Direct Isolation as a Method in Process Development

In  2004, Neil G. Anderson wrote an article,[ Organic Process Research & Development, 2004, 8, 260-265] where he assessed the benefits of what he called direct isolation processes. Anderson is the author of the finest book about organic process development, Practical Process Research & Development.  In the ‘direct isolation’ article he described three choices for work-up and isolation: direct isolation from the reaction mixture, extraction followed by isolation, and telescoping. 

Kilomentor opines that such categorization is too simple, while providing no useful organizing insight to balance the inexactness introduced by the simplification. Rather, what is needed in the 21^st century to advance the process development art is a more widely held view that quench, purification, and isolation each have many options and these combinations of choices need to be tailored to the particular instance as carefully as the chemical reaction conditions to which the overall work-up applies. 

Anderson quotes with approval P. Zurer [Chem. Eng. News  [2000, 78(1), 26] “In a typical chemical operation, 60-80% of both capital expenditures and operating costs go to separations.” Dr. Anderson and I would agree that in process development, where optimization is cost driven, more attention needs to be directed to fishing the desired reaction product cleanly out of the chemical soup; that is, from the reactor contents. For too long chemists have been disadvantaged by training that taught them to “work up the reaction in the usual way.”

Anderson’s simplification makes it more difficult to consider separations conducted after a number of treatments of the reaction mixture, such as, to identify just a few examples, by separation by solvent exchange, by-product precipitation, product derivatization, clathrate complex formation, scavenger resins, or capture and release resins.