In the Laboratory The Microscale Laboratory
A Simple Organic Microscale Experiment Illustrating 1 the Equilibrium Aspect of the Aldol Condensation Ernest A. Harrison, Jr. Department of Chemistry, Penn State York Campus, York, PA 17403
Many organic laboratory (1) and lecture (2) textbooks emphasize the equilibrium aspect of the aldol condensation, but few (if any) experiments can be found that illustrate this important concept. To rectify this, a simple microscale experiment has been developed in which the students carry out two versions (3) of the preparation of tetraphenylcyclopentadienone (5) from benzil (1) and 1, 3-diphenyl-2-propanone (2) (4). In one reaction, high base concentration leads eventually to the formation of the diastereomeric cyclopentenolones 3 and 4 as well as some 5. In the other, concentration of base is kept low to develop an equilibrium between 3, 4, and starting materials 1 and 2. Since the experiment is carried out in conjunction with the preparation/dehydration of 3 (5 ), the students provide themselves with authentic samples of both 3 and 5. Thus, identification of all major components in the reaction mixtures (except compound 4) is made by comparison with authentic samples using TLC. Ph O
Ph OH-
+
O
Experimental Procedure
Ph
O Ph 2
1
HO O HO
+
O
H
H
3 4 Ph Ph O Ph Ph 5
The class is divided into pairs of students. One student in each pair is assigned the responsibility for carrying out reaction A (higher concentration of base); the other carries out reaction B (lower concentration of base). All students monitor both reactions using TLC. As a result, everyone has TLC data on both reactions. Students are instructed to start the equilibrium reactions at the beginning of the lab period and to use the rest of the period for the preparation and isolation of 3. The second lab period is devoted to the conversion of 3 into 5 (started at the beginning of the period) and TLC analysis of the equilibrium mixtures.2 In the case of reaction A, the 636
equilibrium that is established fairly rapidly (~20 min) among 1, 2, 3, and 4 is gradually displaced until, after approximately 6 hours, 3, 4, and 5 are the major components present. This suggests that the formation of 5, like that of most other α, βunsaturated carbonyl compounds, is an energetically favorable process (6 ). The conditions used for reaction B foster the slow formation (~2 h) of an equilibrium mixture of 3 and 4 that maintains its status quo for well over a week, a fact that can be explained by the ready reversibility of the aldol condensation that occurs in polar protic solvents (7 ). Each pair of students is provided with 1H NMR, IR, and MS information on compound 4 (3)3 (the only unknown product in the equilibrium mixtures) and charged with the responsibility of arriving at a structure for the compound based on the available chemical and spectral information.4 Once 4 is identified as the trans isomer, an instructor may choose to discuss how the observed stereochemical result (i.e., formation of 3 and 4) can be accommodated by the aldol mechanism.5
CAUTION: Methylene chloride vapor is potentially harmful if inhaled, so work with this reagent should be carried out under a hood. A 3.0-mL vial equipped with a stir vane was charged with benzil (1) 0.100 g (0.500 mmol), 1,3-diphenyl-2-propanone (2) 0.100 g (0.500 mmol), and 1.0 mL of a 1:1 mixture of CH2Cl2 and MeOH.6 The mixture was stirred until solution was achieved and then 10 drops (for reaction A) or 1 drop (reaction B) of methanolic KOH solution (from 0.55 g of KOH and 2 g of MeOH) was added and the vial capped. Stirring was continued for two hours while the reaction was monitored periodically by TLC using silica gel plates and CH2Cl2:hexanes (2:1) as solvent.7 Under these conditions 5, 4, 3, and 1 have Rf values of .85, .35, .20, and .75, respectively. At the end of this time stirring was discontinued and the tightly capped vial was left undisturbed until the next laboratory period, when students were instructed to co-spot their reaction mixtures along with authentic samples of 1, 3, and 5 on a single plate and interpret the results. Notes 1. Presented at the 25th Middle Atlantic Regional Meeting, Newark, DE, May, 1991. 2. Alternatively, in the first lab period the instructor may have one student prepare 3 from 1 and 2 while the other prepares 5 directly from the same reagents using the standard procedure (4 ). 3. Originally we had the students isolate 3 and 4 by column chromatography and obtain their own NMR and IR spectra for these compounds. This, however, proved to be too time consuming, so we now provide the spectral data (3).
Journal of Chemical Education • Vol. 75 No. 5 May 1998 • JChemEd.chem.wisc.edu
In the Laboratory 4. To help facilitate this process we supply students with a number of (we hope) “helpful hints”. 5. Before discussing this, we have the student pairs attempt to come up with their own mechanistic rationalizations, using clues provided in the “helpful hints” as a guide. 6. A Williamson reaction tube equipped with a flea stirring bar can be used in place of the vial/stir vane combination. 7. Depending on the type of plate used, visualization of the developed plate can be accomplished by exposing the dried plate either to iodine vapors or to an ultraviolet light source.
Literature Cited 1. See, for example: Fieser, L. F.; Williamson, K. L. Organic Experiments, 7th ed.; Heath: Lexington, MA, 1992; p 339. Eaton, D.C.
2.
3. 4. 5. 6. 7.
Laboratory Investigations in Organic Chemistry; McGraw-Hill: New York, 1989; p 463. See, for example: Wade, L. G. Organic Chemistry, 2nd ed.; Prentice-Hall: Englewood Cliffs, NJ, 1991; p 998. Fessenden, R. J.; Fessenden, J. S. Organic Chemistry, 5th ed.; Brooks/Cole: Pacific Grove, CA, 1994; p 718. Fookes, C. J. R.; Gallagher, M. J. J. Chem. Soc., Perkin 1 1975, 1876–1879. Pavia, D.; Lampman, G. M.; Kriz, G. S. Introduction to Organic Laboratory Techniques, 3rd ed.; Saunders: Philadelphia, 1988; p 342. Harrison, E. A., Jr. J. Chem. Educ. 1988, 65, 828. Nielson, A. T.; Houlihan, W. J. Org. Reactions 1968, 16, 1. See, for example: Dubois, J. E.; Dubois, M. J. Chem. Soc., Chem. Commun. 1968, 1567.
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