SCIENCE & TECHNOLOGY
tive diene. The pendant dienophile readily reacts with this diene to close the last two rings of the cholesterol framework. Similarly, E. J. Corey’s 1969 prostaglandin F2α synthesis is a retrosynthetic masterpiece which every aspiring organic chemist needs to study. Only a five-membered Bloggers pen ESSAYS celebrating their favorite chemical reactions ring exists in the product, yet Corey had the vision to see that carbon atoms 6–11 (prostaglandin numbering) could form C&EN RECENTLY invited bloggers to write posts about their favorite chemical reactions. the six carbon atoms of the cyclohexene We received some two dozen posts from seasoned chemistry bloggers and fledgling Diels-Alder product. Diels-Alder reaction writers alike, singing the praises of all kinds of reactions. Excerpts from a few of our of the cyclopentadiene derivative and a favorites are reprinted with permission here. You can read them in full, along with all other ketene equivalent yielded a bridged bicyclic entries, at cenm.ag/rxns. product. Conversion to the ketone, followed by Baeyer-Villiger oxidation, gave the bridged bicyclic lactone. A few steps later, the bridged lactone had been converted into DIELS-ALDER REACTION classified as a [4 + 2] cycloaddition.This is the fused lactone that we now call the Corey No reaction is more elegant, more heartthe bare-bones Diels-Alder reaction we all lactone, in homage to the organic chemistry warmingly satisfying than the Diels-Alder remember from undergraduate organic giant. reaction. No reaction is also more nuanced. chemistry classes. The Diels-Alder reaction is not merely It appears deceptively simple and yet has Peter Vollhardt’s 1980 synthesis of esrestricted to the synthetic lab; nature also the ability to create imenjoys a good Diels-Alder mense structural complexreaction from time to SINCE 1928 A favorite of synthetic chemists everywhere, the Dielsity often without additional time. And who can forget Alder reaction readily creates structural complexity. reagents and sometimes the endiandric acids from solvent-free. Straightforthe pericyclic chemistry ward enough for an underunit in their graduate graduate organic chemistry organic chemistry class? class, yet intricate enough The unsaturated acid to spend several days in a with seven double bonds graduate organic chemisis a naturally occurring try class reading into the polyene. Once formed, engrossing story that is the the molecule spontaneDiels-Alder reaction. It is ously undertakes three by far my favorite reaction. separate pericyclic reacFirst reported in 1928 by tions to form an incredOtto Diels and his graduible amount of molecular ate student Kurt Alder, the complexity as a single pair chemists at once saw the of enantiomers. Initial 8π importance of their work conrotatory electrocycliand wanted the exclusive rights to utilize trone showcases a beautiful example of an zation yields a cyclooctatriene. A 6π distheir reaction. They write in their 1928 paintramolecular Diels-Alder reaction. Under rotatory electrocyclization forms a fused per: “The possibility of synthesis of complex thermal conditions, the benzocyclobutene bicycle. Depending on which diastereomer compounds related to or identical with undergoes a 4π electrocyclic ring opening is formed in this electrocyclization, the natural products such as terpenes, sesquito give an intermediate o-quinodimethbicycle is in perfect orientation to perform terpenes, perhaps even alkaloids, has been ane—a perfectly situated and highly reacone of two Diels-Alder reactions to form eimoved to the near prospect. ... We explicitly ther endiandric acid B or endiandric acid C. reserve for ourselves the application of the All this occurs nonenzymatically in nature. reaction developed by us to the solution of ADAM AZMAN teaches Where would we be without the Dielssuch problems” (Liebigs Ann. Chem., DOI: undergraduates Alder reaction? Two σ bonds, a ring, and 10.1002/jlac.19284600106). Fortunately for organic chemistry at up to four new contiguous stereocenters us, this exclusivity no longer applies. Butler University in prepared in one elegant reaction. Through Stripped of all its layers of complexity, at Indianapolis. He enjoys judicious choice of starting materials, an its core, the Diels-Alder reaction is a reacreading, chocolate, and enormous amount of molecular complexity tion of a conjugated diene (4 π electrons, playing with his foster can be formed. My students always laugh in the s-cis conformation) and an alkene kittehs. Read more of his at me for having a favorite reaction. I don’t (2 π electrons, called the dienophile) to writings under his alias care. The Diels-Alder reaction will always be form a cyclohexene ring—the reaction is azmanam at chemistry-blog.com. my favorite. ADAM AZMAN
A FEW OF OUR FAVORITE CHEMICAL REACTIONS
WWW.CEN-ONLINE.ORG
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gen is a wonderfully tolerant and producinfluence that a few elementary facts of My favorite reaction is so elementary tive one, and we have gained enormously physics and chemistry can have on our that it will occupy barely a tenth of the from this union. fate. The one property of carbon dioxide space on a napkin or T-shirt. And it’s a reacThe right side of the combustion equathat causes us so much agony is the fact tion so important that it both sustains life tion is where our troubles begin. First off, that it’s opaque to long-wavelength infraand has the potential to end it. water. It may seem like a trivial, harmless red radiation and absorbs it, thus warming By now you might have guessed it. It’s by-product of the reaction, but it’s prethe surroundings. The issue has divided the humble combination of hydrocarcisely its benign nature that allows us to the world like no other, and we still haven’t bons with oxygen, known to all of us as use combustion so widely. Just imagine if grasped its full consequences. But whatcombustion. the combustion of carbon had produced ever they are, they will profoundly alter the Combustion is, in one line, a statement SURPRISINGLY SIMPLE Combustion sustains life and may one day end it. about our world that packs at least as much information into itself as all of humanity’s accumulated wisdom and follies. While serving as the fundamental energy source for life and all the glory of evolution, combustion also drives wars, makes enemies out of friends, divides and builds ties between nations, some godforsaken toxic substance (in adlandscape of human civilization for better and will without a doubt be responsible for dition to carbon dioxide) as a by-product. or worse. the fate of human civilization. Making energy from combustion would None of this would have mattered if it Let’s look at the components of this then have turned into a woefully expenweren’t for the most important fact: Comubiquitous process. First, the hydrocarsive activity, with special facilities rebustion produces energy. Energy producbon itself. Humanity launched itself onto quired to sequester the poisonous waste. tion from the reaction is what drives life a momentous trajectory when it learned This would likely have radically altered and human greed. We stay alive by eating how to dig carbon out of the ground and the global production and distribution of carbon-rich compounds, which are then use it as fuel. Since then we have been energy, and human development would burned in a spectacularly controlled and biding our time for better or worse. The have been decidedly hampered. We may efficient manner to provide us with energy. laws of quantum mechanics could not then have been forced to pick alternative It is the all-important energy term in the have supplied us with a more appropriate sources of energy early on in our history, combustion equation that has made life on substance. Carbon in stable hydrocarbons and the face of politics, economics, and Earth possible. is in its most reduced state, which means technology would consequently have been The same term of course is responsible that you can get a bigger bang out of your very different. for our energy triumphs and problems. buck by oxidizing it compared with almost Moving on, we come to what’s almost Fossil-fuel-burning plants are nowhere as any other substance. What billions of conuniversally regarded as a villain these efficient in extracting energy from carbontrolled experiments over the years in oil days—carbon dioxide. If carbon dioxide rich hydrocarbons as our bodies, but and natural gas refineries and coal plants were harmless, we would live in a very what matters is whether they are cheap have proven is that you really can’t do different world. Sadly it’s not, and its enough. It’s primarily the cost of digging, better than carbon when it comes to balproperties again underscore the profound transporting, storing, and burning carbon ancing energy density against availability, that has dictated the calculus of energy. cost, ease of handling, and transportation Whatever the consequences of climate and safety. ASHUTOSH (ASH) change, one thing will never change: We The second component of the chemical JOGALEKAR is a will continue to pick the cheapest fuel. equation is oxygen. Carbon can burn under chemist involved in Considering its extraordinarily fortuitous a wide range of oxygen concentrations, building molecular properties, this cheapest fuel will likely rewhich is a blessing because it means that models of chemical main carbon for the foreseeable future. We we can safely burn it in a very controlled and biological systems. will simply have to find some way to work manner. Varying the amount of oxygen He is interested in the around, over, or through its abundance can also lead to different products and can history, philosophy, and and advantages to pave our way toward minimize the amount of soot and toxic bysociology of science and a sustainable, peaceful, and energy-rich products. The marriage of carbon and oxyblogs at wavefunction.fieldofscience.com. future. WWW.CEN-ONLINE.ORG
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ASHUTOSH JOGALEKAR
COMBUSTION
SCIENCE & TECHNOLOGY
In the lab, the best reactions are ones that are well behaved and predictable. These reactions give high yields and can often bring about transformation of simple molecules to molecules of incredible complexity. You would think that my favorite reaction would involve these qualities. But no, my favorite reaction takes large, complex molecules and breaks them down into much smaller pieces. My favorite reaction has a frighteningly low percent yield. What’s more, its major products can be detrimental. And, I don’t run this reaction in a lab. This reaction is best run in a kitchen. Methods: Temper a steak by taking it out of the fridge and letting it sit at room temperature for about half an hour. Heat up a pan containing a thin layer of oil on the stove top. When the oil in the pan is smoking, place the steak in the pan. Make a note of all the changes that are occurring. Hear the sizzle of the meat in the oil. See the meat, where it touches the pan, start to change colors from deep red to gray to brown. But, most important, smell the new aromas emanating from the pan. Are you hungry yet? I certainly am. A good sear can make a mediocre steak delightful. And a bad sear can render a good steak disappointing. A sear, in this case, doesn’t just give texture to your food. It creates new flavors. It creates new aromas. A good sear is the realization of an uncooked steak’s hidden potential. All of this is a product of the Maillard reaction. The Maillard reaction is the reaction between a nitrogen-containing molecule (particularly the amino acids lysine and proline, in the case of meats and grains, respectively) and a reducing sugar (glucose, for example). Louis-Camille Maillard was the first person to study this chemistry (in the early 1900s), which, fortunate for Maillard’s personal legacy, was much later found to be an important process in cooking. The set of reactions that takes place under the general description of the Maillard reaction can be generalized as follows. A sugar (1) combines with an amine to form an intermediate (2) that rearranges into a glycosylamine (3), which is unstable in these conditions. The glycosylamine rearranges into an aminoketose (5) through an aminoenol intermediate (4). The aminoketose is one of the main products of the Maillard reaction. But the tasty parts of the
KITCHEN CHEMISTRY Grilled meats. Crusty bread. Dark beer. The Maillard reaction gives our favorite foods their taste and aroma.
MATTHEW HARTINGS/AMERICAN U
MAILLARD REACTION
Maillard reaction come about when (4) is converted into a deoxyhexosulose (7) or the aminoketose rearranges into an enediol (6), which is further converted into a deoxyhexodiulose (8). Compounds 7 and 8 are the intermediates that ultimately lead to the small-molecule aroma, flavor, and color compounds that our senses recognize as the products of the Maillard reaction. Before (7) and (8) are made, the Maillard reaction does not yet yield any molecules that are beneficial for humans. Evolutionary arguments would thus suggest that humans should shy away from foods that have undergone the Maillard reaction. But personal observations tell us that this
MATTHEW HARTINGS,
an assistant professor of chemistry at American University, is trying to design artificial photosynthetic proteins that transform harmful greenhouse gases into useful chemicals. Hartings writes about science policy—and occasionally his passion for cooking—at sciencegeist.net. WWW.CEN-ONLINE.ORG
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is not the case. We recognize and hunger for the aroma/flavor/color molecules that the Maillard reaction produces in relatively low amounts. The simplistic argument is that we have developed the ability to sense these molecules in cooked food because cooking kills bacteria. And food with fewer bacteria is less likely to make us ill. A more developed and engaging set of arguments is laid out in Richard Wrangham’s book “Catching Fire: How Cooking Made Us Human.” Unfortunately, the health benefits are not so straightforward. Some of the molecules produced in the Maillard reaction are thought to be detrimental (acrylamide, for example). Certainly, in charred meat, the black, carbon-dense molecules on the surface of the meat are likely carcinogenic. These facts lead many to question the extent to which cooking increases the health benefits of our food. That is, we kill off harmful bacteria before we ingest them while hastening the onset of cancer as we age. How do we balance this information? I, for one, plan on refining my abilities in organic synthesis, trusting my analytical capabilities, and following where evolution has led me. Translation: I’m going to keep searing my steaks. ◾
