Enantioseparation of chiral alcohols by complex formation and subsequent supercritical fluid extraction

Abstract

The very first application of supercritical fluid extraction (SFE) on enantioseparation of alcohols is discussed. Resolution of three chiral alcohols (trans-2-chloro-cyclohexanol, trans-2-bromo-cyclohexanol, and trans-2-iodo-cyclohexanol) were performed by partial complexation with (-)-O,O'-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA). DBTA formed diastereomeric complexes with all S,S-enantiomers stable enough to extract the unreacted alcohols with supercritical carbon dioxide. Resolution efficiency increased with the size of halogen substituents, and by the proper selection of molar ratio, pure (-)-R,R-trans-2-iodo-cyclohexanol (ee > 99%, yield: 39%) or (+)-S,S-trans-2-iodo-cyclohexanol (ee = 98%, yield: 8%) were prepared in one process step. Achieved resolution efficiency values were much higher in all resolution procedures than in any other known enantioseparation of these racemic compounds. The developed method offers an environmentally friendly, efficient alternative of currently applied resolution processes, also on a preparative scale.

Lipase-catalyzed kinetic resolution of 2-methylene-substituted cycloalkanols in batch and continuous-flow modes

“…Enantiomers of five-, six-and seven-membered 2-substituted cycloalkan-1-ols proved to be versatile synthetic intermediates leading to enantiopure cyclic allylic alcohols, including the double bond in the ring [14][15][16][17]. Such cyclic allylic alcohols can be obtained by enzyme-catalyzed kinetic resolution only in low enantiomeric excess [16].…”

Resolution of N-methylamphetamine enantiomers with tartaric acid derivatives by supercritical fluid extraction

“…Diastereomeric salts were formed under supercritical conditions using the solution enhanced dispersion by supercritical fluids (SEDS) technique. 12 Over the last 10 years, several racemic organic acids, 13 bases 14;15 and alcohols 16 have been resolved by SFE in our laboratory. In many cases the extraction pressure (P ) or/and extraction temperature (T ) strongly influenced the efficiency of the resolution.…”

Principles, Concepts and Strategies of Stereoselective Synthesis

“…Preparative, chiral supercritical resolution technology is drawing extensive attention for separation of enantiomers as a result of the green characteristics of supercritical fluids, and it has been successfully used for the resolution of different racemic compounds, among them, e.g., chiral alcohols via complex formation, 143 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, 144 N-methylamphetamine enantiomers, 145 tetramisole, 146,147 an anthelminthic and immunomodulator drug (levamisole-an (S)-enantiomerused to treat parasitic worm infections, studied as a chemotherapy component for colon cancer, melanoma, and head and neck cancer), as well as many other clinically used racemic drugs. 148 Enantioselective membrane extraction technology combines liquid-liquid extraction with the membrane and is oriented for the separation of enantiomers.…”