In the Laboratory edited by
Green Chemistry
Mary M. Kirchhoff ACS Green Chemistry Institute Washington, DC 20036
A Green Alternative to Aluminum Chloride Alkylation of Xylene
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Grigoriy A. Sereda* and Vikul B. Rajpara Department of Chemistry, University of South Dakota, Vermillion, SD 57069; *
[email protected] Environmentally friendly procedures are attracting increasing attention in the design of experiments for the undergraduate organic chemistry laboratories (1, 2). A good teaching experiment should be simple enough for an inexperienced chemist, fast enough to fit in a standard laboratory period, affordable for small undergraduate institutions, and, at the same time, demonstrate as many concepts of the studied topic as possible. Recently, we found that graphite can be used to promote the alkylation of aromatic compounds (3). However, long reaction times (24 h), toxic alkylating agents (benzyl chloride), and relatively complicated NMR spectra of reaction products made this otherwise useful example of a green reaction unsuitable for educational purposes. Our further research resulted in the development of a simple graphite-promoted procedure of alkylation of p-xylene, 1, by less acutely toxic 2-bromobutane, 2 (Scheme I). We propose an experiment that is intended to reinforce these important concepts and skills: 1. Electrophilic alkylation of aromatic compounds 2. Catalytic reactions 3. Principles of green chemistry 4. Pooling experimental data 5. Identification of organic compounds using NMR spectroscopy 6. Spin–spin coupling of protons in COSY spectroscopy
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The suggested reaction, performed by refluxing inexpensive and relatively nontoxic starting materials for 1.5 h, produces the product, 3, in 60–70% yield (4). The yield depends on the quantity of graphite used, which demonstrates to students the importance of the catalyst. The reaction product is sufficiently pure for the NMR and TLC analyses. After the reaction is complete, the catalyst is filtered out and can be reused for another run (another feature of a resource-saving technology) to afford the product in nearly the same yield. If the laboratory course consists of multiple sections, each subsequent section may use the catalyst recovered by the preceding section. This organization of the laboratory would allow the students to pool the data and use them for monitoring the dependence of product yield on the number of times the graphite has been used. As opposed to the similar procedure of alkylation of p-xylene by 2-bromopropane (4), our experiment does not require aluminum chloride, which eliminates the need for the aqueous workup, does not produce waste solutions, and allows for the multiple use of the catalyst. Therefore, the experiment demonstrates four out of twelve known principles of green chemistry (5): it prevents production of waste, maximizes incorporation of all materials used in the process into the final product, uses catalysis, and minimizes the potential for chemical accidents. Discussion The experiment is designed for the second semester of organic chemistry. The students are expected to have basic laboratory skills such as safety, refluxing, distillation, filtration, and interpretation of simple NMR spectra. This experiment can be adapted to several levels of student expertise. For instance, students in an advanced organic chemistry course may be asked to explore how the reaction proceeds with 1-bromobutane or compare reactivities of benzyl chloride and 4-methylbenzyl chloride as alkylating agents. The reaction does not take place with primary halides (3), which indicates that the rate-limiting transition state is less carbocation-like than for the classical Friedel–Crafts alkylation, catalyzed by aluminum chloride. According to our results, 4-methylbenzyl chloride reacts faster, than benzyl chloride (6), which suggests that formation of a carbocation-like intermediate constitutes one of rate limiting steps. This set of additional experiments will allow the students to deduce some mechanistic details of the reaction.
Scheme I. Alkylation of p-xylene on graphite
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In the Laboratory
On the other hand, elimination of the NMR component and the investigative components (reusability of the catalyst and influence of its quantity on the yield of the product) will make an experiment simple enough even for a high school laboratory. In a laboratory lacking any instrumentation, the reaction product can be detected by the blue fluorescence of diluted hexane solutions of the reaction product, excited at 365 nm by a handheld UV lamp. The product 2-sec-butyl-1,4-dimethylbenzene 3 provides a simple and efficient example to demonstrate some important aspects of NMR spectroscopy in organic chemistry. Introduction of the sec-butyl group to p-xylene causes a small difference in the chemical shifts of the methyl protons at the benzene ring, which demonstrates the influence of the chemical environment on the chemical shift. Most interestingly, on a 200–300 MHz NMR spectrometer, this difference is close to the typical vicinal H–H coupling constant, which is observed for the methyl group of the sec-butyl group. As a result, the upfield area of the 1H NMR spectrum contains two groups of signals; each of them resembles both two singlets and a doublet. The off-diagonal peaks on the COSY spectrum, shown in Figure 1, allow us to unambiguously tell the difference between the doublet of the sec-butyl methyl group coupled with the methine proton and the noncoupled singlets of the benzylic methyl groups. If two NMR spectrometers with different proton frequencies are available, two singlets and the doublet can be alternatively distinguished by comparing their resonance frequencies in Hz and ppm. Hazards p-Xylene and 2-bromobutane are flammable. Deuterochloroform is harmful if swallowed, irritating to skin, and a probable carcinogen. W
Grant Award), the University of South Dakota (Research catalyst Award), and the National Science Foundation’s Course, Curriculum and Laboratory Improvement Program under grant DUE-0311303 for financial support of this work. Literature Cited
Supplemental Material
Instructions for the students and notes for the instructor are available in this issue of JCE Online. Acknowledgment We thank the State of South Dakota (2010 Research Initiative and the Governor’s 2010 Individual Research Seed
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Figure 1. COSY spectrum of 2-sec-butyl-1,4-dimethylbenzene, 3.
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1. 2. 3. 4. 5.
Esteb, J.; Schelle, M.; Wilson, A. J. Chem. Educ. 2003, 80, 907. Sereda, G. J. Chem. Educ. 2005, 82, 1839. Sereda, G. T. Lett. 2004, 45, 7265. Sosnovsky, G.; Shende, M. W. Synthesis 1972, 8, 423. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University Press: New York, 1998; p 30. 6. Sereda, G. A.; Rajpara, V. B. University of South Dakota, Vermillion, SD. Unpublished work, 2006.
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