Friedel-Crafts Acylation: Synthesis of 4-Methoxyacetophenone

March 27, 2001

Jacqueline H. Ramirez

Objective:

Synthesize 4-methoxyacetophenone by the Friedel-Crafts acylation of anisole with acetic anhydride. Characterize the product using IR and NMR.

Reagents:

Substance	Quantity (g)	Molar Mass (g/mol)	MP (^oC)	BP (^oC)	Density (g/ml)
Acetic anhydride	0.6 ml	102.1		138-140	1.082
Aluminum Chloride anhy.	1.45	133.3
Anisole	0.55	108.1		154	0.995
Dichloromethane	7 ml	84.9		40	1.325
Magnesium sulfate anhy.	0.5	120.4
4-methoxyaceto- phenone		150.2	38-39
Petroleum ether	1 ml			35-60	0.64
Sodium chloride Saturated	1 ml
Sodium hydroxide 3M	1 ml

Chemical Alert:

Acetic anhydride – corrosive and lachrymator

Aluminum chloride – corrosive and moisture sensitive

Anisole – irritant and hygroscopic

Dichloromethane – toxic and irritant

4- methoxyacetophenone – irritant and light sensitive

Petroleum ether – flammable and toxic

Sodium hydroxide, aqueous – corrosive and toxic

Procedure:

• Assemble the apparatus for reflux.
• Mix Dichloromethane, anisole, and aluminum chloride
• Add acetic anhydride, dropwise
• Warm the reaction for ten minutes
• Pour the reaction onto ice
• Wash the reaction mixture with 3M NaOH and with saturated NaCl
• Dry the reaction mixture with anhydrous MgSO₄
• Remove dichloromethane from the product
• Purify the product by distillation
• Wash the crystalline product with petroleum ether
• Measure the mass and the melting point of the crystals
• Characterize the product using IR or NMR.