In the Laboratory
Comparative Methylation of 1,8-Dihydroxy-9,10-anthraquinone: Chemoselectivity in the Organic Chemistry Laboratory
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Grigoriy A. Sereda Department of Chemistry, University of South Dakota, Vermillion, SD 57069;
[email protected] Solvent-free procedures are becoming common techniques for green technologies (1) and are attracting more attention in the design of organic laboratory procedures (2). These procedures may significantly simplify the process and avoid usage of toxic or flammable solvents. Recently, we found that methylation of 1,8-dihydroxy-9,10-anthraquinone 1 with methyl tosylate (Scheme I) is highly dependent upon reaction conditions (3). When the reaction is carried out by simple heating of the reaction mixture without solvent, it yields dimethylation product 2 in a nearly quantitative yield. Refluxing the same mixture of reactants in tetraglyme selectively leads to the product of monomethylation 3 (Scheme I). The dimethylation reaction is a good example of a synthetic procedure that is safe (no indication of self-heating or the reaction going out of control), fast (heated for 5 min), efficient (provides a nearly quantitative yield), avoids dealing with highly toxic components, and can easily be monitored by TLC. The reaction product is sublimed using a water aspirator. This makes the reaction very suitable for an undergraduate organic chemistry laboratory. A previously described procedure (4) employs flammable tetrahydrofuran, dangerous sodium hydride, carcinogenic dimethyl sulfate and takes several hours. The monomethylation reaction takes two hours of refluxing and selectively leads to monomethylated product 3 in excellent yield, despite the fact that the methylating agent is used in excess. The reaction demonstrates an example of chemoselectivity as well as how the outcome of organic reactions can be strongly dependent upon reaction conditions. We believe that the high selectivity of monomethylation in
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TsOCH3, Na2CO3 pyrolysis, 5 min
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the experiment involving refluxing in tetraglyme, is accounted for by an increased stability of the intermediate mono-deprotonated form of 1 with respect to the deprotonated form of the monomethylated compound 3. In contrast to the deprotonated form of 3, this species is stabilized by intramolecular hydrogen-bonding. When the reaction is performed under the pyrolytic conditions, both the temperature and concentrations are much higher, which results in exhaustive methylation. As usual, the reaction products are identified by their melting points and TLC retention factors. Additionally, dimethylated compound 2 and monomethylated compound 3 behave differently toward alkali. The phenolic compound 3 changes its color in the presence of an alkali owing to partial deprotonation and conjugation of the phenoxide oxygen with the quinone system. The different behavior of monoand dimethylated products toward an alkali teaches the students that the absorption of light by chromophores can be very dependent on the groups capable of conjugation. Deprotonation of the monomethylated product leads to a significant red shift in the absorption, which causes the color change from yellow–orange to deep red. Actually, compounds 1 and 3 are pH-indicators. The experiment can be easily carried out within a fourhour laboratory period and was implemented in the spring 2003 semester into the advanced laboratory course normally taken by chemistry majors. The experiment includes two synthetic procedures (di- and monomethylation) and vacuum sublimation of the dimethylated product 2. Since there are two self-consistent syntheses, the experiments can be used
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Scheme I. Methylation of 1,8-dihydroxy-9,10-anthraquinone 1 with methyl tosylate. The product depends on the reaction conditions.
OCH3
Vol. 82 No. 12 December 2005
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In the Laboratory
together or can be given to students separately. Second, since both reaction products are quite pure even in the crude form, the experiment can be easily simplified by the elimination of vacuum sublimation, the alkaline probe, and TLC.
1,8-Dihydroxy-9,10-anthraquinone and methyl tosylate are toxic and irritating to skin. The pyrolysis must be performed under a fume hood. Acknowledgment We thank the Department of Chemistry of the University of South Dakota for financial support of this work
Journal of Chemical Education
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Supplemental Material
Instructions for the students and notes for the instructor are available in this issue of JCE Online.
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(National Science Foundation Photodynamics grant #0082978).
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Literature Cited 1. Tamaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025. 2. Esteb, J.; Schelle, M.; Wilson, A. J. Chem. Educ. 2003, 80, 907. 3. Sereda, G.; Akhvlediani, D. Tetrahedron Lett. 2003, 44, 51. 4. Quast, H.; Fuchsbauer, H.-L. Chem. Ber. 1986, 119, 1016– 1038.
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