Activity pubs.acs.org/jchemeduc
Synthesis Road Map Problems in Organic Chemistry Chris P. Schaller,* Kate J. Graham, and T. Nicholas Jones Department of Chemistry, College of Saint Benedict/Saint John’s University, St. Joseph, Minnesota 56374, United States S Supporting Information *
ABSTRACT: Road map problems ask students to integrate their knowledge of organic reactions with pattern recognition skills to “fill in the blanks” in the synthesis of an organic compound. Students are asked to identify familiar organic reactions in unfamiliar contexts. A practical context, such as a medicinally useful target compound, helps students to see why the study of organic reactions may be important. Drawing from the primary literature, a small library of these problems was developed.
KEYWORDS: Second-Year Undergraduate, Organic Chemistry, Problem Solving/Decision Making, Synthesis
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propose ways to get from one set of materials to a desired product in a couple of steps.8 An interesting variation on these exercises is to provide some spectral data for missing reaction products, reinforcing both reagent recognition and spectroscopy skills.9 These approaches are also available in second-year undergraduate organic textbooks, but only to a limited extent.10 Only a few problems are presented within the context of total synthesis and with a rationale that underscores the importance of synthesizing that specific target. To compensate for these limitations, a pool of problems derived from the primary literature was built. A number of these examples have easily accessible answer keys, providing rapid feedback, whereas others have solutions only in the primary literature; this approach raises the barrier for giving up too easily.11 Approximately two dozen of these problems are delivered within workbooks used for guided inquiry sessions in the classroom. About sixty-five additional problems are freely available on our course Web site, either in appropriate organic chemistry chapters or in a separate section for synthesis problems.12,13
he canon of organic synthetic reactions presents a unique challenge to introductory chemistry students. Arrays of abstract information must be absorbed and catalogued for future recall in a variety of contexts. Instructors strive to find approaches to deliver this information in ways that motivate learning. Recent efforts include a simple journaling approach, as well as the use of web-based tools to encourage practice with reactions.1 Nevertheless, to most students this part of organic chemistry is particularly bone-dry because they lack an understanding of the significance of synthetic chemistry. There are many ways to underscore the utility of organic reactions. The total synthesis of complex molecules, as described in the primary literature, can be a powerful tool for highlighting this chemistry, especially if the compounds have applications, such as medicinal properties, that are easily grasped by students.2 In recent decades, a few authors have made efforts to promote the study of organic synthesis through highly accessible textbooks that lead the reader through illustrative case studies.3,4 However, only a small number of organic chemistry textbooks devote significant attention to the subject, either in the form of a chapter on synthesis5 or through a concerted effort to incorporate synthetic considerations into other chapters.6 Organic synthesis problems that are complementary to those found in most textbooks have been developed. These “road maps” walk students through a total synthesis, presenting familiar reactions in unfamiliar contexts with exciting applications. Problems of this type are sometimes used in courses devoted to organic synthesis at the graduate or advanced undergraduate level. Workbooks are available that employ road maps in addition to more sophisticated material not typically covered in an introductory-level class.7 Other texts require students to © XXXX American Chemical Society and Division of Chemical Education, Inc.
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ACTIVITY DESIGN
Road map problems are examples of total syntheses of natural products from the current or classic literature. A portion of one of the problems is illustrated in Scheme 1. Students are usually led through the synthesis one step at a time. Reagents or intermediate products are left blank at strategic points so that students have to fill in the missing information based on reactions they have already learned.
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Scheme 1. Portion of a Road Map Based on the Total Synthesis of (−)-Platensimycin14a
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The full problem is available in the Supporting Information.
However, it is unclear whether these exercises actually enhance skill at planning and carrying out a synthesis. Because the entire synthesis is already laid out for students, road maps probably have less value in this regard than a standard question requiring students to propose a short retrosynthesis. Nevertheless, it is hoped that road maps can generate enough interest in synthesis that students may be interested in engaging in the study of synthesis in the first place.
These exercises, based on examples from primary literature, have been used at CSB/SJU for about 15 years. Problems are periodically revised if they prove particularly frustrating to students. Students are certainly not expected to produce the “right” answers for each question; rather, they should give a reasonable response based on what they have seen in class. In some cases, one instructor might accept any hydride reagent for a given problem, whereas another would expect students to choose the right one based on selectivity.
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STUDENT RESPONSE Although anecdotal, the effect of road maps upon a few individual students has been profound, leading them to think about the pursuit of organic synthesis at the graduate level. Although it was not necessarily the intent, some students use road maps to learn new information. There are always unfamiliar portions of syntheses, so those steps are sometimes left filled in, showing both reagents and products. Even if there is no question being posed about that reaction, stronger students will often try to puzzle it out based upon what they already know. Some students have also identified instances in which the stereochemistry of a reaction has been controlled and have speculated on the source of stereocontrol. Occasionally, students hand in a roadmap assigned as homework with clearly unfamiliar reagents taken directly from the original research article. In a sense, the intent of the exercise is subverted in these cases; however, it does not seem like a loss when a first-or second-year chemistry student has successfully navigated a journal article. A more formal assessment was sought in the form of student survey data. Students in a second semester organic chemistry class were asked to rate how road maps affected different aspects of their learning in a Student Assessment of Learning
PEDAGOGICAL VALUE Building a connection between the material students have learned and the primary literature reinforces to students that they are studying real science.15 The fact that they are gaining entry into the world of current research can be deeply motivational.16 Some authors have used the primary literature to incorporate research tools into organic chemistry, including reading and analysis, as well as writing or presentation skills.17 Other authors have used the literature to bridge organic chemistry and biology.18 Primary literature has been used as a tool to incorporate problem-based learning into an advanced organic chemistry laboratory.19 Importantly, some have found the use of the primary literature of organic synthesis to be helpful in consolidating students’ understanding of foundational concepts of organic chemistry.2 Road maps also provide practice in spatial strategies, a key skill in organic chemistry.20 Isolation and identification of the problem is crucial; to do so, students often need to cover up all but the portion of the molecule they are working on. Upon finding the portion of the old molecule remaining and the new moiety that is added, they must identify the probable electrophile and nucleophile. B
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Figure 1. Student perception of roadmaps in a second semester organic chemistry course.
assess the difficulty of identifying the changes taking place in an individual reaction on a roadmap; 48% of second-semester students agreed that this task was challenging, compared to 21% of fourth-semester students. When asked about providing the correct reagent to carry out a reaction, 87% of secondsemester students agreed that this task was difficult, compared to 58% of fourth-semester students. Again, there was a positive shift in responses that correlates with additional experience of students. The principal goal of implementing this activity was to provide students with a motivation for learning organic reactions. Road maps are clearly helpful in this regard, as shown by the student response.
Gains (SALG; spring 2012, 24 students responding). This class was the final section of organic chemistry before switching over to a new curriculum that spreads the content of organic chemistry across other, integrated interdomain courses.21 The course was populated with second-year and upper-division students. Most students were nonmajors who wished to complete organic chemistry requirements for graduate school in biology or the health professions. Key results are summarized in Figure 1. Overall, 79% of respondents rated road maps between “moderate help” and “great help” in their overall learning. The major benefit of road maps was perceived to be the illustration of useful applications of chemistry: 87% rated them between “moderate help” to “great help” in this area. However, students do not find these problems easy. Only 62% felt road maps were between “moderate help” and “great help” in boosting their confidence about reactions. See the Supporting Information for summaries of assessment results. During the spring 2014 semester, students were given another survey that was more narrowly focused on the use of roadmaps; the data are summarized in the Supporting Information. Briefly, students were enrolled in either second-, third-, or fourth-semester chemistry courses (Reactivity in Organic, Biological, and Inorganic Chemistry I, II, or III). Reactivity I involved the largest number of students (170 respondents), mostly first-year undergraduate students. Reactivity II, which most students take in the fall rather than spring, involved smaller numbers of students (20 respondents); about half were first-year students who had started Reactivity I in the fall semester after taking an introductory chemistry course over the summer. Reactivity III was composed mostly of second-year chemistry or biochemistry majors (19 respondents). In general, student assessment was similar to the earlier data in terms of the usefulness of roadmaps in learning organic reactions and seeing the application of organic chemistry. However, responses were strongly dependent on the maturity of students in the chemistry sequence. Thus, in response to a five-point Likert scale, 45% of second-semester students gave a positive rating of the usefulness of roadmaps in learning organic reactions, compared to 84% of fourth-semester students. Similarly, when asked about whether roadmaps highlight useful applications of organic chemistry, 38% of second-semester students responded favorably compared to 90% of fourthsemester students. Additional insight was obtained by asking these groups about the specific challenges of road maps. Students were asked to
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STUDENT PERFORMANCE Road maps have also been used in testing situations to assess students’ use of organic reactions in appropriate contexts. In an introductory version of this activity, students in a first-year, second-semester chemistry course were introduced to road maps on group homework assignments. Students were then presented with a roadmap in an individual testing situation (Scheme S6, Supporting Information; 58 students, spring 2014). The problem was presented as a multiple-choice exercise. A substantial number of choices were provided, representing possible reagents or reaction products (Supporting Information Figure S1). The average score on the test was 81%, indicating that first-year students were able to master the relatively easy task of matching reaction components from a template. In another situation, students in a second-year, first-semester chemistry course were presented with a roadmap in a testing situation, this time without options to choose from (Supporting Information Schemes S12 and S13; 35 students, fall 2012). The average score on this test was 69%, showing the slightly greater difficulty of identifying reagents and reaction products without choices to guide the decision. With the help of officials from the ACS Exams Institute, selected problems from ACS organic exams were also incorporated into final exams in Reactivity I, II, and III (Supporting Information Tables S1−S3). In general, these data do not show much difference between the performance of students on questions involving organic reactions and students nationwide.
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SUMMARY A good resource for problems is always needed. The primary literature in organic synthesis is a valuable source of relevant C
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(9) Taber, D. Organic Spectroscopic Structure Determination; Oxford University Press: New York, 2007. (10) (a) McMurry, J. Organic Chemistry, 8th ed.; Brooks/Cole: Belmont, CA, 2012. (b) Smith, J. G. Organic Chemistry; McGraw Hill: New York, 2006. (c) Jones, M.; Fleming, S. A. Organic Chemistry, 4th ed.; W. W. Norton & Co.: New York, 2010. (11) McGuire, S. Y. Teaching Students How to Learn Chemistry. Strategies for Success 2003, 40, 4−5, http://www.pearsonhighered. com/strategies/assets/pdf/strategies/Strategies_40.pdf, (accessed Dec 2013). (12) Structure and Reactivity in Chemistry: Organic Synthesis. http://employees.csbsju.edu/cschaller/Reactivity/orgsyn/ orgsyn%20roadmap.htm (accessed Dec 2013). (13) See also: (a) Evans Group, Harvard University: Challenging Problems in Organic Chemistry and Chemical Biology. http://www2. lsdiv.harvard.edu/labs/evans/problems/index.cgi (accessed Dec 2013); includes roadmap problems. (b) Connell Group, Texas A&M University: Advanced Organic Roadmap Problems. http://www. chem.tamu.edu/rgroup/connell/roadmapproblems/index.html (accessed Apr 2014); roadmap problems. (c) Reich Group, University of Wisconsin-Madison: Total Syntheses. http://www.chem.wisc.edu/ areas/reich/syntheses/syntheses.htm (accessed Apr 2014); a good resource providing total syntheses that could be adapted to roadmap problems. (14) Ghosh, A. K.; Xi, K. Total Synthesis of (−)-Platensimycin, a Novel Antibacterial Agent. J. Org. Chem. 2009, 74 (3), 1163−1170. (15) (a) Coppola, B. P.; Ege, S. N.; Lawton, R. G. The University of Michigan Undergraduate Chemistry Curriculum 2. Instructional Strategies and Assessment. J. Chem. Educ. 1997, 74 (1), 84−94. (b) Gottfried, A. C.; Sweeder, R. D.; Bartolin, J. M.; Hessler, J. A.; Reynolds, B. P.; Stewart, I. C.; Coppola, B. P.; Banaszak Holl, M. M. Design and Implementation of a Studio-Based General Chemistry Course. J. Chem. Educ. 2007, 84 (2), 265−270. (16) Raker, J. R.; Towns, M. H. Designing undergraduate-level organic chemistry instructional problems: Seven ideas from a problemsolving study of practicing synthetic organic chemists. Chem. Educ. Res. Pract. 2012, 13 (3), 277−285. (17) (a) Rosenstein, I. J. A Literature Exercise Using SciFinder Scholar for the Sophomore-Level Organic Chemistry Course. J. Chem. Educ. 2005, 82 (4), 652−654. (b) Gallagher, G. J.; Adams, D. L. Introduction to the Use of Primary Organic Chemistry Literature in an Honors Sophomore-Level Organic Chemistry Course. J. Chem. Educ. 2002, 79 (11), 1368−1371. (18) Almeida, C.; Liotta, L. J. Organic Chemistry of the Cell: An Interdisciplinary Approach to Learning With a Focus on Reading, Analyzing and Critiquing Primary Literature. J. Chem. Educ. 2005, 82 (12), 1794−1799. (19) Flynn, A. B.; Biggs, R. The Development and Implementation of a Problem-Based Learning Format in a Fourth-Year Undergraduate Synthetic Organic and Medicinal Chemistry Laboratory Course. J. Chem. Educ. 2012, 89 (1), 52−57. (20) Stieff, M.; Ryu, M.; Dixon, B.; Hegarty, M. The Role of Spatial Ability and Strategy Preference for Spatial Problem Solving in Organic Chemistry. J. Chem. Educ. 2012, 89 (7), 854−859. (21) Schaller, C. P.; Graham, K. J.; Johnson, B. J.; Fazal, M. A.; Jones, T. N.; McIntee, E. M.; Jakubowski, E. M. Developing and Implementing a Reorganized Undergraduate Chemistry Curriculum Based on the Foundational Chemistry Topics of Structure, Reactivity, and Quantitation. J. Chem. Educ. 2014, 91 (3), 321−328.
examples of organic reactions. The literature was used to develop a number of roadmap problems for the recognition of organic reactions in unfamiliar contexts. The utility of modern synthesis in pharmaceutical or agrochemical applications helps students to see the “big picture” of organic chemistry. Students start to see how chemists put synthesis to work and understand why they should care about the reactions they have been learning.
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ASSOCIATED CONTENT
S Supporting Information *
Examples of some roadmap problems and assessment data. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors wish to thank Edward McIntee, Rachel Hutcheson, and Alicia Peterson for helpful contributions. REFERENCES
(1) (a) Teixeira, J.; Holman, R. W. A Simple Assignment That Enhances Students’ Ability to Solve Organic Chemistry Synthesis Problems and Understand Mechanisms. J. Chem. Educ. 2008, 85 (1), 88−89. (b) Chen, J. H.; Baldi, P. Synthesis Explorer: A Chemical Reaction Tutorial System for Organic Synthesis Design and Mechanism Prediction. J. Chem. Educ. 2008, 85 (12), 1699−1703. (c) Draghici, C.; Njardarson, J. T. Chemistry By Design: A Web-Based Educational Flashcard for Exploring Synthetic Organic Chemistry. J. Chem. Educ. 2012, 89 (8), 1080−1082. (2) (a) Vosburg, D. A. Teaching Organic Synthesis: A Comparative Case Study Approach. J. Chem. Educ. 2008, 85 (11), 1519−1523. (b) French, L. G. Teaching Organic Synthesis: An Advanced Organic Chemistry Course That Uses the Primary Literature. J. Chem. Educ. 1992, 69 (4), 287−289. (c) Alcudia, A.; Ferris, C.; Violante de Paz, M. Capecitabine: A Classroom Project for the Study of General Principles in Organic Synthesis. Chem. Educ. 2010, 15, 479−483. (3) (a) Fleming, I. Selected Organic Syntheses: A Guidebook for Organic Chemists; John Wiley & Sons: London, 1973. (b) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis; Wiley-Interscience: New York, 1989. (4) (a) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis: Targets, Strategies, Methods; Wiley-VCH: New York, 1996. (b) Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis II: More Targets, Strategies, Methods; Wiley-VCH: New York, 2003. (c) Nicolaou, K. C.; Chen, J. S. Classics in Total Synthesis III; Wiley-VCH: City, 2011. (5) Hornback, J. M. Organic Chemistry, 2nd ed.; Thomson Brooks/ Cole: Belmont, CA, 2006. (6) Bruice, P. Y. Organic Chemistry, 7th ed.; Pearson: Upper Saddle River, NJ, 2014. (7) (a) Gewert, J.-A.; Görlitzer, J.; Götze, S.; Looft, J.; Menningen, P.; Nöbel, T.; Schirok, H.; Wulff, C. Organic Synthesis Workbook; WileyVCH: Weinhiem, 2000. (b) Bittner, C.; Busemann, A. S.; Griesbach, U.; Haunert, F.; Krahnert, W.-R.; Modi, A.; Olschimke, J.; Steck, P. L. Organic Synthesis Workbook II; Wiley-VCH: Weinhiem, 2001. (c) Kinzel, T.; Major, F.; Raith, C.; Redert, T.; Stecker, F.; Tölle, N.; Zinngrebe, J. Organic Synthesis Workbook III; Wiley-VCH: Weinheim, 2007. (8) Warren, S.; Wyatt, P. Workbook for Organic Synthesis: The Disconnection Approach, 2nd ed.; Wiley: Great Britain, 2010. D
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