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highlights
edited by
Susan H. Hixson
projects supported by the NSF division of undergraduate education
National Science Foundation Arlington, VA 22230
Curtis T. Sears, Jr. Georgia State University Atlanta, GA 30303
CAChe Molecular Modeling: A Visualization Tool Early in the Undergraduate Chemistry Curriculum R. David Crouch,* Michael S. Holden,* and Cindy Samet Department of Chemistry, Dickinson College, Carlisle, PA 17013-2896 In Dickinson’s chemistry curriculum, “Synthesis & Reactivity” replaces the traditional organic chemistry sequence and begins in the second semester of the freshman year. A key aspect of our sequence is the correlation of laboratory experiments with lecture topics and the extension of laboratory exercises beyond the usual 4-hour period. With this goal in mind, a number of “Synthesis & Reactivity” experiments have been developed that include an out-ofclass computational chemistry exercise using CAChe (1), a versatile molecular modeling software package. Because the first semester of “Synthesis & Reactivity” has a large number of freshmen, emphasis is placed on developing an insight for where nucleophiles and electrophiles might attack a molecule. The Visualizer+ routine in CAChe generates striking graphical images of these sites and the reaction of NBS/H2O with 3-sulfolene (2) presents an excellent opportunity to introduce CAChe into an experiment. Before the laboratory, students are introduced to CAChe to determine how NBS might interact with a nucleophile such as an alkene. Students then return to the laboratory to perform the bromohydrin synthesis but are asked to consider what the regiochemistry would be were the alkene not symmetric. Specifically, students are instructed to visit the computer laboratory during the week and perform calculations on the bromonium ion formed from 2-methylpropene to determine where a nucleophilic H2O molecule might attack. The MOPAC routine in CAChe provides data that are converted to a graphical depiction of the frontier density of the intermediate, indicating potential reactive sites based on electron distribution of orbitals near the HOMO and LUMO. When these data are manipulated by Visualizer+, the obvious conclusion is that the nucleophilic water molecule should attack the more highly substituted carbon of the bromonium ion (Fig. 1) and generate one regioisomer. In the second semester of “Synthesis & Reactivity”, a more rigorous approach is followed. The reactivity of an aldehyde carbonyl and an ester carbonyl is the subject of an experiment in which students work in groups, with each member treating an equimolar mixture of octanal and methyl caprylate with a different hydride reducing agent. Depending upon the strength of the reducing agent (for example, LiAlH4 vs. NaBH4), students obtain octanol or a mixture of octanol and unreacted methyl caprylate, which is analyzed by gas chromatography. The difference in the reactivity of the carbonyl groups is assayed using CAChe. But in this instance, we sought more precision in comparing carbonyl reactivities than the graphical depic*Corresponding author. email:
[email protected] and
[email protected] 916
tions allowed. CAChe’s Project Leader feature allows the atoms of each molecule to be examined individually and reactivity is indicated numerically. After the laboratory, students are assigned the task of looking at the “Nucleophilic Susceptibility” of the carbonyl carbon atoms of the substrates (Fig. 2). This option examines the electron distribution of orbitals near the LUMO using augmented MM2 to first optimize the geometry and then MOPAC to
Figure 1. Relative nucleophilic susceptibilities for the bromonium ion derived from 2-methyl-propene.
O H 1.222 O OCH3 1.137
O
O H 0.384
Figure 2. Nucleophilic susceptibilities.
Journal of Chemical Education • Vol. 73 No. 10 October 1996
Information • Textbooks • Media • Resources
determine the susceptibility of the atom to attack by a nucleophile. Students are also asked to develop a means to reduce an ester in the presence of an aldehyde and use the calculations that CAChe provides to support their proposed solution. Most students have opted to protect the aldehyde as an acetal, reduce the ester with LiAlH4, and then deprotect the aldehyde. The nucleophilic susceptibility of the acetal carbon clearly indicates that it is unlikely to undergo reduction by LiAlH4. Currently, we are working to expand the use of CAChe to other experiments in “Synthesis & Reactivity” and throughout the curriculum.
Acknowledgment We thank the National Science Foundation’s Division of Undergraduate Education for financial support through the Instrumentation and Laboratory Improvement program (DUE-9450995). Literature Cited 1. CAChe ver. 3.7. 2. Greenberg, F. H. J. Chem. Educ. 1985, 62, 638.
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