Articles by: Crystallinity

Skillful writing of an awful research paper

Apparently, laboratory instructors and undergraduate mentors aren’t the only ones with the bane of reading insanely terrible research papers – the editor of the ACS journal Analytical Chemistry, Royce Murray, clearly has had his fill as well, according to his editorial in the current ASAPs.

His humor is very similar to that found in The Onion, and reminded me of How to Write a Scientific Paper on Improbable Research.

Brilliant. The only thing that has made me laugh out loud this hard lately was catching a part of the show ‘Ancient Aliens’ on the History Channel last night in which someone said that “one possible explanation of why the Mayans vanished was because they were aliens.”

In all seriousness, though, it is an understatement to say it’s quite obvious that scientific writing isn’t emphasized as well as it should be, it should be addressed at the undergraduate level as early as possible.

By January 27, 2011 0 comments chemical education, opinion

Kudos to the Fagnou Group

I am continuously impressed by the publications that have appeared since Prof. Keith Fagnou’s shocking passing a little over a year ago. The chemical community still mourns; it is clear from these post-mortem publications that Fagnou’s – and his clearly dedicated and talented graduate students and post-docs – brilliance lives on. (Note – this is the same article that appears on Chemical Crystallinity.)

The chemistry that Fagnou has truly spearheaded, direct C-H functionalization, is a method of forming C-C, C-N, C-B, etc bonds without having to prepare one of the coupling partners, as in traditional transition-metal catalyzed cross-coupling reactions. Palladium, rhodium and ruthenium are commonly used catalysts in direct C-H functionalization reactions. Fagnou has published a great deal on arylation reactions of a wide variety of substrates and even a bit on direct benzylation reactions. Some fairly recent reviews are linked in a previous post at my own blog.

A recent publication in Journal of Organic Chemistry (doi: 10.1021/jo102081a), “Predictable and Site-Selective Functionalization of Poly(hetero)arene Compounds by Palladium Catalysis,” published by David Lapointe and coworkers, explores the development of two approaches to selectively functionalizing multi-ring systems – 1) using site-selective reaction conditions, and 2) a pathway with a particular order of reactivity according to a concerted metalation-deprotonation (CMD) mechanism. It is well-known in the field that a great many (hetero)arenes can be functionalized with (painfully) rigorous fine-tuning of the catalyst, ligand, additives, and other reaction conditions. Some substrates have been more difficult to functionalize than others, and selectivity of particular positions on these rings is always an issue – this publication tackles both issues.

To explore site-selective functionalization, the group used compounds with more than one available C-H bond for direct functionalization, and using multiple protocols specific for specific C-H bonds (Larossa’s conditions for C2 arylation of indoles, Gaunt’s Cu-catalyzed C3 arylation of indoles which is actually selective for meta to amido groups, and their own protocols for arylation of perfluorobenzenes and aromatic N-oxides) were able to successfully and selectively functionalize targeted C-H bonds in moderate yields. Here is an example with some decent yields, with reaction times ranging from 16 – 24 hours:

The alternative approach relies upon the CMD pathway as the operative mechanism, which favors electron-deficient substrates.  Several years ago, Echavarren published support of this mechanism by finding a preference for the most acidic C-H bond and requirement for a carbonate base, and Fagnou established the use of a pivalate additive, which was speculated to play a crucial role via CMD.   A recent mechanistic paper with aromatic N-oxides as the substrates strongly supports this mechanism.   The metal first inserts into the aryl-X bond, as expected, and in the key transition state, the pivalate coordinated to the metal deprotonates the C-H bond while the palladium forms a bond to the same C.  Reductive elimination (not shown) releases the arylated product.

In the current paper DFT calculations were found to agree quite well compared to competition reaction results of a series of heterocycles to elucidate the order of reactivity of the substrates.  Those presented in the paper are as follows, in order of reactivity – this is extremely convenient for the synthetic chemist who would like to utilize this chemistry.  And it’s just plain neat – the kind of thing that will hopefully end up in a textbook someday. (Note: the last two substrates are either switched in the text or switched in the image – they don’t agree in the paper and I haven’t looked at the supporting information closely.)

Reaction conditions: 0.5 eq. of each of two heteroarenes in the competition experiment, 0.125 eq. 4-bromotrifluorobenzene, Pd(OAc)2 5 mol%, PCy3.HBF4 (10 mol%), PivOH (30 mol%), K2CO3 (1.5 eq.), DMA (0.3M), 100ºC.

And finally, for an example of the method in action – note that the difference between using this method and the previously described is that here, there aren’t necessarily general optimized conditions available for each of the substrate classes here.  Examples of a few of these are peppered throughout the arylation literature but they aren’t like indoles, pyridines, N-oxides, perfluorobenzenes, imidazoles, and pyrazoles and don’t have their own special set of conditions (that I’m aware of at the moment).  Yields of included substrates range from 65-80%. Instead of optimizing conditions for each, the site of reactivity can be predicted with good specificity – here the indolizine C-H bond over the more electron-rich thiophene’s:

Instead of an aryl bromide, benzyl chloride can be used as the coupling partner as well, with published yields from 55-84%.

  • Lapointe, D., Markiewicz, T., Whipp, C. J., Toderian, A., Fagnou, K. (2011). Predictable and Site-Selective Functionalization of Poly(hetero)arene Compounds by Palladium Catalysis Journal of Organic Chemistry : 10.1021/jo102081a
By January 21, 2011 4 comments synthetic chemistry

Maker Faire NYC 2010 was Awesome!

The Maker Faire is a “World Science Fair” event conceived and organized by those who produce Make magazine, which is described as “a do-it-yourself technology magazine written by makers.”  It was held in three cities this year – NYC, Detroit, and the Bay Area.  The Faire happened in NYC at the New York Hall of Science in Queens last weekend and was a fantastic, energetic composite of things going on.  Well worth the trek to get out that far into Queens!

The event embodied the “do-it-yourself technology” theme, featuring exhibits with a heavy focus on science, cool demonstrations, and lots of do-it-yourself booths where “makers” hosted hands-on activities for children and adults alike.   Naturally, something like this was irresistible to me, and I was able to attend for free since I was volunteering at a booth (unrelated to science or technology – I was with a group of a different kind of maker).  I didn’t get too much of a chance to spend time at many of the huge number of booths and exhibits, unfortunately, which was a huge bummer.

The schedule was overwhelmingly packed – definitely intended for people to spend an entire day there.  There was a demonstration stage, multiple craft tents, a huge food area, a beer tent tucked in there (which seemed to result in me getting security to throw out one guy who was harassing one of the women I was working with), and a large handmade craft sale section hosted by BUST magazine called BUST Craftacular.

Activities included “Cardboard Music,” where instruments were made from cardboard and found objects, a live presentation called “Thinking Like a Scientist” (some demonstrations of which are 200 years old) given by Wizard IV (Steve Jacobs), who also happens to be the science consultant for MythBusters.   MakerBot Industries was there – they create 3D printers that you assemble and then can then function as a little factory to make things for you (see the company website for more awesomeness).  One of the biggest pulls for visitors was the “Reverse Geocache (TM) Puzzle” – unlike using GPS to locate boxes around the country/world, you are given the box, but it won’t open unless you are at particular coordinates that’ve been programmed into it, and you have a limited number of clues to find that exact location.   Add this fun kind of intellectually stimulating product, activities and ideas, to children’s rides, music shows, tasty paella, and handmade crafts, and you’ve got one heck of a good sciencey time.

Check out images of the event on their own website, as well as those on CNET, guaranteed to be focused on the super techie stuff.

By October 2, 2010 0 comments fun, science events

The most recycled waste

The most recycled waste is not glass, aluminum cans, plastic, or electronics, according to the EPA’s Municipal Solid Waste Report, last compiled with 2008 data, which I was referred to from a recent Scientific American article.   It is car batteries, almost all of which are recycled.  I actually have wondered what happens when they die, but I’m so glad to know that they ARE recycled.   Just a nice tidbit of knowledge for you there.   Recycling is more or less on the rise overall (see graph from the EPA report), thank goodness, despite the persistent folk out there who firmly believe that recycling has no net benefit and therefore don’t even try.

Recycling is obviously on the minds of environmentally-conscious chemists (and other people, I hear other people exist) – but when you think of recycling and trying to green up your daily work life, what do you think of?  Recyclable catalyst, acetone recycling, reading articles on your computer screen instead of on paper (including opting-out of C&EN’s print issues which, consequently, has decreased the degree to which I use it as a procrastination tool and the depth in which I read the non-science concentrates).  But what do YOU do?  I’m really curious to know.  Do you just shrug and carry on?

Guilt about the waste that we generate – and I can only attest to synthetic organic chemists and those who deal with tissue culture when it comes to the byproducts of science – is so, so heavy on my shoulders.  I’m not a crunchy tree-hugger (despite being a vegetarian, yes), but I AM uncomfortable with generating a crapload of waste in order to obtain a few pieces of paper – a couple JACS articles, a Ph.D., etc.  I know I’m not the only one that is frustrated to burn through so much physical material in the name of progress and intellectual/industrial pursuit.  But what else can you and I do, besides cut down on our chromatography, not use disposable items, recycle our acetone and keep all of our data and journals electronic?   How about big corporations?  Are they making efforts at sustainability so that they can claim they are, or to actually conserve resources?  Does it even matter?  Take for example the new SunChips bag released by Frito-Lay/PepsiCo, the first compostable chip bag ever.  It’s a start, no?

[I didn’t mean for my first post to be so depressing!  It’s an honor to be here and I hope to bring you more lively topics in the future.  Both the Chemistry Blog (naturally) and Chemical Crystallinity are on a list of top chemistry blogs for students; I don’t know why this list was generated from the particular source it is hosted on, but it is pretty reasonable.]

By April 24, 2010 5 comments opinion