In the Laboratory
The Wittig Reaction: Generation, Observation and Reactivity of a Phosphorus Ylide Intermediate An Experiment for the Advanced Organic Chemistry Laboratory Gary W. Breton Department of Chemistry, Berry College, Mount Berry, GA 30149 During the presentation of reaction mechanisms in an advanced organic chemistry course, the involvement of reactive intermediates is often discussed without offering physical proof of their existence. Laboratory courses provide a venue for the investigation of such species. For example, the Wittig synthesis (eq 1) of 1,1– diphenyl–1–propene (3) from ethyltriphenylphosphonium iodide (1) and benzophenone requires the generation of phosphorus ylide intermediate 2 via deprotonation of 1. The existence of the ylide may be inferred by the formation of a deeply colored solution upon deprotonation. However, by running the reaction in an NMR tube, as described below, the ylide may be directly observed by 1H NMR spectroscopy. Furthermore, since the ylide is generated in DMSO–d6, a deuterium exchange between the solvent and the ylide at the C-1 position results, yielding 2–D from initially formed 2–H (eq 1), so that the final product, 3, is also deuterium-labeled. This reaction sequence, therefore, illustrates a convenient method for the synthesis of deuterated alkenes. H3C
+ I—
NaH
CH3CH2—PPh3
– +PPh
C
3
H
1
2-H O
D
DMSO–d6
(1)
CH3 H3C Ph
Ph
– + PPh
C Ph
Ph
3
D
3
2–D
Experimental Procedure The experiment took place during two 3–h classes. In the first session, the ylide intermediate was generated, observed by 1H NMR spectroscopy, and quenched by the addition of benzophenone. The reaction mixture remained in the NMR tube until the following week’s lab session, at which time the alkene was isolated, purified, and characterized as described in the procedure below. 1H NMR spectra were obtained at 60 MHz using a Varian EM-360 NMR spectrometer. Samples were run in DMSO-d6.
Materials (approximate cost per student) 10 mg of freshly washed NaH ($0.05) 0.5 mL of DMSO-d6 ($1.07) 0.157 g (0.9 eq) ethyltriphenylphosphonium iodide1 ($0.10)
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76 mg benzophenone ($0.05) NMR tube, sand bath, Na2SO4, small piece of rubber tubing
Procedure NaH was weighed into a tared, oven-dried NMR tube, and DMSO-d6 was added via a Pasteur pipet. A drying tube (consisting of a short piece of amber rubber tubing with a glass-wool plug supporting a short column of Na2SO4) was fixed to the top of the tube, and the apparatus was placed in a preheated sand bath at 90 °C so that approximately one quarter of the solvent volume was submerged. Setting the tube at a slight angle allowed for generation of a convenient convection current within the tube, which adequately agitated the reaction mixture. H2 gas evolved immediately as the methylsulfinyl carbanion was formed. CAUTION: H2 gas is flammable. These manipulations should be performed in an adequate hood. Once gas evolution had ceased (30–40 min), the resulting clear, pale-yellow solution was removed from the bath and allowed to cool to room temperature. A 1H NMR spectrum of the deuterated methylsulfinyl carbanion solution may be obtained at this point (if time permits) to demonstrate the absence of any signals other than those of residual monoprotio-dimethylsulfoxide. The drying tube was removed and the ethyltriphenylphosphonium iodide was added as a solid. The mixture was shaken well, and the resulting deep red solution of ylide 2-D was analyzed by 1H NMR: δ 7.2 (m, 15 H, aryl H’s), 1.5 (d, J = 19 Hz, 3 H, CH3–). After obtaining the NMR spectrum of ylide intermediate 2-D, benzophenone was added to the NMR tube and the contents were shaken vigorously. The red color of the ylide dissipated, and a 1H NMR spectrum of the resulting solution was obtained. The signals in the aryl region were complicated, while the CH3– signal appeared as a singlet (δ 1.55). The product was purified by pouring into 40 mL of H 2O, and the aqueous layer was washed twice with 20-mL portions of pentane. The organic layers were combined, washed with 20 mL of H2O, dried over Na2SO4, filtered through a short column of Al2O3 into a dry round– bottomed flask, and concentrated. Final purification of the crude white solid (sufficiently pure at this point for spectral analysis) was achieved via preparative chromatography on 2 × 5-cm SiO2 TLC plates using hexane as eluent (Rf = .41). The desired UV active band was scraped from the developed plate and swirled with hexane. The mixture was filtered and the hexane solution was concentrated to afford 2-deutero-1,1-diphenylpropene (3) as a crystalline white solid, mp 48.6–50 °C (literature mp of the 2-protio compound: 52 °C [1]); 1H NMR: δ 7.1 (m, 10 H, aryl H’s), 1.7 (s, CH3–); IR (KBr) cm{1 3030, 2910, 2200, 1485, 1430, 700. Overall yields of 42% were achieved.
Journal of Chemical Education • Vol. 74 No. 1 January 1997
In the Laboratory
Discussion The 1H NMR spectrum of the ylide intermediate agrees with the spectrum reported in the literature (2) except that it lacks the signal of a proton at C-1 due to deuterium exchange of this proton through acid–base equilibration with the solvent. Thus, the observed signal of the methyl group is a doublet produced by coupling with the phosphorus nucleus (literature value of 19 Hz [2]), and not by coupling with an adjacent proton. The students may be allowed to deduce this on their own, given the 1H NMR of the starting material in which the methyl signal appears as a doublet of triplets (J = 19, 7 Hz) due to coupling with the adjacent methylene protons as well as the phosphorus nucleus. Isolation of the alkene formed from the ethylidene ylide and the benzophenone should yield 1,1–diphenylpropene as product. However, due to incorporation of deuterium at C-2, there is no vinyl proton signal in the 1H NMR spectrum, and the methyl group signal appears as a singlet rather than a doublet. The chemical shifts of the signals are, of course, identical to the corresponding protio derivative, and the melting point remains unchanged.2
Acknowledgment Acknowledgment is made to generous financial support provided by Berry College. Acknowledgment is also made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for partial support of this research. Notes 1. This compound may be purchased or easily prepared through reaction of iodoethane and triphenylphosphine in pentane at reflux for 24 h, followed by trituration with ether. The compound should be dried over P2O 5 before use. 2. The all protio derivative may be synthesized in the same manner as described above for 3 by substituting DMSO for DMSOd6. The 1 H NMR spectrum is as follows: δ 7.1 (m, 10 H), 6.0 (q, J = 6.2 Hz, 1 H), 1.7 (d, J = 6.2 Hz, 3 H).
Literature Cited 1. CRC Handbook of Chemistry and Physics, 52nd ed.; Weast, R. C., Ed.; Chemical Rubber: Cleveland, OH, 1971–1972; p C458. 2. Vedejs, E.; Meier, G. P.; Snoble, K. A. J. J. Am. Chem. Soc. 1981, 103, 2823–2831.
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