In the Laboratory
A Research-Based Sophomore Organic Chemistry Laboratory D. Scott Davis,* Robert J. Hargrove, and Jeffrey D. Hugdahl Department of Chemistry, Mercer University, 1400 Coleman Avenue, Macon, GA 31207; *
[email protected] A number of publications in this Journal have focused Each lab is indicated as either microscale or macroscale. on the incorporation of research as part of the undergraduAlthough we see the advantages of a microscale organic seate laboratory experience (1). These experiments are usually quence from an economic standpoint, it is difficult to carry reserved for either an advanced- or senior-level course and are that type of protocol over to the synthesis project. Theredesigned by the instructor. Over the last six years, we have fore, we have a combination of microscale, semi-microscale, developed a research component in our sophomore-level and macroscale organic labs in the laboratory exercises. Through organic chemistry centered on student-designed syntheses of these exercises, the students learn basic lab techniques includorganic compounds of the students’ choice. In this paper, we ing recrystallization, extraction, melting-point determination, describe the evolution and implementation of this lab program.1 simple and fractional distillation, gas and thin-layer chromaOf the 300+ students who complete our general chemistry tography, nuclear magnetic resonance spectrometry, and insequence annually, approximately 150 enroll in organic chemfrared spectroscopy. They perform eight reactions under this istry and 90 of those finish the two-course organic sequence. schedule: a dehydration, reduction, Grignard, Friedel–Crafts The organic classes are a mixture of students with diverse alkylation, esterification, halogenation, sulfonation, and interests, and in addition to chemistry majors include Biology, Diels–Alder. With this schedule, we believe the students have Biomedical engineering, Premedical, and Pre-pharmacy manipulated enough glassware to feel comfortable with the majors. The course evaluations given at the completion of techniques. At the very least, they have run eight reactions the organic courses revealed that the traditional lab sequence that can be used for their project. did not satisfy the students. As part of this evaluation, the An additional feature of this project is that the work is students were asked the following question: “Did the lab assist performed by a team of two or three students. Until this in furthering your knowledge of organic chemistry?” Six years project, students have worked independently. In addition to ago, the answer was a resounding “No!” Students considered the benefits of cooperative learning (2), groups are required the laboratory component to be nothing more than following a so that students learn how to work as part of a team, disrecipe. We were often asked, “Why do we learn manipulatributing responsibilities and resolving conflicts. Group tions and techniques that we will never see again?” or “I do work facilitates discussion about the project with someone not plan on being an organic chemist, so who cares how you other than the instructor, allowing students to sharpen their brominate an alkene!” On the basis of the negative responses problem-solving skills. from the students, we decided to try an approach different A project of this magnitude requires a large commitment from the typical sophomore organic laboratory. It was our from faculty, staff, and students. Students work harder during intent to reshape the laboratory sequence and incorporate a sizable research comTable 1. Organic Chemistry Laboratory Schedule ponent into the experience. After all, Week Semester I Semester II many of the students will eventually gain 1 Safety discussion and molecular models to Synthesis project description; check-in employment in a field where research is describe bonding and functional groups; check-in necessary, albeit not always in organic 2 IR and NMR of an unknown liquid and Friedel–Crafts reaction of 1,4-dimethoxychemistry. benzoic acid benzene (macro) Students take the laboratory as part 3 IR and NMR of an unknown liquid and Grignard preparation of triphenylmethanol of the lecture course, and our current lab benzoic acid (continued) (macro); preliminary proposal schedule is shown Table 1. Although the 4 Extraction (macro) Preparation of banana oil by an esterification most extensive revision was to the secreaction (macro); final proposal ond-semester schedule, we also modified 5 Recrystallization (macro), melting point Preparation of a sulfa drug (macro) our first-semester laboratory sequence to 6 Simple and fractional distillation (semi-micro) Preparation of a sulfa drug (macro) (continued) place NMR and IR spectroscopy labs 7 Analysis of distillation fractions by gas Preparation of a sulfa drug (macro) (continued) early in the sequence. Students gain valuchromatography able experience with the hands-on opera8 Introduction to the chemical literature Synthesis project tion of these instruments a number of 9 Thin layer chromatography Synthesis project (continued) times, as we encourage them to characSynthesis project (continued) 10 Synthesis and NMR of t - pentyl chloride from terize their products by both NMR and t - pentyl alcohol (macro) IR whenever time permits. Like most 11 Alcohol dehydration of 2-methylcyclohexanol Synthesis project (continued) (micro), and GC analysis of mixture universities, we stress techniques early in 12 Diels–Alder reaction of cyclopentadiene with Synthesis project (continued) the curriculum. Reaction-based labs are maleic anhydride (macro) chosen so that the students experience a 1 3 Check-out and catch-up Synthesis project (continued) varied set of synthetic transformations 1 4 — Synthesis project (continued), check-out applicable to a number of substrates. JChemEd.chem.wisc.edu • Vol. 76 No. 8 August 1999 • Journal of Chemical Education
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the second semester, when they are required to devise a synthetic sequence and write a detailed proposal within the first four weeks of the semester, and then attempt to carry out their project and prepare a poster presentation. However, weekly lab reports are not required during the seven weeks of the project. Our three organic faculty have to provide critiques and grades for 45–50 proposals within a short period four weeks into the semester. Timely return of proposals is necessary so that students can compile a list of needed reagents and chemicals. Our stockroom personnel then have three weeks to check our inventory and order chemicals if necessary. Although a large amount of work is required on everyone’s part, the positive feedback indicates that this synthesis project is worthwhile. Project Structure Our synthesis project is composed of four parts: (i) project background, (ii) literature research and proposal writing, (iii) laboratory research, and (iv) presentation of the project. Initially, students are intimidated by the large amount of work necessary to fulfill the requirements of the synthesis project, so we spend a large portion of the first laboratory period providing detailed information for each part of this exercise. Below is a summary of the information we give to students, as well as common difficulties that students have encountered.
Project Background Students are told to choose a product that can be made via a two-step synthetic sequence of their choice. Although initially limited to those reactions that had been performed in lab, we have since expanded the list to include any organic reaction they can find (either in their textbook or in the literature) applied to any substrate of their choice, with the following limitations. First and foremost, proposed reactions cannot pose an unreasonable health or safety hazard, as determined by the instructor. Students are now required to provide MSDS information on all chemicals required for their proposal. Second, we must have the facilities to accomplish the project in our department. For example, we currently do not have the capability to perform an ozonolysis reaction. Third, the starting materials must be available in our stockroom or easily purchased. We set a price limit of one dollar per gram because we expect to the groups to consume up to 25 grams. As instructors, we emphasize to the students that they are allowed to venture into new territory as much as possible and thus push for projects that display originality. Literature Research and Proposal Writing A deadline is given for the final proposal (usually week four of the semester). Before submission of their final proposal, students are required to obtain preliminary approval. They need to sketch out a reaction scheme and informally discuss their project with the instructor. A large portion of the initial discussion is devoted to useful library resources to aid them in their search, for both interesting reactions and the detailed procedures required for their proposal. Typical resources are Chemical Abstracts, Reagents for Organic Synthesis, Organic Synthesis, Comprehensive Organic Transformations, and the Encyclopedia of Reagents for Organic Synthesis. We also direct them to online sources of information such as Current 1128
Contents Online, and occasionally we will perform STN searches with the students. In theory, the students should be familiar with these volumes because they performed a lab on the subject in the first semester. We have evaluated the use of Beilstein Crossfire through a one-month trial (for a flat rate fee, Crossfire allows students to experiment with multiple structural searches). The results of this trial were so positive (in both student satisfaction and quality of research proposals) that the university now subscribes to Beilstein Crossfire on a yearly basis. One common problem during the research phase of the project is that a student returns from a trip to the library extremely frustrated, contending that either the chosen compound has not been prepared or no progress was made. The first question we ask is “How long did you look in Chemical Abstracts?” The typical response is minutes instead of hours. We then explain that a Chemical Abstracts search can involve many hours of research. A second problem is the complexity of the proposed project. Students are not aware of the amount of time required to accomplish the synthesis of a new compound and will propose fairly complex projects. Thus some modifications are made at this stage to simplify the project. After obtaining preliminary approval for a project, students are required to submit a proposal that includes a reaction scheme, a detailed procedure for each synthetic step, proposed methods for purification, proposed methods for product identification including anticipated IR and NMR spectral data (or actual data if the compound is known), and a comprehensive list of chemicals and special glassware needed. To assist in the preparation of the final research plan, we make available to the students a number of proposals of varying quality and originality. Since this project is vastly different from any other lab sequence and this is the first time students have designed their own procedures, the research proposal usually requires major modification. There are several common mistakes associated with the proposals. Many times, the students prepare a lab procedure without regard for the composition of the product. For example, our alcohol dehydration lab from the first semester requires that toluene be used as a chaser solvent. More than once, a group has attempted a dehydration reaction and isolated toluene because they did not recognize that their compound actually boils at a higher temperature than toluene. Therefore, the use of toluene as a chaser solvent was not appropriate. Typically, students do not consider the nature of the product to determine the best method for purification. They also do not realize that there are different methods to purify solids and liquids. We recommend that they try to predict the physical properties of their products, but wait until the compound is isolated before they decide on a purification technique. Students also fail to recognize that remote functionality affects reactivity. Although this concept is taught in lecture, it is difficult to apply the theory to an actual research plan. For example, they learn that a substrate for a Grignard reaction should not contain acidic hydrogens. However, that does not preclude at least one group each year proposing a Grignard reduction of a substrate containing a carboxylic acid group or other acidic hydrogens. Students will often attempt an Organic Synthesis preparation and propose to complete it on that multigram or kilogram scale. We require the scale of the reaction to be reduced, but students often forget that they
Journal of Chemical Education • Vol. 76 No. 8 August 1999 • JChemEd.chem.wisc.edu
In the Laboratory
need to scale down the equipment size for use with smaller amounts of chemicals and solvents.
Laboratory Research After submission and modification of the proposal, the complete chemical lists are compiled, and our stockroom workers have three weeks to collect the chemicals for each
O
O
OH OH
1. PhMgBr, Et2O 2. H3 O+
Ph
OCH3
H3CO O
Ph
O OCH3 1. 4 eq. PrMgBr, Et2 O 2. H3O+
H3CO
AlCl3
+ isomers Ph
O
O +
H+ , ∆
Ph
CH2Cl2
OH
HO
O +
O 1. PhMgBr, Et2O
O O
Ph
CO2CH3
CO2CH3 CO2CH3
CO2CH3
O
1. PhMgBr, Et2O
O Ph
Ph OH
2. H3 O+
OH Ph Ph
O +
Ph
O
+
H3C C Cl
O 1. PhMgBr, Et2O C + CH3 2. H3O
AlCl3
OH
1. PhMgBr, Et2O 2. H3 O+
HO
CH3
Ph
Ph
O
H3 C
O
CO2CH3 + 2
NaOH, CH3OH, ∆
O
Ph
H3 CO2C
O CO2CH3
H3C
HCl, H2O
CH3
H3 CO2C
AcOH, ∆
CO2CH3
CO2CH3
O
5. Spectra (may include GC, IR, NMR, GC–MS, UV– vis) with interpretation. 6. Conclusion or summary.
OH
1. Na2CO3, H2 O
HO3S
2. NaNO2, HCl
OH
N N
NaOH
SO3H
SO3H
Br O
Br
Br
D 1. Mg, Et2O
NaOH
+
2. D2O
O Br
t-BuOK, CHBr3
D
t-BuOK t-BuOH
t-BuOH Br
O
Br
Br
HO
O
Cl + 2 eq.
Cl
CH3
N+ Cl-
NH2
O
H3C
OH
N
1. Title with authors. 2. Abstract, not to exceed 200 words. 3. Introduction with reaction scheme (mechanisms of reactions are not required if they have been covered in class). 4. Full experimental section, following the format used in the Journal of Organic Chemistry.
conc. H2SO4
Ph
OH H3 C
Presentation of the Project In the first years of this laboratory, we asked students to prepare a manuscript in the format of the Journal of the American Chemical Society, complete with abstract, introduction, discussion, and a complete experimental section. Other universities have employed this approach successfully (3). Recently, we converted to a poster session for the final report, and have enjoyed success with this format. Groups are given a four-foot by four-foot space to display their posters. A general guideline for poster content specifies:
O
2. H3 O+
O
project. Needless to say, it is a very hectic time for our stockroom manager. Students then have seven weeks to carry out their proposed research. Each laboratory section is assigned two undergraduate laboratory assistants to answer questions and ensure safe laboratory practices. Faculty members are available to answer questions and provide direction, but we try to emphasize independent problem solving. Each group performs its own analyses (GC, NMR, and IR). In addition to obtaining 1H NMR data on our Varian 360 NMR (a continuous-wave instrument converted to an FT–NMR), students can perform either 13C NMR or an advanced twodimensional technique (COSY, HETCOR, NOESY, etc.) as warranted on our recently purchased a 300-MHz Varian Inova broadband instrument. In addition to problems with reactions not working according to their plan, a few students drop the course at midsemester. The remaining group member is given the option to continue with the project alone or join another group.
AlCl3
NaBH4
Et 2 O
MeOH
O
1. NBS, CCl4 , benzoyl peroxide
Simmons-Smith
OH
All information must be typed, and all structures must be computer drawn. The final projects are evaluated by both the faculty and students according to supplied forms (4). The overall grade for the project is a combination of the faculty and student scores. On the basis of these evaluations, and as a testimony to the hard work put forth by these groups, we present awards at the completion of the research conference. These awards include Best in Show, Superior Achievement, and Most Determined. In addition to recognition, each member of the selected groups receives a plaque. Some of the attempted syntheses from previous years are shown in Figure 1. Approximately 10% of the groups are able to complete the two-step sequence. It is therefore important to explain to the students that actual research is much like this project; that is, 90% of attempted reactions may be unsuccessful. Conclusions
2. t-BuOK, t-BuOH
Figure 1. Examples of attempted syntheses.
In 1990, student evaluations for organic chemistry lab were disappointing. However, after six years of implementation and modification of the approach described here, the student
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assessments of the laboratory component are much more positive. Students now understand why the techniques and reactions learned early in the course are important. They also learned how to apply those skills to projects of their choice. Some general statements from students are included here. I learned more this quarter than ever before. I really like the opportunity to collect my own NMR, IR, and mass spectra. Although this lab was a lot of work, I was excited about doing my own research. I learned techniques I never dreamed about. The hard work was fascinating, as well as invigorating. It was discouraging, but a great learning experience. It taught me a lot about chemistry and myself.
The nontraditional approach of our second semester requires a greater expenditure of time and effort on everyone’s part, but we believe that our approach succeeds in teaching students the art of synthetic design. Students also learn how to implement their plan, solve problems, present their results, function as a member of a team, and most importantly, think independently.
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Acknowledgments We would like to thank the organic chemistry students through the years who have undertaken this project. Special thanks go to Gary McInvale, our stockroom manager. Without his tireless effort, this project would not be successful. Note 1. A preliminary account of this work was presented at the 49th Southeast Regional Meeting of the American Chemical Society, Roanoke, VA, October 19–22, 1997.
Literature Cited 1. Kharas, G. B. J. Chem. Educ. 1997, 74, 829–832. Polniaszek, R. P. J. Chem. Educ. 1989, 66, 970–973. Schatz, P. F. J. Chem. Educ. 1978, 55, 468–470. Cormier, R. A.; Hoban, J. N. J. Chem. Educ. 1984, 61, 927–928. Nuhrich, A.; Varache-Lembège, M.; Lacan, F.; Devaux, G. J. Chem. Educ. 1996, 73, 1185–1187. Buckley, P. D.; Jolley, K. W.; Watson, I. D. J. Chem. Educ. 1997, 74, 549–551. 2. Cooper, M. M. J. Chem. Educ. 1995, 72, 162–164. 3. Dunstran, M.; Bassinger, P. J. Chem. Educ. 1997, 74, 1067–1069. Sisak, M. E. J. Chem. Educ. 1997, 74, 1065–1067. 4. These forms and other materials relevant to this project can be viewed at the Mercer University Department of Chemistry Web page at http://www.mercer.edu/chemistry/.
Journal of Chemical Education • Vol. 76 No. 8 August 1999 • JChemEd.chem.wisc.edu
