Experiment 3-Evan’s aldol reaction(post lab)

Start by preheating an oil bath or heating block to 115 °C.
2. Add a stirring bar and transfer the chiral auxiliary prepared from last period into a 5 mL
round bottom flask. Treat the amount of chiral auxiliary used in this step as the limiting
reagent for subsequent calculations. Use the remaining auxiliary in the vial as a TLC
standard.
3. Add DMAP (x mg, 0.1 equiv) to the reaction flask.
4. Seal the round bottom flask with a rubber septum.
5. Purge the flask with nitrogen gas for ~2 min and maintain an inert atmosphere.
6. To the reaction flask, sequentially add anhydrous PhCH3 (2.5 mL) and triethylamine (x
mL, 1.6 equiv).
7. Then add propionic anhydride (x mL, 2 equiv) to the flask dropwise over ~2 min.
8. Heat the reaction mixture at 115 °C. Ensure that the flask is adequately submerged in
the heating source – all the liquid should be submerged. You may remove the nitrogen
gas inlet at this time.
9. Monitor the reaction by TLC every 10 min. Spot the reaction mixture along side the
starting material. Perform a co-spot as a control. Start by using the optimal TLC
conditions identified for the auxiliary last period.
10. When TLC analysis indicates complete consumption of the starting material (this
should take approximately 30 min), remove the reaction mixture from the heat source
and allow it to cool for ~ 5 min.
† Propionic anhydride is regulated under the Controlled Substances Act (List 1) because it can be used to synthesize
fentanyl and related analogs. Therefore, we must carefully document all usage of this reagent. It cannot be used
for any purpose outside the academic labs.
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11. Add H2O (1 mL) to the mixture and continue heating at 115 °C for 10 min. Why do we
cool the reaction before adding H2O?
12. Remove the reaction mixture from the heat source and allow it to cool to room
temperature. You may use an ice bath to speed up this process.
13. Using a Pasteur pipette, transfer the mixture to a 10 mL test tube. Rinse the flask with
diethyl ether (Et2O, 3 × 1 mL) and transfer these to the test tube as well. This solution
is the organic phase. [Look up the boiling point of Et2O. Why is it necessary to cool the
reaction mixture before adding Et2O]?
14. Wash the organic phase with the following (using the Pasteur Pipette as a mini
separatory funnel):
a. 2 M HCl(aq) (2 mL) [What does this do?]
b. 2 M NaOH(aq) (2 mL) [What does this do?]
c. brine solution (2 mL) [What does this do?]
Combine and set the aqueous phases aside for now. Do not discard until you have
confirmed that the desired product is in the organic phase.
15. Dry the organic phase with anhydrous sodium sulfate and filter the solution into a
tared, labeled, vial.
16. Concentrate the solution on a rotovap. Note the appearance and record the yield of the
product.
17. In addition to recording the 1H, 13C and IR spectra, obtain HPLC/MS (high pressure
liquid chromatography/mass spectrometry) and melting point data.
18. Store the product at low temperature until the next laboratory period.