Friedel-Crafts Acylation: Synthesis of 4-Methoxyacetophenone By Marcelo Martinez February 10, 2011 CHEM2103.

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Background
Benzene, benzene derivatives, and other aromatic compounds are known to commonly participate in electrophilic substitution reactions. This reaction begins with the reaction between the electrophile and the pi bonding electrons of the aromatic ring. The aromatic ring then undergoes resonance creating a resonance stabled carbocation intermediate. The final step is the loss of a Hydrogen ion from the carbocation intermediate, yielding the final product. The rate at which the aromatic ring can undergo electrophilic substitution though can be greatly affected through the substituent attached to the aromatic ring. An electron donating substituent will enhance the stability of the carbocation intermediate, which will result in an increased reaction rate; activating. The opposite is true for a substituent that has electron withdrawing effects. By lowering the electron density within the aromatic ring, the stability of the carbocation intermediate is reduced and in turn the reaction rate for the aromatic ring is reduced; deactivating. Substituents can also have an effect on the amount of isomeric products that are produced. This effect is caused by the influence that the substituents have on the reactivity of certain parts of the ring. The positive charge of the carbocation intermediate tends to be focused on the ortho and para positions, in relation to the carbon to which the electrophile is bonded. Due to this effect, the substituent will have a much greater effect on the stability of the carbocation if it is bonded to either the ortho or para positions. Activating substituents increase the reaction rate at the ortho and para positions much more than the meta .They are said to be ortho and para directing. Deactivating substituents decrease the reaction rate at the ortho and para positions much more than the meta position. Deactivating products are said to be meta directing. Friedel-Crafts reactions are named after named after the men who developed the electrophilic substitution reactions in which the attacking electrophile is a carbocation. There are several ways to generate the carbocation, the most common of which is mixing an akyl of acyl halide with a Lewis acid, such as aluminum chloride. One problem with the Friedel-Crafts alkylation is polyalkylation. Because of the electron donating nature of alkyl groups, the resulting product from an alkylation reaction is more reactive to electrophilic attack than the original compound. This may cause another electrophilic attack, or polyalkylation. The second problem with this type of reaction is the rearrangement of the alkyl groups (rearrangement is common in the carbocation intermediates used in Friedel-Crafts reaction).

Friedel-Crafts reactions can also be performed with acid chlorides or anhydrides. Acylation reactions such as these (in which an acyl group is attached to the aromatic ring) provide a convenient method for the synthesis of aryl ketones. These reactions are also not subject to the disadvantages that akylation reactions are subjected. Because of the electron withdrawing properties that the carbonyl group has, it deactivates the aromatic ring and prevents the subsequent attack from other electrophiles. The product can also be collected in a good yield. In this experiment, 4 methoxyacetophenone is synthesized in a Friedel-Craft acylation of anisole with acetic anhydride.

Materials and Methods

25-mL Round bottom flask Rubber septum Claisen adapter Condenser with Tubing Y tube 100-mL Beaker Boiling chips Pipet 1.

400-mL Beaker Hot Plate Ice Cotton Separatory Funnel Funnel Separatory Funnel

Using a 25-mL round bottom flask prepare the reflux apparatus. Place the rubber

septum over the Claisner adapter opening. Fit the top of the condenser with a rubber stopper equipped with a Y tube. Use the rubber tubing to connect the Y tube to the water aspirator. 2. Prepare an ice bath with the 100-mL beaker. Tare the 25-mL round bottom flask and

measure .55 grams of anisole directly into the flask. Also add 5 mL of dichloromethane and a boiling chip to the flask. 3. Reassemble the apparatus and remove the rubber septum. Weigh out 1.45 g of

anhydrous aluminum chloride and immediately add it to the reaction mixture, taking special

care to minimize its exposure to the air. Replace the septum and cool the mixture in the ice bath. 4. Using a pipet, obtain 0.6 mL of acetic anhydride. Remove the rubber septum once more

and slowly add the acetic anhydride. Mix the reaction periodically by shaking the round bottom flask. Once the addition of the acetic anhydride is complete, remove the mixture from the ice bath. 5. Prepare a 40-50 degree Celsius water bath in the 400 mL beaker. Warm the reaction in

the hot water bath for 10 minutes. Place 5 grams of ice into a 50 mL beaker and place it in the fume hood. When no more gas evolves from the reaction mixture, pour the mixture onto the ice. Rinse the reaction flask with 2 mL of dichloromethane and add it to the ice mixture. 6. After the ice has melted use a separatory funnel to transfer the denser organic layer to a

test tube. Add 1 mL of NaOH to the organic layer and shake to mix the layers. Add the mixture back into the separatory funnel and remove the organic layer once again. 7. Dry the organic layer by adding 0.5 g of anhydrous MgSO4 and swirling the mixture for

five minutes. Separate the final product by passing the mixture through a cotton filled funnel. Record the mass of the final product.

Results
Using 0.545 grams of Anisole and 0.6 mL of acetic anhydride, 0.168 grams of 4methoxyacetophenone were produced through this reaction.

Discussion
In the experiment anisole, an aromatic ring containing OCH3, was allowed to react with acetic anhydride. This acylation reaction takes place when the acetic anhydride is exposed to a Lewis acid, which in this case is the aluminum chloride. The acetic anhydride/aluminum chloride complex, which is formed through the reaction of those two compounds, reacts with the anisole ring. The resulting compound is 4-methoxyacethophenone.

The lab required for us to separate the organic layer from the inorganic layer several times, which could have led to mistakes on our parts. Another possible problem was the fact that although the instructions expressed clearly that the aluminum chloride should not be exposed to air, the chemical that we used had already been thoroughly exposed to air, possibly tainting our sample or not providing the proper amount of reactivity needed. At one point there was also a small spill. This occurred when transferring the organic layer into a test tube. The spill was minimal, but could have caused a rather large loss of product. Regardless of those mistakes, the procedure was followed as closely as possible, leaving little room for other mistakes to have occurred.

Conclusion
The theoretical yield of 4-methoxyacetophenone is .751 grams. Our actual experimental yield was .168 grams. The percent yield was 23.5%. The experiment, although low in yield, still completed the acylation reaction and is still a success.