cg701256e_si_004.cif (4.05 kB)

Predicting the Spontaneous Chiral Resolution by Crystallization of a Pair of Flexible Nitroxide Radicals

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posted on 06.08.2008 by Matthew D. Gourlay, John Kendrick, Frank J. J. Leusen
The separation of racemates into pure enantiomers through crystallization is an important industrial process. This study provides further validation of a novel, predictive approach for spontaneous resolution in which crystal structure prediction simulations are used to explore the relative stabilities of racemic solids versus enantiopure solids. 2-(4-Hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy (compound 1) has previously been shown to be a racemic conglomerate, while a similar compound, 2-(3-hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy (compound 2), was not. A conformational search using the Dreiding force field revealed 10 conformational minima for compound 1, and 20 for compound 2. Atomic charges were calculated using unrestricted DFT B3LYP 6-311G** optimized structures, and a crystal structure prediction was performed using the Dreiding force field, considering all low-energy gas-phase conformations and all relevant space groups. Analysis of the predicted crystal structures suggests that compound 1 is a racemic conglomerate, but compound 2 is not. This is in agreement with the experimental evidence.