In the Laboratory
C–H and C–D Bonds: An Experimental Approach W to the Identity of C–H Bonds by Their Conversion to C–D Bonds Alex T. Rowland Department of Chemistry, Gettysburg College, Gettysburg, PA 17325;
[email protected] Students studying organic chemistry spend significant time examining the C⫺H bond. They learn how to break and form the bond, where certain types of C⫺H bonds will appear in IR and 1H NMR spectra, and why the acidity of one type of hydrogen is markedly different from another type. Examination of the chemical and physical properties of the various C⫺H bonds allows the student to understand the radically different natures of such bonds. This understanding is summarized by the catch words used to describe the various types of covalently-bonded hydrogen atoms: aliphatic, vinylic, allylic, acetylenic, benzylic, and ␣ to a carbonyl function. To learn about the nature of a C⫺H bond from a lecture or a textbook is necessary, but to demonstrate such nature in the laboratory is a much more salutary experience. The three experiments presented in this paper allow students to determine the relative reactivity of C⫺H bonds that are aliphatic, ␣, benzylic, or aromatic by the ease of substitution of deuterium for hydrogen. In 1982, J. R. Hanson reported a series of deuterium labeling experiments for the undergraduate organic laboratory (1). The deuterium substitution was monitored by 1H NMR analysis. Some of the reactions, however, used reagents (metallic sodium, diazomethane, phosphorus pentachloride) that posed safety problems in the laboratory. The reactions described in this paper use readily available materials that are easily handled in the introductory organic laboratory. Relatively few articles (2–7) dealing with deuterium labeling have appeared in this Journal since the appearance of Hanson’s seminal publication (1). The labeling experiments presented here enable students to observe the changes in IR and 1H NMR spectra. Changes in the 13C NMR spectra may be determined, if desired. Two of the experiments involve substitution of deuterium for benzylic hydrogens while leaving aromatic hydrogens unaffected. Thus the methylene hydrogens in fluorene (1, see Figure 1) and p-nitrophenylacetonitrile (2) can be exchanged with no substitution of the aromatic hydrogens in either case, as demonstrated by 1H NMR and IR spectra of the products. Mechanisms for these two reactions may be written in a straightforward manner. The third experiment involves the formation of a highly substituted cyclohexanone (3) by a Michael reaction in MeOD. The assumed mechanism for this reaction (8) plus the known acidity of hydrogens ␣ to a carbonyl function (7) can be combined to explain the formation of the Michael product bearing four deuterium atoms. The lack of exchange involving aromatic, alkyl, and benzylic hydrogens in this case becomes readily apparent by examination of the spectra. The interpretation of the IR and 1H NMR spectra of the starting materials and the products can be accomplished with fundamentals of spectroscopy that are found in introductory organic texts. The IR spectra reported here were ob-
tained in CHCl3 while the 1H NMR spectra were generated on CDCl3 solutions. Results
Fluorene When fluorene is refluxed for 15 min in MeOD containing a trace of NaOMe, both hydrogens at the C-9 position are exchanged with deuterium (1-d2). The aliphatic C⫺H stretch at 2890 cm᎑1 and the aliphatic C⫺H bend at 1400 cm᎑1 that appear in the IR spectrum of the fluorene are missing in 1-d2. In the 1H NMR spectrum, the singlet due to the methylene group at ␦ 3.82 in 1 is absent in 1-d2. p-Nitrophenylacetonitrile When a pre-warmed solution of 2 in MeOD containing a trace of DCl is stirred at room temperature for 20 min, 2-d2 gradually precipitates as the solution cools. The (weak) aliphatic C⫺H stretch at 1415 cm᎑1 and the aliphatic C⫺H bend at 2940 cm᎑1 of 2 disappear in the IR spectrum of 2d2. In the 1H NMR spectrum, the singlet (CH2) at ␦ 3.92 is absent in 2-d2.
Dimethyl trans-2,6-bis(p-methoxyphenyl)4-oxocyclohexane-1,1-dicarboxylate When a mixture of dianisalacetone (see the Supplemental MaterialW ) and dimethyl malonate in MeOD containing a small amount of NaOMe is boiled with swirling on a hot plate, the dienone quickly dissolves and the product (3-d4) separates as tiny colorless crystals within a few minutes. The aliphatic C⫺H stretch at 2840 cm᎑1 appears to be the same in the IR spectra of 3 and 3-d4 due to the presence of the unchanged methyl groups. The C⫺H bending of the CH2 group in 3 at 1315 cm᎑1, however, is markedly decreased in
CN
C -9
1
NO2
O
O
C -3
C -5
O
O O
O
2
O
3
Figure 1. Compounds investigated by IR and 1H NMR.
JChemEd.chem.wisc.edu • Vol. 80 No. 3 March 2003 • Journal of Chemical Education
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In the Laboratory
intensity in 3-d4. The 1H NMR spectrum provides conclusive evidence for the presence of the four deuterium atoms in the reaction product. Whereas the hydrogens at positions C-2 and C-3 in 3 exhibit an AX2 pattern with ␦ 4.22, (t, J = 7.2 Hz, 2 H) and ␦ 2.95, (d, J = 7.2 Hz, 4 H), compound 3-d4 shows a singlet at ␦ 4.19 with no absorption at ␦ 2.95.
hydrogens ␣ to the carbonyl group are exchanged by deuterium during the course of the reaction whereas the benzylic hydrogens stay put. The stereochemistry of the Michael product also provides a valuable point for discussion. How do we know it is the trans isomer and not the cis? The interpretation of the spectra by students with faculty help can be a pleasant exercise in learning.
Hazards W
All reactions should be conducted in a hood and all liquid reagents should be dispensed while in a hood. The 25% NaOMe–MeOH reagent is extremely caustic. The liquid and vapor of MeOH and of MeOD must be considered toxic. Deuterium chloride is highly corrosive: skin contact and inhalation must be avoided. Fluorene, p-nitrophenylacetonitrile, dimethyl malonate, and dianisalacetone must be considered as potentially toxic substances. Conclusion The analysis of the spectra of the deuterated and nondeuterated compounds employed in this experiment provides an opportunity for students to devise reasonable mechanisms for the observed exchanges. The multistep Michael reaction, for example, encourages the student to grasp the basic concepts of the assumed mechanism and to rationalize why the
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Supplemental Material
Detailed procedures for the preparation of dianisalacetone and the deuterium exchange reactions are available in this issue of JCE Online. Literature Cited 1. 2. 3. 4. 5.
Hanson, J. R. J. Chem. Educ. 1982, 59, 342. Henderson, J. J. Chem. Educ. 1988, 65, 349. Lee, M. J. Chem. Educ. 1993, 70, A155. Roper, G. C. J. Chem. Educ. 1985, 62, 889. Harding, C. E.; Mitchell, C. W.; Devenyi, J. J. Chem. Educ. 2000, 77, 1042. 6. MacCarthy, P. J. Chem. Educ. 1985, 62, 633. 7. Rowland, A. T. J. Chem. Educ. 1995, 72, A160. 8. Wade, L. G., Jr. Organic Chemistry, 4th ed.; Prentice Hall: Upper Saddle River, NJ, 1999; pp 1045–1047.
Journal of Chemical Education • Vol. 80 No. 3 March 2003 • JChemEd.chem.wisc.edu
