A Peptoid-like Approach Led to Lactam-Lactam Dimer Formation in 2-Hydroxy-N-alkyl-N-phenyl-nicotinamides and Their Polymorphism and Solvatomorphism

Wanru Gao, Yuping Li, Yunping Zhoujin, Qun Zeng, Liwen Fang, Sean Parkin, Tonglei Li, Shigang Ruan, Sihui Long

Research output: Contribution to journalArticlepeer-review

Abstract

Four 2-hydroxy-N-alkyl-N-phenyl-nicotinamides (1-4) were synthesized, and their crystal structures were analyzed to investigate the effect of substitution on their crystal packing of N-phenyl-2-hydroxynicotinanilides. In these compounds, substituents were introduced on the amide N, leading to a peptoid-like structure. One solvent-free form and two hydrates were harvested for compound 1, and one anhydrous form and one hydrate were obtained for compound 2. Polymorphism was observed in compounds 3 and 4. The molecules were found to be in the keto form rather than the enol tautomer. Because of steric effects, the molecules took on an E configuration, leading to a hairpin-like geometry. A lactam-lactam dimer synthon was formed in all solvent-free structures, and a tetramer motif was observed for the first time. Dehydration of the two hydrates of 1 and the hydrate of 2 led to their respective solvent-free form. Phase transition between the polymorphs was revealed in compound 3. Theoretical calculations, including conformational energy evaluation, hydrate forming propensity assessment, and lattice energy appraisal, were performed to provide a reasonable explanation for the keto tautomer and the formation of the hydrates of compound 1.

Original languageEnglish
Pages (from-to)45447-45456
Number of pages10
JournalACS Omega
Volume8
Issue number48
DOIs
StatePublished - Dec 5 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering

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