Bigger booms, through chemistry

The Klapötke group at LMU is marching relentlessly onward with their quest to find new and interesting ways to stick as many nitrogen atoms onto one molecule in as close proximity as (barely) possible for long enough to get NMR data.

You may remember the Klapötke group from Derek’s post over at ItP in the “Azidoazide Azide” issue of Things I Won’t Work With.  This is the group that would look at pentazole and think “Gee, I wonder if we could replace that proton with an azide…”  I’ve always thought this kind of work was pretty cool; most of these crazy nitrogen heterocycles are practically useless but they serve the important purpose of giving us a better understanding of the nature of chemical bonds at the margin of what is possible.

Klapötke et al is back with a published patent application that showed up on my scanner.  This time, they’ve taken a step back from the realm of the ridiculous and have prepared a reasonable looking energetic active ingredient: 3,3′-dinitro-5,5′-bis-triazole-1,1′-diol (and a couple bis salts thereof).

untitled
And that structure looks not at all unreasonable.  Sure, electron deficient triazoles aren’t the most stable, but that hydroxyl contributes some electron density back to the ring system.  Oxygen balance looks good.  Slightly under-oxidized, actually, which as a rule gives you a bit of stability back.

But enough with speculation, let’s take a look at the thermal and sensitivity data provided in the text.  In energetics, RDX is commonly used as a benchmark: it has good (not great) explosive performance, and it reasonably insensitive to impact, friction, and electrostatic discharge.  Interestingly, the application does not present characterization data on the parent diol, but instead offers three salts: dihydroxylammonium (MAD-X1), diguanidinium (MAD-X2), and di-triaminoguanidinium (MAD-X3).

And the lead compound, MAD-X1, outperforms RDX across the board: better sensitivity in all three metrics, high detonation velocity (9.3 km/s to RDX’s 8.7), greater crystal density, higher thermal decomposition onset, larger heat of formation, and lower detonation temperature.  As anyone who works in the field knows, it’s really hard to have it all; you can always increase you explosive performance… at the expense of sensitivity.  And vice versa.  But, as far as performance metrics go, MAD-X1 seems to pretty handily have a leg up on the competition.

Even the synthesis is pretty straightforward and uses decidedly non-exotic reagents.  First, oxalic acid is condensed with aminoguanidinium bicarbonate in concentrated HCl, then worked up under basic conditions, affording 3,3′-diamino-5,5′-bis-(1H-1,2,4-triazole) (“DABT”).  DABT is then oxidized to the bis-nitro derivative as the corresponding dihydrate, which is fantastic from a energetics processing standpoint.  Treatment with potassium peroxymonosulfate affords the anhydrous diol, which reacts subsequently with an ethanolic solution of hydroxylamine, which yields MAD-X1 in 44% overall yield over four steps.

synthesis of MADx1

While not as concise as the two-step Bachmann process, which yields RDX from hexamethylenetetramine in 57% overall yield on an industrial scale, Klapötke’s preparation of MAD-X1 appears scalable.  Namely, it dispenses with the wildly exothermic nitrolysis process used to make nitramines — if you’ve ever had the pleasure of performing such a reaction you’ll know it’s incredibly easy to end up with a runaway reaction and a resultant yield rapidly approaching zero.  Do that on a large scale, and you’ll have a pilot plant rapidly approaching low earth orbit.

Overall, I’m pretty impressed with this compound’s prep and apparent utility.  My main criticism is: how’s that alkoxide salt going to hold up in an environment where metals are present?  Namely, in a casing or shell.  If the the use of picric acid has taught us anything, it’s that acidic energetics tend to not play well with metals.  I’d love to see some followup formulation work addressing this issue.

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All Bad Things…

Heads up: there are some chemistry terms you may or may not be familiar with in this post.  I’ve tried my best to explain as I go, and make everything as self-explanatory as possible.  If you find yourself lost, head over to the new glossary section, where I have compiled some simple definitions.

Part Three

Up until this point, the synthetic chemistry presented in Breaking Bad has been quite factual.  Conversion of pseudoephedrine to d-methamphetamine using reagents mentioned in the show is a well-known and documented synthesis.  You probably guessed there’s a “but” following the previous statement.  I’ll get to that, but first let’s talk about the synthetic route I propose Walt most likely used.

It is revealed in season one, in the episode “A No-Rough-Stuff-Type Deal,” that their process involves phenyl-2-propanone or phenylacetone, a chemical which Walt and Jesse initially make in a tube furnace.  Phenylacetone is a prochiral compound, meaning that while it is not chiral itself, it can be made chiral after only a single chemical reaction.

Chirality visual

A carbon with four bonds generally takes the shape of a tetrahedron (left) with the carbon in the center, and the four bonded substituents at the peaks of the tetrahedron. Skeletally, this is represented in the middle image. A carbon is said to be chiral if the four substituents it is bonded to are all different (right).

And that chemical reaction involves methylamine, a difficult to acquire chemical that is central to the plot of several episodes in the series.

“We’re going to use reductive amination to yield methamphetamine.  Four Pounds.”           -Walter White

This makes the homework pretty simple.  Walt and Jesse treat phenylacetone with methylamine, a reaction which yields an intermediate called an imine.

synth of imine

Phenylacetone or “P2P” (left) is treated with methylamine (above arrow) to yield an imine intermediate, shown in square brackets.

The process also releases one molecule of water for every imine formed.  You’ll notice the intermediate compound very closely resembles methamphetamine, except for one key detail: the carbon-nitrogen double bond.  With that bond in place, the intermediate is not chiral, and it certainly isn’t methamphetamine.  Luckily, we haven’t yet done the “reductive” part of the reductive amination.  If a mild reducing agent is added to the mixture (usually either gaseous hydrogen or sodium cyanoborohydride), methamphetamine results.

reduction

Reduction of the imine intermediate with hydrogen gas (or a number of other reagents) yields racemic methamphetamine.

Those of you following along since part one may notice a problem here.  We have indeed synthesized methamphetamine; however, we have done so as a racemic mixture.  That is, we have a mixture of dextro and levorotary methamphetamine.  A fifty-fifty mixture, in fact.  Then how is it that Walt claimed to produce 99.1% enantiomerically pure methamphetamine if the reaction cannot possibly do any better than 50%?  The short answer is, we don’t know.  They leave that part out of the methods described in the show.  At one point, Walt sends Jesse to acquire “40 grams of thorium nitrate,” which has catalytic uses, but no documented use in asymmetric synthesis.

From here on out, this discussion is purely speculative.  There is literature available on enantioselective reductive amination processes.  Instead of using either hydrogen gas or sodium cyanoborohydride, as mentioned above, a chiral hydride source could be employed.  However, the highest enantiomeric excess (ee.) found in literature for these products is only slightly better than 70%.  And if Walt could do better than that, so can we.  Certain chiral metal complexes, such as those of rhodium and titanium, have been demonstrated as incredibly expensive ways to achieve 90%+ selectivity.  But those catalysts would cost more than the meth would sell for.

There are some Lewis base catalysts that might do the job: they are relatively inexpensive, but the best yields are only in the 80% range.  After searching exhaustively, I found one procedure that might do the trick, but it’s going to cost you.  Using a catalytic mixture of (get ready for this) 1,1’-Bis{(S)-4,5-dihydro-3H-binaphthol[1,2-c:2’,1’-e]phosphino}ferrocene and Bis(1,5-cyclooctadiene)diiridium(I) dichloride you might be able to break into that ever elusive 99%+ range of purity.

catalysts

If you want to make Walt’s meth with his purity, you’ll need these catalysts, or similar ones. They aren’t cheap.

Therefore, the only possible conclusion is that Walter White is in fact a wizard.

I hope you’ve enjoyed reading about Breaking Bad chemistry; I’ve certainly enjoyed writing about it.  Hopefully, I’ll bring you all some new content early next week.  Thanks for reading!  And if you have any questions, concerns, or suggestions on what I should tackle next, check the about page for my contact info.

Cheers,

Mitchell

Sources:

Angew. Chem. Int. Ed. 2001, 40, 3425

Organometallics 1998, 17, 3308

Angew. Chem. Int. Ed. 1990, 29, 558.3