From the archives of Kilomentor, thoughts on slow addition in the lab versus the plant:
Additions in the laboratory can be very fast indeed. One can pour 100 ml of solution into a 250 ml r.b. flask in a few seconds. On scale it is not possible to copy this. The absolute volume of solution is much more; it must be pumped in or run in by gravity through a constricted line; besides, the enthalpy change would most likely be unmanageable. For these reasons, the rate of addition becomes a variable of significant concern in scale up because when we go to large reactors the addition rate is severely constrained compared to the lab situation.
Besides the instantaneous addition of a solution, which I have just posed as an example which is simply impossible other possibilities are seriously discouraged on scale. In the laboratory so long as a strong stream of inert gas is maintained over the reactor surface and the reaction vessel is in a fume hood, a glass stopper can be removed briefly and a solid reactant poured in through a powder. The equivalent would not be acceptable in the chemical plant. The operators would be exposed to chemical contamination, as would the atmosphere in the plant and the inertness of the reactor atmosphere would be seriously compromised. Also, the addition would not be adequately reproducible and if there were solvent already in the reactor when the solid addition was made there could be a dangerous splash back.
A number of reactions require the slow and controlled addition of a solution containing one reagent to another. These are ideal for scale up. Slow addition is both necessary and simple to achieve on-scale; rather, the technical difficulty that the process development chemist needs to solve is how to duplicate in the laboratory these slow additions on scale to model the process.I think this is one of the biggest worries that I have as a process chemist -- the simple addition that I'm performing on laboratory scale, how will it scale? Will an undesired side reaction happen during the slow addition? What is the best way to simulate what will be run in the plant? (Answers next week.)