CH 104: SYNTHESIS OF ASPIRIN AND OIL OF WINTERGREEN Is it animal, vegetable, or mineral? Until the mid-1800s most scientists thought that all carbon compounds originated from plants and animals. As a result, organic chemistry was defined as the chemistry of carbon. In contrast, inorganic chemistry was defined as the chemistry of minerals.

ORGANIC CHEMISTRY AND FUNCTIONAL GROUPS Today’s experiment is an example of organic chemistry. Organic molecules usually have very complicated structures. Therefore, organic chemists often use specific parts of molecules when they make other compounds. These parts are called functional groups. A functional group is an atom or group of atoms that defines the structure, physical properties, and chemical reactivity of a particular family of organic compounds. In today’s experiment you will use different functional groups to synthesize aspirin (acetylsalicylic acid) from salicylic acid and acetic anhydride, and oil of wintergreen (methyl salicylate) from salicylic acid and methanol.

THE SYNTHESIS OF ASPIRIN This is an esterification reaction. A phenol (the functional group of salicylic acid) reacts with an acid anhydride (the functional group of acetic anhydride) to make an ester (the functional group of acetylsalicylic acid).

THE SYNTHESIS OF ASPIRIN What happens to acetic anhydride? It’s cut in 2. One piece is bonded to salicylic acid. The other piece helps make acetic acid. What happens to the phenolic H from salicylic acid? It goes from salicylic acid to the acetic acid. Which is more likely? This reaction happens in 1 step or more than 1 step? This is a complicated reaction. It probably has more than 1 step.

A reaction mechanism is a detailed account of every valence electron during a reaction. The reaction mechanism for the catalytic esterification of salicylic acid and acetic anhydride has 5 steps. Use Lewis structures to predict the product of each step. What is the catalyst? H+. It is recycled during the reaction. It is not permanently created. And it is not permanently consumed.

THE SYNTHESIS OF ASPIRIN Your aspirin will most likely be contaminated with salicylic acid. It should NOT be ingested. Iron(III) chloride (FeCl3) will be used to detect unreacted salicylic acid. The Fe3+ from FeCl3 usually reacts with phenol ( ) to make a highly colored complex ion. Salicylic acid has a phenol group; therefore, it gives a positive (purple) test with FeCl3. Acetylsalicylic acid does NOT have a phenol group; therefore, it gives a negative (no color change) test with FeCl3.

THE SYNTHESIS OF OIL OF WINTERGREEN In the last esterification reaction the phenolic group ( ) of salicylic acid was attacked. In this esterification reaction the carboxylic acid group ( ) from salicylic acid is attacked. It reacts with an alcohol ( ) to make a different ester ( ), oil of wintergreen (methyl salicylate). What is the difference between a phenol and an alcohol? A phenol has OH bonded to an aromatic ring (Ar). An alcohol has OH bonded to an aliphatic chain (R).

THE SYNTHESIS OF OIL OF WINTERGREEN What happens to methanol? It’s cut in 2. One piece is bonded to salicylic acid. The other piece helps make water. What happens to the alcoholic H from methanol? It goes from methanol to the water. Which is more likely? This reaction happens in 1 step or more than 1 step? Again, this is a complicated reaction. It probably has more than 1 step.

The reaction mechanism for the catalytic esterification of salicylic acid and methanol has 5 steps. Use Lewis structures to predict the product of each step. What is the catalyst? H+. It is recycled during the reaction. It is not permanently created. And it is not permanently consumed.

SAFETY Give at least 1 safety concern for the following procedures that will be used in today’s experiment. Heating glass with a hot plate or a flame. Injury from a burn or causing a fire. Be careful. Do not wear loose clothing or long hair. Glass can shatter when heating; wear your goggles at all times. Using salicylic acid, acetic anhydride, concentrated H2SO4, 1% FeCl3, and methyl alcohol. These are irritants. Wear your goggles at all times. Immediately clean all spills. If you do get either of these in your eye, immediately flush with water. Generating H2O(g) and acidic gases. Again, these are irritants. Wear your goggles at all times. Use the fume hood when handing concentrated H2SO4. Immediately clean all spills. If you do get either of these in your eye, immediately flush with water. Your laboratory manual has an extensive list of safety procedures. Read and understand this section. Ask your instructor if you ever have any questions about safety.

SOURCES The Chemical Heritage Foundation. 2002. Making Aspirin – Teacher’s Guide. http://www.chemheritage.org/educationalservices/pharm/tg/antibiot/activity/asp31.htm Available: [accessed 18 January 2007]. Morrison, RT, RN Boyd. 1983. Organic Chemistry, 4th ed. Boston, MA: Allyn and Bacon, Inc. Pavia, DL, GM Lampman, GS Kriz. Introduction to Organic Laboratory Techniques, 2nd ed. New York, NY: Saunders College Publishing. Joseph Wright of Derby. 1771. The Discovery of Phosphorus.