A Research-Based Laboratory Course in Organic Chemistry

In the Laboratory

A Research-Based Laboratory Course in Organic Chemistry

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Thomas A. Newton,* Henry J. Tracy, and Caryn Prudenté Department of Chemistry, University of Southern Maine, Portland, ME 04104-9300; *[email protected]

We have created a research-based laboratory course as an alternative to more traditional organic laboratory instruction. We have adapted one of our faculty’s research projects to provide the vehicle for introducing this new approach employing combinatory methods. We find this research emphasis not only engages students but also more closely resembles the way chemists do chemistry. Students experience the challenge of devising and executing their own experiments, the satisfaction of determining the outcomes of those experiments, and the thrill of making novel compounds. They also come to appreciate the need to describe those experiments in writing. Prompting our decision for change was our desire to direct students’ focus away from outcomes onto the process of scientific discovery by replacing our traditional experiments with a program that had no “right” answers, namely a research-based course. Earlier research reinforced our decision. In 1994, Amenta and Mosbo (1) concluded that their “research-based problems approach has increased student interest in chemistry”. They also noted “an increase in independent thinking and a decrease in the sophomoric approach to problem solving of looking only to textbooks and faculty for answers”. Other educators (2) have found that exposing students to chemical research increases retention, another long-term goal of our new course. In 1997, Kharas (3) described a program in which students in an introductory organic chemistry course were assigned individual nine-week projects involving the preparation of ethylene–styrene copolymers. During a three-year period the students prepared more than 50 trisubstituted alkenes. These compounds were polymerized with styrene to generate a series of copolymers, none of which had been previously reported in the literature. Given the pedagogical advantages of such a combinatorial approach, in 1998 we initiated a full-year research-based organic chemistry laboratory course involving the synthesis and characterization of a series of group 14 metalloles. The primary goals for this project1 were to:

enhancing their ability to achieve the goals outlined above. However, we want to emphasize that we do not expect others to duplicate the chemistry described below. Indeed the strength of this approach is its flexibility to accommodate large numbers of students by the combination of different substituents in the starting materials. This approach allows each student to prepare a unique compound. Development Our initial project is summarized in Figure 1. In this scheme G represents a substituent that may be attached to the ortho, meta, or para position of the aromatic ring. The groups that we have used include H, CH3, OCH3, CF3, F, and Br. In structures 2–6 the G groups are not necessarily the same. E symbolizes one of the group 14 elements: Si, Ge, or Sn. Using 18 commercially available benzyl bromides and benzaldehydes, Figure 1 implies a synthetic path for the preparation of 972 different metalloles. (This number represents 18 years of unique compounds, given our current enrollments in our organic laboratory course.) Since most of these compounds have never been prepared, each student would have the opportunity to experience the thrill that attends successful synthesis of a new compound and the excitement that is an inherent quality of basic research. While there are more direct methods for preparing alkynes than the route shown in reactions 1–4, we chose this sequence initially because it suited our pedagogical objectives as well as our research goals; these four reactions provide students with firsthand experience with a nucleophilic substitution reaction, a Wittig reaction; electrophilic addition; and a 1,2-elimination, all of which are covered in lecture. We chose these reactions because they are easy for novice experimenters to perform and the products are relatively simple to isolate and purify. For example, the first reaction merely requires refluxing the reactants for several hours before isolating the product by vacuum filtration. Washing the product with an organic solvent yields pure phosphonium salt.

• Create an atmosphere of scientific discovery • Forge stronger faculty–student and student–student collaboration • Increase student interest in the laboratory by introducing the synthesis of new compounds and the planning of the synthesis, and controlling the variables that affect the synthesis • Increase critical-thinking skills • Enable students to achieve mastery of a set of laboratory skills

This article describes the development, implementation, evolution, and evaluation of our efforts. Our experience has convinced us that this combinatorial chemical approach to a research–based laboratory course is enabling us to realize these goals. Furthermore, we believe that such an approach can serve as a model for other institutions that are interested in 1844

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Implementation Adapting a faculty member’s research program to the constraints of an undergraduate teaching laboratory almost certainly requires some modification of existing laboratory facilities. In our case, we needed to address the fact that reactions 5 and 6 (Figure 1) require an inert atmosphere. In the first year of the program, we met this requirement by constructing a six-port manifold for each of the three benches in the laboratory. This meant all 18 students possessed their own source of inert gas. Later, with the help of funds from an NSF grant,2 we installed three glove boxes that students used to conduct the last two reactions of the synthetic sequence. No additional specialized equipment was needed. For work with materials that were not air or moisture sensitive, we relied on the microscale equipment we had used for the previous 12 years.

Vol. 83 No. 12 December 2006

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In the Laboratory

We composed a project overview document, generalized procedures, and pre- and post-laboratory exercises for the sequence of six reactions depicted in Figure 1.3 The pre-laboratory exercises were designed to focus students’ attention on questions involving stoichiometry: balancing equations, identifying limiting reagents, calculating theoretical yields, and so forth. The primary goal of the post-laboratory exercises was to help students organize the results of their experiments prior to the preparation of a formal report in which they describe and discuss those results. Since most scientific research is inherently collaborative and the fostering of collaboration was one of our goals, from

the outset we assigned students to work in small groups on several facets of the laboratory. For example, to determine an appropriate solvent system for TLC analysis of a particular reaction, a group of students would experiment with a variety of solvent mixtures to find the most effective eluant for separation. Also, we trained one student in each group on the operation of a specific instrument; IR, NMR, or GC– MS. That student then helped other students obtain satisfactory spectra. Students also proofread initial drafts of their colleagues’ formal reports before they were submitted to the instructor. We found that assigning group tasks promoted interactions among students within a group and between stu-

ⴙ

P␾ 3

Br P␾3/THF

(1)

ⴚ

Br

G

G

H3Cⴚ2

1 ⴙ

G

P␾ 3 Brⴚ

(2)

base

+

CHO

G

G

G

2

G Br

G Br2

(3)

CH2Cl2

G

Br

2

G

3 G Br base

G

G

(4)

Br

4 G

3

G

G

G

G

(5)

1. n-BuLi/THF 2. Cp2ZrCl2

4

Zr

G

Cp

Cp

G

5

G

G

G

G

R2ECl2

G

Zr Cp

E

G

G

Cp

(6)

R

Cp2 ZrCl2

5

R

G

6

Figure 1. A combinatorial approach to the synthesis of a series of metalloles. G represents H, CH3, OCH3, CF3, F, or Br that may be attached to the ortho, meta, or para position of the aromatic ring. The G groups may not be the same in the structures. E represents Si, Ge, or Sn.

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In the Laboratory

dents in other groups. If one group discovered an effective TLC eluant, the students quickly shared their results. Encouraging group work, also empowered students to ask each other questions as they searched for the most effective strategies for their syntheses and purifications. Evolution Some aspects of the research-based work were implemented successfully. Others were not. We learned by trial and error. During the first year of the program, we were overly ambitious. We did not use model compounds. Furthermore, we asked students to adapt synthetic schemes for their target molecules by analyzing literature procedures for analogous reactions. Even though the students worked in groups, they found this assignment overwhelming. In the second year, we added the syntheses of model compounds (G = H = hydrogen in Figure 1) to help boost students’ confidence in their abilities to perform these reactions. We sequenced the work so that students prepared a model compound one week, followed by a target compound (G ≠ H in Figure 1) the next. While this approach represented an improvement, most students never progressed through the entire sequence of reactions. Consequently, during the third year, we directed the students to execute the complete reaction sequence using model compounds, before repeating the six-step reaction sequence to prepare their target compounds. This change ensured that each student had the opportunity to run all six reactions even if he or she never got to the last few steps of the sequence with their target compounds. At this point we were still directing students to devise their own procedures by analogy to literature procedures. In the fourth year, we reluctantly abandoned this approach; instead we provided students with explicit instructions for the preparation of each of the model compounds. This change proved effective. It enabled students to gain confidence in their ability to do this type of research and boosted their morale. Furthermore, almost all students were able to complete the entire model reaction sequence in the first semester. In the second semester, students focused their attention on the preparation of their target compounds. Here they designed the experiments for the preparation of their target compounds by modifying the procedures they used for the syntheses of model compounds. When attempting to prepare their target stilbene, for example, some students performed the Wittig reaction in THF at ᎑78 ⬚C, using n-BuLi as the base, while others ran it in hexane at room temperature using sodium amide. Throughout the evolution of this project, we sought ways to encourage students to work collaboratively. In our first year, we assigned students to work solely in groups. We quickly learned that the slowest member of the group determined the pace of work. Consequently, from the second year on, we encouraged students within each group to work at their own pace. At the same time, we urged students within a group to share their results and observations. We found students profit both from working alone and working with a group. For example, the results obtained by better students were often helpful to their slower colleagues when they performed similar procedures. Similarly, it was often the case that one student was able to help another record an NMR spectrum, or prepare a KBr pellet, or dilute a sample to the appropriate 1846


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concentration for GC–MS analysis. In fact, we trained one student in each group on the operation of one of these three instruments. That student then helped other students obtain satisfactory spectra. We also encouraged collaboration by having students proofread initial drafts of their colleagues’ formal reports before submitting them to the instructor. Hazards Specific safety considerations will vary from project to project. For the projects described in this article, students are familiarized with the potential hazards of working in an organic chemistry laboratory at the beginning of each semester. The course syllabus contains a section outlining the requirements and recommendations for working in the lab. The Web site contains links to MSDS information and to the Lab Safety Plan that is specific for the organic chemistry laboratory. Specific information about the hazards associated with a particular chemical is provided on a reaction-by-reaction basis. Evaluation Our evaluation procedure relied on four criteria: (i) a grading scheme that allowed students to repeat their work until they receive a satisfactory grade, (ii) a student survey (see the Supplemental MaterialW ) in which students gage their perceived mastery of laboratory skills and their perception of the advantages or disadvantages of a research-based laboratory course, (iii) independent reviews of student work by organic chemistry professors from other institutions, and (iv) qualitative assessments by chemistry laboratory instructors. Comments from both the student surveys and laboratory instructors enabled us to assess the achievement of two of our goals: the creation of a climate of scientific discovery and an increase in student interest in the laboratory approach. Observations of the instructors inside and outside the laboratory attested to our goal of forging strong faculty–student and student–student collaboration. In the realization of our goal to enhance critical-thinking skills, we looked to the comments of outside evaluators who had examined 15 representative student laboratory reports. The laboratory grading schemes and the student surveys determined how well we met the final goal, that of student mastery of a set of laboratory skills. (The student survey was constructed in consultation with the director of the USM Center for Educational Policy, Applied Research and Evaluation. The results of six semesters of surveys were compiled and summarized in the director’s report. See the Supplemental Material.W ) Evaluation of Students To minimize competition and maximize cooperation among students, we devised a grading system that was based upon the students’ mastery of specific laboratory skills. At the outset of the project we identified a group of techniques we believed representative of those used by the majority of practicing synthetic chemists. Those skills entailed four main areas: basic operations (recrystallization, distillation, melting point determination, and inert atmosphere techniques), written communication (laboratory notebooks and formal labo-


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In the Laboratory

ratory reports), chromatography (TLC, GC, and LC), and spectroscopy (IR, NMR, and MS). For each of the six steps of the synthetic scheme, students were required to demonstrate mastery of a particular group of techniques by successfully completing the aforementioned pre- and post-laboratory exercises. Using reaction 2 in Figure 1 as an example, to monitor the reaction by TLC, students were assigned the task of devising a solvent system that would resolve (Z )- and (E)stilbene as well as triphenylphosphine oxide. They also had to recrystallize the crude product and record IR, NMR, and GC–MS spectra of their purified sample. Stress on attaining skill in written communication has been an integral feature in all chemistry courses at this university since 1999. At that time the department adopted a “writing across the chemistry curriculum” requirement, which we have described in this Journal (4). Adhering to our writing policy, the organic laboratory course emphasizes clear written documentation of procedures and observations within the laboratory. An extensive Web document describes acceptable writing and comments on the department’s goal of writing to learn.4 Some of the salient points are • Submitted work should conform to edited standard written English, • Choose words with precision and spell them correctly, • Construct logical and grammatically correct sentences, • Develop a single topic in each paragraph, • Arrange paragraphs in a sensible order, and • Instructors will return unsatisfactory work, with suggestions, and the student will revise and resubmit the work.

In addition to the weekly lab notes, we require students to write a formal laboratory report on each of the 6 reactions described in Figure 1. The report must include an equation describing the chemical reaction performed, a table of reagents used, a detailed procedure describing the chemistry occurring during the reaction, the yield and characterization of the product(s), and a detailed analysis of each spectroscopic technique employed to prove the identity of the product(s). We strongly believe that a student’s writing skills need to be addressed in our courses, at all levels.5 Students’ performance on each of these skills was judged to be either satisfactory (S) or unsatisfactory (U). Students who received a U for a particular skill were encouraged to repeat their work until they received an S. Each semester we evaluated each student’s performance on 30 items. We assigned course grades based upon the number of S’s each student earned. Students receiving 24–30 S’s, earned an A, 21–23 S’s earned students a B, and students receiving 18–20 S’s, received a C. For the three most recent years of the project, the grade distribution was A = 28%, B = 64%, and C = 8%. Evaluation by Students The synthetic scheme outlined in Figure 1 constituted part of the overview of the project that students received at the beginning of the course. In addition to outlining the research objectives, the handout described the skills we hoped students would master by the time they had completed the project. At the end of the course, we asked the students to www.JCE.DivCHED.org

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assess on a scale of 1 to 5, where 1 meant very satisfactory or excellent and 5 meant very unsatisfactory or very poor, whether the project had achieved the stated goals, in particular, mastery of the set of laboratory skills. After three years, the University’s Center for Education Policy, Applied Research, and Evaluation assessed the surveys. The Center concluded “while the analysis shows some variation between semesters throughout, the majority of responses were very positive with the general trend showing improvement or maintaining very positive responses over the length of the project.” The report assessed three categories of the student survey. In assessing whether the course objectives were attained, the analysis found that “Overall the percentage of students whose responses were satisfactory to very satisfactory in each of the 13 course objectives was very high.” Regarding their overall lab experience, “ ... a majority (57.4%) of respondents rated their overall experience in this course superior to excellent when compared to their introductory chemistry laboratory courses.” When asked to rate their understanding and mastery of eight laboratory techniques, student responses varied, with the average ranging between neutral and satisfied. A copy of the entire report is included in the Supplemental Material.W Several representative qualitative statements from students commenting on the differences between more traditional laboratory experiences and this research-based approach include: I previously attended another university where I took the ‘cookbook’ style laboratory. I found the labs just taught technique and they required little thought. This research-based lab I found exciting. We were given a goal and we set out to reach it. Along the way we (I) learned all of the techniques. I personally looked forward to each lab and usually found myself thinking about the lab during the week, which was something I never did with the ‘cookbook’ style method. As a nontraditional student, I have a perspective from which to make a comparison. Previously, as an undergraduate student, I took both general and organic chemistry laboratories, which would be called ‘cookbook labs’. Usually I was lucky to have read an experiment over before setting foot in the lab. I would listen to the TA’s instructions, go through the motions, get results and leave. One experiment forgotten by the time the next lab came around. I have no recollection of any of those experiments or techniques. This ‘research-based’ approach was much more stimulating and educational. Prep work and pre-planning was essential. This was basically one giant lab that continued for an academic year, not a bunch of ‘mini exercises’. Where else could you get this kind of continuity and focus by which one gains ‘real’ understanding? I attended a research-based laboratory in hopes of synthesizing metalloles. This made me feel that I was part of something important. I’ve taken an organic lab at another school that was traditional in its setup. Many students, myself included, attended lab in a ‘fog’ as to what we were actually doing. With the research style you really care about what you’re doing—you go through the frustrations and you prepare yourself…It got me to think and apply what I know!

Not one student who was in a position to make a comparison preferred the more traditional forms of laboratory instruction to this research-based approach.


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Evaluation by Outside Evaluators

search-based approach is superior to the discovery-based approach that it replaced. They found student performance superior in many areas, most notably in spectroscopy. The quality of students’ written work, both their lab notebooks and their final reports, was also superior. Most notable to everyone involved in this project was the change in students’ attitudes. The opportunity to repeat an experiment that did not work, the extension of an experiment that did, the design of a new experiment, the anticipation of making a previously unknown compound were all factors that kept students engaged and excited in ways that more traditional approaches to laboratory instruction had not. After teaching the new course for the first time, one faculty member noted that students routinely asked for advice regarding the synthetic plan they were devising for their upcoming laboratory period and that they expressed more commitment to and ownership of their research project compared to students enrolled in discovery-based courses in previous years.

For each of the six synthetic steps students prepared a concise, word-processed summary of their work as described earlier. Two organic chemistry faculty evaluators from other institutions received copies of 15 representative formal reports and were asked to compare the level of sophistication demonstrated by the reports with that of their organic laboratory students. One reviewer wrote, “From reading the reports it would appear that students in this lab course have engaged the material to a better degree than it most courses and actually understand what is occurring in the flask.” This reviewer summarizes, “The innovations demonstrated in the materials provided to me are clearly an improvement to a traditional laboratory course. With no sacrifice in the area of skills acquisition, the students’ ability to communicate, to observe, to improvise, and to interpret results has been augmented.” In conclusion, he writes, “The real value of the approach evaluated above is that it is extraordinarily flexible. The idea of diversity in instructional lab experiments can be applied to anyone’s ‘pet reaction’ and the benefits of increased student awareness, enhancement of communication, and more engaged learners should be realized, as long as the reactions tolerate the variations incorporated into the dynamic model. I would hope that this way of refining the sophomore organic chemistry laboratory course will find further implementation at other universities.” The second evaluator commented that he “found the reaction sequence to be the most original and novel multiweek lab program I have seen over the last decade and I am impressed with the level of technical sophistication that is evidenced by the individual students.”

Discussion This project continues to evolve. In its most recent iteration students in one section of the course investigated an alternative approach to the synthesis compound 4 (Figure 1), while those in the other sections worked on the project as originally conceived. Furthermore, we have developed a new program based on the research interests of one of the authors involving the chemistry of bioconjugates. An overview of the synthetic scheme we intend to implement is shown in Figure 2. Because of the hazards associated organomercury compounds, students will perform only reactions 1, 2, and 3. Nonetheless the project will be presented in terms of its broader goal, the preparation of mercury-specific antibodies of the type represented by structure 4. With n being 1 or 2, and n´ equal to 2–4, structure 3´ embodies six target molecules. We will divide the 18 students in one of our laboratory sections into six groups of three students. Each group

Evaluation by USM Faculty Five faculty members have supervised one or more laboratory sections for at least one year. All agree that this reO

1. t-BOC

NH2

(1)

NHt-BOC

2. m-CPBA

1ⴕ MgBr

O

n

NHt-BOC 1ⴕ

(2)

NHt-BOC

n

OH 2ⴕ O

O

1. TFA

NHt-BOC

n

2. RO2C(CH2)n′ CO2R 3. BSA

OH 2ⴕ O

O

OH

n′

OH

NHBSA

O

O

O N H

2. NaBr

(3)

3ⴕ

n′

NHBSA

(4)

4ⴕ

n

3ⴕ

NHBSA

n′

HgBr 1. Hg(OAc)2

N H

n

N H

n

Figure 2. A combinatorial approach to the synthesis of a series of bioconjugates: BOC is butyloxycarbonyl, CPBA is chloroperbenzoic acid, TFA is trifluoroacetyl, and BSA is bovine serum albumin.

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will attempt to prepare one of the target compounds. This new program will give students more choice in terms of the type of research they conduct. Our experience has convinced us that almost any research project that entails a synthetic component may be incorporated into an undergraduate laboratory course. We offer the following suggestions for anyone interested in doing so: • Use model compounds to introduce students to the techniques they will require, • Balance your pedagogical goals with your research objectives, • Have students work in small groups, • Identify specific techniques you expect students to master, • Allow sufficient time for students to characterize their products, and • Require final reports for each reaction.

In conclusion, our experience has demonstrated that a research-based laboratory excels in four areas: 1) Students experience the fundamentals of basic research, where experimental results inform subsequent experiments. Students are exploring unknown territory. 2) The research-based laboratory fosters collaboration between students and between students and faculty. 3) The research-based laboratory emphasizes the development and mastery of chemical analysis skills to determine what is happening in a reaction and to identify the products of a reaction. 4) The research-based laboratory requires the mastery of written communication skills to both convey to the instructor the student’s progress and also to allow the student to exactly repeat a successful reaction or to be able to intentionally modify the reaction conditions.

Acknowledgments The authors are grateful to Brian Hodgkin, Director of the Bioscience Research Institute at USM, for significant and

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continuing financial support of this project, including funds for the purchase of a new GC–MS instrument. The purchase of a 300 MHz NMR spectrometer and three research-quality glove boxes was made possible by grant 0087862 from the National Science Foundation’s CCLI Adaptation and Implementation Program. Notes 1. The USM O=CHem Web site is available at http:// www.usm.maine.edu/~newton/Chy251_253/Welcome.htm (accessed Sep 2006). 2. Newton, T. A.; Tracy, H. J. A Research–Based Organic Chemistry Laboratory Curriculum Employing Combinatorial Techniques, NSF-DUE-CCLI Adaptation and Implementation grant 0087862. 3. These handouts are online at http://www.usm.maine.edu/ ~newton/CHY252_254/252/LabMaterials_02.html (accessed Sep 2006). 4. The USM Chemistry Department’s writing policy is available online at http://www.usm.maine.edu/chy/writepol.htm (accessed Sep 2006). 5. Every summer USM offers a two-week program to help faculty learn to analyze and critique students’ written work. Members of the chemistry department have been both participants and presenters in these programs. W

Supplemental Material

Examples of student reports, the assessment instrument and analysis, and reports by the outside evaluators are available in this issue of JCE Online. Literature Cited 1. Amenta, D. S.; Mosbo, J. A. J. Chem Educ. 1994, 71, 661. 2. (a) Holme, T. A. J. Chem. Educ. 1994, 71, 919. (b) Eichstadt, K. E. J. Chem. Educ. 1992, 69, 48. 3. Kharas, G. B. J. Chem. Educ. 1997, 74, 829. 4. Gordon, N.; Newton, T. A.; Rhodes, G.; Ricci, J. S.; Stebbins, R.; Tracy, H. J. J. Chem. Educ. 2001, 78, 53.


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A Research-Based Laboratory Course in Organic Chemistry

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