When you get down to it, most of the ways that we chemists have to make our reactions work are not very elegant. We can change solvents, mess with ligands, drip A into B slowly instead of B into A, etc. But we’re still depending on the molecules involved just running into each other. We set up our catalysts, nucleophiles, leaving groups, and all the rest of it so that as many of those collision events are as productive as we can manage, but in the end, it’s generally a bunch of stuff stirring around in solution, banging off the walls of the container and everything else in the flask. We can speed up reactions by heating them, of course, which just makes them bang around harder and faster, or (as is often the case) we just throw in more excess reactants and reagents, which increases the chance of the things we want to whack into each other at the expense of other (less productive) whacking. “Add more stuff” and “Heat it up” are without a doubt the two most common ways of getting reactions to produce more product, and crude tools they are.
It would be much nicer if we could somehow reach in there and selectively weaken the bonds that we’re wanting to break or make particular parts of a molecule vibrate more vigorously instead of just heating up the whole gemisch. That would be the domain of infrared spectroscopy – the bands and peaks in an IR spectrum, as chemists learn in undergraduate courses, do indeed represent specific stretching, bending, and wagging motions of particular bonds. It has occurred to many people over the years that this could (in theory) be a way to induce selective reactivity, but realizing that in practice is a lot harder than it sounds.
A big problem is that the stimulation provided by IR irradiation tends to get lost as heat (general molecular motion) pretty quickly. The energy gets transferred to the rest of the molecule within picoseconds, and out into the nearby molecules on a bit longer timescale, and in the end all you do is heat things up, which can be done far more easily by more primitive means. In recent years, the advent of extremely fast, bright pulses of light has brought this idea back, though, and here’s a new paper where they actually get things to work.
The reaction is a simple one – an alcohol (cyclohexanol) and phenyl isocyanate in tetrahydrofuran (THF) as solvent. That’s going to make a carbamate for you, and it’s not a hard reaction to run. But it makes a good test bed for this technique, because it’s slow until you start heating it, and if you can demonstrate an increase in product formation without an increase in temperature, you may have something going. The group (a multicenter team from Berlin, Cairo, and Rostock) studied the transition state of the reaction in detail (which required calculating the effect of the solvent as well), and tried exciting the O-H bond in one set of experiments and the isocyanate double bonds in another. The structure of the transition state suggested that the latter had a better chance than the former of affecting the rate, but they tried it both ways.
Nonetheless, hitting the sample with femtosecond IR pulses at the frequency of the O-H stretch accelerated the reaction rate by 24%. You can use the good ol’ Arrhenius equation to calculate that thermally this would need the sample to be heated up by about six degrees, and they observed no such heating. There’s still the question of what’s happening right in the path of the beam and right around the molecules themselves, but the group addressed this with extremely fast time-resolved spectra. It looks like the effects on the reacting bonds happen on too short a time scale for it to be strictly a heating effect – the new bond is forming before the vibrational energy should have a chance to transfer. (Note that the THF solvent itself does not absorb at the wavelength used; that would scramble things up pretty thoroughly). Even with this noticeable acceleration, though, the actual quantum yield was not very good – a lot of photons are being dumped into the reaction to get this to happen.
They also tried a different alcohol/isocyanate pair (chloral hydrate and toluene diisocyanate) with IR pulses directed at the isocyanate group as well as the alcohol (in separate experiments). They saw acceleration in both cases, but the quantum yield was better with the isocyanate excitation. A possible reason for that had shown up (as mentioned) in the transition state calculations. It looks like the isocyanate’s position starts off closer to where it needs to be in the actual reaction, whereas the alcohol doesn’t – only a small proportion of those molecules are in a conformation where they’re ready to reach the transition state and go on to product.
That, of course, is one of the reasons we brutal chemists heat things up as well – not only does that bang molecules together more vigorously, it causes each individual reactant to flop around more, which can increase the chances of it getting into a position where it can react. Alternatively, it can actually decrease those chances if it’s already in a good conformation at room temperature, but the increase in intermolecular whacking vigor generally makes up for that. In this case, though, you can apparently see the effects of ground-state conformation on reaction rate, because you’re not really heating things up. This sort of thing can be investigated by looking at a series of different related structures that have easier or harder times getting into position, which is classic physical organic chemistry, but in this case you can see the different populations of the same molecule.
I don’t necessarily see this as a technique that’s going to migrate to the organic chemistry lab bench, partly because of the expensive femtosecond pulse IR gear needed. (It could make a nice addition to the flow chemistry module of that automated system I was imagining yesterday, though!) But you can think of applications where the tight directional IR beam is used as a feature. The paper itself shows some photolithography, using the IR to write across a film of alcohol/isocyanate mixture and leaving a trail of urethane product, and if this effect can be generalized there are surely many other possibilities.
Postscript: it is difficult for me to talk about infrared vibrational modes without referring people to this.