Chirality driven crystallization behavior of ortho, meta, and para-cyanophenyl glycerol ethers

Enantiopure and racemic samples of ortho, meta, and para CN-substituted phenyl glycerol ethers 1–3 were investigated by differential scanning calorimetry and single-crystal X-ray analysis. The absolute configuration for (S)-1 was established through Flack parameter method. Whereas ortho-derivative 1 demonstrates spontaneous resolution upon crystallization, homochiral lattice for scalemic meta-derivative 2 is exceeded in stability by heterochiral lattice of racemic compound. This tendency becomes all the more evident for the para-derivative 3, in which case the difference in Gibbs free energy between rac and scal lattices amounts ΔG0 = −4.48 kJ mol−1. Most of these phenomena could be understood by reference to crystal packing details.