Wouldn’t it be great to just perform all your reactions in one reactor, flask, vessel, etc ? I remember when I was working on developing processes how I got some satisfaction out of telescoping reactions, taking the product from one reaction into the next without a preparative workup, crystallization or some sort of purification. I think my record was 3 consecutive reactions in one flask using one reagent after another. That could be some savings in the solvent used, the amount of work taken. At bench-scale, this is really trivial, but it could really be helpful on pilot-plant and manufacturing scale.
I found this review in Green Chemistry, namely, “Multicomponent reactions: advanced tools for sustainable organic synthesis”, Răzvan C. Cioc, Eelco Ruijter* and Romano V. A. Orru, Green Chem., 2014, 16, 2958. It seems appropriate to talk about “greener” chemical synthesis after introducing the topic covered a few weeks ago, about life-cycle assessment of solvents, namely https://developingtheprocess.wordpress.com/2014/06/05/hey-did-you-consider-the-impact-of-waste-disposal-as-part-of-the-cost-of-your-api-synthesis/.
It is proposed that by combining chemical steps together to produce high-valued chemicals, that you are helping with atom economy, reducing waste, decreasing the amount of solvent used, etc. This will lead to dramatic shortening of synthetic routes.
Multicomponent routes should exhibit high yields, high chemoselectivity and high enantioselectivity. These steps should not require waste associated with column purification, high-molecular weight by-products, etc. There were a few examples of the use of MCR in literature and these are a few of them. I haven’t checked these out myself, but I may when I get back to the library. For those of you that have readily accessible access to scientific journals, you can check these out.
Eli Lilly’s synthesis of the anticonvulsant drug candidate LY30016417
B. A. Anderson, M. M. Hansen, A. R. Harkness, C. L. Henry, J. T. Vicenzi and M. J. Zmijewski, J. Am. Chem. Soc., 1995, 117, 12358–12359.
ABT-341 Synthesis in one-pot
H. Ishikawa, M. Honma, Y. Hayashi, Angew. Chem. 2011, 123, 2876;
Angew. Chem. Int. Ed. 2011, 50, 2824.
A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions
You can find it here. <==Oseltamivir paper, it’s free.
This reaction is done on gram-scale, but still is interesting.
This review has a few other examples. I think it is worth taking a look. Hope everyone has a great weekend.