The hydrogenation of acetophenone with chiral catalyst (R)-CAT (2 mol%) at −40 °C for 8 hours gives — Analytical Chemistry Chemistry Question
Enantioselective hydrogenation
The hydrogenation of acetophenone with chiral catalyst (R-CAT (2 mol%) at −40 °C for 8 hours gives a crystalline solid, (R-1-phenylethan-1-ol, in 70% yield and 90% enantiomeric excess (ee). The specific rotation [α]D20 (c 1.00, EtOH) of the product was determined to be +45°.
Draw the structure of the product.
Model Answer
Structure:
The rate constant of the reaction leading to the (R)-product is kR = 2.5 × 10−5 s−1 at −40 °C. What is the rate constant kS of the reaction that leads to the (S)-product at the same temperature?
The activation energy for the reaction leading to the (S)-product is Ea(S) = 80 kJ mol−1. Provided that the pre-exponential factor A is the same for both reactions, what is the activation energy Ea(R) for the reaction leading to the (R)-product?
Model Answer
From the previous question; at −40 °C kR = 19 × kS. Substitute from the Arrhenius equation:
What temperature is needed to obtain 99% ee? What is a potential drawback?
Model Answer
At any given temperature T:
Equation (‡)
Therefore:
At this temperature, the reaction is likely to be really slow which would prevent its actual use.
Determine the specific rotation [α]D20 (c 1.00, EtOH) of the product if (S-CAT (4 mol%), an optical antipode to the catalyst (R-CAT, is used at 0 °C and the same machine and cuvette are used for the measurement.
Model Answer
The main difference is that (S-CAT will provide the (S)-product. We will do all the calculations for (R-CAT and just invert the sign at the end. It should be noted that the amount of catalyst does not influence the enantiomeric excess; it only accelerates the reaction.
From equation (‡):
For 90% ee: [α]D20 (c 1.00, EtOH) = +45°,
which means [α]D20 (c 1.00, EtOH) = +42.5° for 85% ee
The same conditions are used for the measurement of the specific rotation, namely, the temperature, solvent, concentration and wavelength of the light used. Therefore, we can just invert the sign to obtain the result for the (S)-product:
[α]D20 (c 1.00, EtOH) = −42.5° = −43°
Note: The specific rotation should be formally stated in ° dm−1 cm3 g−1, but in most of the current scientific literature this is simplified to ° only.
How would you increase the optical purity of the final product after the reaction?
Model Answer
Since the product is crystalline, the easiest method would be recrystallization. Different chiral resolution methods can also be used, for example crystallization with a chiral agent or separation by HPLC with a chiral stationary phase.