poisoning and this can lead to catastrophic failure of conversion with no easily identifiable cause.  
Catalyzed reactions are inherently less rugged than the uncatalyzed because the catalytic substance by definition is used in lower than stoichiometric quantity and so would be disproportionately affected by a particular quantity of a catalyst poison. Impurities in the inputs to a catalytic process can also accelerate reaction. When they are not added, as after a switch to a different source of an input, the performance may deteriorate or fail. Neal G. Anderson wrote in Practical Process Research & Development, First Edition, pg. 194: “The importance of trace beneficial impurities may become evident only by failure of the reaction when using different lots of starting materials, reagents, or solvents.” Thus the recommendation to perform laboratory experiments with the same materials to be used in the plant goes double for catalyzed reactions and this includes chemicals used to wash and prep the reactor.
That last part is a healthy reminder to me -- do I think that the plant uses Dawn soap and acetone to clean out the reactors? No? Hmmmm....

(What are examples of reactions that can be accelerated through impurities? I suppose there's the classic serendipity of the Nozaki-Hiyama-Kishi...) 


  1. Don't even mention the NHK reaction, I could post a story about that one.

  2. If you like reaction impurities, I have a few sodium carbonate-promoted "metal-free" reactions I'd like to show you...

  3. a small change of reaction conditions in process can easily result in new polymorph (with a different solubility) showing up - it turns out that even trace amounts of some impurity can direct shape and size of crystals or formation of a particular polymorph and without it (or in its presence) things don't crystallize as they are supposed to