If Bis-nitrotriazoles weren’t enough for you…

A couple weeks ago, I talked about a patent published by the Klapötke group in which a series of bis(aminotriazole) salts were prepared and characterized.  It’s pretty neat stuff, and the molecules showed pretty solid energetic performance across the board.

Well, as luck would have it, another publication from the same group came out last week.  This piece is a followup on some chemistry from back in 2015 [1], wherein they prepared some triazole tetrazoles bearing nitro, azido, and amino ring substituents (compounds 5–8).  You know, for the severely carbon-averse out there.  A quick snapshot of this chemistry is reproduced below.  Compound 5 is afforded in ~64% overall yield in 5 steps.  The process chemists out there will appreciate this detail: all compounds are prepared by chromatography-free means.

Reproduced from [1]

Get your azoles, now with 33% more nitrogen!  — Reproduced from [1]

As one might expect, the sensitivities of the four parent compounds to external stimuli (impact, friction, ESD) ranged from “quite” to “extremely.”

The scope of the recent offering is to use these materials as energetic anions with various metallic and non-metallic cations [2].  Since the tetrazole proton is basically holding on for dear life — as evidenced by a 1H chemical shift of 16.19 ppm — preparing these salts was a matter of treating the parent compounds with a basic solution of the desired cation.  The goal here being use metal cations (a–c) to produce sensitive primary explosives, and nitrogen-rich cations (d–h) to produce less sensitive secondary explosives.

Get your nitrogen heterocycles, now with 33% more nitrogen!

Nitrogenous energetic materials 5–8 and corresponding metal (a–c) and nitrogen rich (d–h) cations — Reproduced from [2]

Silver’s an interesting choice; I’m generally content to not find myself in the same room as large quantities of any compound with both “azido” and “silver” in its name, but nonetheless, compound 6c exists, albeit only briefly.  The compound has impact and friction sensitivities below the minimum test threshold using the BAM method.  To quote the text:

The yield [of 6c] was not determined owing to the extremely high friction sensitivity of this compound.

The cesium analog, 6b, fares slightly better.  It holds together long enough to get some spectroscopy data, and the impact, friction, and ESD sensitivities of this compound were high, but measurable.  The text notes the ESD value is slightly less sensitive than lead azide, which is commonly employed in blasting caps.  But high sensitivity alone does not necessarily make for a good primary explosive — the material must be capable of initiating detonation in a secondary explosive.  To that end, a mass of RDX was loaded into a copper tube sealed at one end, and 50 mg of compound 6b was layered on top.  Firing with an electrical detonator resulted in the image below:

rdx det

Left to right: intact copper tube; copper tube after deflagration of 100 mg 6b; copper tube fragments after detonation of 300 mg RDX initiated by 50 mg 6b — Reproduced from [2].

So it does in fact kick off secondary explosives quite nicely — fragments of metal casings are often a welcome sign in energetic research.  It is also noted that compounds 6a–c all undergo a deflagration to detonation transition (DDT), although it’s not clear how this was determined.  Small samples of explosives generally do not detonate unless they are confined or there is a critical diameter present.  But I digress.

Now onward to the so-called “nitrogen rich” salts.  A total of 14 nitrogenous salts were prepared, however four were only isolable as the corresponding dihydrates: 5d, and 8-2e–g (compound 8 formed the corresponding dianion).  The remaining ten demonstrated a very high degree of insensitivity.  With the exception of 7e, all were less sensitive than RDX in BAM impact and friction, and ESD tests.  Additionally, all were within a 10% margin of RDX in both detonation velocity and detonation pressure according to EXPLO5 calculations.  Likewise, almost all burned cooler than RDX.

One major advantage of using nitrogen-based HEDMs is that they are non-oxidative.  That is, no oxidizing salts (say, perchlorate, nitrate), and minimal organic nitro-groups, so metal components of gun barrels won’t break down as quickly.  Since deflagrations/detonations are far from ideal from a stoichiometry standpoint, you can end up with significant amounts of NO and NO2 (and even HCl if your propellant is ammonium perchlorate).  Those gases get pretty warm in armament combustion chambers and can seriously damage barrel bores, which can lead to critical failure.  But with nitrogen heterocylces, you reduce the formation of nitrogen oxides and instead form mostly N2, and eliminate chlorine entirely.

So to that end, the authors reformulated two propellants, HN-1 and HN-2 (HN = “High nitrogen”), which are used in very large bore guns.  The compositions are mostly RDX, with some TAGzT, a relatively sensitive triaminoguanidinium salt of 5,5′-azotetrazole.  Substituting compound 5h, for TAGzT resulted in about a 10% boost in the specific energy of the formulation, with a modest increase in combustion temperature.

This is a perfect example of one of the fundamental challenges of energetics research, which I mentioned in passing in my previous post: you can’t have it all.  You can always cram more energy density into a molecule — just stick more nitro groups on it, or replace a triazole with a tetrazole.  But increasing the energy density comes at a price, almost without exception: your molecule burns hotter, or is more sensitive, or both.  And the authors acknowledge this, stating that while the combustion temperature increases, it is still well below the critical temperature for gun propellants.

References

  1. Dalton Trans., 2015, 44, 17054, DOI: 10.1039/c5dt03044g
  2. Euro. J. Inorg. Chem., 2016, DOI: 10.1002/ejic.201600108
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The Other Fieser and Fieser Text

Last night, I was killing some time while waiting for a particularly stubborn 13C-NMR experiment to run by browsing through my company’s library.  I came across something particularly interesting there; everyone knows Fieser and Fieser’s classic Reagents for Organic Synthesis, but did you know before that series was published, the duo authored a first-year organic chemistry text book?  That’s right, I found an original 1950 edition of Louis and Mary Fieser’s Textbook of Organic Chemistry.

It’s got some really beautiful illustrations, and some discussions you’d probably not find in a more modern o-chem book.  I thought the readership here might appreciate some of the artwork:

cover

The cover, complete with debossed gold lettering

pub page

We open with electron shells:

electron shells

Argon was represented by “A” until 1957

Soon, we are met with a discussion about the structure of benzene.  Correctly ascertained in 1865, the Fiesers present a short history of alternative benzene structures:

benzene structure

Structural elucidation was a laborious task in the early-to-mid 1900’s.  FT-IR was only just discovered in the late 1940’s, and it wasn’t until the 1960’s that is was widely available as a characterization tool.  Without mass spectrometry and NMR, chemists had to rely largely on elemental analysis:

CH determination

A CH combustion analysis apparatus

The principals of stereochemistry were known, and optical rotation could be determined using a polarimeter.  Chemists were still a ways off from the digital polarimeters used today:

polarimeter

The text describes a method for hydrogenation of olefins at atmospheric pressure in elegant style:

hydrogenation

And distillation:

distillation app

Next up, my favorite part: a short section on explosive chemistry.  Although those picrates land squarely in the category of things I won’t work with:

explosives

And did you know that the first chemotherapeutic agent was an organoarsenic compound?  The text describes the synthesis of arsphenamine, a treatment for syphilis in the early 1900’s, until it was supplanted by the much safer and more efficacious penicillin.

chemotherapeutic

And check out these subsequent illustrations of steroids and the heme group from hemoglobin:

steroids
heme

 

You Are What You Eat

This one’s for all you foodies out there.  The average American consumes somewhere around 2700 calories every day [1].  To put that number in perspective, a human consumes enough food energy to power a 100 Watt light bulb.  A family of four could power a desktop computer.  Your body functions by taking the chemical energy stored in the bonds of saccharides, proteins, and lipids (fats) and converting it into mechanical energy through a process called metabolism.  Micronutrients, such as vitamins and metal ions (iron, cobalt, sodium) are also introduced to the body through metabolic processes.

But not only does the body get much needed nutrients through eating, harmful substances can also be introduced in this way.  Toxic heavy metals can be introduced through contaminated ground water, or even fish.  Carcinogens, such as polycyclic aromatic hydrocarbons and dicarbonyls, can be found in cooked meats and liquors, respectively [2].

With that in mind, let’s examine some of the hazardous chemical compounds you didn’t know where in many of the foods you consume daily.

(2E)-3-phenylprop-2-enal

img1

Where it’s found: desserts, breads, baked goods, some perfumes, used as insecticide [7]

What it does: (2E)-3-phenylprop-2-enal is a skin and respiratory irritant.  In high enough doses, this compound is acutely toxic [3].

(9Z)-Octadec-9-enoic acid

img2

Where it’s found: most meats, including chicken, turkey, and beef, peanuts, and olives

What it does: In the blood stream, (9Z)-Octadec-9-enoic acid has been shown to induce severe respiratory failure and subsequent death by pulmonary edema in sheep [4].  It has furthermore been associated with increased incidence of breast cancer [5].

1,3,7-Trimethyl-1H-purine-2,6(3H,7H)-dione

img3

Where it’s found: many over the counter pain relievers and decongestants (Excedrin, DayQuil, others), chocolate, soda, tea, and coffee

What it does: First and foremost, 1,3,7-Trimethyl-1H-purine-2,6(3H,7H)-dione is teratogenic and mutagenic [6].  It is addictive and frequent consumption causes rapid physical dependence.  Furthermore, it is acutely toxic at certain doses, causing death by cardiac arrest.

8-Methyl-N-vanillyl-trans-6-nonenamide

img4

Where it’s found: fruits of plants belonging to the Capsicum genus, including bell peppers and jalapenos, paprika

What it does: In the laboratory, 8-Methyl-N-vanillyl-trans-6-nonenamide is classified as a hazardous material and requires the use of a respirator for safe handling.  Contact with skin or eyes results in severe irritation and burning, accompanied by local swelling.  Inhalation results in respiratory tract irritation.  It is acutely toxic in sufficient doses, and may have neurotoxic effects [8].

I Have a Confession to Make…

Up to this point, this entire article has been quite deceptive.  Intentionally so.  But I wrote it that way for a good reason, I promise.  Time for a quick poll: how many of you Google’d any of the compounds I just listed?  If you did, you would have found that I gave the systematic IUPAC names for quite common chemicals.

  • (2E)-3-phenylprop-2-enal is more commonly referred to cinnamaldehyde, and is the chief favorant in cinnamon.  Pure cinnamaldehyde, isolated from the essential oil of cinnamon tree bark, is a skin irritant; however, the cinnamaldehyde content in ground cinnamon is low enough for this to be a non-issue.  Furthermore, while it is technically toxic, the amount you would need to eat for negative effects to occur is huge – about half a pound for a healthy adult.
  • (9Z)-Octadec-9-enoic acid might be more recognizable as oleic acid, and makes up about 60% by mass of olive and canola oils.  It’s a very common fatty acid, usually found as a triglyceride in animal fat and many seeds and nuts.  Consumption of such monounsaturated fatty acids has been shown by trial after trial to have health benefits such as lower “bad” cholesterol.  While one study did show a link between high consumption of these fats and breast cancer, others have shown quite the opposite [9].  As for respiratory failure and pulmonary edema?  The researches induced these conditions in sheep intentionally by injecting pure oleic acid directly into their bloodstream.  So as long as you’re not shooting up olive oil, you should be alright there.
  • 1,3,7-Trimethyl-1H-purine-2,6(3H,7H)-dione might wake you up every morning, you probably just call it caffeine.  It is in fact mutagenic, hence why expectant mothers are instructed to avoid it.  However, the study demonstrating these properties in rats used injections of caffeine equivalent to a human dose of 100 cups of coffee.  This amount is incidentally very close to the median lethal dose in humans, which would of course be impossible to achieve by drinking coffee alone [10].
  • 8-Methyl-N-vanillyl-trans-6-nonenamide is what gives your chili its kick, but you most likely know it as capsaicin.  It’s in every chili pepper you cook with, from serranos to jalapenos to those absurd Indian ghost peppers.  Of course it’s an irritant, ever rubbed your eyes after eating something spicy?  The pure stuff, extracted and isolated from the peppers, is just much, much more potent.

So What’s the Point Here?

There seems to be some sort of pervasive fear of chemistry in society.  To a degree, I understand it; the 1950’s, gung-ho blind devotion to “Better Living Through Chemistry” brought us thalidomide and agent orange.  Carelessness brought us the tragic Bhopal incident in 1984.  It seems as though in a number of ways, chemical research has changed from “this is useful” to “this is dangerous” in the mind of the public.  I seldom go two days without seeing a link to some blog touting the horrors of synthetic food additives, GMO foods, or fluoride in the water.  The repeated chanting of “synthetic is bad, natural is good” ignores the fact that chemistry itself is indifferent.  I could just as easily have written this article from the opposite perspective: “All-Natural Drugs Found in Food.”  Hydrogen cyanide in Yuca plants, coniine in the hemlock bush, and amanitin in Amanita mushrooms, all of which are natural but deadly.

All science, let alone chemistry, requires a certain level of skepticism, without which true objectivity would be impossible.  A double-dose of skepticism may be necessary when dealing with things you ultimately put in your body.  With that being said, I hope the take-home message from this article is simply “think critically.”  Remember, any Joe (myself included) with some free time and $20 can set up a website and say whatever they want.  There is a vast amount of wonderfully useful information out there.  Unfortunately, there is also a huge quantity of misinformation mixed in with it.  As the 16th century German physician Paracelsus said, “All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.”

Cheers,

Mitchell

P.S. This post is a bit different from what I usually publish, so as always, I welcome feedback.  Leave me a comment or shoot me an email (mtantalek@gmail.com).  I’m also interested in hearing what you would like to read about in future posts.

Sources:

  1. http://www.usda.gov/factbook/chapter2.pdf
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379645/pdf/canfamphys00111-0173.pdf
  3. http://www.ncbi.nlm.nih.gov/pubmed/10866983
  4. http://jap.physiology.org/content/60/2/433.long
  5. http://jnci.oxfordjournals.org/content/93/14/1088
  6. http://onlinelibrary.wiley.com/doi/10.1002/tera.1420080109/abstract
  7. http://pubs.acs.org/doi/abs/10.1021/jf0497152
  8. http://www.sciencelab.com/msds.php?msdsId=9923296
  9. http://onlinelibrary.wiley.com/doi/10.1002/ijc.2910580604/abstract
  10. http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1967.tb00034.x/abstract

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.

My Baby Blue

Prologue

When I started writing this, I planned on it being a single post covering some background about organic chemistry methods discussed in Breaking Bad.  But more importantly, how accurate those methods are.  However, I soon realized covering everything I wanted to would turn this post into an essay.  So I decided the best course of action would be to break it into parts.  Part one will cover the structure and properties of the drug, while parts two and three will discuss its synthesis in regards to the show.

Part One

Welcome back, faithful viewers.  As promised, this time around I will tackle (with no spoilers!) some of the chemistry from the series Breaking Bad.  For those of you living under a rock for the last five years, Breaking Bad chronicles protagonist Walter White’s descent from beloved high school chemistry teacher to methamphetamine-producing drug kingpin “Heisenberg.”  You also may be quite tired of your friends’ raving reviews about the show, and probably wish they’d shut up about it already.  But I digress.

Let’s briefly discuss the structure and properties of meth.  This is methamphetamine:

meth full formula

Or more succinctly (in what chemists call “skeletal formula”):

meth skeletal

You’ll notice the wavy line representing a carbon-carbon bond.  A wavy line exists because there are two possible enantiomers of methamphetamine.  The dash (left) represents a bond going into the screen, while the wedge (right) represents a bond sticking out at you. Remember, organic molecules are three-dimensional, not flat.

enantiomers

We differentiate these two enantiomers with the Latin prefixes dextro and levo, or simply d and l for short.  The structure on the left is levo-methamphetamine.  It’s rather innocuous and there’s a good chance you’ve unknowingly used it before; it goes by the brand name Vick’s VapoInhaler.  The one on the right is dextro-methamphetamine, and that’s the one favored by recreational methamphetamine users.  A seemingly minor difference in structure turns a highly addictive and very destructive drug into a nasal decongestant.

Methamphetamine is a psychostimulant, belonging to the broader class of psychoactive drugs.  It acts on the central nervous system by increasing the amount of dopamine in the body, causing a variety of physical and psychological effects; hyperactivity, alertness, headaches, increased libido and self-confidence, heart palpitations, psychosis, stroke, and paranoia are just a few of the many effects induced by methamphetamine usage.

Recreationally, the drug is introduced to the body virtually any way you could imagine, and in at least one way you probably can’t.  Meth tablets were given to pilots during WWII to help them stay awake on long bombing runs, and it’s currently prescribed to treat attention deficit hyperactivity disorder (ADHD) and as a last-ditch treatment for severe obesity.

Look out for my next post, where I’ll be talking about Walt and Jesse’s first cook in that run-down Winnebago.