The Wrapup from ACS in SLC

It’s a wrap.  My bags are more or less packed, and I’m waiting on the airport shuttle.  So, while it’s still fresh in my mind, I’ll give the last update from SLC. 

The last two days were spent shuttling between organic and CHAL presentations.  Hearing some lawyers (entrusted with protecting millions of research dollars) talk about rudimentary chemistry is an unbelievably painful experience.  As a matter of necessity, I had to go to organic presentations to make sure I hadn’t lost my mind.  In terms of the organic chemistry presentations, I didn’t see anything groundbreaking per se.  Though, it was good to see that there’s some really interesting chemistry going on around the world. The ORG/MEDI poster session last night was particularly nice because it was a fairly reasonable mix of small molecule synthesis and methodology.  I was most impressed with the work coming out of Matt Sigman’s lab at Utah.  I admittedly never heard of him, though that’s probably understandable because U. of Utah is Peter Stang’s stomping ground.  Anyhow, Sigman’s got a post doc working on copper-free Wacker oxidations, a methodology first discovered a few years ago (see: Org. Lett. 2006, 8, 4117-4120).  Apart from using a DMA/water solvent system, the method looks pretty cool, and it could be interesting to see where Sigman takes the project in the future.

Additionally, I caught one of Sigman’s students give a talk on the development of an oxazoline catalyst used in hetero-Diels-Alder chemistry (ACIE 2007, 46, 4748-4750).  Sigman (and his grad student, Jensen) altered the CF₃ on the catalyst to a relatively less electron-withdrawing group then watched the change in rate and enantioselectivity.  Sigman and Jensen ultimately concluded, “reaction rate and enantioselectivity can be directly correlated to catalyst acidity.”  Pretty cool linear free energy relationship. 

In summation, I think the meeting was a pretty good experience, subjectively.  I got a ton of networking accomplished, developed several ideas I’m bringing with me back into the lab and may have found my PI a post doc for his lab (though, I’m still keeping an ear open).  

Monday Update from ACS in SLC

Generally Speaking.  Aaron from Wired Blog made the comment that attendance looks low at ACS in Salt Lake City.  I agree, and I wonder if it’s a function of the economy.  On the humorous side of science, there was a vendor in front of the Salt Palace this morning selling “Obamium” t-shirts.  I didn’t get one (we live in a McCain/Palin household).  Also, I’ve noticed that there isn’t a lot of ground-breaking synthetic organic chemistry being presented. 

LENR = Cold Fusion?  Not quite a tabletop source of energy, but interesting nevertheless.  Pamela Mosier-Boss, Steve Krivit, Antonella De Ninno and a few other experts took questions from a packed house about the interpretation of recent results surrounding advancements in low energy nuclear reactions (LENR).  Those in attendance included Scott Chubb (of Infinite Energy fame), KSL-TV Channel 5 and the legendary Mitch Andre Garcia.  I’m not even going to try and explain the crux of the talk (being a synthetic organic chemist, and all).  However, the video of the press conference is available here, and I encourage you to check it out if you’re interested.  Perhaps if you ask Mitch really nice, he’ll write a post on the ins and outs of the debate.  While there are several critics of the research (for example, click here), the crux of the talk appeared to focus on recruiting young chemists to explore this “new” area of science. 

Feel the Burn.  The U.S. Geological Survey (USGS) announced their discovery of gas hydrates—“a frozen form of natural gas that bursts into flames at the touch of a match.”  Tim Collett (project co-leader) claims that this work may bridge the gap between relatively dirty fossil fuels and clean energy because gas hydrates purportedly leave a small carbon footprint. 

Just Scan it.  I took a few moments to speak with Dr. Jeffrey Silk, president of Silk Scientific, about his digitizing software.  I haven’t seen this sort of program before, so I’ll make the assumption that others haven’t either.  The product (called “UN-SCAN-IT”) takes a chart, graph, HPLC trace, etc. and converts the image into data points, which can be dropped into a program such as Excel.  With the “raw” datapoints, UN-SCAN-IT allows you to integrate, take derivatives, and perform curve fitting.  If this sort of thing tickles your fancy, you can download a demo of the software here.  For all of you bio-type peeps, Silk Scientific also sells a second program called “UN-SCAN-IT gel,” which acts as a densitometer for gel images.  As for future generations of products for Silk Scientific, I suggested he make a program that will automatically solve ¹H-NMR spectra.

Sunday Update from ACS in SLC

On my flight into Salt Lake City, I was greeted to nasty turbulence, an overcast sky but a comfortable mid-50 degree temperature, which eventually turned to rain (there’s a chance of snow tonight). 

So, what happened today?

The Inorganic/Medicinal Version of Brown.  M. Frederick Hawthorne is slated to win the highly coveted ACS Priestley medal for his contributions to boron chemistry in SLC this week (March 24, 2009).  In addition to synthesizing polyhedral borane clusters such as B₁₂H₁₂^2- in the 1950’s, he is noted for his boron neutron capture therapy (BNCT)—a promising technique in the war on cancer (see: J. Am. Chem. Soc. 2007, 129, 6507-6512).  I realize this isn’t really news per se since C&EN covered it last June, but some of you might have missed it.

Smith’s Dithiane Chemistry.  I caught most of Amos Smith’s talk about his lab’s recent efforts in the realm of dithiane transformations (you should be thinking “umpolong”).  He did a nice presentation on multicomponent anion relay chemistry (“ARC”; for example see: J. Am. Chem. Soc. 2006, 128, 12368-12369 and Angew. Chem. Int. Ed.  2008, 47, 7082-7086) while making a cute comment that the resultant “protected” alcohols are easily removed with Philadelphia tap water.  For those not familiar, the Smith lab has been applying hybrid umpolong/Brook rearrangement chemistry to synthesize cool “proof-of-concept” natural product-like molecules.  Smith mentioned that this type of work has caught Jeff Johnson’s attention (hence the umpolong connection) evidenced by a fairly recent publication about the synthesis of zaragozic acid C (J. Am. Chem. Soc. 2008, 130, 17281-17283).  I had to leave the talk a bit early, but from my vantage point I noticed a lot of male chemists slowly starting to assemble for M. Christina White’s talk.  I was truly sorry that I missed it.  Oh, in case you were wondering, I did not notice her trademark ostentatious belt buckle.

CAS and Nanotechnology.  In the few hours I’ve been at the ACS conference, I’ve noticed that there’s an awful lot of material (no pun intended) on nanotechnology.  While nanotechnology touches areas of pharma, materials and even the molecular automotive industry, the issue of classification is making its way through the chemical community.  Roger Schenck (of CAS) did a fine presentation on the issue from Chemical Abstracts Service’s vantage point.  CAS currently catalogs 80 sections of chemistry (#1 is pharmacology), and, according to Schenck, CAS is not planning on adding #81 (which would be nanotechnology) anytime soon. It seems that the issue will be tabled for a bit longer while the field continues to grow/evolve.  For you history buffs out there, Schenck contends that nanotechnology probably began with Kroto’s C₆₀ discovery (Nature 1985, 318, 162-163). Interesting tidbit: Kroto even mentioned that he’d “prefer to let this issue of nomenclature be settled by the consensus.” 

Oh Finkelstein

In the midst attempting to alkylate a couple of our novel compounds, my PI recently suggested converting my alkyl bromide into an iodide via Finkelstein reaction.  Having performed several of these reactions in the past, I’m no stranger to this transformation.  A garden-variety Finkelstein reaction involves the treatment of an alkyl halide (or any other good leaving group for that matter) with sodium/potassium iodide in refluxing acetone (see: Tetrahedron 2004, 60, 10943-10948).  The resultant byproduct salt is more or less insoluble in acetone thus your reaction mixture can be filtered over celite or florasil.  Variations in this reaction include substituting methyl ethyl ketone (MEK) or toluene for the typical acetone since all three solvents typically do not dissolve salts (more specifically KBr, KCl, etc.).  Employing MEK in place of acetone (for example) has an advantage of an increased boiling point, which can give your reactants a nice kick in the butt thus speeding up your reaction time. 

Comparison of Common Finkelstein Solvent Temperatures

Acetone: 56 ^oC;   MEK: 80 ^oC;   PhMe: 111 ^oC          

In a quick SciFinder search, I was shocked to learn that more off-the-wall variations of this reaction involve use of aqueous solvent systems.  For example, this sort of transformation was demonstrated by Pauline Chiu and co-workers in the formal synthesis of pseudolauric acids (J. Org. Chem. 2003, 68, 4195-4205; also covered in Li’s Modern Organic Synthesis in the Laboratory).  Instead of installing the typical iodide, Chiu’s team opted to substitute the chloride for the bromide using phase transfer conditions.  While the reaction offers amazing yields, it’s not readily clear as to why this procedure was employed instead of classical conditions.  Additionally, the alkyl halide is allylic, which raises questions over the mechanistic details (i.e. is it S_N2 or more like an allylic substitution).  Still the transformation’s pretty cool.  Maybe not as cool as going to see Menudo as your first concert experience, but cool nevertheless.  (Inside joke).

Subjectively speaking, I’ve found that progress of this sort of reaction can be monitored by crude ¹H-NMR analysis.  More convenient methods such as TLC may not discern an alkyl chloride (for example) from an alkyl iodide. 

P.S. I’ll be attending the ACS meeting in Salt Lake City next week with Mitch over at Chemistry Blog.  In addition to contributing to his site, I’ll be keeping a running daily post to satisfy your synthetic curiosities.  Keep checking back here for updates.  

Brominate like a Wizard...a Lesson in Gen Chem

Organobromides are a necessary part of synthetic organic chemistry.  Think of all of the functionalization and carbon-carbon bond forming a chemist can accomplish through the installation of a bromine atom into their molecule of choice.  Admittedly, there are alternatives to bromides such as iodides, sulfonyl esters, acetates and carbonates (for example see: Adv. Syn. & Cat. 2000, 343, 34-36).  However, in most cases you cannot beat the ease and simplicity of bromine installation.  By comparison, the installation of other comparable synthetic handles often requires more than one step and/or several reagents to accomplish.

Despite the utility, there is an obvious concern over the safety of using magical element #35.  It’s nasty stuff, and bromine burns can take quite some time to heal (see: Jap. J. Tox. 2005, 18, 141-147).  On top of that, physiologically speaking, there are a silent few who cannot tolerate organobromides (see: Risk Management for Hazardous Chemicals by Jeffrey W. Vincoli).  For what it’s worth, I learned that I was a member of this club (mind you, the hard way) my second year of graduate school, but I cannot do my job without them.  Then again, I’m deathly allergic to cats and dogs, but I can’t think of life without Miss Piggy or Isabelle (respectively).

The installation of a bromine atom is a task that successful organic chemists must master.  Despite the inherent danger of working with pure, elemental bromine, there are alternate ways of installing a Br atom without using the characteristically, brown/red chemical.  The obvious solution to an organic chemist is to use NBS or pyridinium bromide perbromide.  There’s another way that’s even cooler, is pure alchemy and covered in most general chemistry classes (high school or college).  I discovered this beauty during my third year of graduate school and never gave it much thought until I started writing my dissertation.  For my purposes, the procedure in question (an old Chem. Ber. paper from the 1950’s), called for dissolution of the starting material in strong, aqueous acid, followed by the slow addition of KBr then KBrO₃.  After 2 hours of reacting, the solution was then neutralized, which precipitated a solid that was filtered off.  Analysis of the resultant solid confirmed the addition of a bromine atom. 

The whole equilibrium is very interesting.  As confirmed by my dear, Midwestern inorganic Jedi friend, if you add acid to a solution of KBr and KBrO₃, the equilibrium shifts toward bromine formation.  If, however, you add base (i.e. NaOH), the equilibrium shifts back to the left and you get sodium hypobromite—a powerful oxidant (of course, on the scale of Clorox bleach).  While this chemistry has been applied as far back as the early 1900’s (J. Am. Chem. Soc. 1903, 25, 2169-2171), more recent examples have been lightly peppered through the literature (J. Org. Chem. 1981, 46, 2169-2171).

Bonus Material

Everything you’ve ever wanted to know about Br₂ can be found here (Courtesy of Great Lakes Chemical Corporation). 

Derek Lowe has a great story about how not to brominate like a wizard.