Hydrogen Bonding and Dynamic Behaviour in Crystals and Polymorphs of Dicarboxylic–Diamine Adducts: A Comparison between NMR Parameters and X‐ray Diffraction Studies

Abstract

Fumaric, malonic, maleic, and hydromuconic (HOOCCH2(CH)2CH2COOH) acids were used to prepare a series of hydrogen-bonded adducts or salts, depending on whether acid-base proton transfer takes place, with the dibase [N(muCH2CH2)3N] in various stoichiometric ratios. The resulting compounds have been investigated by using the 1H MAS, 15N, and 13C cross polarisation magic-angle spinning (CPMAS) methods and discussed in relation to X-ray diffraction studies to ascertain the nature of the O-HO, NH-O, and N+-HO- hydrogen bonds between the various species. In addition, two polymorphic forms of the malonic compound and a hydrate in the maleic case were examined. We also present the correlations between the chemical shifts of the hydrogen-bonded protons and those from the proton transfer reaction (acid-to-base) with the heavy atom distances. The dynamic behaviour in the solid-state of the [N(muCH2CH2)3N] adducts with fumaric 2:1, maleic 1:1 hydrate, and hydromuconic acids, and a malonate 2:1 polymorph adduct have been investigated by using variable-temperature 1H spin-lattice relaxation times. A substantial agreement between the activation energies obtained from fitting the T1 data and the results of potential energy barrier calculations demonstrates that the facile reorientation of the [N(muCH2CH2)3N] molecule occurs in several of the adducts.

Three Polymorphic Forms of the Co‐Crystal 4,4′‐Bipyridine/Pimelic Acid and their Structural, Thermal, and Spectroscopic Characterization

“…This is in agreement with the co‐crystal nature of the adducts observed by single‐crystal X‐ray diffraction and confirmed by 15 N CPMAS spectra. Several 15 N NMR studies on hydrogen‐bonded systems have shown that formation of hydrogen bonds results in high‐ or low‐frequency shifts of the nitrogen signal, according to the type of nitrogen atom and the nature of the interaction 13c. 15d–f In our case, the free bipyridine nitrogen signal falls at δ =288.2 ppm, whereas in the three co‐crystal forms it falls around δ =262 ppm.…”

Structure and physicochemical characterization of a naproxen–picolinamide cocrystal

“…It is likely that the chemical shifts of some of the protons are affected by intermolecular ring-current effects due to the edge-to-face herringbone structure of NPX-PA, which is similar to that of pure NPX (Carignani et al, 2013). Whilst the broad linewidths of 1 H SS-NMR can hinder the ability of SS-NMR to distinguish between protons in hydrogen bonds of the same type, there are many cocrystals/salts for which it is possible (Vogt et al, 2009;Gobetto et al, 2005;Sardo et al, 2015;Harris et al, 2010), including this case of NPX-PA. Not all 1 H peaks could be assigned, but the peaks of the two protons involved in the synthon E dimers, i.e. H31 and H361, can be distinguished.…”

“…Solid-state NMR (SS-NMR) is sensitive to the local structure, and NMR crystallography studies have been employed extensively to characterize hydrogen bonding in a variety of cocrystals (Harris et al, 2009;Stevens et al, 2014;Vogt et al, 2009;Gobetto et al, 2005;Chierotti & Gobetto, 2013;Brown, 2012), including cocrystals of NPX. For example, 2NPX-NA was investigated by two-dimensional (2D) 1 H-13 C heteronuclear correlation (HETCOR) experiments that confirmed the hydrogen-bonding network was a relatively rare example of a single carboxyl group giving rise to two different intermolecular synthons in the same cocrystal, probably due to the 2:1 stoichiometry (Ando et al, 2012).…”

Proton transfer and hydrogen bonding in the organic solid state: a combined XRD/XPS/ssNMR study of 17 organic acid–base complexes

“…26,27 Over the last decade, solid-state NMR (ssNMR) methods combined with computational chemical shift analysis 5,28,29 have been added to the inventory of techniques for the characterisation of hydrogen bonding and Brønsted interactions in the organic solid state. Studies have shown that H-bonding and proton transfer in two-component systems can be distinguished using 15 N ssNMR, 5,21,[29][30][31][32] as for example shown for co-crystals and salts of a cancer-treatment API 5 and for theophylline (1,3-dimethyl-7H-purine-2,6-dione) systems. 21,28,30 Density functional theory (DFT) can be applied to correlate 15 N ssNMR parameters with crystal structures.…”