Question

The alcohol could easily be converted to a tosylate, a good leaving group, and a conventional substitution reaction could have been performed instead of the nucleophilic aromatic substitution (NAS) reaction. Why was the NAS reaction the preferred method? (Hint : Look up the nucleophiles of both reactions on chemical manufacturing site.)
Part A: Synthesis of (t)-N,N-dimethyl-3-phenyl-3-(4- trifluoromethylphenoxy)propanamine 1. To the 250-mL round-bottom flask (RBF) containing (t)-3-(dimethylamino)-1-phenylpropanol (product from Lab 6) and a magnetic stir bar, add 4 mL of 4- chlorobenzotrifluoride and 30 mL of dimethylacetamide (DMA) 2. With stirring, add to this mixture 30 mL of 1.0 M potassium tert-butoxide (caustic alkali!) in tert-butyl alcohol using a syringe 3. Using a simple distillation apparatus, distill the mixture slowly, with stirring, over a 15-20 minute period until the temperature of the refluxing solvent mixture reaches 125-150 °C 4. Remove the heating mantle, and disconnect the RBF from the distillation apparatus. Cool the RBF by briefly immersing it in a cold water bath or a stream of running water a. RBF will be hot, so use a towel! 5. Add 40 mL water and 30 mL ether to the flask, swirl to dissolve, remove the stir bar, and pour the contents of the flask into a 125-mL separatory funnel 6. Shake well, allow the layers to separate, and drain the 7. Transfer the upper ether layer into a separate 100-mL 8. Return the water layer to the separatory funnel, add 10 lower aqueous layer into a 100-mL beaker beaker mL fresh ether, then shake and separate. Remove the lower layer, and combine the ether layer with the previous 30 mL extract 9. Return the water layer to the separatory funnel and extract it a third time with 10 mL of fresh ether. Discard the aqueous layer 10. Pour the ether extracts back into the separatory funnel and add 25 mL of water. Shake well, allow the layers to settle, and discard the lower aqueous layer. Add a final 25 mL of water to the separatory funnel, and again shake well, allow the layers to settle, and discard the lower aqueous layer. If the aqueous washings are still cloudy at this point, add 25 mL water to the ether solution in the separatory funnel, and once again shake well, allow the layers to settle, and discard the lower aqueous layer. Repeat this process until the lower aqueous layer is completely clear 11. Dry the combined ether extracts with anhydrous Na2SO4, and decant the ether solution to a separatory funnel

Answer 1

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