New Vistas in Reaction Kinetics

As a holdover from grad school, I still get a little pain in my stomach whenever someone mentions “kinetics studies.” I never had the displeasure of running one myself, but I’ve heard many stories of others’  painful nights camped out at the NMR, running hours-long kinetics runs on slow reactions. And really, not a whole lot has changed with respect to reaction kinetics over the years. Sampling rates have gotten larger, and the repertoire of analytical methods used to follow concentration(s) has grown, but the underlying theory of reaction kinetics has largely remained the same.

Historically, the development of reaction kinetics has been a story of increasing cleverness. At some point, someone figured out that using a reactant in “drowning” concentrations causes its concentration to remain basically constant over the course of the reaction, removing its influence on the reaction rate—and thus was born the “isolation method.” Yet another clever chemist figured out that only initial rates are necessary to determine kinetic orders, provided multiple runs of a reaction are feasible—and thus emerged the “method of initial rates.”

Why stop there? Increasingly complicated mechanisms (especially catalytic mechanisms) have created a demand for ever more clever methods of kinetic study. Plus, technological advancements are pushing the Δt between data points ever smaller and the sizes of data sets ever larger. Concentration versus time data are basically continuous these days (as are rate versus time data), so why not use the entire span of a kinetics run to the best of our ability? A recent article by Blackmond shows just how far this approach can take chemists studying reaction mechanisms. With data for just a couple of cleverly structured reaction runs, one can propose pretty good guesses for reaction mechanisms. Continue reading →

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Finding Teaching Skills in Unexpected Places

The other day as I was recording a video (on planes of symmetry and chirality) for my organic chemistry class, I realized that the video wasn’t really about what I thought it was about. While my lips were moving and I was scribbling on the screen, I was busy contemplating a new way to think about chirality, one that had never really crossed my mind before. It was a very interesting moment!

One reason I like recording videos is that it gives me that feeling of being on the hot seat, of playing to an audience surrounded by distractions and burdened with a limited attention span. An interesting structure, logical consistency, and “sticky” take-home ideas are all essential. In a face-to-face environment where a student can meet you halfway and instructor and student engage in dialogue, much of that pressure is off (though dialogue has a completely different set of challenges!). Good questioning and a warm demeanor can draw students into a dialogue, but great videos have to be fundamentally compelling in and of themselves.

While recording this video on chirality, I got thinking about the difficulties some students have in seeing that chiral molecules lack a plane of symmetry. I’ve seen students who gain great facility with identifying planes of symmetry in achiral molecules, but who don’t build enough confidence to assert that such-and-such chiral molecule has no planes of symmetry at all. I ended up having to pause the recording—how do organic chemists see a lack of a plane of symmetry in a chiral molecule? How do we see something that’s not there?

Brute force is one option: we could try reflection through every possible internal mirror plane and verify that none of them leave the appearance of the (chiral) molecule unchanged. Though a computer might be able to approximate this in some reasonable time frame, no human could hope to apply this approach with any success. What we need to really move forward with solving the problem is a set of candidate mirror planes that are the most likely to be planes of symmetry. Given an efficient method to generate a few candidate planes, we can try reflecting through them to come to a good educated guess about whether a molecule is chiral or not (“educated” in the sense that the guess is not rigorous but still correct something like 99% of the time).

Enter the idea of “corresponding structures,” identical portions of a molecule that must either stay put or exchange positions upon reflection through a plane of symmetry. In practice, we use corresponding structures to whittle down the list of candidate planes of symmetry: a huge range of possibilities is cut down to three or four at most. If one of them is a “hit” we call the molecule achiral right then and there; if not, we also know with great confidence that the molecule is chiral (never mind inversion centers).

If a student in conversation had asked me “how do you see something that isn’t there?”, I might have awkwardly fumbled my way to this idea. But recording a video gave me a chance to do it in an artificial environment, which was very cool. I wonder if anyone has studied the development of teaching skills during preparation of digital content?

Organic Chemistry Curriculum: A Step in the Right Direction

Alison Flynn’s latest in the Journal of Chemical Education is an instant classic. She describes a redesign of the organic chemistry curriculum at the University of Ottawa that tackles head on the issue of “curved arrows as decorations” that has been well documented by Cooper, Bhattacharyya, and others.

Her approach begins with four units on the basics of organic structure and physical properties, which is standard stuff. An entire unit on reaction mechanisms that precedes the first reaction covered comes next, and this is really the pièce de résistance of the design. Acid-base reactions come next (pretty standard), followed by nucleophilic additions to π electrophiles and electrophilic addition to π electrophiles, including reactions of alkenes and arenes. That’s organic 1. Note the complete absence of substitution and elimination—a huge plus in my opinion!

Organic 2 begins with eliminations and oxidations—love how these two are grouped together, as many oxidations are glorified eliminations. Next come activated π nucleophiles (enols and enolates), π electrophiles with a leaving group (e.g., acid chlorides), and π electrophiles with a “hidden” leaving group (e.g., imine formation). Seems a little odd to loop back to carbonyl chemistry at the end of organic 2 after hitting nucleophilic addition to carbonyls near the beginning of organic 1, but let’s not allow “we’ve always done it this way” to rationalize away the change. Continue reading →

Percent Yield, Movie Times, and the “Science Unseen”

It’s that time of year again: labs are gearing up. Drawers are being filled with new glassware, students donning lab coats are beginning to fill the halls…the ol’ machine is revving up to roll again. For me, this time of the semester means emphasizing good practices when working up data and results. I’ve written in past semesters about significant figures and some of the interesting issues that come up when teaching them—it’s about the mindset, not the rules, I swear…!

Take percent yield, a measure that has been reported with false precision by countless numbers of students across the generations. Percent yield is really interesting because the balance is one of the most precise instruments that exist in general chemistry laboratories—depending on the range and precision of the balance, measurements with five, six, and even seven significant figures are possible. Thus, it seems like percent yields (which are really just ratios of masses) should in turn have five, six, or seven significant digits. The measured mass of product points to this level of precision.

Students often struggle to understand that the precision of the balance is irrelevant—inevitable variations between runs of the reaction introduce massive uncertainty into yields. Such variations are gargantuan compared to imprecision in balance measurements and essentially render the precision of the balance meaningless. Continue reading →

Yin and Yang: Electrophilic and Nucleophilic Reactions

In my opinion, the most awkwardly named reaction in all of chemistry is electrophilic aromatic substitution (and all of its three-worded cousins). This name suffers from the same problem as other named reactions: it is deceptively uninformative. I still recall raising an eyebrow in undergrad when I found out that the aromatic involved in this reaction is not the electrophile—the other reagents combine to generate the electrophile. The aromatic is the nucleophile. “Why the heck is the word ‘electrophilic’ stuffed before ‘aromatic’ in the name, then?!” When you really get down to it, the name doesn’t tell you much and has the potential to feed a novice a lot of incorrect information:

“So the reaction mixture is electrophilic, then?”
“Well no, the reaction involves a nucleophile and an electrophile, just like all polar organic reactions…”

“So the aromatic is electrophilic?”
“No, the aromatic is the nucleophile in these reactions.”
“But the name says electrophilic aromatic…!”
[Professor places face in palms]

Only once the student has seen copious examples of other electrophilic substitutions does s/he realize that the adjective refers to the conditions surrounding the substrate, not the substrate itself. The naming convention makes sense to a synthetic chemist interested in “decorating” a given substrate: the substrate is what it is, and we treat it with electrophilic or nucleophilic conditions to add groups to it. The names of substitution reactions clarify the reactivity of whatever’s coming into contact with the substrate (the reagents). To a student without a synthetic frame of mind though, without an inkling of the primacy of the substrate or even its identity, I don’t think this naming convention comes naturally. Continue reading →

Chain Mechanisms and Catalysis: What’s the Difference?

In a recent authoring project on organic chemistry, I came across the following statement:

A chain mechanism involves two or more repeating steps.

Is this a true statement? Well, yes and no. Yes, a chain mechanism involves the same process happening again and again. But so does a catalytic mechanism—are both mechanisms the same? If they were, we’d just call all chain mechanisms catalytic (it sounds much better, right?). In fact, the two are not the same, and there’s far more to the definition of a chain mechanism than two repeating steps.

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Naively, chain initiators (let’s use radical initiators for the present discussion) look a lot like catalysts. They’re around in substoichiometric amounts and they promote the combination of reactants that would otherwise sit dormant. Clearly then, they decrease the activation energy of the reaction relative to a situation without initiator. However, radical initiators are missing a key feature of catalysts: they are consumed by the reaction. They’re about as close as one can get to a catalyst without being a catalyst!  Continue reading →

Lone Electron Pairs: Beyond the Rabbit Ears

In chemistry, quantum mechanics and orbital theory often rub up uncomfortably against more naïve bonding theories, such as VSEPR and Lewis structures. For example, VSEPR tends to give the impression that the positions of lone pairs (or better yet, the orientations of filled non-bonding orbitals) are dictated by the number of electronic domains around the atom. Water, then, which has four electronic domains around oxygen—two single bonds and two lone pairs—apparently has lone pairs at 109.5º angles in a plane perpendicular to the H–O–H plane. The carbonyl oxygen, which VSEPR suggests is “really” trigonal, has two “rabbit-ear” lone pairs at 120º angles. These pictures make the lone pairs look equivalent, and helps us slot these structures in mentally with analogous structures, like imines (for the carbonyl) and ammonia (for water).

MO theory suggests that the lone pairs shown are not equivalent.

MO theory suggests that the lone pairs shown are not equivalent.

Yet, MO theory suggests that the lone pairs shown are not in equivalent orbitals! The simplest explanation for water is that the atomic 2p orbital on oxygen perpendicular to the H–O–H plane cannot interact with the 1s orbitals on hydrogen (there’s zero net overlap), so one of the 2p orbitals on oxygen must show up as a non-bonding molecular orbital. But this orbital can only hold two electrons, so the other lone-pair-bearing orbital on oxygen must be a hybrid. In a nutshell, one lone pair is best characterized as a π MO (the pure 2p orbital) while the other is a σ MO. The two lone pairs are not equivalent. As it turns out, this situation holds up even for lone-pair-bearing atoms in larger molecules. The inequivalency holds for both canonical and natural bond orbitals (NBOs), but the paper that inspired this post focuses on the usefulness of NBOs in the correct description. Continue reading →