Environmentally Benign Chiral Resolution of trans-1,2-Cyclohexanediol by Two-Step Supercritical Fluid Extraction

A racemic mixture of trans-1,2-cyclohexanediol (CHD) is reacted with S,S- or R,R-tartaric acid in ethanol with a 0.5 or higher molar ratio of resolving agent to racemic CHD. The tartaric acid (TA) forms a diastereomeric cocrystal with only one of the enantiomers; the other enantiomer remains unreacted at any molar ratio. The unreacted mixture of enantiomers is recovered from the sample by supercritical fluid extraction at 20 MPa and 33 °C. A subsequent extraction is then performed at 20 MPa and at least 73 °C. During this second extraction step, the diastereomeric cocrystal is decomposed in situ. Both enantiomers are recovered in nearly 50−50% yield with enantiomeric excess values of 65−90%. The mixtures of enantiomerss rich in S,S-CHD and R,R-CHD are then reacted with S,S-TA and R,R-TA, respectively, and the procedure is repeated. In two resolution steps, both enantiomers of CHD were produced in quantitative yields in a purity of ee > 99%.