In the Laboratory
Synthesis of a 7-Oxanorbornene Derivative: A Two-Step Sequence Preparation for the Organic Laboratory Marcia B. France,* Lisa T. Alty,* and T. Markley Earl Department of Chemistry, Washington and Lee University, Lexington, VA 24450; *
[email protected] (MBF)
We have developed a two-step synthetic sequence for our introductory organic laboratory that demonstrates key reactions that the students learn concurrently in the lecture portion of their organic chemistry course. Both steps produce crystals in a dramatic manner that catches the students’ attention. This sequence can stand on its own as part of an organic laboratory, or the product can be utilized as a monomer for ringopening metathesis polymerization (ROMP) studies. For instance, our students have polymerized this compound with a ruthenium catalyst in our subsequent advanced inorganic laboratory course (1). The first step of the synthesis is the Diels–Alder reaction between furan and maleic anhydride (Scheme I) (2–4 ). O O
O
O
THF Room Temperature
O maleic anhydride
furan
O O O
exo-7-oxabicyclo[2.2.1] hept-5-ene-2,3-dicarboxylic anhydride
Scheme I
Although this is a common undergraduate organic laboratory experiment, our reaction conditions differ from those presented in most laboratory manuals (5). Our procedure has the advantage that it is well suited to the “multitasking” system under which our laboratory is run (6 ). Students typically work on several experiments simultaneously, in a manner more similar to that in which chemical research is actually done. This particular procedure requires a relatively short setup time (less than one hour), after which the reaction mixture can be left until the following laboratory period while the student continues work on another experiment. A second advantage of our procedure is that under our conditions, instead of the small crystals typically obtained in this reaction, long spears (approximately 1 cm in length) grow from the bottom of the flask like stalagmites.1 Our students are very impressed when they return the following week to see their reaction flasks filled with these beautiful crystals. The second step of the sequence involves converting the anhydride to the diester in refluxing methanol (Scheme II) (7). O
O O
MeOH HCl
O
∆
exo-7-oxabicyclo[2.2.1] hept-5-ene-2,3-dicarboxylic anhydride
O CO2Me CO2Me
exo,exo-5,6-bis(methoxycarbonyl) -7-oxabicyclo[2.2.1]hept-2-ene
This ring-opening involves the reaction of an anhydride with an alcohol to yield a half-ester (one ester and one carboxylic acid), which undergoes a Fischer esterification under the reaction conditions to give the diester. Upon completion, cooling the solution in ice results in the formation of a semisolid mass of crystals. However, the crystal formation often must be induced by scratching with a glass stirring rod. This generally causes instantaneous formation of the solid mass.2 The students are excited to see the crystals form before their eyes. Experimental Procedure
Reagents All reagents were used as received without prior purification. Each student requires maleic anhydride (5 g), furan (3.3 mL), THF (25 mL), methanol (20 mL), concd HCl (0.5 mL), and CDCl3 (2 mL, if NMR spectra are planned). Equipment The following equipment is needed: 50- and 25-mL round-bottom flasks, spatulas, mortar and pestle, graduated cylinders, Pasteur pipets, cork or rubber stopper, Buchner funnel, filter paper, filter flask, glass rod, vacuum tubing, reflux condenser, hoses, heating mantle, Variac, boiling chips, ice bath, NMR tubes. NMR spectra were recorded on a JEOL Eclipse+ FT–NMR spectrometer operating at 400 MHz. Step One: Synthesis of exo-7-Oxabicyclo[2.2.1]hept5-ene-2,3-dicarboxylic Anhydride via the Diels–Alder Reaction of Furan and Maleic Anhydride A 50-mL round-bottom flask was charged with maleic anhydride (5 g, 0.05 mol). Maleic anhydride typically comes in large briquettes that must be ground into powder with a mortar and pestle. A briquette weighs approximately 15 g, so three students can share the work of grinding each one. Tetrahydrofuran (THF) (15 mL) was added and the reaction flask was swirled until the maleic anhydride completely dissolved. Furan (3.3 mL, 0.045 mol) was added and the flask was swirled for several minutes to completely mix the contents. The flask was stoppered and allowed to stand until the following laboratory period (one week).3 The crystals were collected by suction filtration and washed with cold THF. Average yield: 4.7 g, 63%; mp: 116–117˚ C;4 1H NMR (CDCl3, sparingly soluble): δ 6.56 (s, 2H, HC=), 5.43 (s, 2H, CHOCH), 3.17 (s, 2H, CHC=O); 13C NMR (CDCl3): δ 170.53 (C=O), 137.33 (C=C), 82.13 (CHOCH), 48.38 (CHC=O).
Scheme II
JChemEd.chem.wisc.edu • Vol. 76 No. 5 May 1999 • Journal of Chemical Education
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In the Laboratory
Step Two: Preparation of exo,exo-5,6Bis(methoxycarbonyl)-7-oxabicyclo[2.2.1]hept-2-ene The students were instructed to use all of their Diels– Alder adduct and scale the amounts given in the following procedure to match their yield in step one. A 25-mL round-bottom flask was charged with the Diels–Alder adduct (5 g, 0.03 mol) and methanol (10 mL). The solid did not dissolve, but the reaction flask was swirled to ensure mixing of the contents. Concentrated HCl (0.5 mL) was added dropwise, 5 swirling the flask between drops. The flask was fitted with a reflux condenser and heating mantle and heated at reflux (2 h). During the heating time, all the solid dissolved. After heating, the reaction mixture was allowed to cool to room temperature and then immersed in an ice bath to induce crystal formation. If no crystals had formed after approximately ten minutes, the flask containing the reaction mixture was scratched and then returned to the ice bath. The product was collected by suction filtration and washed with cold methanol. It may be recrystallized from methanol if necessary. Average yield: 49% based on the amount of Diels–Alder adduct obtained in step one; mp: 120˚ C; 1H NMR (CDCl 3): δ 6.42 (s, 2H, HC=), 5.22 (s, 2H, CHOCH), 3.66 (s, 6H, OCH 3), 2.78 (s, 2H, CHCO2Me); 13C NMR (CDCl3): δ 171.98 (C=O), 136.67 (C=C), 80.45 (CHOCH), 52.27 (OCH3), 46.98 (CHCO2Me). Results and Discussion Although we ran this sequence in the second semester of introductory organic chemistry, the laboratory techniques involved are relatively simple; therefore, this experiment could easily be run in the first semester. Fifty-four students ran the sequence during the 1996–97 school year, and both steps were highly successful. All of the students obtained product in the first step, with yields ranging from 5.5 g (73%) to 2.1 g (28%). The average was 63% and the median was 65%. The yields in the second step ranged from 73% to 4%, with an average of 49% and a median of 56%. The students who needed to recrystallize their final product generally obtained yields at the lower end of the range.6,7 Two students failed to isolate any product from their recrystallization. The Diels–Alder reaction in the first step is unusual in that it gives the exo product instead of the endo product obtained in most cycloadditions of this type. Although the reason for this selectivity is not fully understood, this reaction provides an opportunity to illustrate to the students the trend for furan to give exo-7-oxanorbornene derivatives as Diels–Alder products. Students can obtain NMR spectra on their products in each step. Although the anhydride is not highly soluble in CDCl3, we generated both 1H and 13C NMR spectra. Both
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compounds possess a mirror plane of symmetry and produce relatively simple NMR spectra. Even though one might expect to see splitting of the signals for the protons in the 7-oxanorbornene ring, it is not observed in this case. These spectra illustrate that changing the anhydride to the diester functionality has a relatively small effect on the chemical shifts of the protons and carbons in the molecule and that this effect decreases with distance. In conclusion, we have developed a two-step synthetic sequence that illustrates common organic reactions and appeals to undergraduate students. Acknowledgments MBF thanks Washington and Lee University for a Glenn Grant and TME thanks Washington and Lee University for a Robert E. Lee Summer Undergraduate Research Fellowship. Support from the National Science Foundation Instrumentation and Laboratory Improvement program toward the purchase of a JEOL 400 MHz FT–NMR spectrometer is gratefully acknowledged. Notes 1. The crystal formation was even more dramatic when the reaction was carried out on a larger scale than described here. 2. In a few cases, continued cooling in ice following the scratching was required. 3. A reaction time of 48 hours is sufficient, but the crystallization can be left indefinitely. 4. Literature reports of the melting point of this compound vary from 116–117° C to 125° C. Most of our students obtained the lower value, but a few observed higher melting points. 5. The students can measure small quantities of concentrated HCl with a Pasteur pipet using the approximation 22 drops/mL. 6. The decision to recrystallize was based upon whether the student could obtain a sharp melting point (2° range) within 5° of the literature value. We accepted melting points of either 116–117° C or 125° C. 7. Approximately 10% of the class needed to recrystallize their product.
Literature Cited 1. France, M. B.; Uffelman, E. S. J. Chem. Educ. 1999, 76, 661– 665. 2. Novak, B. M., Ph.D. Thesis, California Institute of Technology, 1989. 3. Woodward, R. B.; Baer, H. J. Am. Chem. Soc. 1948, 70, 1161. 4. Alder, K.; Bachendorf, K. H. Ann. Chem. 1938, 535, 101. 5. For example, see Ault, A. Techniques and Experiments for Organic Chemistry, 5th ed.; Waveland: Prospect Heights, IL, 1994; p 441. 6. Alty, L. T. J. Chem. Educ. 1993, 70, 663. 7. Mühlebach, A.; Bernhard, P.; Bühler, N.; Karlen, T.; Ludi, A. J. Mol. Catal. 1994, 90, 143.
Journal of Chemical Education • Vol. 76 No. 5 May 1999 • JChemEd.chem.wisc.edu
