Joelle Khouri, Chem 213 Synthetic #2 FFR 24 April, 2014

Experiment 63: Wittig Reaction

Khouri 1 Introduction The Wittig reaction is a very popular synthetic reaction used to synthesize alkenes from ketones or aldehydes. Much of its importance stems from its ability to form carbon-carbon bonds.1 It is widely used in the organic laboratory and is also often used in the synthesis of drugs.2 The Wittig reaction makes use of a triphenylphosphorus ylide, which is a neutral compound with both a positive and a negative charge. Originally, use of the Wittig reactionwhich was discovered by George Wittig in the late 1970s1was not as widespread because of the difficulty associated with forming ylides, but alternative preparation methods have since been introduced.3 Even more recently, innovative methods of solvent-free Wittig reactions have been proposed to address environmental, heath, and economic concerns.4 The Wittig reaction is a stereoselective reaction,1,5 with E/Z selectivity of the product depending on many factors, including substituents on aromatic aldehydes and nucleophilicity of the ylide.6 A stabilized ylide leads to formation of the E isomer, whereas an unstable ylide forms the Z alkene.1 The mechanism of this experiments Wittig reaction is shown in Scheme 1.

Scheme 1. Mechanism of the synthesis of trans-9-(2-Phenylethenyl)anthracene.

Khouri 2 After first being deprotonated by sodium hydroxide, benzyltriphenylphosphonium chloride ylide adds to the carbonyl starting material. The newly-formed zwitterion closes to form a four-membered cyclic intermediate, which then collapses into a stable phosphine oxide and the product alkene. The purpose of this experiment was to create trans-9-(2-Phenylethenyl)anthracene by a Wittig reaction using 9-anthracenecarboxyaldehyde and benzyltriphenylphosphonium chloride. Because this reaction includes a conjugated, resonance stabilized ylide, the E alkene was formed. The product was characterized by melting point, IR, UV/Vis, 60 MHz 1H NMR, and 400 MHz 1H NMR. Analysis of alkene coupling constants in the 1H NMR spectrum was used to confirm the formation of the trans configuration.

Experimental Trans-9-(2-phenylethenyl)-anthracene. Benzyltriphenylphosphonium chloride (411 mg, 1.06 mmol), 9-anthracenecarboxyaldehyde (246 mg, 1.19 mmol), and dimethylformamide (1 mL), were stirred vigorously in a flask. 50% NaOH solution (w/w) (0.5 mL) was added drop wise. The mixture was stirred vigorously for 2 hours. The reaction progress was monitored using TLC by spotting against a 9anthracene standard with 40:60 ethyl acetate:hexanes as the mobile phase. The product was precipitated by the addition of a 1:1 mixture of propanol:water (8 mL) and collected by vacuum filtration. The product was recrystallized with 1-propanol, collected by vacuum filtration, and allowed to dry to yield a light orange solid (162 mg, 56.1%); mp 128-131C; IR (ATR) max 3031, 1947, 1672, 1623, 1580, 1492, 1446, 1283, 1206, 1167, 1075, 1018, 964, 877, 849, 813, 781, 735, 690; UV/Vis max 386 nm; 1H NMR (60 MHz, CDCl3) d (ppm) 8.389-7.242 (m, 40H), 7.068 (s, 1H), 6.786 (s, 1H); 1H NMR (400 MHz, CDCl3) d (ppm) 8.3859 (s, 1H), 8.3585-8.3415 (d, 2H), 8.3391-8.2829 (t, 1H), 8.0114-7.9875 (t, 2H), 7.92457.8832 (d, 1H), 7.7035-7.7591 (t, 1H), 7.6790-7.6608 (d, 2H), 7.4809-7.4291 (m, 6H), 7.3695-7.3511 (t, 1H), 6.9620-6.9206 (d, 1H).

Khouri 3 Results and Discussion In this reaction, trans-9-(2-Phenylethenyl)anthracene was synthesized in a Wittig Reaction from 9-anthracenecarboxyaldehyde and benzyltriphenylphosphonium chloride. After purification by recrystallization, the calculated percent yield was 56.1%, which is on the lower end of the 50-70% range provided in literature.7 TLC was used to monitor the reaction; however, the plates showed little difference over time. As expected, the ionic benzyltriphenylphosphonium chloride was displayed as a spot near the baseline in the reaction mixture lane. This spot decreased in intensity as the reaction progressed. The other expected result was that 9-anthracene-carboxyaldehyde would travel a smaller distance than the nonpolar trans-9-(2-Phenylethenyl)-anthracene, but the spots in the reaction mixture were hard to differentiate. There appeared to be 2 or 3 spots in the upper portion of the reaction mixture lane, depending on the plate, but the spots varied in shape and intensity. The 9-anthracene standard rarely developed well, making it hard to compare to. Because it was hard to distinguish the other spots, the reaction was allowed to run for a full 2 hours, the upper end of the time suggested, to ensure completion. The product was found to have a melting point range of 128-131 C, compared to the literature value of 131 C.1 The range was only slightly lower than the given value, pointing to the presence of few impurities. The product was characterized by IR spectroscopy (Figure 1, Supplemental Information). As expected, there is a peak at 3031 cm-1, in the 3300-3000 cm-1 range of both an aromatic carbonhydrogen stretch and an alkene carbon-hydrogen stretch. There is also a peak indicative of a trans carbon-carbon double bound at 1972 cm-1. Although these stretches are also present in the starting material, there is no carbonyl carbon-hydrogen stretch at 2720 cm-1 and furthermore no carbon-oxygen carbonyl stretch in the 1730-1705 cm-1 range that would have been present had starting material remained.

Khouri 4 Trans-9-(2-Phenylethenyl)anthracene displays florescent properties when irradiated with UV light at 364 nm.6 According to the UV/Vis spectrum acquired (Figure 4, Supplemental Information), the wavelength of maximum absorption of the synthesized product is 386 nm, which closely corresponds to the literature value. NMR spectroscopy was also used to analyze and characterize the product. The 60 MHz (Figure 2, Supplemental Information) spectrum displays one of the alkene protons at 6.786 ppm and also displays an integration value of 40 in the aromatic region. The 400 MHz 1H NMR (Figure 3, Supplemental Information) provides a much clearer image of the aromatic region. The first alkene proton doublet appears at 6.9620-6.9206 ppm and the other at 7.9245-7.8832 ppm, with coupling constants of 16.56 Hz and 16.52 Hz, respectively. These coupling constants of greater than 14 Hz confirm the formation of the trans isomer.1 The 400 MHz spectrum integrates for a total of 18 protons, two more than are found the product. The additional protons may indicate a residue of 9-anthracenecarboxyaldehyde starting material, which would also appear in the aromatic region, likely in the 6 proton multiplet at 7.4809-7.4291 ppm. Aside from the two extra protons, all other peaks and protons match up to the product as expected. Not counting the aforementioned two alkene doublets and the 6 proton multiplet, the product containsand the NMR spectrum confirmsthree pairs of protons that integrate as doublets, along with a single proton that also integrates as a doublet. There are also three single protons that integrate as triplets. The identity and position of these protons are indicated in Figure 3. This experiment used a very common synthetic reaction, the Wittig reaction, to form an alkene, trans-9-(2-Phenylethenyl)anthracene, from an aldehyde, 9-anthracenecarboxyaldehyde, and a ylide, benzyltriphenylphosphonium chloride. Though TLC was not conclusive in determining reaction completion, analysis of melting point, IR, UV/Vis, 60 MHz 1H NMR, and 400 MHz 1H NMR indicates formation of the product, specifically the trans isomer, with little reactant remnant.

Khouri 5 References 1. Rummel, S, Ed. Experiment 63: Wittig Reaction. Chemistry 213, The Pennsylvania State University. [Online] 2011. https://cms.psu.edu/section/default.asp?id=MRG-131217-132758-SAD270&goto= (accessed April 19, 2014). 2. Babin, P.; Devaux G., J. Chem. Ed., 1989, 66, 522. 3. Warner, J.; Anastas, P.; Anselme JP., J. Chem. Ed., 1985, 62, 346. 4. Leung, S.; Angel, S., J. Chem. Ed., 2004, 81, 1492. 5. Silversmith, E, J. Chem. Ed., 1986, 63, 645. 6. MacKay, J.; Wetzel, N. Exploring the Wittig Reaction: A Collaborative Guided-Inquiry Experiment for the Organic Chemistry Laboratory, J. Chem. Ed [Online early access]. DOI: 10.1021/ed3003836. Published Online: Apr 7, 2014. http://pubs.acs.org/doi/ipdf/10.1021/ed3003836 (accessed Apr 24, 2014). 7. Jaworek, C.; Iacobucci, S., J. Chem. Ed., 2002, 79, 111.