In the Classroom
Introducing Stereochemistry to Non-science Majors Hannia Luján-Upton Chemistry Department, Long Island University, University Plaza, Brooklyn, NY 11201
Stereochemistry is often a difficult topic for first-time organic chemistry students to learn. The challenge is made even greater when students are non-science majors. In our university we teach stereochemistry to a very wide audience, ranging from chemistry majors through health professions majors to liberal arts majors. The level of the course determines the depth of the coverage, but at all levels, some of the simplest concepts in stereochemistry are often completely alien to many students. Judging from the number of articles published in this Journal, it is evident that this problem is by no means a new one (1–4 ). A common problem encountered by instructors at any level is the inability of students to master the most elementary concepts of stereochemistry. This inability handicaps them throughout the remainder of the course. The first time I taught stereochemistry to the sophomores at our university, it was very obvious from the room full of blank faces that the lecture was unintelligible. After considerable thought, I incorporated the exercises that follow into my lectures. They have been used since that first lecture four years ago and have always proved to be surefire “icebreakers” when introducing my classes to stereochemistry.
book’s cover. The students’ response is “Yes”. In this way, the point is made that objects that are identical have exactly the same corresponding characteristics even if superimposed on one another. This simple exercise introduces the concept of superimposability as a test for sameness. The two texts are presented again, this time with the bottom book’s front cover turned 180 degrees (Fig. 2c). When questioned if the texts are still identical, the students respond affirmatively. They explain that a simple rotation of either book would restore it to perfect superimposability with the
Red
Yellow
Red
Blue Green
Blue
Yellow Green
Figure 1. Simple models of enantiomeric molecules.
Exercise 1. Are These Two Things “the Same”? Molecular models have been used extensively to provide students with a hands-on approach to stereochemistry (5– 7).One of the problems, however, is that most students are not familiar with modeling kits. Hence, asking them to use an unfamiliar tool to grasp abstract ideas is problematic, at best. The following exercise uses models in conjunction with everyday items to introduce the concept of “sameness” and its relationship to stereochemistry. Before class I make two fictitious enantiomeric molecules from a ball-and-stick chemistry modeling kit (Fig. 1). I begin by showing these molecular models to the class, pointing out that each molecule contains balls of four different colors (red, green, yellow, and blue) each attached to the central black ball. I offer 15 points on the next exam to anyone who can logically answer the question: “Are these molecules the same?” I allow two minutes for this exercise and then ask the class to keep the question in mind as we perform the following exercise with a familiar object, such as their textbooks (Fig. 2). After borrowing identical texts from two students, I ask the class if the book of one student is the same as that of the other (Fig. 2a). The overwhelming response is affirmative. At this point I inquire how the students arrived at this response. To answer satisfactorily, they must consider exactly what properties led them to the conclusion that the books are, indeed, the same. I question whether the books have identical front and back covers, and whether they find the same words on page 594, for example. The students are then instructed to react to my placing one text directly over the other, both covers facing in the same direction (Fig. 2b). I question whether every word on the top book’s cover would coincide identically with the position of the words on the bottom
a
b
c
d
Figure 2. Demonstration of superimposability using identical textbooks. One of the books appears in gray shading. This is done solely to differentiate one text from the other. (a) The two textbooks. (b) One text placed directly over the other, both covers facing in the same direction. (c) The bottom book’s front cover is turned 180°. (d) The front covers of the books face one another.
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In the Classroom
other text. The concept of manipulation in testing superimposability is thus introduced. Finally, I flip the top text so that the front covers of the books face one another (Fig. 2d). Students are now ready to confirm superimposability for the texts as they suggest flipping the top text appropriately. We now study our hands. I ask the students whether their hands are identical or different. I remind them that if they are able to superimpose one hand over the other, finding that all other aspects of one hand correspond to those of the other hand, the two hands are the same. I suggest that they try superimposing their hands with both palms facing the floor. The students respond that the hands are not the same because pinkies and thumbs are not superimposed. The question emerges: what is the relationship between hands if they are not the same? It often happens that a student will tell me that he or she thinks that hands are superimposable as the palms face one another. It is true that the fingers align perfectly, but one palm faces upward while the other faces downward. Inverting one so that both palms face upward leads to the conclusion that right and left hands are not identical. This exercise in the form of an illustration is found in most organic textbooks. It teaches students that although two things may appear to be identical at first glance, if they are not superimposable, they are not the same. I introduce the term “mirror image” to describe the relationship between hands and remind the students that the relationship between their hands is indeed different from the relationship between the textbooks observed earlier. This is a good opportunity to introduce the term “chiral”. Of course most texts mention hands as examples of objects possessing chirality. However, students will not often pursue the exercise of proving the presence or absence of chirality in familiar objects on their own. These exercises have enabled them to understand that chirality requires that two substances, which are mirror images of one another, be nonsuperimposable. I return now to the two molecular models previously presented (Fig. 1). After showing them again to the class, I ask, “Are these two molecular models the same?” After attempting to superimpose the molecules in several different ways, the students realize that this is impossible. At this point I place the two molecules facing one another in such a way that an imaginary mirror exists between them. Once the mirror image concept is obvious to the class, I introduce the concept of enantiomers. I have found that these exercises teach the students the following points. 1. The concepts of “identical” versus “different” exist whether in textbooks or in molecules. Identical objects have corresponding characteristics when superimposed; superimposability serves as a test for sameness. 2. If two objects are not readily recognized to be identical, one can manipulate them with the objective of testing for superimposability. If this is accomplished, the objects are indeed the same. If not, the objects are chiral and the relationship is stereoisomeric. 3. The type of relationship in which two objects are not superimposable and are mirror images of one another is known as an enantiomeric relationship.
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It has been my experience that these exercises not only help students to increase their understanding of concepts such as superimposability, chirality, and enantiomers; they also motivate students to purchase inexpensive modeling kits to test the concepts themselves.1 I invite students to bring kits to class and even to use them during examinations when required to determine configurations and relationships between larger, more complex molecules. Most students find homework problems related to stereochemical principles easier to solve with the aid of models than without them. I also suggest that students use the kits to build some appropriate molecules and to test their friends and even family members about the concept. I’ve actually noticed many students doing just that around the campus after my lectures! I then realize that I may have made this difficult concept more understandable. Exercise 2. Is There a Poisonous Fungus among Us? After demonstrating the concepts of stereoisomerism, I find it useful to use a little mystery to introduce the ideas of optical activity in naturally occurring molecules versus those synthesized in the laboratory (8–10). My version is similar to the source, written by Dorothy L. Sayers, except that I have used the more familiar Sherlock Holmes instead of the original detective. A very famous English botanist and professor by the name of George Harrison had invested his wages wisely for fifty years, thus amassing quite a considerable fortune. He was a recognized authority on mushrooms and various other fungi. Since he was occupied with his intense love of science, he hadn’t married. With no heirs of his own, he often relied upon his nephew, John Lathom, who was twenty-five years of age, to carry out his everyday errands. Although his uncle didn’t know it, Lathom had a very severe gambling problem, which had led him into considerable debt. Lathom devised what he thought was “the perfect murder” so that he would inherit his uncle’s fortune. Because he was a familiar face about the university, Lathom had access to the research laboratories of various chemists. One chemist was synthesizing muscarine (see structure below), the toxin found in a type of poisonous mushroom, Amanita muscaria. Lathom thought that this would be the perfect chemical to achieve his evil purpose and planned to add synthetic muscarine to his uncle’s weekly meal of beef and mushroom stew. His uncle’s death would then be viewed as an unfortunate accident. HO R S
S O
+ NMe3 X-
L-(+)-Muscarine
Professor Harrison did enjoy his beef and mushroom stew one night and was indeed found dead the following morning. As Lathom had hoped, the death was labeled an accidental poisoning by Amanita muscaria. The executor of the estate, also Harrison’s good friend and legal counsel, had his doubts. He thought it baffling that his good friend, an
Journal of Chemical Education • Vol. 78 No. 4 April 2001 • JChemEd.chem.wisc.edu
In the Classroom
authority on fungi, could have made such a pedestrian error as to pick the deadly mushroom for his stew. He also knew of Lathom’s debt and this caused him to be suspicious of the nephew. Bothered by these inconsistencies, he commissioned the investigative powers of the master sleuth Sherlock Holmes. Holmes also suspected Lathom, but proof was lacking. While questioning Harrison’s university colleagues, Holmes happened upon a chemistry lecture discussing some new and interesting properties of molecules that were being observed with an apparatus known as a polarimeter. This, by the way, is a great opportunity to explain optical activity and the use of the polarimeter as an instrument for analysis. In this discussion I explain that natural products, including toxins, are made by stereospecific molecules such as enzymes, and are therefore enantiomerically pure. I remind the students that an enantiomerically pure substance exists as a single enantiomer and is therefore, optically active. However, the same compounds synthesized in the laboratory, unless extraordinary efforts are used, are seldom enantiomerically pure. Synthetic chiral compounds exist as equal mixtures, called racemates, or as unequal mixtures. A racemic mixture is not optically active. A mixture containing an enantiomeric excess of one enantiomer is still optically active, but will rotate plane polarized light to a lesser degree than an enantiomerically pure product. I usually stop the story here and ask the class to consider what has been said. Then, considering all of this information, I invite them to respond to this question: How was Holmes able to prove that Lathom murdered his uncle? I am pleasantly surprised at this point to find that I still have virtually every student mesmerized by this account. Frequently, a student will give the correct answer, explaining that the stew was analyzed with the aid of a polarimeter. Since the stew contained synthetic muscarine, which is enantiomerically impure, it did not rotate the plane of polarized light like the toxin taken directly from the mushroom. Hence the poison was synthetic and was deliberately placed in the stew. Harrison’s death was indeed a homicide and the logical suspect was Lathom. As an aside, I tell the students that the fortune was then willed to the university and used to increase the salaries of organic chemistry teachers! Note. One might want to consider using muscarine as an example of a molecule with more than one chiral center to introduce the van’t Hoff rule. Since tetrahydro-4-hydoxyN,N,N-5-tetramethyl-2-furanmethanaminium, C9H20NO2+, possesses three stereocenters, muscarine is only one of eight possible stereoisomers (see structures below; the R or S configuration of each stereocenter and the counterion X ᎑ are omitted for clarity). This topic can lead to a discussion of diastereomers and meso compounds. This would be where we end our discussion on stereochemistry with health science majors. Undergraduate organic students need to apply the concepts described in this manuscript in greater depth than do nonscience majors. Therefore, going into further detail would be beneficial. It may also be of benefit to go through this exercise with graduate students as a review, and then to delve into the
syntheses of the eight stereoisomers in detail (11–15). HO
HO + NMe3
+ NMe3 O
O
muscarine HO
HO + NMe3
+ NMe3
O
O
HO
HO + NMe3
+ NMe3 O
O
HO
HO + NMe3 O
+ NMe3 O
Note 1. Proteus Organic Chemistry Models Kit, Molecular Design Inc., Tesuque, NM ($8–10).
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10. 11. 12.
13.
14. 15.
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