Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

Abstract

,-Dialkyland -alkyl--aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various -substituted cyclic imides, lactams, and acetamides were reported, no indepth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three ,-diethyl-substituted compounds-3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide-in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

Racemic and enantiopure forms of 3‐ethyl‐3‐phenylpyrrolidin‐2‐one adopt very different crystal structures

“…Rac-EPP forms centrosymmetric dimers where the molecules are connected by N-H⋅⋅⋅O hydrogen bonds, thus forming eight-membered rings (Figure 4, Table 3). These dimers are similar to those formed by achiral 3,3-diethylpyrrolidin-2-one, 20,21 by unsubstituted pyrrolidin-2-one at 173 K, 22 and by unsubstituted hexahydro-2H-azepin-2-one. 23 This is quite different from the one-dimensional zigzag chains with syn orientation of the phenyl rings relative to the lactam ring plane observed by Michon et al 24 The hydrogen bond parameters (Table 3) in rac-EPP are very similar to those we previously observed in achiral 3,3-diethylpyrrolidin-2-one.…”

“…The hydrogen bond parameters (Table 3) in rac-EPP are very similar to those we previously observed in achiral 3,3-diethylpyrrolidin-2-one. 21 In enantiopure forms of EPP, the H-bond angle is substantially (by about 18 degrees) smaller than in the racemic form, resulting in a shorter donor-acceptor distance.…”

“…23 This is quite different from the one-dimensional zigzag chains with syn orientation of the phenyl rings relative to the lactam ring plane observed by Michon et al 24 The hydrogen bond parameters (Table 3) in rac-EPP are very similar to those we previously observed in achiral 3,3-diethylpyrrolidin-2-one. 21 In enantiopure forms of EPP, the H-bond angle is substantially (by about 18 degrees) smaller than in the racemic form, resulting in a shorter donor-acceptor distance.…”

“…Solid-state IR spectra of rac-EPP and (+)-(R)-EPP are shown in Figure 6; since the IR spectrum of (−)-(S)-EPP is identical to that of (+)-(R)-EPP, the former was omitted H-bond parameters of an achiral lactam, 3,3-diethylpyrrolidin-2-one, 21 are given for comparison.…”

Insight into polymorphism of the ethosuximide (ETX)

“…In the literature, one can find publications on its bioactivity studies [6,7], while there is less information about ETX polymorphism and physicochemical properties. Most of physicochemical parameters were obtained at room temperature [8][9][10]. In this paper, results of differential scanning calorimetry (DSC), polarizing microscope observation (POM) and TOA thermooptical analysis are presented.…”