Benzyne

August 10, 2020
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Benzyne is a highly reactive organic molecule that has not been isolated. Its existence only can be inferred by the stable molecules it produces. Its instability is the result of its extremely strained triple bond.

One of the first demonstrations of the existence of benzyne was reported in 1940 by Georg Wittig1 and colleagues at the University of Freiburg (Germany). They combined fluorobenzene and phenyllithium at –78 ºC to produce o-fluorophenyllithium, which, when warmed to room temperature, eliminated lithium fluoride. The resulting high-energy cycloalkyne reacted with another phenyllithium molecule to form o-biphenyllithium.

In 1953, carbon-14 labeling experiments conducted by John D. Roberts2 and co-workers at MIT (Cambridge, MA) showed that the transitory triple bond in benzyne is electrically neutral—as opposed to the double-bond zwitterion that Wittig proposed. In one example, the reaction of [1-14C]chlorobenzene with ammonia gives equal amounts of [1-14C]aniline and [2-14C]aniline, establishing the equivalency of the adjacent carbon atoms.

For more on the history and utility of benzyne, see “The Chemistry of Benzyne” by Joseph F. Bunnett at Brown University (Providence, RI) and “The Benzyne Story” by Curt Wentrup at the University of Queensland (Brisbane, Australia).

1. Wittig won the 1979 Nobel Prize in Chemistry for developing the eponymous olefin synthesis in which an aldehyde or ketone is treated with an organohalide-derived triphenylphosphonium ylide.

2. Roberts, despite his pioneering work in physical and organic chemistry, including the development of nuclear magnetic resonance spectroscopy as an important analytical tool, never won the Nobel Prize. 

Benzyne fast facts

CAS Reg. No. 462-80-6
SciFinder
nomenclature
1,3-Cyclohexadien-5-yne
Empirical formula C6H4
Molar mass 76.10 g/mol

MOTW update

Thimerosal was the Molecule of the Week for August 8, 2011. It is a mercury-based topical antiseptic and antifungal agent that is sold under the trade name Merthiolate. It is also used as a vaccine preservative. Timerosal is claimed to be an inert ingredient in medications, but a recent study performed at the University of California, San Francisco, and the Novartis Institutes for BioMedical Research showed that it reaches blood levels in rats that may interact with biological targets. This finding doesn’t necessarily imply toxicity but it might be sufficient to prompt drug manufacturers to revisit vaccine formulations.

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