Conformational Analysis with Both Experimental and Computational Data for Both Gaseous and Crystalline Phases:  Unexpected Interactions in N-Methyldichloroacetamide

Abstract

The structure of N-methyldichloroacetamide (MeNHCOCHCl 2 ) has been elucidated in the gaseous and solid states experimentally by gas electron diffraction and X-ray crystallography, and computationally with ab initio and plane-wave DFT methods. Although the main structural parameters generally agree well, the orientation of the CHCl 2 group relative to the carbonyl oxygen was found to be very different in the solid and gas phases. X-ray crystallography and solid-state plane-wave DFT methods indicate that the bond torsion angle φ(HCCO) is 180.0°, while ab initio and gas electron diffraction methods return φ(HCCO) as -13.1°a nd -31.8(22)°, respectively. Further investigation of this phenomenon was carried out by using various computational methods. The possibility of intermolecular H‚‚‚O and Cl‚‚‚O bonds, which would stabilize the solid-state structure, was investigated by both solid-state plane-wave DFT and single-point ab initio methods. Ab initio SCRF calculations were also employed to evaluate solvent effects on the structure, using the Onsager reaction field model.

The conformation of chloramphenicol in the ordered and disordered phases

“…2d) [11]. Both structures have received similar attention in the literature, and none has been discarded yet [17,18,19,20,21,22]. c a b…”

“…The occurrence of other split bands in this spectrum suggests the presence of different conformers over Fermi resonance as the origin of the splitting. Carbonyl groups containing electronegative atoms in the alpha carbon (the two Cl atoms in the case of CHL) are known to show conformational sensitivity [58,18].…”

“…According to Chatterjee, the primary hydroxyl group acts as hydrogen bond donor and the secondary one as acceptor, but according to Acharya the opposite holds. Both structures are considered in the current literature [17,18,19,20,21,22]. Dilute solution studies of free CHL molecules also show conflicting results.…”

Molecular Conformation of Crystalline and Amorphous Chloramphenicol

“…Bustard [10] concluded using NMR spectroscopy that ϕ4 adopts the anti conformation. In addition, ϕ5 is known to adopt both the anti and syn conformations in condensed phases (though it prefers exclusively the syn conformation in vacuum) [22]. Hence, ϕ1 = 90º, ϕ4 = 180º and ϕ5 = 0º & 180º have been assumed here.…”

“…Hence, there is a very good agreement between the computed results and the experimental spectrum in the Amide I region. The conformational sensitivity of the C=O group can be attributed to the presence of electronegative (chlorine) atoms in the alpha carbon relative to the C=O group [25,22,26,27].…”