I'm on record saying that I don't love activated carbon; since I wrote that post, I still don't love activated carbon even though it can be incredibly useful. Via a recent Org. Process Res. Dev. paper [1], here's a perfectly cromulent use of it for its main purpose: decolorization:
In addition to a potential excessive level of heavy metals in 1 carried over from the Negishi reaction, the kilo-lab runs were faced with some residual yellow-to-brown discoloration carried over from the Friedel−Crafts acylation step. To address the color issue the workup procedure after the final coupling reaction was modified to include treatment with active carbon.
Thus, the solid material obtained after precipitation of the product with ethanol was redissolved in DCM and treated with Darco KB at 35 °C. After filtration through a Celite bed, the DCM solution was washed with 5% aqueous ammonium chloride to remove residual DMF.The supporting information has more details, including the dissolution of the crude material in 80 liters of dichloromethane and the addition of 2.3 kilograms of Darco KB, stirring for an hour at 30°C (is that all it took?), followed by filtration through a bed of Celite. Man, that must have been a mess... Glad it worked for the authors!
[Incidentally, this article is an interesting example of the non-profit pharma model at work, in that it is a BMS compound, licensed to an organization (the International Partnership for Microbicides) for use in the developing countries.]
1. Pikul, S.*; Cheng, H.; Cheng, A.; Huang, C.D.; Ke, A.; Kuo, L.; Thompson, A.; Wilder, S. "Synthetic Process Development of BMS-599793 Including Azaindole Negishi Coupling on Kilogram Scale." Org. Process Res. Dev. ASAP, dx.doi.org/10.1021/op400012p
I echo my earlier comments about the potential value for using activated C, especially to process chemists. Although probably every lab has a bottle or two of the stuff around I am doubtful that many people ever get trained or learn how and when to use properly (including removal) since it may be one of those techniques that can lean more towards chemistry Art than Science at times. Commonly the expected approach for C is "generic one size fits all" however there are many types of Cs and many variants on usage. Success can involve extensive systematic experimentation (akin to DoE) to determine how to best integrate into particular process/material (so could be heavy Science which many people don't want to bother with). With experience can learn where and how to focus effort faster to narrow explorations which I would call the Art part.
ReplyDeleteAs to scale in most cases column chromo effectively eliminates the needs for any C treatment so for bench work means a less valuable technique, it falls back to process chemists to consider when they have been able to achieve non-chromo purifications that use of C can be an aid at times if appropriately implemented.
CMCguy