Synthesis of aspirin

In recent years, examples from organic chemistry have come to play increasingly prominent roles in the first-year university general chemistry course. The American Chemical Society has recommended more integration of biological concepts into college-level introductory general chemistry courses. Following this recommendation, at least two current general chemistry textbooks make liberal use of organic examples (1), and some universities are bringing organic chemistry much more into the forefront of the introductory course (2).

At California State University, Fullerton, the first-semester general chemistry laboratory has been redesigned over the past several years. The redesign has added an organic component and provided students with explicit examples of several types of operations in which chemists engage: observation, synthesis, quantitative measurements, construction of apparatus, and chemical analysis. Our experiment that accentuates accurate quantitative measurements was reported earlier (3).

Over the course of the first semester and the beginning of the second, our general chemistry students synthesize two organic substances (aspirin and methyl orange) and two inorganic substances (alum and potassium ferrioxalate). An earlier paper described our ferrioxalate synthesis experiment (4). This paper describes the first of our organic synthesis experiments, the synthesis, purification, and qualitative spectroscopic characterization of aspirin.

Aspirin (acetylsalicylic acid) is a pain-relieving compound familiar to virtually all students. The synthesis of aspirin from oil of wintergreen is an example of one of the most prevalent, profitable, and honored activities of chemists: the conversion of a naturally occurring substance into one with therapeutic value. Simple enough to be accomplished and understood by beginning students, this synthesis nevertheless serves as a paradigm for the pharmaceutical industry, from tranquilizers and antibiotics to yet-undiscovered agents for treating cancer, heart disease, and AIDS.

Rationale

The two-step conversion of oil of wintergreen (methyl 2hydroxybenzoate) into salicylic acid (5) and then into aspirin (6) serves as an introductory example of multistep sequential synthesis. It also provides practice in molecular pattern recognition, as the reactions modify the periphery of a structural core common to the starting material, intermediate product, and final product (Fig. 1).

Viewed from another perspective, this sequence exemplifies two of the most common types of chemical reaction, hydrolysis and condensation:

As illustrated in Figure 2, the hydrolysis reaction proceeds in several steps involving deprotonation and protonation as well as cleavage of a...