Solvent‐induced chirality control in the enantioseparation of 1‐phenylethylamine via diastereomeric salt formation

Abstract

Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine 1 by N-(p-toluenesulfonyl)-(S)-phenylalanine 2 via diastereomeric salt formation was studied. (S)-1·(S)-2 was preferentially crystallized as a less-soluble salt from aqueous alcohol, while (R)-1·(S)-2 salt was mainly obtained by addition of solvents with a six-membered ring such as dioxane, cyclohexane, tetrahydropyran, and cyclohexene to 2-propanol. Further investigations were carried out from the viewpoints of molecular structures, optical rotation measurement, and X-ray crystallographic analyses. Crystallographic analyses have revealed that incorporation of the six-membered ring solvent molecule in (R)-1·(S)-2 without hydrogen bonds changed the molecular conformation of (S)-2 to stabilize the salt, which changed the selectivity of 1 in the enantioseparation.

Formation of Ternary Inclusion Crystal and Enantioseparation of Alkyl Aryl Sulfoxides by the Salt of Urea-Modified l-Phenylalanine and an Achiral Amine

“…First, we selected L-phenylalanine as a natural amino acid considering our previous result that the salt of N-(p-toluenesulfonyl)-L-phenylalanine and (R)-1-phenylethylamine cocrystallized with six-membered cyclic compounds such as 1,4-dioxane and cyclohexane. 51,52 The urea-modified chiral carboxylic acid (1a) was directly synthesized from Lphenylalanine and phenyl isocyanate according to the reported procedure with some modifications. 46 The enantiopurity of 1a did not decrease, as was confirmed by HPLC analysis after esterification.…”

Comparing the Energetic and Dynamic Contributions of Solvent to Very Low Barrier Isomerization Using Dynamic Steady-State Vibrational Spectroscopy

“…The strength of the interaction between solute and solvent is a critical parameter for controlling solution-phase chemistry and impacts a host of molecular behaviors, from solubility to reaction kinetics. For instance, the polarity of solvent can control association constants between molecules, the enatomeric selectivity of organic reactions, and the rate of chemical and electrochemical transformations. − The kinetic effects are often explained within the framework of transition state theory and its modifications, where the solute–solvent interactions are assumed to affect either the barrier height ( E A ) and curvature of the potential energy surface that underlies the reaction or the manner in which the reactive surface is explored. In general terms, we can classify these effects as either energetic or dynamic, respectively.…”

New Opportunities to Improve the Enantiomeric and Diastereomeric Separations

“…According to the single-crystal studies, the dielectric constant of the solvent [27] also influences the hydrogen bonding system thus forming the chiral recognition process. This phenomenon was demonstrated via several other resolution experiments [28][29][30][31][32].…”