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Three Of Our Favorite Chemical Reactions

Bloggers pen essays celebrating their favorite chemical reactions

December 12, 2011 | A version of this story appeared in Volume 89, Issue 47


C &EN recently invited bloggers to write posts about their favorite chemical reactions. We received some two dozen posts from seasoned chemistry bloggers and fledgling writers alike, singing the praises of all kinds of reactions. Excerpts from a few of our favorites are reprinted with permission here. You can read them in full, along with all other entries, at


No reaction is more elegant, more heartwarmingly satisfying than the Diels-Alder reaction. No reaction is also more nuanced. It appears deceptively simple and yet has the ability to create immense structural complexity often without additional reagents and sometimes solvent-free. Straightforward enough for an undergraduate organic chemistry class, yet intricate enough to spend several days in a graduate organic chemistry class reading into the engrossing story that is the Diels-Alder reaction. It is by far my favorite reaction. 

SINCE 1928
Diels Alder reaction
Credit: Azman
A favorite of synthetic chemists everywhere, the Diels-Alder reaction readily creates structural complexity.

First reported in 1928 by Otto Diels and his graduate student Kurt Alder, the chemists at once saw the importance of their work and wanted the exclusive rights to utilize their reaction. They write in their 1928 paper: “The possibility of synthesis of complex compounds related to or identical with natural products such as terpenes, sesquiterpenes, perhaps even alkaloids, has been moved to the near prospect. ... We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems” (Liebigs Ann. Chem., DOI: 10.1002/jlac.19284600106). Fortunately for us, this exclusivity no longer applies. 

Stripped of all its layers of complexity, at its core, the Diels-Alder reaction is a reaction of a conjugated diene (4 π electrons, in the s-cis conformation) and an alkene (2 π electrons, called the dienophile) to form a cyclohexene ring—the reaction is classified as a [4 + 2] cycloaddition. This is the bare-bones Diels-Alder reaction we all remember from undergraduate organic chemistry classes. 

Peter Vollhardt’s 1980 synthesis of estrone showcases a beautiful example of an intramolecular Diels-Alder reaction. Under thermal conditions, the benzocyclobutene undergoes a 4π electrocyclic ring opening to give an intermediate o-quinodimethane—a perfectly situated and highly reactive diene. The pendant dienophile readily reacts with this diene to close the last two rings of the cholesterol framework. 

Adam Azman headshot
Credit: Courtesy of Adam Azman
ADAM AZMAN teaches undergraduates organic chemistry at Butler University in Indianapolis. He enjoys reading, chocolate, and playing with his foster kittehs. Read more of his writings under his alias azmanam at

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 ring exists in the product, yet Corey had the vision to see that carbon atoms 6–11 (prostaglandin numbering) could form the six carbon atoms of the cyclohexene Diels-Alder product. Diels-Alder reaction of the cyclopentadiene derivative and a ketene equivalent yielded a bridged bicyclic 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 the fused lactone that we now call the Corey lactone, in homage to the organic chemistry giant. 

The Diels-Alder reaction is not merely restricted to the synthetic lab; nature also enjoys a good Diels-Alder reaction from time to time. And who can forget the endiandric acids from the pericyclic chemistry unit in their graduate organic chemistry class? The unsaturated acid with seven double bonds is a naturally occurring polyene. Once formed, the molecule spontaneously undertakes three separate pericyclic reactions to form an incredible amount of molecular complexity as a single pair of enantiomers. Initial 8π conrotatory electrocyclization yields a cyclooctatriene. A 6π disrotatory electrocyclization forms a fused bicycle. Depending on which diastereomer is formed in this electrocyclization, the bicycle is in perfect orientation to perform one of two Diels-Alder reactions to form either endiandric acid B or endiandric acid C. All this occurs nonenzymatically in nature. 

Where would we be without the DielsAlder reaction? Two σ bonds, a ring, and up to four new contiguous stereocenters prepared in one elegant reaction. Through judicious choice of starting materials, an enormous amount of molecular complexity can be formed. My students always laugh at me for having a favorite reaction. I don’t care. The Diels-Alder reaction will always be my favorite.


My favorite reaction is so elementary that it will occupy barely a tenth of the space on a napkin or T-shirt. And it’s a reaction so important that it both sustains life and has the potential to end it.

This simple reaction sustains life and may one day end it. Combustion reaction drawn by Ashutosh Jogalekar
Credit: Ashutosh Jogalekar
Combustion sustains life and may one day end it.

By now you might have guessed it. It’s the humble combination of hydrocarbons with oxygen, known to all of us as combustion.

Combustion is, in one line, a statement 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, and will without a doubt be responsible for the fate of human civilization

Let’s look at the components of this ubiquitous process. First, the hydrocarbon itself. Humanity launched itself onto a momentous trajectory when it learned how to dig carbon out of the ground and use it as fuel. Since then we have been biding our time for better or worse. The laws of quantum mechanics could not have supplied us with a more appropriate substance. Carbon in stable hydrocarbons is in its most reduced state, which means that you can get a bigger bang out of your buck by oxidizing it compared with almost any other substance. What billions of controlled experiments over the years in oil and natural gas refineries and coal plants have proven is that you really can’t do better than carbon when it comes to balancing energy density against availability, cost, ease of handling, and transportation and safety.

Ashutosh (Ash) Jogalekar head shot
Credit: Courtesy of Ashutosh Jogalekar
ASHUTOSH (ASH) JOGALEKAR is a chemist involved in building molecular models of chemical and biological systems. He is interested in the history, philosophy, and sociology of science and blogs at

The second component of the chemical equation is oxygen. Carbon can burn under a wide range of oxygen concentrations, which is a blessing because it means that we can safely burn it in a very controlled manner. Varying the amount of oxygen can also lead to different products and can minimize the amount of soot and toxic byproducts. The marriage of carbon and oxygen is a wonderfully tolerant and productive one, and we have gained enormously from this union. The right side of the combustion equation is where our troubles begin. First off, water. It may seem like a trivial, harmless by-product of the reaction, but it’s precisely its benign nature that allows us to use combustion so widely. Just imagine if the combustion of carbon had produced some godforsaken toxic substance (in addition to carbon dioxide) as a by-product. Making energy from combustion would then have turned into a woefully expensive activity, with special facilities required to sequester the poisonous waste. This would likely have radically altered the global production and distribution of energy, and human development would have been decidedly hampered. We may then have been forced to pick alternative sources of energy early on in our history, and the face of politics, economics, and technology would consequently have been very different.

Moving on, we come to what’s almost universally regarded as a villain these days—carbon dioxide. If carbon dioxide were harmless, we would live in a very different world. Sadly it’s not, and its properties again underscore the profound influence that a few elementary facts of physics and chemistry can have on our fate. The one property of carbon dioxide that causes us so much agony is the fact that it’s opaque to long-wavelength infrared radiation and absorbs it, thus warming the surroundings. The issue has divided the world like no other, and we still haven’t grasped its full consequences. But whatever they are, they will profoundly alter the landscape of human civilization for better or worse.

None of this would have mattered if it weren’t for the most important fact: Combustion produces energy. Energy production from the reaction is what drives life and human greed. We stay alive by eating carbon-rich compounds, which are then burned in a spectacularly controlled and efficient manner to provide us with energy. It is the all-important energy term in the combustion equation that has made life on Earth possible.

The same term of course is responsible for our energy triumphs and problems. Fossil-fuel-burning plants are nowhere as efficient in extracting energy from carbonrich hydrocarbons as our bodies, but what matters is whether they are cheap enough. It’s primarily the cost of digging, transporting, storing, and burning carbon that has dictated the calculus of energy. Whatever the consequences of climate change, one thing will never change: We will continue to pick the cheapest fuel. Considering its extraordinarily fortuitous properties, this cheapest fuel will likely remain carbon for the foreseeable future. We will simply have to find some way to work around, over, or through its abundance and advantages to pave our way toward a sustainable, peaceful, and energy-rich future.


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.

Grilled meats. Crusty bread. Dark beer. This reaction gives our favorite foods their taste and aroma.
Grilled meats. Crusty bread. Dark beer. The Maillard reaction gives our favorite foods their taste and aroma.

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.

Matthew Hartings, an assistant professor of chemistry at American University. Hartings writes about science policy—and occasionally his passion for cooking—at
Credit: Courtesy of Matthew Hartings
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

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 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 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.


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