You could add a little bit of soap to that.

What does that mean ?  You could add a bit of soap to that ?  I came across this review in Green Chemistry that discusses adding custom surfactants (a few wt %) to water to carry out reactions.  I think that is phenomenal.  I am, at least, a little interested in reducing the amount of waste produced.  Why wouldn’t you try running a reaction in water ?  If your aqueous phase has come into contact with the organic phase, you don’t necessarily dump it down the sink.  (I say this, and I realize it depends on the concentration of organic in the aqueous, what the regulations in your country, etc.) But it has always gone with organic waste in my case.    The paper that I am referencing comes from Green Chemistry, namely the following article, “Transitioning organic synthesis from organic solvents to water. What’s your E Factor?” by Bruce H. Lipshutz and Subir Ghorai, Green Chem., 2014, 16, 3660, doi:   10.1039/C4GC00503A.

This review delivers quite a few different points.  I hadn’t realized the breadth of scope of applications of using water with added surfactant.  I will list the types of reactions covered, but I will only provide a few examples, based on what I have used in the past.   After all, I want you to check this out.    The reactions presented are Zn-mediated reductions of nitroarenes and -heterocycles,  copper-catalyzed conjugate addition, zinc reduction of alkyl halides, Suzuki-Miyaura couplings, Stille-couplings, aminations of aromatic rings, hydroformylations, trifluoromethylation of heterocycles and oxidation of alcohols.

I wanted to introduce the stars of this post.  They are these surfactants.  Apparently, there is a Organic Synthesis paper by Lipshutz in review about how to prepare one of these.  Additionally, I think it is quite nice to find  β-sitosterol (the precursor) comes from a commercially-available mixture of plant extracts.

 

surfactants

Not all the reactions will be of interest to everyone.  I am only interested in the ones that I typically have used in the past.

There are a couple of examples of palladium-catalyzed reactions with typical “pharma conditions” and the equivalent reactions using micellar conditions.  I would refer to you, the reader to the following reference if you want further information. B. H. Lipshutz, N. A. Isley, J. C. Fennewald and E. D. Slack, Angew. Chem., Int. Ed., 2013, 52, 10952.  I haven’t checked out these calculations, so you might want to do so yourself.  It is interesting to see the comparison of  E-factors of reactions using typical pharma conditions and those conditions using an aqueous system with added surfactant.

sonogashira-09112014

I am surprised about the absence of CuI.  I certainly needed this when I performed my Sonogashira reaction a while back.  Using the micellar conditions, there certainly is a world of difference when looking at the E-factors.  What I would be most interested was the residual palladium left in the intermediates that were produced using micellar conditions.  I have tried water-soluble phosphines  in the past to make a water-soluble palladium catalyst in the hopes of reducing residual palladium in the resultant product (this is only really a consideration in pharma).  Water can be the most abundant solvent out there (depends where you are in the world).   I would expect the easiest workup would be precipitation from the reaction.

The yields on this Suzuki-Miyaura reaction using MIDA boronates are good, considering this is done at room temperature.

boronMIDA

I was looking at this trifluoromethylation reaction and the ability to recycle the solvent.  I have talked to other process chemists about this before.  It is certain that, in any other business, except pharma, you might get away with recycling solvents.

recycle-09112014

I need to get some new literature.  This review took a little longer to look through, but I think it is well worth a look.  Some interesting ideas.

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