Wednesday, July 25, 2012

Process Wednesday: Solvent swaps

In searching for an azeotrope database yesterday, I found an old Kilomentor post that resonates with me:
The need for solvent exchanges in the sense of displacing one solvent by another without passing through a liquid free state practically does not exist outside of process chemistry. At laboratory scale, when one solvent needs to be replaced with another, the solution contents are placed in a r.b. flask, set spinning on the vacuum rotary evaporator with appropriate heating and strong condensing efficiency. When the first solvent has been completely evaporated then the required new solvent is added and the solutes brought back into solution by swirling and scraping. 
On scale, evaporation to dryness is not possible without caking and possibly charring. Even if it were possible to avoid degradation, the layer of non-volatile residue would become so thick on the reactor's wall that heat transfer to complete the evaporation would be made impractically. Combined with this difficulty, at low volumes in a normal reactor stirring becomes ineffective. Thus solvent replacements must be done without completely removing the liquid phase at any point.
Kilomentor goes on to describe the various less well-known azeotropes within typical solvent swaps -- bet you didn't know that "An azeotrope exists between IPA and EtOAc with bp 74.8 C and composition 77% ethyl acetate and 23% IPA."

The amount of time required to perform a solvent swap on scale can be frustrating to a plant manager or owner -- think about the amount of time you spent in graduate school, rotavapping, rotavapping, rotavapping. Crystallization out of the reaction solvent is a better technique to hope for -- but sometimes, vacuum distillation of 1500 gallons of methanol is going to happen, whether you like it or not. Sigh.


  1. Here's my favoured database. Azeotropes, like zwitterions, have an awesome name.

  2. "...vacuum distillation of 1500 gallons of methanol is going to happen, whether you like it or not. Sigh."

    I guess you just cross your fingers and hope it doesn't bump just like on a lab scale?

  3. evaporating methanol (or water) is particularly atrocious on large scale because of the high enthalpy of evaporation. Toluene on the other hand... I had a very good experience with azeotrope-drying super hygroscopic stuff like 18-crown-6 to make them into organometallics-ready super dry stage by simply azeotroping them with toluene.

  4. In addition to the database pointed out by Brandon my favorite sources of info are:

    - asking a question on a ChemE forum like or an expert at

    - Wikipedia

    - CHERIC database

    - VLE simulators like this one:

    - googling the solvent composition can return an open access article or an MSDS with the data

    - if you have any access to ACS journals then this paper has 93 pages of azeotrope tables:

    - using open software like COCO or DWSIM

    - test run of software like CHEMCAD

    (some $ involved)
    - CRC Handbook of Chemistry and Physics
    - membership in AIChE gives access to some publications from Knovel including VLE data
    - books from ACS past: Azeotrope Data, Azeotrope Data - II, and Azeotrope Data - III.