Synthesis of new heterocycles by SNAr reactions of perfluoroarenes
thesisposted on 23.06.2016 by Shahzad Riaz
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The reactivity of perfluoroarenes and hetarenes towards SNAr reactions was studied as part of a synthetic programme to form an assembly of novel heterocyclic aromatic compounds for material and pharmaceutical applications. In chapter 1 the chemistry of perfluoroarenes is reviewed together with the use of conjugated compounds in organo-electronic applications. In chapter 2 the successful replacement of the remaining fluorine atoms in 6,12-difluorobenzo[1,2-b:4,5-b']bis[b]benzothiophene through SNAr reaction with long chain alkoxy and alkylthio nucleophiles is reported. An X-ray crystallographic investigation into their solid state packing was undertaken which would provide useful information for organoelectronic applications. Reactions with nitrogen and carbon based nucleophiles were also studied but met with little success. In chapter 3, alternative methods for the reductive cyclization of aryl and 2-bromoaryl perfluoroethers and sulfides to replace the currently used lithium-bromine exchange were explored, namely the use of radical cyclizations, palladium, magnesium, copper and Rieke metals. Some success was found using magnesium as a reagent although yields were low. Attempts to effect cyclisation reactions by ortho-lithiation and Ullmann coupling reaction with fluoroarenes is also reported. In chapter 4 attempts to generate alternative ring fusion in annulation reactions to form fused benzothiophenes by a dianion strategy are described. Development of methods to synthesise helicene or curved polycyclic structures from dibenzothiophene precursors is reported. In chapter 5 the synthesis of nitrogen containing fluorinated compounds with potential bioactivity is described. A series of novel amino substituted fluoroaromatics were successfully synthesised by adding different nitrogen based nucleophiles to pentafluoropyridine. Smiles rearrangement of a tetrafluoropyridyl sulphonamide was found to occur. A number of fluoropyridyl aniline derivatives were successfully synthesised some of which were submitted for biological screening. Substitution reactions of bis-nucleophiles bearing two heteroatom groups to form fused six membered rings were also studied. A Smiles rearrangement was identified in the reaction with an aminobenzenethiolate and confirmed by X-ray crystallography. Experimental procedures are given in chapter 6 as well as characterisation and crystallographic data of molecules synthesised during the research.