My graduate school mentor use to say that you could synthesize anything if you had the right precursors. With enough clever reagent artistry, most small molecules can be assembled, though if only enough for an NMR spectrum.  With chromatography and small glassware, it is not unreasonable to do a few reactions on 1 mg of material and recover enough mass to get a proton and carbon NMR.  Yes, I know that with microfluidics and labs on a chip, much lower quantities can be handled. But I refer to getting your hands on enough material to see.

What most of us who came through graduate chemistry have learned is that there are enough acids, bases, protecting groups, oxidants, reducers, latent functionalities, and catalysts out there to choose from so that some combination should get you to an endpoint in your synthesis.  If not, then  NMR, mass spec, IR, and imagination (with ample hand waving) should at least give an idea of why something won’t work.

Reaction chemistry (not including biochemical transformations!!) can be thought to occupy two broad domains- 1) low temperature, ambient pressure transformations with highly reactive species (preferably named after dead chemists), and 2) high pressure, high temperature transformations with lower reactive species. Most chemists fresh out of school know the former better than the latter. And that drives our problem solving strategies: Finding reactive intermediates that will react between -30 C and 150 C with a 5 lb nitrogen sweep in a kettle reactor.

Sometimes, the dumber brute force approach is worth considering.  What can be done under pressure and at elevated temperature?  Or, what can be done at high temperature and short contact time?  That dusty Parr reactor sitting in the corner may be capable of a goodly bit of magic.  Behind a shield. It is good to visit the high temperature, high pressure world now and then. Of course, our engineering friends already know this.

As far as the search for simplicity goes, consider what merits there may be in thermally driven transformations. Every once in a while it may be a viable avenue for something useful. Try thinking of heat as a kind of reagent. Chemical plants are good at producing heat.

 

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