In the Classroom
Models and Molecules—A Workshop on Stereoisomers Robert W. Baker, Adrian V. George,* and Margaret M. Harding School of Chemistry, University of Sydney, N.S.W. 2006, Australia
In teaching organic chemistry to first year undergraduates, in our experience, the students find stereochemistry one of the most difficult concepts to grasp. This arises largely owing to the restrictions inherent in a lecture-theater environment where molecular shapes are necessarily drawn, using standard conventions, on a blackboard or by use of material from a textbook. While we use large ball-and-stick molecules to illustrate the ideas of shape (particularly enantiomers and diastereomers), the best teaching exercise for the students is to convince themselves—for example—that molecules are or are not mirror images, by using models. We have designed a molecular models workshop, to be completed in approximately 3 hours, for first-year undergraduate chemistry students. It is run as one of the exercises in our laboratory program in an informal session with the opportunity for group discussion and a tutor available to answer questions. The concepts of isomerism and stereochemistry are illustrated by a range of key examples. Exercises completed during the workshop assist students to relate twodimensional representations in texts with three-dimensional models. The figures represented here are those presented in the workshop notes and are completed by the students during the workshop. Model Kits We have used Molymod molecular model kits1 to which we have added a few extra parts representing bonds and carbon and hydrogen atoms. 2 We found the model kits robust and long lasting and the ball-and-stick representation of molecules one that the students can understand easily. Structure of Workshop Prior to the workshop, the students are asked to revise the initial concepts and definitions (Fig. 1). Both the (R)/(S) and (E)/(Z) nomenclature is used throughout the workshop and a summary of the general rules for naming is supplied as reference material for consultation if required. The use of this nomenclature has been the subject of a recent article (1) and will not be reviewed here.
Exercise 1: Conformational Isomers Conformational isomers are illustrated by preparing models of ethane. Sawhorse and Newman projections are used to illustrate the conformers and an energy profile diagram shows their relative energies (Exercise 1.1 and Fig. 2). The students construct a model of 1,2-dichloroethane and use it to draw Newman projections of three conformations and rank them in terms of relative stability (Exercise 1.2). Using butane, students are asked to draw Newman projections of the two possible eclipsed conformations and the two possible staggered conformations resulting from rotation about the central C–C bond, and label them A to D (Exercise
ISOMERS
CONSTITUTIONAL ISOMERS different atom connectivities
STEREOISOMERS same atom connectivity, different arrangement in space
CONFORMATIONAL related by rotation around a single bond
CONFIGURATIONAL separable
DIASTEREOMERS stereoisomers that are not mirror images
ENANTIOMERS non-superposable mirror images
Figure 1: Summary of the relationship between isomers.
1.3). They then transfer these labels to the appropriate places on the energy profile diagram of butane (Exercise 1.4). By constructing models and noting that the single bonds are all freely rotating and do not remain fixed, the fact that individual conformers cannot be isolated is reinforced in the student’s mind.
Exercise 2: Enantiomers The first concept illustrated here is the relationship between mirror images and the symmetry of the molecule. A model of 2-chloropropane is constructed, and a threedimensional representation of the molecule is sketched showing the location of the plane of symmetry. The mirror image of 2-chloropropane is built and the two models are shown to be superposable. Next, two models of a 2-chlorobutane molecule are constructed, which are mirror images of one another. Each of the enantiomers is identified as either (R) or (S), (the students draw the two enantiomers). The students now have the opportunity to see how swapping any two adjacent groups on the stereogenic center gives the enantiomer of the compound. Comparison of the two sets of models helps students appreciate that enantiomeric molecules contain no plane of symmetry and that a stereogenic carbon center possesses four
Potential Energy
~12 kJ mol–1
0
60
120
180
240
300
360
Dihedral Angle (φ) º
*Corresponding author.
Figure 2. Energy profile of the conformers of ethane.
JChemEd.chem.wisc.edu • Vol. 75 No. 7 July 1998 • Journal of Chemical Education
853
In the Classroom ϕ
Angle (φ) between C-H bonds on adjacent carbons of eclipsed form of ethane:
H HH H
H
H
H H
0.229 nm H
HH
H
H2C
C
C
CH2 H2C
C
C
CH2
H2C
C
C
CH2 H2C
C
C
CH2
A
ϕ H
H
Angle (φ) between C-H bonds on adjacent carbons of eclipsed form of ethane:
H
H
H
H
H
0.255 nm H
H
H
H
C
B
D
Relationship between isomers: A and B:
B and C:
A and C:
B and D:
A and D:
C and D:
H
“Saw-horse Projection”
“Newman Projection”
Exercise 1.1 Exercise 3.1
Cl H
Cl H
H Cl
H H
H
CH3
CH3
H
Cl H
Cl
C
C
C
C CH3
CH3
Cl
H
H
H
CH3
CH3 C
C
C
C
CH3
CH3
H A
C
B
D
Relationship between isomers: A and B:
B and C:
A and C:
B and D:
A and D:
C and D:
Exercise 3.2
Exercise 1.2
Cl
Cl Cl
H
H H
H Cl
Type of symmetry
cis-1,2-Dichlorocyclobutane trans-1,2-Dichlorocyclobutane
Exercise 1.3
Exercise 3.3
Potential Energy CH 3 15.1 k
H N
Jmol -1
NHCH3 H
H
CH 3
CH3
OH HO
18.8 kJ mol–1
3.7 k Jmol -1 0
60
120
180
240
300
Dihedral Angle (φ) º
Exercise 1.4
854
360
H
CH3
H HO H3C
H
H3C
C C
H
H
NHCH3 OH
NHCH3 NHCH3
H
OH
H
Figure 3: Representations of ephedrine.
Journal of Chemical Education • Vol. 75 No. 7 July 1998 • JChemEd.chem.wisc.edu
H
In the Classroom
different substituents. It should also be noted that chirality exists in a number of other molecules (e.g., some allenes, spiro compounds, and coordination compounds). These are not discussed in this workshop, but instructors should make students aware that the existence of enantiomers is not restricted to a carbon bearing four different substituents. The workshop could be extended to include examples of this type for more advanced classes.
Exercise 3: Diastereomers Diastereomers are illustrated initially with alkenes. By drawing possible structures and constructing models of several examples, students are able to validate the general rule that (E )/(Z ) isomers exist only when two different groups are attached to each carbon atom of the double bond. (Some good examples are CH2=CHCH3, CH3CH=CHCH2CH3, CH3 CH=C(CH3)2, and CH 3CH2C(CH 3)=CHCl.) The models clearly illustrate that conversion of one isomer to another can only be achieved if bonds are broken and reformed. We find that students usually have little problem understanding diastereomers in the cases of E/Z alkenes and cis/trans disubstituted cycloalkanes. However, diastereomers in open-chain compounds with two or more stereogenic carbon centers can cause confusion. In this workshop, the transition between the diastereomers of 2-chlorocyclobutanol and the diastereomers of 3-chloro-2-butanol helps to convince students of the equivalence of the isomerism in the two cases, despite the conformational mobility of the latter. Models of the four possible stereoisomers of 2-chlorocyclobutanol are constructed and the students confirm that none of the isomers are superposable on the others and that there are two pairs of enantiomers. Three-dimensional representations of the molecules are drawn, the stereogenic carbon centers are labeled as either (R ) or (S ), and pairs of isomers are indicated (Exercise 3.1) as either enantiomers (mirror images) or diastereomers (not mirror images). The second part of the exercise involves conversion of the models of 2-chlorocyclobutanol into models of 3-chloro2-butanol by removal of the C–C bond between the CH2 carbon atoms and replacing it with one hydrogen on each carbon. The students are asked to confirm that none of the isomers, in any conformational form, are superposable on the others. They draw three-dimensional representations of the molecules, indicate whether the stereogenic carbon centers are (R ) or (S ) and again indicate the relationship between pairs of isomers (Exercise 3.2).
This exercise may be extended to include a discussion of meso isomers. First, models of cis- and trans-1,2-dichlorocyclobutane are constructed and students are asked to determine which stereoisomer contains a plane of symmetry and which an axis of symmetry (Exercise 3.3). The mirror image models are made. trans-1,2-Dichlorocyclobutane will form an enantiomeric pair, whereas cis-1,2-dichlorocyclobutane contains a plane of symmetry and the two mirror image models will be superposable on one another. The students discover there are only three stereoisomers in this case. “Cutting” the bond between the CH2 groups in the models and replacing it with one hydrogen on each carbon atom will again reveal there are only three stereoisomers of 2,3-dichlorobutane. It can be pointed out to students at this stage that the constitutional isomer, 1,3-dichlorocyclobutane, has no enantiomeric forms in either cis or trans configurations because there is a plane of symmetry in both configurations of the molecule. Summary We find that many students experience difficulties understanding stereoisomers and a hands-on approach using molecular models helps considerably in teaching the relationship between different isomers and the importance of symmetry and structure. The students are encouraged to think of molecules and construct models of their own. Our students have responded well to this workshop and find it helpful in understanding the difference between isomers. As a final illustration of molecular shape and the different representations that are used in organic chemistry, students are asked to verify the equivalence of several two-dimensional representations of ephedrine, (1R, 2S)-2-methylamino-1-phenyl-1-propanol, used medically as a bronchodilator for the treatment of asthma (Fig. 3). Notes 1. Available as the Prentice Hall Molecular Model Set for Organic Chemistry, ISBN 0-205-08136-3, Prentice Hall, Englewood Cliffs, NJ 07632, USA. 2. Purchased directly from the manufacturer, Spiring Enterprises Ltd., Beke Hall, Billingshurst, W. Sussex RH14 9HF, England.
Literature Cited 1. Barta, N. S.; Stille, J. R. J. Chem. Educ. 1994, 71, 20.
JChemEd.chem.wisc.edu • Vol. 75 No. 7 July 1998 • Journal of Chemical Education
855
