Sunday, November 29, 2015

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!) a430 ± 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.

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"?


*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.

Friday, November 27, 2015

Chemistry from the Deep: Geomimicry

Hydrothermal vent
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 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?

Monday, November 16, 2015

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!

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

Thursday, October 8, 2015

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?

(More chemistry posts coming soon...whenever the 'interesting times' become slightly less hectic for a while...)

Wednesday, August 26, 2015

Giving Up Benzyne

From Rolf Huisgen's highly detailed and comprehensive biography The Adventure Playground of Mechanisms and Novel Reactions comes this rather eyebrow-lifting passage:
"I had several reasons for abandoning benzyne chemistry at the beginning of the 1960s. Many groups were active in the field, and other areas like 1,3-dipolar cycloaddition began to blossom in Munich. In addition, Georg Wittig, my venerated senior colleague, signaled in print and word that he regarded dehydrobenzene as his domain."

Left, benzyne, in one of its (many) accepted resonance forms
Right: Emeritus professor Rolf Huisgen, of dipolar cycloaddition fame

I wonder: Given the advances in benzyne chemistry over the past 112 years, and that up-and-coming groups make its study a central piece of their research portfolios, would this choice be made in today's research landscape? Readers, have you ever been asked to cease your studies in a certain area because someone more prestigious laid claim?

Tuesday, August 18, 2015

Fall ACS: Epic Tweet-up

Kudos to all who braved the blinding snow searing heat one-mile walk to Lucky's Lounge last night for the biggest ACS tweet-up on record (at least among the few I've attended!).

Folks I remember dropping by include:
N.B. Please toss me your name in the comments if I've inadvertently left you out!

@Dichtel, fresh off his Kavli lecture success
@SuperScienceGrl, our fierce vegetarian
@stephengdavey, Nature editor
@CrimsonAlkemist, polymers guy in sharp shirt
@DrRubidium, Communicator, Forensicist, superstar
@ChemProfCramer, needs no introduction to this crowd
Jeff Seeman, chemical historian extraordinaire
@curiouswavefn, molecular modeler and chief organizer

A candid shot from inside Lucky's
Names are withheld to protect the innocent.
@sciencegeist, professor and blog stalwart
@Free_Radical1, nice dude from DE
@UnstableIsotope, polymer chemist and sometimes spider-kitten
@gagliardi8, Modeler and fellow Italian
@petercarlton, keeps CAS social media in line. Also, Dungeness crabs.
@CMcCinDC, looks like Derek Lowe. Nice tie!
@Waghornscience, ACS videos star
@laurenkwolf, (also) famous for ACS vids and, y'know, editing, too!
@amandayarnell, (see above). Too popular.
@CHADNANO, Nano-ink Prof at NW
@MurphysLab, polymer defects, live from Canada
@barneygrubbs, the nicest, tallest tweep you'll meet
@JuliaKalow, MIT wunderkind
@katmatcher, another MIT wunderkind who helped vet reactions!
@CEN_Onion, secret secret, I got a secret (and no, he's not me)
@JamesBatteas, TAMU 2D polymer champ
@GriceChemistry, super-nice wrangler of undergrad research group

Thanks to all for a great night out!

Saturday, August 15, 2015

Hyperspeed Hyperforin

Kudos to the Maimone group (UC-Berkeley), who have published in JACS ASAP what seems to be the speediest synthesis of a hyperforin on record - just ten steps!

Perhaps this lends more credence to the Eastgate's "current complexity" index, which measures synthetic simplification over time thanks to improved methods. But who would have guessed that in just five short years this synthesis would telescope from 50 steps down to just 10? Strychnine, albeit a very different challenge, took nearly 60 years to simplify from 30 steps down to Vanderwal's highly-convergent six.

For Chemists: Steps of interest include a highly-oxidized [4+2] diketene cycloaddition, a iodoacetate-promoted ring expansion, and a highly modular synthesis widely amenable to analogue production.

For Everyone Else: Why should I care that this ungainly-looking molecule was made faster than before? First, hyperforin and related secondary metabolites (natural products produced by living organisms) isolated from famous folk remedy St. John's wort suggest new avenues for the treatment of of malaria and certain forms of depression. Second, if chemists can make variations on this molecule in roughly one-fifth the time, we can expect a venturesome start-up somewhere to begin fleshing out the SAR (what chemical modifications product what activities?) in record time.