In the Laboratory W Wittig Reaction Using a Stabilized Phosphorus Ylid An Efficient and Stereoselective Synthesis of Ethyl trans Cinnamate Traci J Speed Jean P McIntyre and Dasan M Thamattoor Department of Chemistry Colby College Waterville ME 04901 dmthamat colby edu The conversion of aldehydes and ketones into olefins by means of the Wittig reaction 1 is an important synthetic procedure that is usually covered in most introductory organic chemistry courses In a typical Wittig reaction Scheme I a phosphonium salt 1 is treated with a base to generate the ylid 2 which is subsequently reacted with a ketone or aldehyde to produce the alkene 3 As the reaction is often performed under anhydrous conditions with strong bases implementing the procedure in the undergraduate instructional laboratory could involve substantial resources and pose significant hazards It is not surprising therefore that our present repertoire of Wittig reactions for teaching purposes is limited to a few creative experiments most of which use aqueous sodium hydroxide as the base 2 7 There is also a report of an experiment using an instant ylid 8 a solid mixture of phosphonium salt and sodium amide and an advanced procedure using dimsyl anion 9 Phosphorus ylids such as 2 in which R1 is an electron withdrawing group are particularly stable and are commercially available While the use of such ylids is widely reported in the chemical literature there is no indication that these reagents have been used in the laboratory in a teaching context In this article we describe an instructive experiment for the synthesis of ethyl trans cinnamate 6 Scheme II a pleasant smelling ester used in perfumery and flavoring by the reaction of benzaldehyde 4 with the stable ylid carbethoxymethylene triphenylphosphorane 5 This reaction has also been reported in the literature 10 The experiment is well suited to the teaching laboratory and offers several important advantages The synthesis workup and characterization of 6 may be accomplished in a single laboratory session with commonly available laboratory equipment and glassware The reagents are also relatively in expensive which might be an important consideration in courses with large enrollments Furthermore the product is obtained in high yield and excellent purity and no special precautions are necessary to dry glassware solvents and reagents The reaction is highly stereoselective in that the product is formed predominantly as the trans isomer and the students can use 1H NMR spectroscopy to ascertain the stereochemistry about the double bond At the instructor s discretion molecular modeling of the two isomers may be also included as an informative exercise to complement the wet chemistry Experimental Procedure Benzaldehyde 0 50 g 4 7 mmol 1 was weighed into a clean and dry 50 mL round bottomed flask equipped with a magnetic stir bar and dichloromethane 20 mL was added The flask was loosely stoppered placed in an ice bath and stirred for at least 10 minutes After this time carbethoxymethylene triphenylphosphorane2 2 0 g 5 7 mmol was slowly added to the flask Stirring was continued in the ice bath for an additional ten minutes after which time the solution was allowed to warm up to room temperature The stir bar was removed from the flask and the reaction mixture was freed of solvent using a rotary evaporator 3 Subsequently 20 mL of hexanes was added to the residue in the flask and the suspension was gently stirred with a glass rod The mixture was filtered by vacuum using a B chner funnel and another 20 mL of hexanes was used to rinse the flask The filtrate was transferred to a dry clean preweighed roundbottomed flask and the solvent was removed using a rotary evaporator The pale yellow product was obtained in essentially quantitative yield4 and was of adequate purity for analysis by 1H NMR 13C NMR IR and GC MS X Ph3P CH2R1 base CHR Ph3P 1 CHO 1 4 2 Ph3P CH CO2Et 5 O R2 R3 R2 CO2Et CHR1 Ph3P O R3 6 3 Scheme II Wittig reaction to synthesize ethyl trans cinnamate Scheme I Generalized Wittig reaction www JCE DivCHED org Vol 81 No 9 September 2004 Journal of Chemical Education 1355 In the Laboratory 1H NMR 400 MHz CDCl3 7 69 d J 16 Hz 1H 7 52 m 2H 7 36 m 3H 6 44 d J 16 Hz 1H 4 26 q J 7 Hz 2H 1 34 t J 7 Hz 3H 13C NMR 100 MHz CDCl3 166 9 144 5 carbon to carbonyl 134 4 130 2 128 9 128 0 118 3 carbon to carbonyl 60 4 14 3 IR neat cm 1 3083 3047 2992 1722 1650 MS m z 176 131 103 77 Hazards The Wittig reaction proved to be a valuable teaching resource in our experience and was also well received by students In addition to illustrating the reaction itself the experiment emphasizes important aspects of organic chemistry such as stereochemistry instrumental analysis and molecular modeling It is anticipated that this exercise will augment and add variety to the limited pool of experiments currently available for teaching this important reaction Acknowledgments Caution should be exercised when using flammable solvents such as hexanes Benzaldehyde and carbethoxymethylene triphenylphosphorane are potential irritants Dichloromethane is a suspected carcinogen Results and Discussion The reaction is straightforward and proceeds in essentially quantitative yield Isolation of the product is also simple and relies on the fact that triphenylphosphine oxide a byproduct of the reaction is insoluble in hexanes whereas the product ester 6 is soluble This separation protocol demonstrates clearly how chemists take advantage of differential solubilities to purify compounds There was also an excellent match between the 1H NMR IR and GC MS data obtained by students and the literature data for 6 In particular students were able to use 1H NMR spectroscopy to verify that 6 has the trans configuration about the olefinic double bond The coupling constant of 16 Hz displayed by the protons that are and to the carbonyl group falls into the 12 18 Hz coupling constant range typical of the hydrogens of trans alkenes A cis configuration would have displayed a coupling constant of 6 12 Hz Furthermore we found it worthwhile to have our students model the E and Z isomers of 6 using the semiempirical PM3 method and compute charges on the and carbon atoms The calculation which did not take much time indicated that the E isomer was more stable than the Z isomer and to the surprise of some students there was less electron density at the carbon than at the carbon This exercise also provided an excellent opportunity to demonstrate the