The formation of paracetamol (acetaminophen) adducts with hydrogen-bond acceptors

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 characterized by the formation of chains of paracetamol molecules, which are linked via either OHtriplebondO=C interactions [C(9) chains in graph-set notation] or NHtriplebondO=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 adducts these chains are connected by hydrogen-bond interactions with the guest molecules, which reside on crystallographic inversion centres. In the bipyridine adduct this linkage also involves a pi-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.