Question

QUESTION: Show the mechanism of the reduction of 3-dimethylaminopropiophenone hydrochloride to form the alcohol?

PROCEDURE:

1. Add 2.00 g of 3-dimethylaminopropiophenone hydrochloride, 10 mL of distilled water and a magnetic stir bar to a 100 mL beaker, and stir to dissolve. This is the reaction beaker.
2. Add (with stirring) sufficient 10% NaOH (about 5–6 mL) to bring the solution to pH >10. The free base will form and come out of solution as a milky oil.
3. With continued stirring, add enough 95% EtOH (about 9–10 mL) to dissolve the free base and to form a clear solution again.
4. In a vial or small beaker, make 10 mL of water basic with three drops of 10% NaOH; add 0.40 g of NaBH4, and stir to dissolve. While stirring, add the NaBH4 solution to the reaction beaker. To ensure a complete reaction, stir for 15 minutes.
5. At the end of the of the 15-minute time period, remove a small aliquot (0.5 ml) from the reaction mixture, and add 6 M HCl until the “fizzing” stops, followed by enough 10% NaOH to make the solution basic. Add 0.5 ml of ether and spot the ether layer on the TLC plate. The mobile phase for the TLC is 30% EtOAc: 70% Hexanes.
6. If the TLC shows a complete reaction, cautiously, and with continued stirring, make the mixture acidic by drop-wise addition of 6.0 M hydrochloric acid. This destroys the excess NaBH4. About 5 mL will be needed; add the acid until the "fizzing" stops.
   1. Note: This can cause vigorous evolution of hydrogen gas!
7. To form the free base, which is needed for the next step in the synthesis, make the solution basic again to pH > 10 with 10% NaOH. About 15 mL will be needed to make the solution neutral, and a further 5–7 mL will be needed to bring the pH to >10.
8. Transfer the solution to a separatory funnel.
9. Add 20 mL of diethyl ether, shake well, vent, allow the layers to settle, and separate them.
   1. Shake carefully, as pressure can develop!
10. Remove the bottom, and save in a beaker. Put the upper ether layer in a beaker and save. Take the lower aqueous layer, and extract more product by adding an additional 10 mL portion of ether; add the second ether extract to the beaker containing the first ether extract. Discard the aqueous layer in the waste container, and dry the combined ether extracts over anhydrous Na2SO4.
11. Decant the solution into a 250-mL round-bottom flask containing a magnetic stir bar. Use simple distillation to remove the ether. Most of the ether will distill over near its boiling point of 36 ºC; continue the distillation until the temperature of the distilling solvent is about 55-60 ºC, at which point about 30 mL of ether should have been collected. The colorless oil that remains is (±)-3-(dimethylamino)-1-phenylpropanol, along with some residual ether. Leave the stir bar in the flask, let cool to room temperature, stopper it with a ground-glass stopper (grease the stopper), and follow the laboratory instructor’s directions for storage. Depending on the amount of residual ether, on standing for a few days at cool temperatures, the oil may solidify to a waxy white/yellow solid.

Answer 1