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Web Date: March 22, 2007

Brute Force Breaks Bonds

Ultrasound directs ring-opening reactions in more than expected ways
Department: Science & Technology
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STRESSFUL Applying a stretching force (orange arrows) to the two isomers of benzocyclobutene pulls apart the substituents and induces a disrotatory (dis) ring opening in the cis isomer against its thermal preference for conrotatory opening. Applying a similar type of force to the trans isomer gives the same product but now as a result of conrotatory (con) opening. Purple spheres denote methoxy groups; black arrows indicate the direction of orbital rotation.
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STRESSFUL Applying a stretching force (orange arrows) to the two isomers of benzocyclobutene pulls apart the substituents and induces a disrotatory (dis) ring opening in the cis isomer against its thermal preference for conrotatory opening. Applying a similar type of force to the trans isomer gives the same product but now as a result of conrotatory (con) opening. Purple spheres denote methoxy groups; black arrows indicate the direction of orbital rotation.

Chemists commonly use heat, light, pressure, or electricity to kick-start reactions. Taking a different tack, Jeffrey S. Moore, Charles R. Hickenboth, and colleagues at the University of Illinois, Urbana-Champaign, have used mechanical energy to trigger ring openings and, in the process, steer the reactions away from products predicted by orbital symmetry rules (Nature 2007, 446, 423).

In this case, the mechanical energy is provided by the collapse of cavitation bubbles that form in solution during exposure to ultrasound. Applying ultrasound to accelerate reactions is not new, but it has never caught on for organic synthesis because it has tended to generate a mix of products. Ultrasound has been used to fracture large molecules, such as polymers, in nonspecific locations and thus create a variety of carbon radicals.

The new work is precise, says Martin Beyer, a research chemist at Technical University of Berlin. "For the first time, the effect of ultrasound is unambiguously related to mechanochemical activation of a specific site." He adds that this advance shows the potential of mechanical force in organic synthesis, especially for natural products and medicinal chemistry, and that "it may very well be that nature uses mechanochemistry for enzymatic synthesis of complex compounds."

Directing force into small molecules is difficult. Therefore, the Illinois researchers linked mechanically sensitive 1,2-disubstituted benzocyclobutene isomers to two polyethylene glycol chains, applied ultrasound, and analyzed the bulk solutions by using 13C nuclear magnetic resonance spectroscopy. The spectra revealed that both the cis and trans isomers provide the same ring-opened product, the one expected from the trans isomer.

The Woodward-Hoffmann rules of orbital symmetry predict that for these ring-opening reactions each isomer of the reactant will form a different isomer of the product. So what makes this situation different?

Moore explains that thermal energy subjects reactants to random Brownian motion, whereas mechanical energy provides a direction to atomic motions. Therefore, forces from ultrasound efficiently direct the energy by straining the molecule, and thus reshaping the potential energy surface, he says.

The claims are bold, but they bear out, according to a Nature commentary by chemistry professor Virgil Percec and graduate student Brad M. Rosen at the University of Pennsylvania. "Although chemists might not immediately rush to adopt this technique, the work is a remarkable first step in using mechanical stress to break bonds in a synthetically useful organic reaction," they write.

Because the molecular rearrangement occurs before the polymer chain breaks, Moore notes the possibility and benefits of incorporating mechanically sensitive compounds into materials like climbing or parachute ropes. The researchers hope to link the mechanical component to a visual indicator so, for example, the stress in a rope could be assessed before one uses the rope to rappel down a mountain.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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