SYNTHESIS OF (S)-(—)- AND (R)-( +)-1-PHENYLETHANOL

All reagent additions should be made with a suitable syringe.

(S)-(—)-1-Phenylethanol. 

• Equip an oven-dried three-necked 250-ml round-bottomed flask with a precision-ground stirrer unit, a reflux condenser con­nected to a mercury bubbler, and a rubber septum with a syringe needle attached to a dry nitrogen supply. 

• Flush the apparatus with nitrogen. 

• Transfer 53.2 ml of an 0.5 M ethereal solution of lithium aluminium hydride (0.026 mol) (1) to the flask. 

• Prepare a solution of 8.8 g (0.025 mol) of 3-0- benzy1-1,2-0-cyclohexylidene-a-D-glucofuranose in 50 ml of ether and add it dropwise to the stirred hydride solution. 

• Heat the mixture under reflux with stirring for 30 minutes, then add a solution of 3.0 g (0.025 mol) of acetophenone in 50 ml of dry ether. 

• Heat under reflux for a further 2 hours, cool the reaction mixture, and decompose excess hydride by the cautious dropwise addition of 5 ml of water. Filter the ethereal solution using a Celite filter pad, dry the filtrate over magnesium sulphate and concentrate on a rotatory evaporator. 

• Transfer the concentrated solution to a small fractional distillation unit, and first remove the remaining solvent before distilling the secondary alcohol under reduced pressure. 

• The yield of (S)-( —)- 1-phenylethanol is 2.5 g (83%), b.p. 79 °C/3 mmHg, [a]_D²⁰ 14.4° (neat), ee 33.5% (maximum reported specific rotation —42.86°).

(R)-(+ )-1-Phenylethanol. 

• Using a 500-ml three-necked round-bottomed flask equipped as in the foregoing experiment, react 117 ml of an 0.5 M ethereal solution of lithium aluminium hydride (0.058 mol) (1) with 8.8 g (0.025 mol) of the monosaccharide derivative in 50 ml of dry ether, and heat under reflux as above for 90 minutes. 

• Then add dropwise a solution of 4.5 g (0.098 mol) of ethanol and heat under reflux for a further 1 hour before the dropwise addi­tion of a solution of 1.5 g (0.012 5 mol) of acetophenone in 50 ml of dry ether. 

• Heat under reflux for a further 2 hours, cool and add cautiously 15 ml of water. 

• Work up the reaction mixture as in the foregoing experiment to obtain 1.2g (80%) of (R)-( + )-1-phenylethanol, [o]e + 22.9° (ee 53.4%).

Notes to keep in mind:

1. For the standardisation of ethereal solutions of lithium aluminium hydride; adjust the volume of addition to ensure that the recom­mended molar quantity of reagent is used.