Conformational Landscape and Polymorphism in 5-Acetic Acid Hydantoin

Abstract

The conformational space of 5-acetic acid hydantoin {5AAH; [2-(2,5dioxoimidazolidin-4-yl)acetic acid]} was investigated by quantum chemical calculations performed at the DFT(B3LYP)/6-311++G(d,p) level of theory. A total of 13 conformers were located in the potential energy surface of the molecule, 6 of them bearing the carboxylic group in the cis arrangement (O=C-O-H dihedral equal to ~0º) and the other 7 possessing this group in the trans configuration (O=C-O-H dihedral equal to ~180º). The most stable conformer (cis-I) was trapped from the gas phase into a low temperature argon matrix (10 K), and its infrared spectrum was fully assigned, also with help of results of normal coordinates' analysis based on the DFT computed vibrational data. The electronic structure of this conformer was analyzed by using the Natural Bond Orbital (NBO) method.The investigation of the thermal properties of 5-AAH was undertaken by differential scanning calorimetry (DSC), polarized light thermal microscopy (PLTM) and Raman spectroscopy, allowing identification of five different polymorphs. Very interestingly, in the room temperature stable polymorph the molecular units of 5-AAH assume the geometry of the highest-energy conformer predicted by the calculations for the isolated molecule.

The crystal structure and Raman spectrum of the sodium salt of 5-Acetic acid hydantoin

“…Besides the crystallographic study, we present also the Raman spectrum of the salt and interpret it in comparison with the spectrum of the crystalline hydantoin (polymorph I [24]), taking into account the X-ray diffraction structural information now determined for the salt and that previously reported for the ligand [24]. The analysis of the Raman spectroscopy data is also supported by theoretical results obtained within the scope of the density functional theory (DFT).…”

“…From left to right: cis-I, the most stable conformer for the isolated molecule and observed experimentally for the compound isolated in cryogenic inert matrices [24]; trans-I, the conformer present in the investigated sodium salt of 5AAH; trans-III, the conformer present in the room temperature most stable crystal (polymorph I) of the neat hydantoin [24]. On total, the molecule has 13 different conformers [24]. The numbers in parentheses are the DFT(B3LYP)/6-311++G(d,p) calculated relative energies of the conformers [24].…”

“…Within the scope of our research programme on hydantoin derivatives [19][20][21][22][23][24], we have recently shown that 5AAH exhibits five different polymorphs, from which the most stable one at room temperature (polymorph I) has the peculiar characteristic of being formed by 5AAH molecules that assume a conformation identical to the highest-energy conformer for the isolated molecule [24]. In fact, this higher-energy conformer, which has an energy as large as ~40 kJ mol -1 higher than that of the conformational ground state, is selected upon crystallization from among 13 different conformers of the molecule.…”

“…On total, the molecule has 13 different conformers [24]. The numbers in parentheses are the DFT(B3LYP)/6-311++G(d,p) calculated relative energies of the conformers [24].…”

“…We were particularly interested to determine the conformational preferences of the 5AAH molecules in the crystal of the newly synthesized salt, and compare the results with what has been observed for the neat hydantoin [24]. We were also very much interested to compare the crystal structures of the hydantoin and of its salt regarding the most relevant intermolecular interactions defining their structures, in particular hydrogen bonding.…”