Convertional methods for the synthesis of biaryl compounds Involve
free radicals as intermediates and,in the case where unsymmetrLeal biaryls
are desired,give rise to mixtures of products. A more elegant,
and certainly more specific, approach would be to define the site oE
substitution on the aryl substrate by suitably positioned electron-withdrawing
substituents for attack by an aryl anion. Generation of the
latter by using aryl lithium compounds, and their use as partners in
coupling reactions with aryl halides formed the basis of this study.
As the literature on organolithium chemistry is highly controversial
and confusing, the present study initially involved a thorough investigation
of the reactions of aryl halides with various organolithium
reagents. It was found that the aryl halides could couple with themselves
after metal - halogen exchange to give rise to biaryl and t n a r y 1
products. The reaction explored most fully was that between 2,4,6-tnbromophenol
and methyl1ithium.
The effects of varying the nature of the substituents and their
position on the aromatic ring were also investigated. When the para
substituents on a series of brominated phenol derivatives were varied
through -F, -Cl, -Br, -H, am. -CH^, it was found that as the substituent
became more electron-withdrawing the yield of biaryl product trom the
reaction increased. In a parallel series of reactions, the hydioxyl
group of the substrate was replaced by -OCH^, -CHj, -H and -Br. Biaryl
products were then obtained only from those brominated aromatic compounds
containing substituents capable of metal - hydrogen exchange.
These results led to more specific reactions to clarify various
points of mechanism and to the proposal that the aryl lithium species
resulting from metal - halogen exchange may exist as dimers in solution.
Two types of dimers are postulated to occi one type which collapses
via an ionic pathway with elimination of lithium halide to form a biaryl
product, and a second type of dimer which yields a biaryl product via a
radical pathway with the concomitant and transient production of lithium
metal. Evidence for the existence of both pathways is presented.
Finally, applications of the results of this research were studied.
Several avenues to the syntheris of a cannabinol analogue related to the
constituents of Cannabis sativa were pursued but this target remained
elusive. Other unsymmetrical biaryl compounds were howevei prepared in
yields comparable to those quoted in the literature (usually by different
methods) and a successful instance of "ionic " steering ot an ionic
pathway for such a reaction was realized.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/18200 |
| Date | 07 August 2015 |
| Creators | Huddle, Penelope Ann |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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