Benjamin Sepe, Chem 213 Synthetic #1 FFR A Diels Alder Puzzle Introduction The Diels-Alder reaction, detected in 1950

by Otto Diels and Kurt Alder, is a Nobel Chemistry prize-winning discovery that has been a source of useful synthetic products since its unearthing 62 years ago. The mechanism, often referred to as diene synthesis is very versatile, and the compounds it has helped to develop range from dyes and textiles to coatings.1 One example of a compound that the Diels-Alder mechanism is responsible for synthesizing is Chlordan, a strong insecticide.1 Another reason that this mechanism is such a significant force in chemical synthesis is its ability to create complex polycyclic rings, synthetic products that were almost impossible to produce easily before 1950.3 One of the particular reasons that this mechanism is of such great use to synthetic chemists is that is allows extremely complex molecules to be constructed from relatively simple starting materials and with careful consideration to stereochemistry throughout the duration of the process.3 This being said, an important governing principal of chemical synthesis that one must consider when attempting to understand the Diels-Alder mechanism is the difference between thermodynamic and kinetic control.5 At their most basic, these controls are ways of determining the outcome of a particular combination of reactants. A kinetic product, for instance, is typically formed as a result of lowest activation energy in a reaction, whereas thermodynamic controls are formed when

enough energy is put into the system to over come the influence of activation energies and yield a different product. In this experiment, Furan and Maleic Anhydride were synthesized to one of two cyclic adducts, either an exo or endo adduct, each with unique properties. The relative geometries of these two products can be understood from Figure 1., below.

Figure 1. Endo/Exo adducts of Furan and Maleic Anhydride6

The mechanism, depicted below in Scheme 1, is simple. The reaction is a one step concerted reaction between the conjugated diene of Furan and the double bond on the ring of Maleic Anhydride, resulting in a polycyclic adduct.2, 4 There are no intermediates in this cyclic redistribution, however there is still much discussion about whether or not the reaction is synchronous.4 This is to say, that despite being accepted as concerted, the equivalency of the new C-C bonds is still undecided.

SCHEME 1. Mechanism of Furan and Maleic Anhydride to Exo Adduct

The Diels-Alder reaction is a simple reaction with numerous applications in industry. The purpose of this lab is to investigate the Diels-Alder reaction as a way of creating a polycyclic adduct from reagents Furan and Maleic Anhydride. Additionally, the reaction is an interesting expose into relationship of endo versus exo product formation and thermodynamic versus kinetic controls. Moreover, upon completion the product of this synthesis can be quantified and analyzed using NMR instrumentation.

Experimental Exo/Endo-Adduct. Maleic Anhydride (0.593 g, 3.57 mmol) and Anhydrous Ether (5 mL) were added to a 10 mL Erlenmeyer flask. The solution was warmed until Maleic Anhydride completely dissolved. Upon returning to room temperature, Furan (0.50 mL) was added. The Erlenmeyer flask was stoppered, sealed with Parafilm, and allowed to sit for 45 hours. Upon completion of the reaction, the crystals were collected and dried to yield a translucent crystalline product (0.473 g, 47.07 %) mp 110-115 oC; 1H NMR (60 MHz, CDCl3) (ppm) 6.575-6.544 (t, 2H), 5.459-4.425 (t, 2H), 3.153 (s, 2H); 1H NMR (400 MHz, CDCl3) (ppm) 6.5850 (s, 2H), 5.469 (s, 2H), 3.1846 (s, 2H); 13C NMR (400 MHz, CDCl3) (ppm) 169.80, 136.91, 136.42, 102.89, 102.87, 101.70, 101. 68, 99.91. 99.90, 98.11, 82.14, 77.26-76.62, 48.63.

Results and Discussion The synthesis of the adduct product for this lab utilized the Diels-Alder mechanism on the conjugated pi bonds of Furan and the single cyclic pi bond of Maleic Anhydride to form a polycyclic compound. The redistributed adduct synthesized can be of either the endo or exo formation, as determined by the relative orientation of the Maleic Anhydride component to Furans ether component. One interesting facet of these particular experimental reagents is that they do not follow the usual mechanism of the Diels-Alder reaction, which typically favors the kinetic endo adduct, instead opting for the less favorable thermodynamic exo adduct.2 The reasoning for this unexpected product is based on the low

thermodynamic stability of Furan [4 + 2] adducts, which induces a retro-Diels-Alder reaction that opts for the more thermodynamically stable adduct (exo) over the normally synthesized kinetically stable adduct (endo). 2 The geometric instability can be better understood by the relationship between these two adducts seen in Figure 1. The specific adduct was identified by melting point analysis. This is a useful analysis in the identification of the product as the endo or exo geometry because the most significant difference between the two is their melting point. The endo adduct has melting point of 80-81 OC, and the exo adduct has a melting point 114 OC. Upon analysis, it was determined that the isolated product had a melting point of 110-115
OC.

This gave reasonable insight into the identity of the isolated product as the exo

adduct, though further analysis was needed to identify the structure of this particular stereoisomer.
1H

NMR further characterized the product. 1H NMR analysis is an invaluable

tool in determining the proton arrangement of a compound under question. Specifically, when analyzing the NMR spectrum of the exo adduct, a few important qualities are notable that provide evidence of successful adduct formation from Furan and Maleic Anhydride, found in supplementary Figures 1 & 2. The first is a set of two protons at 6.571 ppm, which splits into a triplet, telling of the shifted single alkene bond formed in the concerted reaction. The second sign that this is the appropriate product is the two protons on the ether from Furan found in the polycyclic compound, represented by a triplet at 5.453 ppm. Lastly, potentially the most important peak in the NMR spectra falls at 3.164 ppm with an integration

value of 2, and is clearly indicative of the protons at the joining site of Furan and Maleic Anhydride that are subjected to the ester from Maleic Anhydride. It is important to note that these peaks for all protons in the exo adduct are subjected to a strong downfield shift because of the inductive effect from numerous electronegative oxygen atoms in the compound. This is the reason why some of the peaks fall at higher ppm values than expected. Another tool to characterize the structure of the product is 13C NMR, similar to 1H NMR, is used in determining the carbon skeleton of a compound. The conversion of Furans double bond to a single alkene bond is an important part of this particular Diels-Alder reaction. In Figure 3, this single alkene is featured as the strong peak at 136.9 ppm, within the typical range of 110-150 ppm for C=C bonds. Another bond that is noticeable is the ester carbon-to-carbon bond that shows up as the peak at 169.8 ppm. Additionally, peaks at 82.1 and 77 ppm represent ether bonds. Lastly, the peak at 48.6 is indicative of the C-C bond adjacent to the C=C of the alkene discussed previously. Melting point and NMR analysis confirmed the identity of my product as the exo adduct of Furan and Maleic Anhydride. The two forms of analysis also indicated that the products were relatively pure and contained inconsequential amounts of undesired starting material or impurity. The yield of the exo adduct crystals was 47.07%. Some of the reasons that this product was held in only about half he expected yield include known issues in preparing this specific Diels-Alder product, or possibly even an insufficient amount of reaction time allocated. These issues could arise from common retro Diels-Alder reactions or the inflexible 48 hours

between lab periods, respectively. In the future, if given the opportunity to repeat this experiment, I would consider allowing the solution to precipitate crystals for longer than the time between lab periods. The Diels-Alder reaction has been a useful synthetic tool since it was developed in 1950. Its applications transcend numerous fields and products, namely for its ease of synthesis and its ability to make polycyclic rings. In this experiment, Furan and Maleic Anhydride were fused to a polycyclic exo adduct product using the Diels-Alder reaction with relatively good yield. MP and NMR spectroscopy analyzed the products in order to confirm their identities.

References 1. Diels-Alder Reaction Proves Potent Chemical Ally. Chem. Eng. News, 1950, 28, 4266 http://pubs.acs.org/doi/abs/10.1021/cenv028n049.p4266?prevSearch=diels%2Balder&searchHistoryKey= (accessed Nov 9, 2012) 2. Rusilek, L.; Sebek, P.; Havlas, Z.; Hrabel, R.; Capek, P.; and Svatos, A. An Experimental and Theoretical Study of Stereoselectivity of Furan-Maleic Anhydride and Furan-Maleimide Diels-Alder Reactions. J. Org. Chem. [Online], 2005, 70, 62956302. http://pubs.acs.org/doi/abs/10.1021/jo050759z (accessed Nov 9. 2012) 3. Silva, L.C.; Lacerda, V.; Constantino, M.G.; and Silva, G.VJ. High Stereoselectivity on Low Temperature Diels-Alder Reactions. Beilstein Journal of Organic Chemistry. [Online], 2005, 1-14. http://www.biomedcentral.com/1860-5397/1/14 (accessed Nov. 9, 2012) 4. Dewar, M.J.S.; Pierini, A.; Mechanism of the Diels-Alder Reaction. Studies of the addition of Maleic Anhydride to Furan and MethylFurans. J. Am. Chem. Soc. [Online], 1984, 106, 203-208 http://pubs.acs.org/doi/abs/10.1021/ja00313a041 5. Cooley, J.H.; Williams, R.V.. Endo- and exo-Stereochemistry in the Diels-Alder Reaction: Kinetic versus Thermodynamic Control. Journal of Chemical Education [Online] 1997, 70, 582-585, http://www.umich.edu/~chemh215/CHEM216/BasicTraining/Experiment3/da%2 0reaction.pdf (accessed Nov. 18, 2012) 6. Saturno, C.L.; Suarez, D.. Stereochemistry of the Furan-Maleic Anhydride Cycloaddition: A Theroetical Study.; J. Am. Chem. Soc. [Online], 2000, 122, 390-391, http://atarazanas.sci.uma.es/docs/articulos/16671223.pdf (accesssed Nov. 18, 2012)