Kekulene! This is one of those molecules that someone who’s learning organic chemistry might sketch out on a whiteboard, wondering if it really exists. It does, but it’s not like we have a lot of recent information about it. There was a preparation of it in 1978 (from the Staab group at the Max-Planck Institute for Medical Research in Heidelberg), but that one-off is it for experimental data. As you would imagine, the synthesis was a taxing and low-yielding one, so there’s not exactly a big jar of the stuff sitting on a shelf somewhere in Germany. If you want to have a look at it by more up-to-date instrumental techniques, you’re going to have to make it yourself.
That’s what this group (a team from Spain, Portugal, and the IBM center in Zürich) did, and many of you will have guessed that the IBM folks are in there in order to provide a look via high-end single molecule atomic force microscopy. That’s just the sort of thing you’d want for this molecule, because for many years there was a debate about what sort of structure it has. You can draw it two ways, as shown above: as six aryl rings connected by bridging groups or as a fully delocalized collection of conjugated double bonds, and those two options are going to give you very different patterns of bond lengths (aromatic rings alternating with nonaromatic ones versus pretty much everything the same).
I note that Wikipedia has it drawn in the latter form. (Edit: actually, it’s correct).
The original synthesis is quite an achievement; this is not the kind of molecule that’s just going to zip itself together. It has eleven steps, and as the current authors note, the last four go in about 20% yield, and the middle three are 23% overall, but the first four. . .well, that intermediate (2 in the scheme at right) is only produced in 2.8% yield, which is a pretty fearsome beating to start off your synthesis with. I realize that it’s probably better than taking a hammering in the last four steps, after you’ve already put the work in, but still. These authors have done a lot of work in the polyaromatic field in recent years, and they have a much-improved aryne Diels-Alder route that’s one step from commercially available starting materials. It gives you a mixture of regioisomers, true, but that can be separated by SFC or by repeated crystallization, either of which are a lot more enjoyable than the previous route. From there, the authors mention trying to explore some newer methods to get to kekulene, but ended up just pushing through the seven steps of the 1978 route, which worked exactly as described.
When examined by AFM at various tip heights above a single molecule, the structure becomes clear (see at right; the lower image is the upper one after Laplace filtration, which highlights edges and other sudden contrast changes in an original image). What you can see is that alternating rings have different character (shape, size, and AFM response), and the tip seems to be picking up the isolated bridging alkenes as higher-contrast features. That argues strongly for structure 1a in the scheme above, and it’s in agreement with the X-ray bond lengths determined by the Staab group. So the delocalized structure just doesn’t reflect reality; kekulene is indeed a sextet of benzene rings stitched together by non-aromatic bonds, and we now have experimental proof by two different methods.
I should note the experimental difficulties in obtaining any of these data. In the current work, the group had to sublime kekulene onto a copper surface by rapid heating under high vacuum, at high enough temperatures that most of the molecules broke up – scanning the AFM tip around showed mostly “small and often mobile” molecules on the surface, which are surely shattered pieces of the original. But they tracked down a few intact molecules by searching around on the copper-atom plain, whose snowflake form immediately stood out. Meanwhile, back in 1978-79, Staab and co-workers crystallized the stuff from pyrene, of all things, heating the mixture up to 450C in a sealed tube and gradually cooling it to 350 to get yellow needles of kekulene crystals to form at that relatively chilly temperature. They then removed the pyrene by careful sublimation to leave the pure crystals behind, and you can be sure that this was not exactly the first attempt that they made at getting X-ray quality crystals. It would take a while for that method to occur to you.