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JCE Featured Molecules
William F. Coleman Wellesley College Wellesley, MA 02481
Molecular Models from a Greener, Solvent-Free Synthesis Biginelli Product, Ethyl Acetoacetate, Monastrol, and Nifedipine June 2009 Featured Molecules As increasing emphasis is placed on sustainable chemistry, the inclusion of concepts related to this topic across the chemistry curriculum also becomes more essential, in both lecture and laboratory. The paper by Evangelos Aktoudianakis, Elton Chan, Amanda R. Edward, Isabel Jarosz, Vicki Lee, Leo Mui, Sonya S. Thatipamala, and Andrew P. Dicks is an excellent example of one approach to introducing a sustainable approach to a particular synthesis and comparing the results to those from the more traditional synthesis (1). Several molecules from that paper are this month’s featured molecules. One of these, the kinesin Eg5 inhibitor monastrol, can also be prepared in a sustainable reaction using microwave oven heating (2). Structural optimization of monastrol (Figure 1A) at the HF/6311++G(p,d) level indicates the presence of substantial delocalized pi bonding involving the thionyl group, the two nitrogens and the two carbons in the double bond of the dihydropyrimidine ring and, to a lesser extent, the carboxyl group of the ester side chain. In addition to the specific synthesis of ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenylpyrimidine-5-carboxylate (Figure 1B), references 8 and 9 of the paper and the online supplement (1) describe a variety of other useful molecules that are prepared using the Biginelli approach (Figure 1C). Many of these molecules would make excellent assignments in both
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organic chemistry and also in courses relating chemistry and society, and offer the possibility of bringing both sustainability and economic arguments into the discussion. Literature Cited 1. Aktoudianakis, E.; Chan, E.; Edward, A. R.; Jarosz, I.; Lee, V.; Mui, L.; Thatipamala, S. S.; Dicks, A. P. J. Chem. Educ. 2009, 86, 730–732. 2. Dallinger, D.; Kappe, C. O. Nature Protocols 2007, 2, 317–321.
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2009/Jun/abs768.html Full text (HTML and PDF) with images in color Link to cited JCE article Supplement Find “Molecular Models from a Greener, Solvent-Free Synthesis” in the JCE Digital Library at http://www.JCE.DivCHED.org/ JCEWWW/Features/MonthlyMolecules/2009/Jun/
The molecules added to the collection this month are: ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenylpyrimidine5-carboxylate (Biginelli product) ethyl acetoacetate monastrol nifedipine
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Figure 1. Molecules added to the JCE Featured Molecules collection from the article by Dicks et al. (1): (A) monastrol; (B) ethyl 1,2,3,4-tetrahydro6-methyl-2-oxo-4-phenylpyrimidine-5-carboxylate (Biginelli product); and (C) nifedipine.
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Journal of Chemical Education • Vol. 86 No. 6 June 2009 • www.JCE.DivCHED.org • © Division of Chemical Education
