Hydrogen Bonding in Crystal Structures of N,N‘-Bis(3-pyridyl)urea. Why Is the N−H···O Tape Synthon Absent in Diaryl Ureas with Electron-Withdrawing Groups?

The urea tape α-network of bifurcated N−H···O hydrogen bonds is a common motif in diaryl ureas and their molecular complexes. We analyzed the X-ray crystal structures of N,N‘-bis(3-pyridyl)urea 3 and some of its derivatives:  hydrates of stoichiometry 3·(4/3)H₂O and 3·2H₂O, cocrystals 3·SA and 3·FA·H₂O with succinic acid and fumaric acid, bis pyridine N-oxide 8, and bis N-methylpyridinium iodide 9. Crystal packing in pyridyl urea structures is directed by N−H···N_pyridyl, N−H···O_water, N−H···O_acid, and N−H···I^- hydrogen bonds instead of the common one-dimensional N−H···O_urea tape. We postulated that the urea tape is absent in these structures because the CO acceptor is weakened by two intramolecular C−H···O_urea interactions (synthon III) in a planar molecular conformation. Electrostatic surface potential (ESP) charges (DFT-B3LYP/6-31G*) showed that the C−H···O interactions sufficiently reduce the electron density at the urea O, and so other electronegative atoms, such as pyridyl N, H₂O, COOH, and I^-, become viable hydrogen-bond acceptors for the strong NH donors. ¹H NMR difference nOe confirmed that the planar conformation of dipyridyl urea 3 in the solid-state persists in solution. Interestingly, even though the strong hydrogen-bond motifs changed in structures of 3, the C−H···O interactions of synthon III (energy 4.6−5.0 kcal/mol) occurred throughout the family. In addition to dipyridyl urea, other electron-withdrawing diaryl ureas, e.g., those with phenylpyridyl and phenyl-nitrophenyl groups, also deviated from the prototype N−H···O tape because of the interference from weak C−H···O hydrogen bonds. Therefore, when one or both aryl rings have hydrogen-bond acceptor groups (e.g., pyridine, PhNO₂), the NH donor(s) preferentially bond to pyridyl N, nitro O, or solvent O atom instead of the urea CO acceptor. We classify supramolecular organization in diaryl ureas into those with the α-network (twisted molecular conformation) or non-urea tape structures (stable, planar conformation) depending on the substituent group. Our results suggest a model to steer urea crystal structures toward the tape synthon (Ph and electron-donating groups) or with non-urea hydrogen-bond motifs and a high probability for urea···solvent hydrogen bonding (electron-withdrawing groups) by appropriate selection of functional aryl and heterocyclic groups.