Substituent and Solvent Effects on Intermolecular Interactions in Crystals of N-Acylhydrazone Derivatives: Single-Crystal X-ray, Solid-State NMR, and Computational Studies

Abstract

New crystalline forms of hydrated and anhydrous N-acylhydrazones are reported. The studied crystal structures were determined by single-crystal X-ray diffraction at 90 or 100 K. Transferred aspherical atom model (TAAM) structure refinements were performed with the aid of the most recent version of the University at Buffalo Databank (UBDB). The resulting crystal structures were analyzed in terms of molecular conformations, intermolecular interaction energies, and crystal packing motifs. For this purpose, solid-state NMR studies and theoretical calculations were conducted supplementarily. It was found that all studied hydrazones adopt the E configuration around the azine N–N bond and imino NC function in the solid state, whereas the hydrazide N–N–CO moiety exhibits the E and Z arrangement in the N-acyl and N-aroyl derivatives, respectively. The constrained energy scans confirmed the E conformation of the hydrazide unit and the E arrangement of pyridine and hydrazone N atoms as the most stable ones. The association modes in the studied crystals are dominated by strong hydrogen bonds of the N–H···O or N–H···N-type involving the amide group as a proton donor. Consequently, as indicated by lattice energy calculations, a significant increase in the crystal cohesive energy per asymmetric unit is observed when water molecules are incorporated into the crystal structure, because this enables efficient saturation of the hydrogen bond acceptor and donor atoms. On the other hand, a substantial contribution of π···π stacking interactions to the overall stabilization of the crystal nets was also found. Thus, when more bulky phenyl substituents are introduced, the cohesive energy becomes more favorable.

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety

“…It is well-known that N -acyl- and N -aroylhydrazones may exist as geometric isomers E / Z with respect to the C=N double bond and cis / trans amide conformers due to rotation of the amide HN–C(O) single bond ( Figure 2 ) [ 39 , 40 ]. Literature reports for N -acyl- and N -aroylhydrazones derived from aryl- and heteroaryl aldehydes indicate that these compounds may exist both in DMSO- d 6 solution [ 39 , 40 , 41 , 42 ] and solid phase [ 43 , 44 , 45 , 46 ] in the form of E -geometrical isomers. Other studies revealed the presence of the mixtures of two forms: cis and trans amide conformers of N -acyl- [ 39 , 40 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ] and N -aroylhydrazones [ 52 , 53 ] in solution.…”

Experimental and computational evidence for stabilising parallel, offset π[C(O)N(H)NC]⋯π(phenyl) interactions in acetohydrazide derivatives

“…HC(O)N(H)NCH(2-pyridyl) (5.06 kJ mol −1 ) and PhC(O) N(H)NCH(2-pyridyl) (15.28 kJ mol −1 ), by relatively little energy. 73 The absence, or very low proportions, of forms involving the Z-conformer about the imine CN bond is a consequence of steric hindrance. The NMR study conducted on 1 follows these general findings.…”

Crystal Structures of Tiotropium Bromide and Its Monohydrate in View of Combined Solid-state Nuclear Magnetic Resonance and Gauge-Including Projector-Augmented Wave Studies

“…Such methodology has been successfully applied by us several times recently. 8,32,33 In the present case, to create the input files for CASTEP calculations, we took advantage of the deposited crystal structures of TIOA (GUYGOX03) and TIOH (GUYGUD01). The obtained GIPAW results, collected in Tables 2 and 3, have then been used to simulate the 13 C NMR stick spectra, presented in Figures 2 and 3.…”