In the Laboratory edited by
Advanced Chemistry Classroom and Laboratory
Joseph J. BelBruno Dartmouth College Hanover, NH 03755
The Iodochlorination of Styrene: An Experiment That Makes a Difference
R. Gary Amiet and Sylvia Urban* School of Applied Sciences, RMIT University, Melbourne, Victoria 3001, Australia; *
[email protected] The most frustrating aspect of a laboratory exercise is that all the students achieve the same result; hence, all the students’ reports are more-or-less identical. This fact encourages plagiarism and the submission of reports that are based on the highest scoring reports in the past. We have designed an exercise that has variable results and each student has to evaluate their own results based on a set of experimental spectra unique to each individual student. Experimental Procedure The chemistry involved is rather simple, applying theory typically covered in first- and second-year chemistry courses. The principal mechanistic theory involves addition of unsymmetrical addends to unsymmetrical olefins, SN1, SN2, E1, and E2 reaction mechanisms. The exercise can be completed in either a six-hour (one day) time frame or alternatively can be completed in two three-hour laboratory sessions provided there is adequate access to both NMR and GC–MS facilities. The laboratory exercise is typically conducted with up to 20 students at one time. The reaction sequence involves the addition of iodine monochloride to styrene, followed by the sodium methoxideinitiated dehydrohalogenation of the product (Scheme I). In the experiment published by Buckles and Knaack in this Journal only a single product was obtained, namely, styrene iodochloride (1). A variation of the original experiment is described here: by varying the addition time of methoxide, a range of substituted styrenes is obtained.
The challenge to the student is to determine the orientation of the initial addition reaction, based on the structures of the products and to explain the results by way of suitable mechanisms. Hazards The experiment has been recently modified to conform to green chemistry standards. Previously, the experiment was conducted in carbon tetrachloride (CCl4), which is a well- known carcinogen, and has now been replaced with the use of petroleum spirits (40–60 °C). In terms of other hazards, iodine monochloride is corrosive. Sodium metal should not be exposed to the air and it explodes in water. The safest method for the preparation of sodium methoxide (NaOMe) is detailed in the online supplement. Petroleum spirits (40–60 °C) and methanol are flammable. Methanol is also a poison. Deuterated chloroform is a possible mutagen. Styrene is a carcinogen and corrosive. Results and Discussion As outlined in Scheme I when adduct 1 is treated immediately with sodium methoxide the only product is α-chlorostyrene (4, X = Cl). However, if adduct 1 is refluxed in methanol for an hour, an SN1 (solvolysis) reaction occurs and subsequent treatment with sodium methoxide yields only α-methoxystyrene (4, X = OCH3). Neither of these outcomes presents much of a challenge to the student, but when the reflux
2
Y or X
and/or NaOMe/MeOH reflux
X or Y à
XY 1
Y or X
Y or X 3 and/or
X or Y
4 Scheme I. Iodochlorination of styrene showing possible substitution and elimination products.
962
Journal of Chemical Education • Vol. 85 No. 7 July 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
In the Laboratory
Cl
1
I
OCH3 H(A)
H(A)
1
H(B)
I
H(C)
H(B)
H(C)
Figure 1. Diastereotopic nature of 1-chloro-1-phenyl-2-iodoethane (1, X = Cl, Y = I) and 1-phenyl-1-methoxy-2-iodoethane (1, X = OCH3, Y = I).
period in methanol is shorter than one hour (we recommend 20 to 30 minutes) the result is a complex mixture of substituted styrenes and other products in variable quantities. In our experience, the typical result is a mixture of six compounds in variable proportions, namely, styrene (minor), α-chlorostyrene (4, X = Cl), (E)-ω-chlorostyrene (3, X = Cl), α-methoxystyrene (4, X = OCH3), acetophenone (minor, formed when α-chlorostyrene is hydrated), and 1-phenyl-1-methoxy-2-iodoethane (1, X = OCH3, Y = I). In addition, there may be small quantities of 1,2dichlorostyrene, and 1-phenyl-1-methoxy-2-chloroethane. Each student has his or her own unique result (due to the variable reflux time in methanol) and is now faced with a considerable challenge to interpret their own result. To determine the structures of the products a combination of NMR and GC–MS is required. The GC indicates how many products are present and the MS determines which halogen or substituent occurs (the presence of chlorine is obvious from its isotope pattern), as well as providing the molecular masses of the components. While the GC should in essence provide the relative proportions of the components, there is more of a response for some of the products than others. Unless the GC–MS is calibrated, the NMR provides a more accurate estimate of the relative proportions of the components. This can be used in com-
8.0
8.0
8.0
7.0
7.0
7.0
bination with the GC–MS to estimate the proportions of each product formed. In addition, students use the fragmentation in the mass spectrum to aid in the assignment of their products. For instance, the loss of Cl is evident from α-chlorostyrene as is the loss of methoxy from α-methoxystyrene. As the mass spectrum breakdown patterns of 1- and 2-chlorostyrene are virtually identical, an NMR spectrum is required to determine the orientation of the major products α-chlorostyrene (4, X = Cl) and α-methoxystyrene (4, X = OCH3). This requires knowledge of the coupling constants between olefinic hydrogens, namely Jtrans ~ 15 Hz, Jcis ~ 10 Hz and Jgeminal ~ 2 Hz. As the chemical shifts of the olefinic protons are quite different, there is no overlap of signals, even on low field (60 MHz) NMR spectrometers. To assist the students in their NMR interpretation, they are supplied with the spectrum of styrene, which clearly shows the trans, cis, and geminal coupling constants, and the spectrum of the adduct, 1-chloro-1-phenyl-2-iodoethane (1, X = Cl, Y = I; Figure 1). This is necessary because the spectrum is complicated by the chirality of the 1-carbon that makes H(B) and H(C) diastereotopic and non-equivalent in the spectrum. Hence H(A) appears as a doublet of doublets (dd), as does H(B) and H(C). The same situation occurs in one of the products, 1-phenyl-1methoxy-2-iodoethane (1, X = OCH3, Y = I) so that again, all three hydrogens are seen as doublets of doublets (dd). Students manipulate their own spectra with readily available programs. For NMR, students use MestReC (2), while for the GC–MS, students use the Wsearch program (3), which was developed at this university. Students also rely on software, such as ChemDraw (4), for predicting the chemical shifts of their expected products. Figure 2 illustrates the NMR spectra of a sample of three different products obtained by students and clearly illustrates the “individuality” of each student’s resulting mixture of products.
6.0
6.0
6.0
5.0
5.0
5.0
4.0
4.0
4.0
3.0
3.0
3.0
Chemical Shift (ppm) Figure 2. 1H NMR spectra (200 MHz, CDCl3) obtained by three students. © Division of Chemical Education • www.JCE.DivCHED.org • Vol. 85 No. 7 July 2008 • Journal of Chemical Education
963
In the Laboratory
Conclusion
Literature Cited
Over the years, the experiment has been carried out on a number of NMR spectrometers including a 200 MHz Varian Gemini, a 300 MHz Bruker Avance, as well as a 500 MHz Varian Inova. This has allowed for better resolution of overlapping signal resonances and of course greater sensitivity. The spectra for the resultant product mixtures are recorded in CDCl3 and it is critical that spectra are acquired with optimized shims to accurately determine and differentiate the coupling constants of the products present in the final mixture. We believe this exercise satisfies many of the requirements for a successful practical experiment; it produces individual results of moderate complexity from simple compounds, it requires the application of mechanistic principles to explain the results, it is a safe and green chemistry approach to the exercise, and finally, it requires a basic knowledge of GC–MS and NMR and the ability to apply this knowledge in combination to solve a problem. This is in contrast to the recent publication of the iodochlorination of styrene (involving the use of toxic chlorinegas!) that only results in one of two possible regioisomers with high selectivity and the purity of the product obtained is solely assessed by a comparison of its melting point (5–7). While NMR has been previously used to analyze additions to alkenes (8–12), only one other experiment relies on the use of NMR for interpretation of a series of styrene derivatives that are prepared and then their 13C NMR spectra are determined (13). Our unique approach to the preparation of styrene derivatives is the only one that combines the use of 1H and 13C NMR as well as GC–MS to deduce the identity of a complex mixture of styrene derivatives.
1. Buckles, R. E.; Knaack, D. F. J. Chem. Educ. 1960, 37, 298–301. 2. MestReC, version 2.3; magnetic resonance companion NMR processing software; Departamento de Química Orgánica, Universidade de Santiago de Compostela, Spain, 1996–2005, Now maintained by Mestrelab Research, Santiago de Compostela, Spain. 3. Wsearch32, version 1.1.2004; mass spectrometry software developed and maintained by Frank Antolasic, RMIT University, School of Applied Sciences, Australia, 2005. 4. ChemDraw, versions 5 and above; chemical drawing and prediction software; Cambridgesoft Corporation: Cambridge, MA, 1985–2004. 5. Sereda, G. A. J. Chem. Educ. 2006, 83, 931–933. 6. Nipe, M. R.; Sereda, G. A. J. Undergrad. Chem. Res.2004, 3, 161–163. 7. Zyk, N. V.; Sereda, G. A.; Sosonyk, S. E.; Zefirov, N. S. Russian Chemical Bulletin 1997, 46, 843–844. 8. Singh, A. K.; Verma, S. M. Indian J. Chem. 1984, 23B, 635– 638, 9. Brown, T. M.; Dronsfield, A. T.; Ellis, R. J. Chem. Educ. 1990, 67, 518. 10. Brown, T. M.; Dronsfield, A. T.; Hitchcock, I. J. Chem. Educ. 1991, 68, 785. 11. Weiss, H. M. J. Chem. Educ. 1992, 69, 172. 12. Bortolini, O.; Bottai, M.; Chiappe, C.; Conte, V.; Pieraccini, D. Green Chemistry 2002, 4, 621–627. 13. Blunt, J. W.; Happer, D. A. R. J. Chem. Educ. 1979, 56, 56.
Acknowledgments We thank Zahra Homan of the School of Applied Sciences (Discipline of Applied Chemistry) for her dedication and patience in developing the green chemistry aspect of this experiment as well as Colin Wilkinson for his work in developing the experimental parts of this experiment.
964
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2008/Jul/abs962.html Abstract and keywords Full text (PDF) with links to cited URLs and JCE articles Supplement
Student handout including questions
Instructor notes including mechanisms, answers to questions, reagent lists, hazard alerts, NMR and GC–MS spectra
Journal of Chemical Education • Vol. 85 No. 7 July 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
