I bet on sulfur

Bad odor is often the biggest barrier between some interesting reactivity and scientists. Of course, toxicity is also a challenge, but lethal molecules can be tamed in trained hands. Odor, on the other hand, is pervasive. This tends to stop many reactions from reaching the mainstream of chemistry. It’s rather sad, especially with such versatile reagents as organosulfur compounds. We don’t even need to go that far: dirt cheap elemental sulfur is rich enough in what it can do for you.

This brings me to the main subject of tonight’s post: the Willgerodt-Kindler reaction, one of the more bizarre and ill-understood processes at the fringes of organic chemistry. Despite what’s written about this fascinating process, you won’t find a definitive account describing the mechanism of the reaction. Some hints do appear from time to time. Below you see the reaction itself on the left. In the box on the right I am presenting a curious result obtained by Hartung and colleagues (the reaction medium – Dimsulf – is awesome). This is considered to be as close as we get to isolating the relevant intermediate of the Willgerodt-Kindler reaction. All of this is rather confusing, but my friend Professor Carsten Bolm did a nice overview of the reaction not too long ago (the last link).

2

 http://scripts.iucr.org/cgi-bin/paper?bx0590

http://pubs.rsc.org/en/Content/ArticleLanding/2013/CS/c3cs60154d

4 thoughts on “I bet on sulfur

  1. It is not the smell, rather the substrate scope and yield. Like Skraup quinoline synthesis, Wilgerodt became unpopular because of its inherent messiness – any electron rich aromatic substrate and you will get a dumpster fire of a reaction mixture. Especially now that more clean zipper reaction alternatives have been developed. (Acetylene zipper, Schwarz regent olefin adduct isomerization, etc. Even the plain alkylborane thermal isomerization followed by Jones oxidation in situ is preferable to Wilgerodt-Kindler, I know this from a guy who worked on omega-aryl substituted fatty acids). People will do Skraup, and modern (less painful workup) variants exist but there is an activation barrier requiring certain degree of desperation.

  2. You make a good point. However, while there is indeed such a thing as a reaction turning obsolete, the inherent redox chemistry of sulfur is still quite special. The lack of good technologies is particularly seen when you do need to have sulfur in the final product and there is no alternative in terms of synthesis (thiamides, thiophenes, etc). Thiophenes in particular are tough: furans always form as by-products with the Lawesson’s reagent…

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