Wednesday, April 29, 2015

Process Wednesday: the dos and don'ts of scale-up

Credit: Dr. Clemens Brechtelsbauer
But hot filtrations are fun! (No, they're not.)

(Found via a random Googling of "minimum stir volume" a good list of "dos and don'ts" for scale-up included in a presentation by Dr. Clemens Bretchelsbauer of Imperial College, London. The list is credited to F.X. McConville, the author of the strongly recommended "The Pilot Plant Real Book.")


  1. All in & heat is acceptable but you must know for sure that there is not going to be an exotherm runaway of a vicious gas evolution or frothing.

    Rotovap evaporation on scale sucks, avoid it altogether or do distilation and solvent replacement with a higher boiling solvent whenever possible.
    Shoveling sticky solids into open reactor port and stuff sticking is a major pain. They now sell organic solvent soluble plastic bags of NaH and LiAlH4 that you can rapidly throw in, although you end up with a soluble polymer in your product...
    And everything takes so much longer - if you must deal with a time-sensitive workup stage/race against decomposition, it really makes sense to subdivide the batch for that operation and recombine the material once it is less unstable/

  2. Opening a port on a reactor with something flammable can be exciting especially at low air humidity. When dropped into a production or pilot reactor solids travel a much longer distance and pick up a lot more static charge than in a small lab reactor. Local exhaust (aka "elephant trunk") helps a bit but can add its own hazards.

    Once we blew an exhaust fan off the roof when the trunk picked up a lot of vapor from the reactor port and then sucked up some solids. The solids must have picked up static charge from traveling up the tube and ignited the solvent vapor. The bang tossed the operator to the ground. As a former Marine he was used to handling 82mm mortars and remarked that it was "just like in Beirut. Just roll with the punch." The trunk was stripped of all the cladding (think "slinky") and we didn't find the fan for a couple of weeks. It ended up on the side of an interstate nearby.

    Sometimes chemistry can be more fun than one can manage.

  3. Paracetamol production has a hot water charcoal treatment followed by a filtration whilst still hot.