Synthon Polymorphism and π–π Stacking inN-Phenyl-2-hydroxynicotinanilides

Abstract

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−π stacking. Other than the commonly observed LLD in the crystals, π−π stacking 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.

Polymorphic solvates, ionic cocrystals and C–N bond formation to form ionic cocrystals in sulfamethoxazole and sulfathiazole-derived urea

“…A recent study suggested the role of the π-stacking contribution in generating independent types of synthons in each case, leading to synthon-polymorphs. 12 In the present case, it is the competition of the DMF molecule for the hydrogen bond with the urea moiety and the ability to adopt hydrogen-bonded dimer that were the key factors. The difference between the types of assemblies was that in one case, it had a sulfonamide⋯5-methyl-1,2-oxazole and urea⋯DMF synthons and in the other cases, urea⋯5-methyl-1,2-oxazole and DMF⋯amine synthons were present.…”

“…Synthon competition in certain two-component systems of such derivatives causes polymorphism. [12][13][14][15][16] Having several polymorphs of a compound presents diverse new properties, but sometimes this is disadvantageous. For example, special techniques are required to enhance the selectivity of a form 17 when there is a possibility of concomitant polymorphs in conventional crystallisation.…”

Discovering crystal forms of the bio-based nylon 5O monomer 1,5-pentanediamine-O-phthalate: insight into the crystal structures, transformations and stability

“…† Although we did not get the single crystal structure of anhydrate-III, we think that its structure should be like that of anhydrate-I, which is filled with abundant π⋯π interactions, and both have high packing efficiency; thus, anhydrate-III exhibits a high melting point and extremely weak hygroscopicity. [81][82][83][84]…”

Inter- vs. Intra-Molecular Hydrogen Bond in Complexes of Nitrophthalic Acids with Pyridine

“…Besides, extensive studies of the influence of hydrogen bonding on the isomeric state of acylaminopyridines were performed by Ośmiałowski et al [ 21 , 22 , 23 , 24 , 25 , 26 ]. In addition, phthalic acids and lactams are interesting in terms of conformational changes [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. These compounds contain two carboxyl groups not coupled together and, therefore, the steric repulsion can induce significant conformational changes.…”