In the Laboratory
The Base-Induced Reaction of Salicylaldehyde with 1-Bromobutane in Acetone
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Two Related Examples of Chemical Problem Solving Holly D. Bendorf* and Chriss E. McDonald Department of Chemistry, Lycoming College, Williamsport, PA 17701; *
[email protected] At Lycoming we continue to search for novel investigational experiments with which to challenge our organic chemistry students (1–8). We believe it is important to rotate experiments from year-to-year to minimize the opportunity for current students to gain information about the solution to the problem outside of the laboratory. There are several features deemed to be desirable in the experiments we select. First, we believe the experiment should emphasize modern synthetic and spectroscopic techniques. We are particularly interested in problems that require students to use mass spectrometry and NMR spectroscopy in substantive ways to unravel the structure of a nonobvious unknown product. From a mechanistic point of view, the experiment should complement the material covered in the lecture portion of the organic chemistry course. Procedures where (apparently) modest changes in reaction conditions have dramatic effects on product distribution are especially intriguing (9). We have also noted that experiments can be designed to enhance the learning experience by encouraging students to share data or work in small groups to solve the structural portion of the problem. Reactions This particular exercise examines the behavior of salicylaldehyde 1 under two different but related sets of conditions (Scheme I). The polyfunctional nature of the starting material leads students to consider an array of potential reactivities (the nucleophilicity of the arene and phenol, and the
O CH3CH2CH2CH2Br
H
K2CO3, n-Bu4NBr acetone
∆
O
O(CH2)3CH3 2
H O
OH
CH3
CH3CH2CH2CH2Br KOH, n-Bu4NBr acetone
H
∆
O(CH2)3CH3 3
Scheme I. Reaction of salicylaldehyde with 1-bromobutane in acetone with (top) potassium carbonate and with (bottom) potassium hydroxide.
electrophilicity of the carbonyl). In one experiment, salicylaldehyde is treated with 1-bromobutane in acetone with potassium carbonate. Because of the heterogeneous nature of the reaction conditions, tetrabutylammonium bromide is included as a phase transfer catalyst (10, 11). Under these conditions an SN2 reaction occurs using the conjugate base of salicylaldehyde as the nucleophile to produce the indicated butyl salicyl ether 2 as the major product (12). When the stronger base potassium hydroxide is substituted for potassium carbonate, a dehydrative aldol condensation (Claisen– Schmidt condensation) with the acetone solvent occurs along with the etherification to afford enone 3 as the major product. The effect of the base change on the identity of the major product can be explained using pKa data. Hydroxide (pKa of H2O = 15.7) is a strong enough base to irreversibly deprotonate the phenolic hydrogen of salicylaldehyde (pKa = 8.3) and to generate substantial equilibrium concentrations of the enolate of acetone (pKa = 20) (13). Thus both the SN2 reaction and the aldol condensation are facilitated (14). The much weaker base carbonate (pKa of HCO3− = 11.7) can generate the phenoxide but cannot deprotonate acetone to a significant extent. Kugelrohr vacuum distillation of the crude product affords each product in > 95% purity. Experiment This project is one of a group of experiments typically conducted over a two-week period in our advanced organic chemistry course. Our approach is to place the students in a team of four. Each student does his or her own synthetic work (two do the carbonate procedure and two do the hydroxide procedure). Students set up the reaction at the beginning of a four-hour lab period. The rest of this first lab period is used for extraction, solvent removal, and thin-layer chromatographic analysis of the crude reaction mixture (versus salicylaldehyde). The second lab period is used for purifying the compounds and acquisition of the requisite spectra. Yields of the major product for each reaction are typically in the 70–90% range. Identification is accomplished within the group using a combination of spectroscopic techniques. Infrared spectroscopy clearly reveals the absence of the phenolic OH for both products. Electron impact mass spectrometry provides molecular weights as well as information regarding connectivity from the fragmentation patterns (especially in the case of 2). Proton NMR analysis clearly indicates the presence of the n-butyl moiety in each case. The aldehydic hydrogen is obvious in 2 as is the trans enone and the deshielded methyl singlet in 3. Carbon NMR further assists in identifying functionality and reveals the lack of carbon symmetry in the products. If desired by the instructor, the presence of the aldehyde functionality in 2 can be further substantiated using
JChemEd.chem.wisc.edu • Vol. 80 No. 10 October 2003 • Journal of Chemical Education
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In the Laboratory
the Tollen’s test (15) and the absence of the phenol in both products can be confirmed by the FeCl3兾pyridine test (16). Both product compounds afford dark orange crystalline 2,4dinitrophenylhydrazone derivatives. Once both products have been identified, the students within the group are asked to note the similarities of each reaction and postulate reasonable mechanisms based on their knowledge of alcohol and carbonyl reaction chemistry. They are also asked to discuss why the reactions take different courses. Hazards There are several potential safety hazards associated with these procedures. Hand and eye protection should be worn. The procedures should be conducted in a well-ventilated area, ideally a fume hood. The organic reactants, solvents, and products are flammable. Potassium hydroxide can cause burns to the skin. 1-Bromobutane, salicylaldehyde, and tetrabutylammonium bromide are irritating to the eyes, skin, and respiratory system. Acknowledgments The authors gratefully acknowledge the support of the National Science Foundation (CCLI grant no. DUE0087767), the Dreyfus Foundation (SG-01-030), the Steve Stout Fund, and Lycoming College for funding the purchase of the mass spectrometer used in this experiment. W
Supplemental Material
Materials for the students and notes for the instructor (experimental procedures, procedural notes, and spectral data) are available in this issue of JCE Online.
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Literature Cited 1. Ditzler, M. A.; Ricci, R. W. J. Chem. Educ. 1994, 71, 685– 688. 2. Pickering, M. J. Chem. Educ. 1988, 65, 143–144. 3. McDonald, C. E. J. Chem. Educ. 2000, 77, 750–751. 4. Wachter-Jurcsak, N.; Reddin, K. J. Chem. Educ. 2001, 78, 1264–1265. 5. Adrian, J. C., Jr.; Hull, L. A. J. Chem. Educ. 2001, 78, 529– 530. 6. Pelter, M. W.; Macudzinski, R. M.; Passarelli, M. E. J. Chem. Educ. 2000, 77, 1481. 7. McGowens, S. I.; Silversmith, E. F. J. Chem. Educ. 1998, 75, 1293–1294. 8. Mohrig, J. R.; Hammond, C. N.; Morrill, T. C.; Neckers, D. C. Experimental Organic Chemistry; W. H. Freeman: New York, 1998. 9. Centko, R. S.; Mohan, R. S. J. Chem. Educ. 2001, 78, 77– 78. 10. Shabestary, N.; Khazaeli, S.; Hickman, R. J. Chem. Educ. 1998, 75, 1470–1472. 11. Hulce, M.; Marks, D. W. J. Chem. Educ. 2001, 78, 66–67. 12. Allen, C. F. H.; Gates, J. W., Jr. In Organic Syntheses, Collective Volume 3; Horning, E. C., Ed.; John Wiley and Sons, Inc.: New York, 1955; pp 140–141. 13. Dean, J. A. Lange’s Handbook of Chemistry, 14th ed.; McGrawHill: New York, 1992. 14. Smith, M. B. Organic Synthesis, 2nd ed.; McGraw-Hill: New York, 2002; p 740. 15. Shriner, R.; Hermann, C.; Morrill, T.; Curtin, D.; Fuson, R. The Systematic Identification of Organic Compounds, 7th ed.; John Wiley and Sons, Inc.: New York, 1998; p 234. 16. Shriner, R.; Hermann, C.; Morrill, T.; Curtin, D.; Fuson, R. The Systematic Identification of Organic Compounds, 7th ed.; John Wiley and Sons, Inc.: New York, 1998; pp 296–297.
Journal of Chemical Education • Vol. 80 No. 10 October 2003 • JChemEd.chem.wisc.edu
