Escher: An Even More Explosive Octanitrocubane
Original Publication: Synthesis 2020, 52, 3295–3325.
Just when I thought octanitrocubane couldn't get more dangerous, I found this horrific rendition of it in a review article on the C–H activation of rigid organic compounds:
I will once again reiterate that the goal of these posts is not to trash the authors' work, but rather it is to educate––not just on the dangers of Chemdraw errors, but also on relevant organic chemistry concepts. The review article in question is filled with beautiful structures and does a great job summarizing everything from the history to the current state-of-the-art of rigid, caged organic compound synthesis.
Perhaps the most important person in the history in the synthesis of rigid compounds is the legendary Philip Eaton, who was the first chemist to synthesize cubane along with his graduate student Thomas W. Cole. Sadly, both Eaton and Cole have recently passed away, but their contributions to the field of synthetic organic chemistry have been immortalized. Anyone who has taken a graduate level synthesis course has seen and studied Eaton's cubane synthesis; it's the archetypical example of a target oriented synthesis where the target is a figment of the chemists' imagination and not an existing compound made by nature.
Octanitrocubane, where each carbon atom of cubane is bound to a nitro group rather than a hydrogen atom, was also first synthesized by the Eaton lab. The compound was assessed as an explosive (see linked paper), and it seems like a pretty damn good one at that with a 1150-fold expansion volume (at 1 atm) and 3475 kJ/mol (830.5 kcal/mol!!) of energy release.
The synthesis of octanitrocubane is shown below, as drawn by the authors of the review article (notice the perspective of compounds 30 and 31, more on that later). Basically, the synthesis of 31 requires starting from cubane tetracarboxylate and forming the tetra acyl chloride 27, which then undergoes a quadruple Curtius rearrangement and subsequent oxidation of the tetraisocyanate 28 to form the tetranitrocubane 29. At this stage, the C–H bonds on the cubane scaffold are sufficiently acidic for deprotonation with NaHMDS, which can then be treated with dinitrogen tetroxide to form 30. This transformation, however, only nitrates three of the four carbon atoms. For the nitration of the final carbon, nitrosyl chloride had to be used as the electrophilic N-atom source; the nitrosylated cubane could then be oxidized with ozone to generate the octanitrocubane 31.
So now we've gone from something insanely explosive to, with the help of a little Escher magic, something that would probably detonate if you looked at it the wrong way. Notice how in compound 31 that the nitro substituent coming off of the back right carbon is eclipsing the bond that's in the front of it? Yeah, that's what we're working with here.
Getting this structure actually wasn't that hard: I manipulated the bond angle for our stray nitro group so that it would point through the middle of the cube (as in the drawing of 31). Then, I froze the nitrogen atom of that wonky nitro group plus all eight carbon atoms to maintain the cubane core. Upon optimization with molecular mechanics, the remaining seven nitro groups kind of jerked as if they had been jump-scared (I totally get it), but they eventually relaxed into pretty reasonable orientations.
The strain energy for this compound was calculated to be 1729 kcal/mol (relative to regular octanitrocubane). I'm a little surprised with how high that number is considering how strained octanitrocubane already is to begin with! The side view (shown below) illustrates where a lot of this excess energy might be coming from.
First of all, that C–N bond that threads through the cubane core is 3.36 Å long, which cannot be great. Additionally, the placement of the nitro group in that position introduces five new repulsive oxygen-oxygen interactions with nearby nitro groups that are not present in the parent structure. Also, check out the geometry of our strained carbon:
Of course a carbon in cubane is going to be more strained than usual because it is confined to ~90° angles to other carbon atoms, but this is especially horrendous! If you ever come in proximity of this compound in real life, I would suggest run away at your earliest convenience.