Structural systematics of halogenated benzamides
Hehir, Niall (2017) Structural systematics of halogenated benzamides. PhD thesis, Dublin City University.
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This PhD Thesis, entitled "Structural Systematics of Halogenated Benzamides", describes the synthesis, characterisation and analysis of a series of 3×3 isomer grids.
A range of bromo- and iodo- substituted compounds based on both the benzamide and carboxamide backbones were synthesised and fully characterised by 1H NMR, ATR-IR and X-ray crystallography. The goal of this work was to explore the effect of different functional groups and their position on small drug-like molecules and analyse the trends noted in the compounds, including the formation of an imide moiety, following placement of the pyridine nitrogen and bromine moiety in close proximity in the ortho- position.
Further work was carried out on the benzamide backbone, with two isomer grids synthesised in which the positions of both a difluoro- and methyl moiety were varied and trends in 1H NMR, 19F NMR and solid state structure were analysed and rationalised. This data allowed us to observe how the addition and position of various functional groups drive or inhibit the formation of mixed amide/imide (foldamer) structures.
A number of modifications to the benzamide backbone were carried out, with a carbamate based alternative being the primary backbone investigated. The reactions, combined with the previous data gathered from the isomer grid analysis, allowed us to rationalise an approach using the most suitable compounds from our earlier work to synthesise larger conformationally constrained foldamers. Using this information, compounds with a mixed imide/amide backbone were synthesised and a number of interesting variations on the basic 2:1 fluoroaminopyridine: pyridinedicarbonyl structural motif found in the earlier isomer grids, were found. Compounds containing 3:2 and 4:3 ratios were synthesised and characterised fully.
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