The crystal structures of five hemiadducts of paracetamol with 1,4-dioxane, N-methylmorpholine, morpholine, N,N-dimethylpiperazine and piperazine, and a related 1:1 adduct of paracetamol with 4,4’-bipyridine are described. All structures are characterised by the formation of chains of paracetamol molecules, linked either via OH…O=C interactions [C(9) chains in graph set notation] or NH..O=C interactions [C(4) chains], depending on the presence or absence of substituent groups on the guest molecule. In all cases except for the morpholine and bipyridine adduct these chains are connected by H-bond interactions with the guest molecules residing on crystallographic inversion centres. In the bipyridine adduct this linkage also involves a π-stacking interaction; in the morpholine adduct it is formed between the OH groups of two opposed paracetamol molecules. Most adducts (that with 4,4’-bipyridine is an exception) decompose on heating to give monoclinic paracetamol. This is the first systematic study of a series of co-crystals containing paracetamol. The crystal structures of eight new co-crystals of quinol with pyrazine, piperazine, morpholine, pyridine, piperidine, 4,4’-bipyridine, N-methylmorpholine and N,N’-dimethylpiperazine are also reported. Quinol forms 1:1 co-crystals with pyrazine, piperazine and N,N’-dimethylpiperazine, but 1:2 co-crystals with morpholine, 4,4’-bipyridine, N-methylmorpholine, pyridine and piperidine. This difference can be rationalised in most cases by the presence of respectively two or one strong H-bond acceptor(s) in the guest molecule. The exception to this generalisation is 4,4’-bipyridine, which forms a 1:2 co-crystal, possibly to optimise crystal packing. All structures are dominated by hydrogen bonding between quinol and the guest molecules. A doubly-bridging motif, which connects pairs of quinol and guest molecules via NH…O or CH…O interactions, is present in all but the sterically-hindered N,N’-dimethylpiperazine and N-methylmorpholine co-crystals. Existing methodologies for crystal structure prediction work tolerably well for small, rigid molecules, prediction tests often appear to fail to predict known polymorphs, even though many hundreds of energetically similar structures may be predicted instead. Many algorithms attempt to maximise density, it is possible that ‘failed’ prediction attempts have in fact yielded polymorphs which are stable at high pressure, but which have not yet been identified experimentally. Crystal structures of all isomers of monofluorophenol and monochlorophenol have been determined both at low temperature and high pressure. All except the 3-subsittued isomers show some degree of polymorphism with applied pressure. 2-chlorophenol, for example, forms H-bonded chains in the solid state; thee are disposed about crystallographic 3<sub>2</sub> screw axes at low temperature, but 2<sub>1</sub> axes at high pressure (0.12 GPa). Previous work on the packing characteristics of alcohols suggests that the chlorophenyl group in this case is behaving as a large group at low temperature, but a small group at high pressure.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660244 |
| Date | January 2004 |
| Creators | Oswald, Iain D. H. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15564 |
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