While perusing the process literature, it was fun to see a group of chemists make a purchasing decision based on quality, not on cost. From an older Org. Process Res. Dev. article [1]
1. Slade, J.; Parker, D.; Girgis, M.; Wu, R.; Joseph, S.; Repic, O. "Optimization and Scale-Up of the Grandberg Synthesis of 2-Methyltryptamine." Org. Process Res. Dev. 2007, 11, 721-725.
One other problem which we addressed was the quality of 8 (5-chloro-2-pentanone). All of our initial work had been carried out using the distilled ketone, since the commercial grade was only 85% pure and contained a large amount of black residue. Although the latter did not adversely affect the reaction, it was found that the impure material caused problems with the workup and isolation due to the presence of intractable impurities. Thus, we determined that the quality of the 5-chloro-2-pentanone (8) had a significant impact on the reaction in terms of the ease of purification of 2. Fortunately, we were able to locate a supplier of 8 who provided us with material of sufficient quality to be used “as is”.One of the funny things about chemical manufacturing is learning about what matters and what doesn't; I wonder how long it took them to figure out that it was the impure material that was making their lives more difficult, and how they found a better supplier. (Specs! It's always the specs!)
1. Slade, J.; Parker, D.; Girgis, M.; Wu, R.; Joseph, S.; Repic, O. "Optimization and Scale-Up of the Grandberg Synthesis of 2-Methyltryptamine." Org. Process Res. Dev. 2007, 11, 721-725.
I think sourcing of raw materials and solvents of the appropriate quality on the upper end of Spec is obvious for process chemistry development. It is much hard to convince people to explore use of lower/cheaper grades early on in investigations to determine is still might provide acceptable products and thus eliminate the need of a later study and switch when go to large scales and those cost differences have significant impact of economic viability of application.
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