Synthon Polymorphism and π-πStacking in N-Phenyl-2-hydroxynicotinanilides

Yunping Zhoujin, Xing Yang, Mingtao Zhang, Ju Guo, Sean Parkin, Tonglei Li, Faquan Yu, Sihui Long

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12 Scopus citations


A lactam-lactam dimer (LLD) and lactam NH···O=C (amide) catemer (LAC) are two competing motifs in N-phenyl-2-hydroxynicotinanilides (PHNAs). Steric effects play an important role in determining the outcome of this competition, and in general, PHNAs with no or negligible steric hindrance take on a near-planar conformation and form LLDs, rather than the widely observed amide NH···O=C hydrogen-bond chains. Conversely, those with significant steric hindrance are forced to take on a twisted conformation and form a lactam NH···O=C (amide) hydrogen bond. Nevertheless, steric factors are not the only criteria, as an LLD and an LAC have been observed in the two polymorphs (1-I and 1-II) of 2-hydroxy-N-m-tolyl-nicotinamide (namely 2-oxo-1,2-dihydropyridine-3-carboxylic acid m-tolylamide, compound 1), although the molecules in both forms have a nearly identical conformation, in contrast to five other newly synthesized PHNAs (2-6), whose crystal structures are sustained on the LLD. Thus, synthon polymorphism is possible in conformationally planar PHNAs. Theoretical studies were performed to provide an explanation for this observation. The lattice energies of the two forms of 1 showed only an insignificant difference. A Hirshfeld analysis revealed that the loss of stability due to less hydrogen bonding in 1-II is compensated by the participation of π-πstacking. Other than the commonly observed LLD in the crystals, π-πstacking provides a significant stabilization for each crystal, with its particular effects being dependent on the substitution pattern of the compound. A noncovalent interaction (NCI) analysis further provided a visual demonstration of the important intermolecular interactions. Potentially the other planar compounds could behave in a similar manner.

Original languageEnglish
Pages (from-to)6155-6165
Number of pages11
JournalCrystal Growth and Design
Issue number11
StatePublished - Nov 3 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics


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