Synthesis of Acetaminophen: A Laboratory Procedure, Study notes of Medicine

Download Synthesis of Acetaminophen: A Laboratory Procedure and more Study notes Medicine in PDF only on Docsity! Shanbhag Acetaminophen 2006 Synthesis of Acetaminophen Techniques: Decolorization, Filtration, Crystallization, Craig tube use, Preparation of an Amide Preparation of acetaminophen involves treating an amine with an acid anhydride to form an amide. In this case, p-aminophenol, the amine, is treated with acetic anhydride to form acetaminophen (p-acetamidophenol), the amide. CH OH NH2 O O O CH3 CH3 + OH NH CH3 O + O OH CH3 p - Aminophenol Acetic anhydride Acetaminophen Acetic Acid OH NH 3 O Acetaminophen (paracetamol) an analgesic and fever-reducing medicine similar in effect to aspirin. It is an active ingredient in many over-the-counter medicines, including Tylenol and Midol. Introduced in the early 1900s, acetaminophen is a coal tar derivative that acts by interfering with the synthesis of prostaglandins and other substances necessary for the transmission of pain impulses. Although its action is similar to that of aspirin, it lacks aspirin’s anti-inflammatory and blood-thinning effects, is less irritating to the stomach, and can be used by people who are allergic to aspirin. Heavy use, however, has been linked to an increased incidence of liver failure, especially in heavy drinkers of alcoholic beverages and in those who are not eating enough, and overdose, especially in children, can be fatal. Synthesis The crude solid acetaminophen contains dark impurities carried along the p- aminophenol starting material. These impurities, which are dyes of unknown structure, are formed from oxidation of the starting phenol. While the amount of the dye impurity is small, it is intense enough to impart color to the crude acetaminophen. Most of the colored impurity is destroyed by heating the crude product with sodium dithionite (sodium hydrosulfite Na2S2O3). The dithionite reduces double bonds in the colored dye to produce colorless substances. The decolorized acetaminophen is collected on a Shanbhag Acetaminophen 2006 Hirsch funnel. It is further purified by a microscale crystallization technique utilizing a Craig tube. Caution: • Acetic anhydride can cause irritation of tissue, especially in nasal passages. Avoid breathing the vapor and avoid contact with skin and eyes. p-Aminophenol is a skin irritant and is toxic. • Aqueous solutions obtained from filtration operations may be diluted with water and flushed down the drain. Procedure Reaction Mixture Weigh about 0.150 g of p-aminophenol (MW = 109.1) and place this in a 5-mL conical vial. Using an automatic pipet (or a dispensing pump or a graduated pipet), add 0.450 mL of water and 0.165 mL of acetic anhydride (MW= 102.1, d = 1.08 g/mL). Place a spin vane in the conical vial and attach an air condenser. Heating Heat the reaction mixture with an aluminum block or sand bath at about 115°C and stir gently. If you are using a sand bath, the conical vial should be partially buried in the sand so that the vial is nearly at the bottom of the sand bath. After the solid has dissolved (it may dissolve, precipitate, and re-dissolve), heat the mixture for an additional 10 minutes to complete the reaction. Isolation of Crude Acetaminophen Remove the vial from the heat and allow it to cool. When the vial has cooled to the touch, detach the air condenser, and remove the spin vane with clean forceps or a magnet. Rinse the spin vane with two or three drops of warm water, allowing the water to drop into the conical vial. Place the conical vial in a small beaker and allow it to cool to room temperature. If crystallization has not occurred, scratch the inside of the vial with a glass stirring rod to initiate crystallization. Cool the mixture thoroughly in an ice bath for 15-20 minutes and collect the crystals by vacuum filtration on a Hirsch funnel. Rinse the vial with about 0.5 mL of ice water and transfer this mixture to the Hirsch funnel. Wash the crystals on the funnel with two additional 0.5-mL portions of ice water. Dry the crystals for 5-10 minutes by allowing air to be drawn through them while they remain on the Hirsch funnel. Transfer the product to a watch glass or clay plate and allow the crystals to dry in air. It may take several hours for the crystals to dry completely, but you may go on to the next step before they are totally dry. Weigh the crude product and set aside a small sample for a melting point determination and a color comparison after the next step. Calculate the percentage yield of crude acetaminophen (MW = 151.2). Record the appearance of the crystals in your notebook.