Expt #4. Friedel Crafts Acylation of Anisole

Relevant textbook reading - Klein, Chapter 19.1-19.10

Overview - You will react anisole with propionyl chloride/FeCl₃ to form propionylanisole . NMR and GC/MS will be used to determine the regioselectivity of the reaction, i.e., which product(s), ortho, meta, or para, actually form.

Procedures

Running the reaction.

• Using the balance located in the dispensing fume hood, weigh out 1.65 g anhydrous FeCl₃ into a dry 25-mL round bottom flask.
• Add a small stir bar and 10 mL dichloromethane (DCM).
• Cautiously add 1.0 mL propionyl chloride.
  
• Attach a reflux condenser, Claisen adapter, and addition funnel as shown in Fig 7.4a (p 63) in Mohrig.
• Prepare a solution of 1.1 mL anisole in 5 mL DCM and add this to the addition funnel.
• Add the anisole solution dropwise over a period of approx 2-4 min to the stirring solution.
• Stir for an additional 20 min.

Work-up procedures.

• Slowly add 2.5 mL cold water via the addition funnel to stop the reaction and quench any left over acyl chloride. Stir for 5 min.
  
• Transfer the reaction mixture to a separatory funnel and add 25 mL water.
  
• Extract with 5 mL DCM collecting the organic layer into a small Erlenmeyer flask. Avoid getting any of the aqueous layer.
• Extract the aqueous layer with 5 mL additional DCM and combine the organic layer with the previous organic layer.
• Wash the combined organic layers with 25 mL 0.5 M NaOH.
• Dry over Na₂SO₄.
• Before decanting from the drying agent add activated charcoal ("Norit") and swirl for 5 min.
  
• Use a vacuum filtration, packing the Buchner with a 1-cm layer of Celite (see "Use of a Filter Aid" in Mohrig p 106) setup to filter off the norit and sodium sulfate.
  
• Transfer the filtrate to a r.b. flask (rinsing with more DCM if necessary) for rotary evaporation to remove the DCM solvent.
• Determine the yield of propionylanisole.
  

Characterization of Product

• Obtain the ¹H NMR spectrum using CDCl₃ as the solvent. One group will also be asked to obtain a C-13 NMR.
  
• Dilute 1-2 drops of the NMR sample solution in 5 mL DCM and submit the solution for GC-MS analysis.