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

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This is Glass Grade

Part Two

Hello again!  In this installment, we’re going to get down to brass tacks with methamphetamine synthesis.  Season one of Breaking Bad opens with Walt cooking meth in a run-down RV with his partner Jesse.  I had to do a little “research” to refresh my memory about the process they claimed to use.

Research

It’s a tough job, but someone had to do it.

Jesse and Walt began their meth making operation by converting pseudoephedrine to methamphetamine.  Commercially available pseudoephedrine (PSE), often known as Sudafed, is generally sold over-the-counter in boxes of 24, each tablet containing 30 milligrams of the active ingredient.  In recent years, PSE has been phased out, in favor of phenylephedrine phenylephrine, a compound with similar decongestant properties, but one which cannot be easily modified to make methamphetamine.

Phenylephedrine (top left) has recently replaced pseudoephedrine (top right) in OTC decongestants because it cannot be easily converted to methamphetamine (bottom).

Phenylephedrine (top left) has recently replaced pseudoephedrine (top right) in OTC decongestants because it cannot be easily converted to methamphetamine (bottom).

Remember last time when I talked about the two enantiomers of methamphetamine?  When making meth, stereochemistry is important and we only want the dextrorotary enantiomer because the levorotary enantiomer is not as potent of a stimulant.  Pseudoephedrine makes for a convenient starting point because it is already dextrorotary.  You’ll notice pseudo and methamphetamine look very similar.  In fact, the only difference is that -OH group we need to get rid of.  Fortunately (or unfortunately), a simple, one-step process called reduction does just that, yielding enantiomerically pure d­-methamphetamine.  All you need is some red phosphorous, hydroiodic acid, some solvent, and a blatant disregard for your personal safety.

On a small scale, this method was favored because the materials needed are all readily available, and fairly inexpensive.  The difficulty, as Walt and Jesse discussed, was scalability.  Each box of PSE will yield only about 600 milligrams of methamphetamine, but purchasing fifty boxes of Sudafed from your local Walgreens is sure to attract some attention.  To give you an idea about how little that is, consider a heavy meth user may use as much as 1000 milligrams each day.  Not to mention the reaction will generate deadly phosphine gas, and can spontaneously ignite.

pseudoephedrine

You’d need a lot of these.

From that lengthy list of drawbacks, it’s no wonder Walt began to look for an alternative method of making meth.  He later settled on a synthetic route involving phenyl-2-propanone, referred to as “P2P” in illicit drug manufacturing.  So check back next time, when I’ll be discussing the famous P2P cook, producing Walt’s signature blue meth.