Carbocation Rearrangement in an Electrophilic Aromatic Substitution


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In the Laboratory

Carbocation Rearrangement in an Electrophilic Aromatic Substitution Discovery Laboratory Victoria Polito, Christian S. Hamann, and Ian J. Rhile* Department of Chemistry and Biochemistry, Albright College, Reading, Pennsylvania 19612-5234 *[email protected]

Rearrangements are an iconic feature of carbocations. A hydrogen or alkyl group and its electrons migrate to the electron deficient center to form a more stable carbocation in such a carbocation rearrangement, often called Wagner-Meerwein rearrangement. Classic studies compared the migratory aptitudes of different groups and NMR studies of isotopically labeled substrates (1). Computational and gas-phase investigations reveal the involvement of nonclassical carbocations such as protonated cyclopropanes (2). Reaction in solution can change the potential energy surface through solvation of the intermediates. Most introductory and advanced textbooks cover these rearrangements (3-7). However, only a few introductory organic laboratory experiments illustrate these rearrangements (8-13). Of the experiments that allow students to synthesize a product of rearrangement, two involve epoxide rearrangements (10, 11) and another involves a Ritter reaction (12), all of which most introductory textbooks do not cover. Another involves a steroid system with an involved NMR analysis (13). We report a laboratory experiment on electrophilic aromatic substitution that includes a rearrangement with a product that can be completely characterized with 1H and 13C NMR and infrared spectroscopies and mass spectrometry. Electrophilic aromatic substitution represents the most important reaction type of aromatic compounds presented in undergraduate organic chemistry courses. A common laboratory experiment illustrating the reaction is the alkylation of 1,4dimethoxybenzene with tert-butanol and sulfuric acid in acetic acid (14). Under the conditions of the experiment, two tert-butyl groups replace hydrogen atoms of the aromatic compound to form 2,5-di-tert-butyl-1,4-dimethoxybenezene. Students justify the number of substitutions using steric effects and justify the substitution pattern using directing effects. In our modification of this laboratory, students perform two reactions (Figure 1). One group of students reacts 1,4-dimethoxybenzene with 2-methyl-2-butanol, while the other group reacts 1,4-dimethoxybenzene with 3-methyl-2-butanol. Both reactions give 1,4-bis(1,1-dimethylpropyl)-2,5-dimethoxybenzene. The rearrangement parallels other rearrangements in the literature (15). The students do not know the identity of the reaction products, but must determine the products via 1H NMR, 13C NMR, GC-MS, and infrared spectra. Students compare the spectra of both reactions to determine that the products are identical and that one reactant alcohol underwent rearrangement. Hence, it is a discovery laboratory (16).

equipped with a stir bar. The slurry is chilled in an ice-water bath, and sulfuric acid is added over a 10-15 min period via a mounted separatory funnel below eye level. After stirring for 20 min, ice or ice-cold water is carefully added to the flask and the solid is filtered. Recrystallization from ethanol provides white plates. A complete procedure with safety precautions is given in the supporting information. Students obtain 1H NMR, 13C NMR, infrared, and mass spectra, and a melting point during the second week of laboratory. Students obtain data from a partner who used the other alcohol for the experiment. Instructors could provide spectra or a molecular formula if one or more of these instruments are unavailable. Instructors encourage students to discuss their spectra before leaving laboratory. Students can complete work within two 3- or 4-h laboratory periods. Hazards Students employ concentrated sulfuric acid (17) and glacial acetic acid (18) for this laboratory. Concentrated acids are highly corrosive. All spills should be treated with sodium bicarbonate, and exposed skin should be flushed for at least 20 min followed by immediate medical attention. 2-Methyl-2-butanol and 3-methyl-2-butanol are flammable and may cause skin or eye irritation upon contact. 1,4-Dimethoxybenzene is an irritant and is combustible. Results and Discussion Students can readily determine the product identity with spectroscopic and physical characterization data. Comparison of all data establishes that both compounds are identical. (The melting points for the products of the two reactions may differ by 4 °C, but are close enough to establish an identical structure.1 The gas chromatogram indicates a small quantity of impurity in

Experiment In the laboratory, students suspend 1,4-dimethoxybenzene and their alcohol in glacial acetic acid in an Erlenmeyer flask

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Figure 1. Electrophilic aromatic substitution reactions of 1,4-dimethoxybenzene with different alcohols that produce the same product.

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r 2010 American Chemical Society and Division of Chemical Education, Inc. pubs.acs.org/jchemeduc Vol. 87 No. 9 September 2010 10.1021/ed9000238 Published on Web 07/08/2010

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In the Laboratory

the product from 2-methyl-2-butanol.) The molecular ion in the mass spectrum indicates that two C5H11 groups have substituted for two hydrogen atoms in the starting material. The ratio of aromatic proton integrations to the various alkyl proton integrations in the 1H NMR also confirms the disubstitution. The singlet at 6.74 ppm in the 1H NMR, the three absorptions at 152, 135, and 113 ppm in the 13C NMR, and the aromatic carboncarbon bond stretch at 1506 cm-1 indicate that the aromatic ring is preserved from the starting material. The singlet at 3.78 ppm in the 1H NMR and the absorption at 56 ppm in the 13C NMR indicate that methoxy absorption is preserved as well and that they are equivalent in the product. The infrared spectrum indicates a lack of carbonyl or hydroxyl groups. These data eliminate a phenol as a possible structure. The NMR spectra establish the tert-pentyl group. Three hydrogen environments and four carbon environments establish a degree of symmetry in the alkyl group. The triplet at 0.64 ppm and quartet at 1.79 ppm at an integral ratio of 2:3 establish an ethyl group, and a singlet at 1.31 ppm establishes two equivalent methyl groups. The only connectivity pattern consistent with C5H11 and these splitting and integral patterns is a tert-pentyl group. A peak at charge-to-mass ratio of 249 is consistent with loss of an ethyl group from the molecular ion. The product from unrearranged 3-methyl-2-butanol is excluded based on the 1H and 13C NMR. Although it appears to students that each alcohol provides a unique product, after incorporating this data, the symmetry implied by the 13C NMR indicates that only 1,4-bis(1,1-dimethylpropyl)2,5-dimethoxybenzene and 1,2-bis(1,1-dimethylpropyl)-3,6-dimethoxybenzene are possible isomers of the product. Any physical or computational molecular model readily indicates that adjacent tertpentyl groups are unfeasible. Hence, 1,4-bis(1,1-dimethylpropyl)2,5-dimethoxybenzene is the only reasonable product. We implemented this laboratory in the second semester of introductory organic chemistry to illustrate carbocation chemistry and electrophilic aromatic substitution. This laboratory could also be used in an upper-level course with the extensive literature on the pentyl cation potential energy surface.2 The laboratory provides a basis to use inductive reasoning with spectral data to determine a structure and serves as an introduction to mechanistic work. Acknowledgment The Albright Creative Research Experience program provided funding for this work. We would like to thank Beth L. Buckwalter and Ryan A. Mehl of Franklin and Marshall College for initial NMR spectra.

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Vol. 87 No. 9 September 2010

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Notes 1. A reviewer recommended a mixed melting point for further verification that the compounds are identical. 2. Interestingly, the protonated cyclopropane is calculated to be more stable that the 3-methyl-2-butyl cation (2).

Literature Cited 1. Shubin, V. G.; Borodkin, G. I. Some Aspects of Carbocation Rearrangements. In Stable Carbocation Chemistry; Prakash, G. K. S., Schleyer, P. v.R., Eds.; Loker Hydrocarbon Research Institute Symposium on Carbocation Chemistry, Los Angeles, January 1992; Wiley: New York, 1997; pp 231-264. 2. Farcas-iu, D.; Norton, S. H. J. Org. Chem. 1997, 62, 5374–5379. 3. Eg e, S. Organic Chemistry, Structure and Reactivity, 5th ed.; Houghton Mifflin: New York, 2004; pp 289-291. 4. Carey, F. Organic Chemistry, 7th ed.; McGraw Hill: New York, 2008; pp 202-205, 235-236, 335-336. 5. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part A: Structure and Mechanism, 4th ed.; Kluwer Academic/Plenum: New York, 2000; pp 316-326. 6. Miller, B. Advanced Organic Chemistry, Reactions and Mechanisms, 2nd ed.; Prentice: Upper Saddle River, NJ, 2004; pp 143-171. 7. Carroll, F. A. Perspectives on Structure and Mechanism in Organic Chemistry; Brooks/Cole: Pacific Grove, CA, 1998. 8. Kjonaas, R. A.; Tucker, R. J. F. J. Chem. Educ. 2008, 85, 100–101. 9. Moroz, J. S.; Pellino, J. L.; Field, K. W. J. Chem. Educ. 2003, 80, 1319–1321. 10. Christensen, J. E.; Huddle, M. G.; Rogers, J. L.; Yung, H.; Mohan, R. S. J. Chem. Educ. 2008, 85, 1274–1275. 11. Sgariglia, E. A.; Schopp, R.; Gavardinas, K.; Mohan, R. S. J. Chem. Educ. 2000, 77, 79–80. 12. Colombo, M. I.; Bohn, M. L.; Ruveda, E. A. J. Chem. Educ. 2002, 49, 484–485. 13. Green, B.; Bentley, M. D.; Chung, B. Y.; Lynch, N. G.; Jensen, B. L. J. Chem. Educ. 2007, 84, 1985–1987. 14. Willamson, K. Friedel-Crafts Alkylation of Benzene and Dimethoxybenzene; Host-Guest Chemistry. In Macroscale and Microscale Organic Experiments; Heath: Lexington, MA, 1989; pp 399-408. 15. Khalaf, A.; Roberts, R. M. Rev. Roum. Chim. 1985, 30, 507–510. 16. Gaddis, B. A.; Schoffstall, A. M. J. Chem. Educ. 2007, 84, 848–851. 17. Young, J. A. J. Chem. Educ. 2001, 78, 722. 18. Young, J. A. J. Chem. Educ. 2001, 78, 721.

Supporting Information Available Notes for the instructor; instructors for the student; representative data. This material is available via the Internet at http://pubs.acs.org.

pubs.acs.org/jchemeduc

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r 2010 American Chemical Society and Division of Chemical Education, Inc.