Wednesday, April 13, 2011

Process Wednesday: water-free plant equipment

Want to do a water-free reaction in the lab? Throw your glassware in the oven, assemble it quickly under nitrogen and you're good to go. Want to do that in the plant? Well, our mentor-by-literature Neal Anderson says you can't:
But large-scale equipment cannot readily be dismantled, dried in hot ovens, and reassembled quickly. Therefore, it is essential that water be flushed from all portions of equipment. On scale, cleaning equipment takes thought and time. Since not all internal surfaces can be reached with a cleaning brush, residues are usually dissolved with an appropriate solvent.
Anderson recommends:
  • Refluxing solvent through the system and making sure all surfaces of the "equipment train" are contacted
  • Making sure that dead legs (areas that have liquid that's difficult to displace) are washed out
  • Or, use water then a water-miscible solvent
  • Rinsing the equipment with the solvent for the next reaction
  • Testing that rinsate via Karl Fischer titration for residual water
The best way to learn this sort of thing, of course, is shooting compound to the top of your 20 L rotovap condenser. Don't want to clean that sucker out with a brush? You learn to trust the power of refluxing solvent really fast.


  1. Freedom from all the Lab Stills common in grad school/med chem is great in Process realm. Its funny how significant worries from lab about water typically do not translate to scale for many reactions as control of the moisture of incoming materials along with techniques Anderson recommends generally are suitable. Larger scale can be more forgiving of residual moisture to non-observable impact that noticeably interferes in the lab. Often Newbies have difficultly accepted this.

  2. Moisture is not really a problem on scale as you also have way better means to avoid it. A colleague of mine had an interesting experience with a Friedel-Crafts reaction that failed miserably on scale while working very well in the lab. Open handling of the AlCl3 in the lab gave the material enough time to catch enough water to make the reaction work, whereas in the plant the AlCl3 did not see the light of the day. They ended up adding (literally) a bucket of water to the reaction mixture...

    Exchange "Water-free" with "residual material from previous campaigns" and you are right in the middle of the day-to-day cleaning validation nightmare at your GMP multi-purpose plant.


looks like Blogger doesn't work with anonymous comments from Chrome browsers at the moment - works in Microsoft Edge, or from Chrome with a Blogger account - sorry! CJ 3/21/20