We’ve examined a number of highly reactive species, such as carbenes and nitrenes,
so let’s check out one more, arynes. Arynes utilize the same prefix as arenes, or aryl groups,
which refers to simple aromatic structures, as well as the suffix “yne”, because they are often
written as alkynes, with a triple bond. Let’s learn about this interesting functional group now.
Though we may be more familiar with Nobel-prize winning German chemist Georg Wittig from the
reagent and accompanying reaction that bears his name, he discovered some other interesting
chemistry as well. In 1940, Wittig was examining the following reaction, involving fluorobenzene
and phenyllithium. Phenyllithium is a very strong base, strong enough to get this alpha proton,
to produce the carbanion. This can be followed by beta-elimination of fluoride, which in the
presence of another equivalent of phenyllithium produces this biphenyl compound, with the
carbanion coordinated to lithium. What Wittig did was to describe the intermediate as benzyne,
meaning a benzene ring with a triple bond. Because alkynes are linear species, a true triple bond
is unable to form, given the torsional strain that would be generated by the benzene ring.
So the intermediate could also be represented by this zwitterion, or a diradical, but some triple
bond character is still present, and we will typically represent the intermediate that way.
The nature of this intermediate was confirmed by American chemist John Roberts in 1953. Interested
in demonstrating that this type of substitution went through a benzyne
intermediate rather than direct substitution, he did some experiments utilizing isotopic labeling.
Starting with chlorobenzene labeled with C-14 at the ipso position, meaning the carbon that bears
the chlorine atom, a substitution was carried out with sodamide. If substitution was direct,
we would expect only one product, but instead a mixture was produced, with 50%
of the resulting aniline labeled with C-14 at the ipso position, and 50% at the vicinal, or ortho
position. This demonstrates that there must be a symmetrical intermediate, and that is the benzyne.
So let’s first examine methods of producing arynes. We have already learned one,
where a halobenzene is treated with a strong, poorly nucleophilic base, resulting in carbanion
formation and subsequent beta-elimination. Another method involves a dihalobenzene,
which can be mono-metalated using something like n-butyllithium. Elimination can then occur just
as we’ve seen, in this case producing the lithium halide. For another method, we can start with this
compound called anthranilic acid, which can be treated with nitrous acid, and then diazotized
and decarboxylated to again produce benzyne. And lastly, a similar desilylative elimination can be
used, where a fluoride ion attacks silicon to generate an extremely strong silicon-fluorine
bond, which allows again for elimination, in this case of this triflate, a leaving group derivative.
As we can see, the commonality between these approaches is that a carbanion is somehow
produced adjacent to a leaving group, which is what allows for elimination to take place.
Now arynes like benzyne are far too reactive to be isolated, even at very low temperatures.
They are typically formed and then reacted in situ,
such as the case where the base that generates the carbanion is also the nucleophile that attacks
once benzyne has formed, as is seen here with the production of aniline from bromobenzene.
Now to get a little more interesting, let’s examine substituted benzynes.
In such a case, we will have two possible regioisomeric products. Let’s say that the
substituent is adjacent to the triple bond. If the substituent is electron-withdrawing,
the meta product will be strongly favored, because the intermediate negative charge
is better stabilized by the electron withdrawing group if it is adjacent. But if the substituent is
electron-donating, there is no strongly directing effect and we get a mixture of regioisomers.
If the substituent is one carbon farther removed from the triple bond,
this also diminishes the directing ability, and a mixture of products will be produced.
Finally, we should mention that in the absence of nucleophiles,
such as with the above examples, arynes tend to undergo cycloaddition reactions. For example, if
benzyne has nothing to react with, it will quickly dimerize to produce the following structure.
In addition, benzyne is also quite useful as a dienophile in a Diels-Alder reaction, due to the
strain in its structure. Here it is reacting with this activated diene to produce this compound,
which has a number of synthetic applications. And that’s a bit of information on arynes.