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Molecular Orbital Animations for Organic Chemistry Steven A. Fleming,* Greg R. Hart, and Paul B. Savage** Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602-5700 *
[email protected]; **
[email protected] There are several approaches to teaching organic chemistry (1), and a current trend is presentation of the various subjects (alkanes, alkenes, ketones, etc.) with a theme. Students benefit when they can find a common element that ties the subject matter together. One such theme for organic chemistry is the use of electrophile + nucleophile for the description of organic reactions. We have also found that students can understand simple molecular orbital explanations of electrophile and nucleophile. In this paper we describe our teaching methods, including an animation package that we have developed, which build upon a fundamental understanding of molecular orbital (MO) interactions. Background Use of electrophilic and nucleophilic molecular properties to understand and predict organic reactions is not a new approach to teaching mechanistic organic chemistry (2). It is well understood that electrophiles are Lewis acids that are characterized by a positive or partial positive charge and nucleophiles are Lewis bases because they have an available pair of electrons. Chemical reactivity then can usually be represented as a nucleophile (negative character) attacking an electrophile (positive character). Most organic chemistry textbooks treat this subject well and there appears to be increasing attention given to this logical approach to understanding chemical reactions (3). Typically, the reactions are shown using an electron-flow formalism, which is sometimes referred to as “arrow pushing”. This Lewis dot approach effectively describes some aspects of reaction mechanisms but does not provide a realistic picture of electron flow between molecular orbitals.
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Few organic texts have taken the next step of analysis (MO interactions), which allows the students to consider “why” a molecule is a nucleophile or electrophile (4 ). Use of molecular orbitals can be very instructive (5). The basic concept is that an electrophile has an energetically low-lying empty MO, which is referred to as the lowest unoccupied molecular orbital (LUMO). It is precisely an empty orbital that can receive electrons and is the reason an electrophile is a Lewis acid. It is this molecular orbital that is an electron pair acceptor. Similarly, a nucleophile has electrons that are relatively high in energy (i.e., a lone pair of π electrons). These electrons, which make the molecule a nucleophile and a Lewis base, can be discussed in terms of the highest occupied molecular orbital (HOMO). It is from this molecular orbital that an electron pair is donated. The HOMO of the nucleophile must mix with the LUMO of the electrophile in order for the new bond to form. We have found that students can benefit from threedimensional computer representations of chemical events (6 ). Therefore, we have combined our molecular orbital approach to understanding organic chemistry (a HOMO attacking a LUMO) with the advantages offered by computer animations, to produce a series of reaction clips. The goal in preparing our animations was to facilitate visualization and understanding of these topics, including electronegativity differences, bond polarization, delocalization of charges and partial charges through resonance and hyperconjugation, steric environments, and electron distribution within molecules (7). By viewing threedimensional representations of the molecules involved in a reaction, students can gain a better mental image of the course of the reaction. Careful observation of the animated spacefilling molecular models, for example, will help reveal steric
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Figure 1. Representations of the SN2 reaction of cyanide with ethyl bromide (for simplicity in each representation the cyanide counterion is not included). Representations B–D include key structures used in creating animations. A: “Arrow-pushing” description of the reaction. B: Ball-and-stick representation of the reaction. C: Superimposition of the calculated HOMO for the reaction. D: Superimposition of the calculated LUMO for the reaction.
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Journal of Chemical Education • Vol. 77 No. 6 June 2000 • JChemEd.chem.wisc.edu
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effects on reactions such as the E2 reaction. Viewing molecular orbital interactions will help in understanding how electrons flow in a reaction and why certain molecules react the way they do. We hope that these animations will make learning organic chemistry easier and more enjoyable. Samples can be viewed on our Web page (http://chemwww.byu.edu/ora/). Any feedback on how these cartoon aids facilitate learning or suggestions for improvement would be greatly appreciated.
C-1 carbon, the unconstrained minimization would result in a new distance between the nucleophile and C-1 that matches the final product. Therefore, to determine the reaction picture at 1.6 Å, we constrained the distance between the nucleophile and the carbon bearing the leaving group. The calculations at each step along the reaction pathway represent the energyminimized angles and distances for the two groups at the specified distances. In Figure 1, we show 5 steps (1–5) from the animation of this particular reaction in the ball-and-stick (B), HOMO (C), and LUMO (D) perspectives. Similarly, the E2 reaction was calculated at several points along its pathway (see Fig. 2). As the base approaches the alkyl halide, it may undergo attack at the back side of the carbon–bromine bond (see the large LUMO density calculated in that area in Fig. 2D-1) or it may attack the β-hydrogen, which has LUMO density due to hyperconjugation (hyperconjugation is also visible in the LUMO calculation for the final product as shown in Fig. 2D-4). The space-filling version of the animated E2 reaction is illustrated in Figure 2E. The space-filling model is a useful tool for comparing the E2 with the competing SN2 reaction between methoxide and 2-bromopropane, since sterics resulting from the angle of approach by the methoxy group determines the outcome of the reaction. This is obvious in the space-filling version of the E2. The Friedel–Crafts reaction animation is particularly informative because it shows students a clearer picture of resonance. There is a tendency to think of contributing resonance
Results These animations were produced by performing semiempirical (AM1 or PM3) or ab initio (HF/3-21G*) calculations using Spartan (Wavefunction, Inc.). Between 15 and 45 steps along the pathway were calculated for each reaction. The energy-minimized geometries were determined, then HOMO and LUMO surfaces were calculated. We prepared animations showing a ball-and-stick perspective, a space-filling representation, a HOMO surface change, and a LUMO surface flow. An estimated energy diagram is also sketched for each reaction. The relative energies for the species along the reaction coordinate were approximated rather than taken from the calculated structures.1 Melding between the minimized points was accomplished using the program Alias Wavefront. Usually the minimization for an individual step had to be constrained. For example, if a step in the SN2 reaction (see Fig. 1) were minimized with the nucleophile (cyanide ion) 1.6 Å from the back-side of the
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Figure 2. Representations of the E2 reaction of methoxide with isopropyl bromide (for simplicity in each representation the methoxide counterion is not included). Representations B–E include key structures used in creating animations. A: “Arrow-pushing” description of the reaction. B: Ball-and-stick representation of the reaction. C: Superimposition of the calculated HOMO for the reaction. D: Superimposition of the calculated LUMO for the reaction. E: Space-filling representation of the reaction.
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Figure 3. Representations of the carbocationic intermediate in the Friedel–Crafts acylation of toluene (for simplicity in each representation a counterion is not included). A: A resonance structure description of the intermediate is shown. B: Two views of a ball-and-stick representation of the cation. C: Two views of the cation with the LUMO superimposed. These two views show the LUMO density located on alternating carbons in the ring and the hyperconjugation from the methyl group bonded to the ring.
structures as being “in equilibrium” on the basis of chalkboard drawings, as shown in Figure 3A. The LUMO density for the intermediate in Friedel–Crafts acylation of toluene clearly depicts a simultaneous buildup of positive charge distributed between the para and two ortho positions illustrated from two angles in Figure 3C (the ball-and-stick version is shown in Fig. 3B from two angles for clarity). One can also see the hyperconjugation from the methyl group stabilizing the intermediate cation in the side-on LUMO view of the intermediate. We have omitted solvent from our calculations. Although Spartan is capable of giving reasonable data for solvation of stable compounds, we did not feel comfortable with its ability to determine solvent interactions of transition states and species along the reaction pathway. More importantly, we did not want to tackle the animating nightmare that solvent shells would pose. As a result, the reactions are closer to those under gas-phase conditions. 2 The major goal of this project, showing the reactions in 3-D with electron flow, is still accomplished. Another shortcut in the animations relates to the issue of vibrational and translational energy. The molecules appear in static form with no kinetic energy, and only the productive collisions are shown. One can easily imagine all the nonreactive collisions that could potentially occur. Most of the reactions require considerable heat in order to go on to the products shown (intermolecular more so than intramolecular). Once again, we believe the major goal is better accomplished without this extra layer of detail. A few of the reactions have HOMO or LUMO densities that are very difficult to animate. This is particularly true of carbonyl compounds and proton-transfer reactions with molecules containing many oxygens. For example, a HOMO picture for a compound with three oxygens will have 6 MOs that are essentially equivalent. This is shown in Figure 4 for the intermediate in Fischer esterification. Owing to the complexity and to the lack of information transfer to the student, we have elected not to include some portions of the HOMO and LUMO movies in these cases.3 Our initial animations included orbital phase information. The positive lobes were blue and the negative lobes were red. 792
We found that the node information did not enhance the mechanistic understanding of most reactions, nor did the different colored orbitals help the students see why one reagent would interact with another.4 A simple illustration of the complexity added by a change of color between each node is shown in Figure 5. We plan to have the two-color orbitals available for the Diels–Alder reaction and the Cope rearrangement so that students can see both versions. We have used our animations in several settings. We have shown them to general chemistry students (a class of 20), health profession students in a one-semester organic chemistry course (two classes of 80 each), students in a typical twosemester organic chemistry course (four classes of 150–250 students each), the students in an undergraduate organic spectroscopic identification course (two classes of 20 students each), and students in the 1st-year graduate-level physical organic chemistry course (two classes of 10 students each). In each of these settings we have chosen to spend a limited time (ca. 5 minutes) of any given class period presenting the animations (8). We have found that information can be gained from the movie clips regardless of the course level. Beginning chemistry students have expressed appreciation of finally “seeing” the molecules undergoing reactions in the ball-and-stick movie. The space-filling models give them additional perspective on the relative sizes of the atoms. The advanced undergraduates and beginning graduate students have found more subtle details. For example, they can observe stereoelectronic effects, π-complex formation, reaction reversibility, and the role of orbital symmetry. Many of these issues can be addressed at a research level based on the animations. The HOMO/LUMO presentations are a great aid for undergraduate students who are using a molecular orbital approach in the classroom. We don’t expect this information to be immediately obvious to students who are coming from a traditional, non-molecular-orbital approach to organic chemistry. In other words, the HOMO/LUMO aspects of this program are not “stand alone” for the average undergraduate who has not been taught using molecular orbital concepts.
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Figure 4. Representations of an intermediate formed in the Fisher esterification of acetic acid. A: Conventional drawing of the intermediate. B: Ball-and-stick representation of the intermediate. C: Representation of the intermediate showing the complexity of the superimposed HOMO.
Class surveys from the one-semester and two-semester organic courses indicate that students feel they benefit from use of these animations in class. In the one-semester course, 77% of 157 responses were favorable when students were asked if they benefited from the animations. In the two-semester course there were 91% of 965 responding students felt the animations were helpful in learning organic chemistry. The major difference between the two levels of instruction is that the two-semester course uses the molecular orbital reasoning for electrophilic and nucleophilic properties. Thus, we believe that the higher appreciation of the animation package in the two-semester course is a result of the HOMO and LUMO clips. We asked two separate classes the question “The E2 mechanism requires a β hydrogen that is anti-periplanar to the halogen. Why is this arrangement necessary for the elimination?” The class that had been using these animations in the classroom and in homework (247 students) had an average score of 7.1 out of a possible 10. The class that did not use the animations (207 students) averaged 2.8 out of 10. We are currently attempting to quantify the improvement that students experience as a result of these animations. It is very difficult to separate the teaching approach from the benefit of the visualization. Conclusion Although there are many approaches to teaching organic chemistry, having a central theme for the course is critical. We have presented our approach, which integrates frontier molecular orbital concepts into each reaction the students see. This theme has allowed students to better understand the “whys” and “hows” of organic chemistry. Our animations incorporate this molecular orbital approach and they have been well received by all levels of students. W
Supplemental Material
This article is available with color figures in this issue of JCE Online. Notes 1. Semiempirical methods are not very reliable for their absolute calculated energy values. Since solvent is not included in the
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Figure 5. Two drawings of a key structure used in the animation of an E2 reaction. A: Structure with the LUMO of a single color superimposed. B. Structure with the LUMO showing phase differences.
modeling, realistic numbers would not be obtained. The energy levels used are only a guide for the student. 2. Solvent plays a major role in the rate and outcome of most organic reactions and gas-phase calculations avoid additional complicated situations. 3. We have also opted not to simplify the orbital representations by using localization methods. Those models are the common textbook pictures that are presented elsewhere. 4. Student responses to in-class surveys. Of the few students who were not helped by the animations (ca. 10%), many expressed that they were uncertain about the meaning of the red and blue lobes in our initial animations.
Literature Cited 1. See for example: Libby, R. D. J. Chem. Educ. 1995, 72, 626– 631. Katz, M. J. Chem. Educ. 1996, 73, 440–445. Viola, A.; McGuinness, P.; Donovan, T. R. J. Chem. Educ. 1993, 70, 544–546. Schearer, W. R. J. Chem. Educ. 1988, 65, 133–136. 2. Termed electron sources and sinks by: Scudder, P. H. J. Chem. Educ. 1997, 74, 777–781. Scudder, P. H. Electron Flow in Organic Chemistry; Wiley: New York, 1992. Weeks, D. P. Pushing Electrons; Saunders: Orlando, FL, 1976. 3. For example see: McNelis, B. J. J. Chem. Educ. 1998, 75, 479– 481. Bruice, P. Y. Organic Chemistry; Prentice-Hall: Upper Saddle River, NJ, 1995; Chapter 3. 4. One recent example: Jones, M. Organic Chemistry; Norton: New York, 1997. 5. Menger, F. M.; Mandell, L. Electronic Interpretation of Organic Chemistry; Plenum: New York, 1980. Fleming, I. Frontier Orbitals and Organic Chemical Reactions; Wiley: New York, 1977. Fukui, K.; Fujumoto, H. Frontier Orbitals and Reaction Paths; World Scientific: Singapore, 1997. Hout, R. F.; Pietro, W. J.; Hehre, W. J. A Pictorial Approach to Molecular Structure and Reactivity; Wiley: New York, 1984. Shusterman, G. P.; Shusterman, A. J. J. Chem. Educ. 1997, 74, 771–776. Lenox, R. S. J. Chem. Educ. 1979, 56, 298–300. 6. For other examples see: Buell, J. R.; Montana, A. Organic Reaction Mechanisms [CD-ROM]; Falcon Software: Wentworth, NH. Lipshutz, B. H. Mechanisms in Motion [CD-ROM]; Exeter Multimedia: Sudbury, MA. Liu, R. S. H.; Asato, A. E. J. Chem. Educ. 1997, 74, 783–785. 7. Wiberg, K. B. J. Chem. Educ. 1996, 73, 1089–1095. 8. Robinson, W. R. J. Chem. Educ. 1997, 74, 16.
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