Tough-to-Swallow Propargylation

As I thumbed through the recent Tet Lett abstracts, I encountered this title:

"Regioselective propargylation of aldehydes using potassium allenyltrifluoroborate promoted by tonsil"

Turns out, the authors were referring to Tonsil (R), an acid-treated calcium bentonite clay, not the fleshy pockets in the back of the throat associated with immune response. I guess BRSM  doesn't have to update his "Desperate Conditions" list quite yet...

So, in summary:

This.

Source: Sud-Chemie

Not This.

The NMR Laundromat

Source: OPRD / CNRS

The simplest, most practical solutions* are often the best.

I'm reminded of classic papers for pragmatic lab procedures, like Clark Still's on flash chromatography, or Gottlieb & Nudelman's on detecting trace NMR impurities. Everyone has encountered their lab's version of the Kugelrohr setup - run by an old electric kettle and a windshield-wiper motor!

From the ASAP of Organic Process Research and Development comes this handy one-pager: a how-to on cleaning dozens of NMR tubes simultaneously, using glassware readily available in just about any synth lab.

Seeing this instantly triggered a "Well, duh!" moment for me - the amount of time I've stood before a stoppered 500mL vacuum flask impaled with a cannula, washing single tubes by hand...I'm sure it reaches into hours, if not days.

If you try this, leave a comment; I'm really quite interested to see how it turns out. I'd also wonder if OPRD might be angling for other quick one-offs. Couldn't hurt to try, right?

*Of course, I'd be remiss if I didn't point unfamiliar readers to the treasure trove that is Not Voodoo.

xkcd Quiz in the New Yorker

Source: Randall Munroe, for the New Yorker

If you haven't taken Randall Munroe's Thing Explainer quiz in the New Yorker, click on over for 5 minutes of fun.

I'm sure anyone reading this blog'll get a perfect score, but it's an interesting approach to scientific outreach all the same.

Click here to try your luck!

Molten Salt Bath, Anyone?

While paging through Organic Reactions, Vol 1 in the chemistry library*, I encountered some unusual conditions in a review of the Elbs reaction. If you're not familiar, it's a high-temperature pyrolysis** of ortho-tolyl ketones to produce polycyclic aromatic hydrocarbons (PAHs). Products produced from the reaction find use as analytical standards for oil processing, in studies of DNA intercalation, and as molecular wires.

PAH prepared by heating at 500 ^oC
Bonus: Roman numerals in older reviews? Classy, but confusing.
Source: Organic Reactions 1, p. 154

As alluded to above, the chemistry itself wasn't what caught my attention, but rather this sentence:

"The flask is charged with 152 g of the crude ketone and heated in a nitrate-nitrite bath (care!) at 430 ± 5 ^oC."

Four hundred degrees! During all my years in lab, I can't remember heating reactions past about 300, and those were with machined blocks of aluminum on an ancient Thermo hotplate.*** 

I realize that pyrolysis technologies have advanced in 70 years' time - FVP permits higher temperatures for much shorter residence times - but the concept of a molten mixture of sodium nitrate and potassium nitrite seemed both dangerous and alluring.

This is either Hawaii's Mt. Kilauea, or a molten salt bath. Or both.
Source: thelandofshadow.com

Looking through SciFinder, it seems that molten salt baths still find regular use in case-hardening and nitriding of steelwork, along with applications in cleaning organic residues off polymer extrusion dies. For extreme data-philes, the Molten Salts Research Center thoroughly analyzed a variety of salt mixture properties in a 150-page reference. Park Thermal International has published what seems to be a very conservative safety manual for nitrate-nitrite baths, and with good reason: aluminized leather aprons, tinted visors, and gauntlets help protect workers from glowing pools of salts at temperatures just below "decomposition...with extreme explosive violence."

Though I've never worked with molten salts, that doesn't mean none of my readers have. I see Milkshake has softened a 2L round-bottom flask by heating up to 380 with a graphite flake dry bath. How about you, Chemjobber?

Or are molten salt baths potential entrants in Derek's "Things I Won't Work With"?

Update (29 Nov): A commenter points out some previous Milkshake high-T campaigns.

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*Real books! Complete with yellowing pages, musty smells, and indexes full of names like Fuson, Fieser, and Bachmann.
**Can't get enough Elbs? Curious readers are directed to Name Reactions for Carbocyclic Ring Formations, 2010, Jie Jack Li and Timothy T. Curran. Review starts on p. 324.
***Obviously not counting use of a butane torch to pull pipettes, heat sieves and salts, etc.

Chemistry from the Deep: Geomimicry

Hydrothermal vent
Source: Geotimes.org

Lots of fascinating chemistry occurs in places humans can't routinely visit. Deep-sea hydrothermal vents, super-hot fissures formed from volcanic activity below the ocean floor, produce plumes of minerals and organic compounds. Through "geomimicry," researchers hope to harness similar conditions for use in labs here on dry land.

A team from Arizona State University - a geochemist, a biogeochemist, and a physical chemist  - report in JOC ASAP some interesting oxidation conditions using only copper salts and hot, pressurized water. With cupric chloride as an additive, benzyl alcohol and phenylacetic acid are oxidized to the corresponding benzaldehyde and benzoic acid in water at 250 Celsius and 40 bar (580 psi). The researchers speculate that the copper ions form different chloride species at high T and P, capable of promoting a series of single-electron transfers out of the organic substrates.


The article closes on an intriguing, somewhat humbling note:

"The vast majority of the organic material on Earth does not participate in the familiar, conventional surface carbon cycle because it is located deep within the crust and therefore undergoes chemical reactions under hydrothermal conditions. In contrast to the majority of reactions close to ambient [temperature and pressure], which tend to be controlled by enthalpic and kinetic factors, reactions...under geochemically relevant conditions tend to be controlled by entropic and thermodynamic forces...this suggests that much new useful organic chemistry may be inspired...by geology."

In other words, the reactions and catalysis we tend to study in labs "above ground" are just the tip of the organic chemistry iceberg....err, volcano?

3D Recipe: Drug Design Meets Virtual Reality

I still remember the distinct sense of wonder upon seeing the first immersive chemistry visualization environments in pharmaceutical companies' hiring brochures. These culminated in CAVEs*, where groups of scientists could congregate, done special glasses, and be surrounded by room-size, manipulable molecules. Now, the promise of bringing virtual reality to every bench chemist seems a little closer, thanks to the Molecular Rift.

Source: UIC CAVE virtual environment

In last week's ASAP issue of the Journal of Chemical Information and Modeling, a team of researchers from Lund University (Sweden) and AstraZeneca teamed up to deliver a relatively inexpensive ($500) virtual reality setup based on the Oculus Rift, a VR headset, paired with the Microsoft Kinect, a motion sensor popularly used with the Xbox. The paper prescribes a collage of open-source software - including the video game engine Unity and the chemistry informatics package Open Babel - that the Swedish researchers utilize to model metal complexes and a CB1 receptor, complete with undulating ribbons of secondary structure.

Source: Lund University / AZ

So, what's the big advance here? It's all in the control: the Kinect sensor watches the user's hands, allowing navigation of the molecular model using intuitive hand gestures. This way, the chemist doesn't have to intrude on the immersive VR with keyboards, joysticks, or mouse clicks.

Hoping to "...stimulate further development in a collaborative fashion," the authors have released the source code to the public** through the open-source code repository GitHub. If you're among the first to try it out, drop me a line!

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* Cave Automatic Virtual Environment. It wouldn't be software without a good recursive acronym...
**VR headset and Kinect sensor not included : )

Chemistry Soliloquy

Good evening, honored blog readers. It's been pretty sparse 'round these parts lately.

Found at a country market out in the woods.
Perfect Fall sunflower.

Not to worry...I'm not hanging up my proverbial spurs just yet. But life sure is different, nearly two years into my latest #altchemjobs venture. Remember my initial post, where I couldn't quite come to terms with the size and intricacy of my new professional home?

Well, I still haven't.

It's a strange feeling: I spent nearly 14 years at the bench, setting up reactions, drawing schemes and mechanisms in ~20 line-ruled, hardcover lab notebooks with the respective companies' names etched in gold along the spine. I distilled solvents, sourced intermediates, rinsed reactors, and held forth at innumerable whiteboard (and chalkboard!) arrow-pushing sessions. At the end of the day, success was measured in off-white, crystalline powders and clear liquids in scintillation vials or crowded lab refrigerators.

I don't do much chemistry nowadays. At least, not the type you'd be familiar with from the foregoing description.
The script now unfolding? Facilitating chemistry - helping to transform thoughts, dreams, and ideas into reactions, systems, and products.

New cross-coupling? Let's invite in a consultant or speaker. Lab equipment? We'll get a prototype. Must-have software? Arrange some demos and evaluations. Along with the never-ending study that accompanies this career choice: stay abreast of the literature, learn from your competitors' mistakes, build your network out to compensate for the tangled web of interdependent departments in modern pharma. I can proudly say that I work with some of the smartest people I know, and I field calls from time zones all over the globe.

To paraphrase aprochrypha - "May you live in interesting times." And, I do. I really do.

Who could ask for anything more?
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(More chemistry posts coming soon...whenever the 'interesting times' become slightly less hectic for a while...)