Chemical Education Today
Letters Synthesis of a Lactone In an intriguing microscale laboratory project, “Convenient Synthesis of a Lactone, γ-Butyrolactone”, which appeared in this Journal (1), a classic γ-lactone is synthesized from sodium γ-hydroxybutyrate or “GHB”. GHB is a fascinating substance which is most likely an endogenous neurotransmitter or neuromodulator. In mammals at large doses (orally, about 7 grams for an average adult), it produces amnesia; doses at twice this level produce sleep, and a five-fold increase can induce surgical anesthesia. Indeed, it is employed for this purpose in Europe. The sleep it induces has a normal REM architecture, and anesthetic doses seem to be neuroprotective, allowing the brain to survive without damage what would otherwise be fatally low levels of oxygen. It is possible that endogenous GHB is involved in mammalian hibernation. It has found experimental use in the treatment of alcoholism (2). However, it has also gained a reputation in the shadowy world of recreational drug use, where it is believed (with little or no warrant) to be an anabolic steroid or an aphrodisiac. It seems to have been used in several date-rape cases (see the somewhat overblown article in Newsweek (3) captioned “Death of the Party: GHB is a Hot Drug in the Nightclub and Rave Scenes. But this Cheap High Can Bring Fatal Lows”). It is quite possible that the DEA will soon place GHB in a Schedule I or Schedule II classification of the Controlled Substances Act, making its possession as difficult as heroin or cocaine (4). None of this has anything to do with the pedagogical merits of the lab described in J. Chem. Educ. But for the protection of their students and for their own legal liability, instructors using GHB should be more than ordinarily wary that none is diverted into the hands of inquisitive students who may be interested in something beyond lactonization. Literature Cited 1. 2. 3. 4.
Bozak, R. E.; Knittel, J.; Hicks, R. J. J. Chem. Educ. 1998, 75, 84. The Lancet 1998, 351, 38. Newsweek, October 27, 1997, p 55. JAMA 1997, 277 (19), 1505–1506; 1997, 278 (21), 1724. Daniel M. Perrine Loyola College in Maryland Baltimore, MD 21210 (Author of The Chemistry of Mind-Altering Drugs: History, Pharmacology, and Cultural Context, ACS Books, 1996.)
Magnetic Nonequivalence in Proton NMR I believe the article by Christopher J. Welch (1) actually causes confusion rather than creating clarity. The parameters that determine the complexity of a proton NMR spectrum are the numbers of nuclei at different chemical shift (the question of chemical shift equivalence) and the equality or inequality of the coupling constants between members of a set of nuclei at one chemical shift and the members of a set of nuclei at a different chemical shift (the question of magnetic equivalence). For example, if a spin system consists of exactly two sets of chemical shift equivalent nuclei, as in ethyl bromide, and the 6 coupling constants between the two methylene pro-
tons and the three methyl protons are exactly the same, as they are in ethyl bromide, the appearance of the spectrum will depend only upon the difference in chemical shift between the methylene and methyl protons and this single interset coupling constant. An N + 1 rule spectrum will be observed. The methylene protons are chemical shift equivalent, the methyl protons are chemical shift equivalent, and these two sets of protons are magnetically equivalent because all interset coupling constants are equal. The intraset coupling constants (between the chemical shift equivalent methylene protons and among the chemical shift equivalent methyl protons) have no effect upon the appearance of the spectrum. The concepts of chemical shift equivalence and magnetic equivalence are discussed at length in references 2 and 3. In the proton NMR spectrum of compound 1, which is discussed by Welch, all spin systems involve magnetic equivalence; there is no example of magnetic nonequivalence. O CH3
CH2
O
O
O
O
CH2
CH3
O N
N
CH3
CH3
1 all spin systems are magnetically equivalent
Analysis of the Spectrum The N-methyl groups have the same chemical shifts and contribute coincident singlets at δ = 2.86 ppm. The implied protons on the carbons next to the nitrogen atoms are diastereotopic and thus have different chemical shifts. Each will split the resonance of the other into a doublet, and these doublets appear at δ = 3.74 and δ = 3.98 with a splitting that corresponds to an interset coupling constant of J = 10.2 Hz. Since there is only a single interset coupling constant when there is only one proton in each set, magnetic equivalence is necessarily involved. These two pairs of methylene protons have the same chemical shifts and so the pairs of doublets are coincident. We turn now to the ethyl groups. The ethyl groups are equivalent and so their resonances will be coincident, just as the two N-methyl resonances and the two methylene resonances discussed above are coincident. The 5 protons of each ethyl group comprise an ABX3 spin system because the methylene protons of the ethyl groups are diastereotopic and the resonance of each methylene proton will appear at a different chemical shift. We are told that this difference is 0.053 ppm, which is about 14.3 Hz in a 270-MHz machine but only 3.2 Hz in a 60-MHz machine. There can be only one coupling constant between the single A proton and the single B proton, all AX coupling constants are equal owing to free rotation of the methyl group, and all BX coupling constants are equal for the same reason. Thus this ABX 3 system also involves magnetic equivalence, not magnetic nonequivalence. Since the methyl resonance of the ethyl group, which appears at δ = 1.18, appears as a 1:2:1 triplet, JAX and JBX must also be about equal, though it is not necessary that this be so. Since the methylene protons of each ethyl group differ in chemical shift, each should appear as a pair of doublets,
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each line of which should be further split into 1:3:3:1 quartets by coupling with the methyl group. We therefore expect to see a total of 16 lines, 8 from each of the two methylene protons. As the author says, the small chemical shift difference (∆δ = 14.3 Hz) between the chemical shifts of the methylene protons and the fact that ∆δ is twice JAX and JBX leads to overlap and coincidences. A more clear example of the resonance of a spin system of this type is provided by the coincident ethyl resonances of the diethylacetal of acetaldehyde, compound 2. H
CH3
CH2
O
C
O
CH2
CH3
CH3 2
Although there is some overlap, there are no coincidences, and all 16 lines of the expected pair of doublets, each further split into a 1:3:3:1 quartet, can be seen clearly (4, spectra 285a and 285c). Finally, I think the author’s criticism of the data reported in the literature is a bit harsh, since at 60 MHz ∆δ would be only 3.2 Hz rather than the 14.3 Hz in a 270-MHz machine. Literature Cited 1. 2. 3. 4.
Welch, C. J. J. Chem. Educ. 1997, 74, 247. Ault, A. J. Chem. Educ. 1970, 47, 812. Ault, A. J. Chem. Educ. 1974, 51, 729. Ault, A.; Ault, M. R. A Handy and Systematic Catalog of NMR Spectra; University Science Books: Mill Valley, CA, 1980. Addison Ault Department of Chemistry Cornell College Mount Vernon, IA 52314-1098
The author replies: I think that Addison Ault and I are in agreement concerning the points he has raised—that in the molecule presented, the methylene groups discussed are magnetically equivalent. That is to say that the two endocyclic CH2 groups are in every way identical to each other and that the same is true for the two exocyclic CH2 groups. The published article discussed the nonequivalence of the two component protons of each of the methylene groups. If these were magnetically equivalent they would show the same chemical shift. A consequence of this would be that the strong geminal coupling between the two protons would not be seen in the spectrum. The experiment described is aimed at advanced undergraduate students studying organic chemistry. The problems to be highlighted include the misconception that chemical shift differences in methylene groups are due to restricted rotation (see J. K. M. Sanders and B. K. Hunter, Modern NMR Spectroscopy, Oxford University Press, 1987, p 299). The compound used was chosen because it is easily prepared; I believe that students show more interest in the spectra if the compounds have been prepared as part of the course. Most common spectroscopy books used as course literature for undergraduate courses include a section on magnetic equivalence: for example, Introduction to Spectroscopy by D. L. Pavia, G.
M. Lampman, and G. S. Kriz, Saunders College Publishing. In this book we can read, on page 199, that the requirements for magnetic equivalence are (i) identical chemical shifts and (ii) equal coupling constants to all other protons. The first of these criteria is clearly not met in the compound presented; therefore the protons discussed are not equivalent. Finally, I agree with Ault that my criticism of the results presented in paper 1 is too harsh. My intention was to encourage students to interpret their own data independently of previous reports, and to seek explanations of differences. The formulation I have used is rather clumsy. I meant no offense and shall contact the authors with an apology. I hope that this clarifies the confusion I may have caused. Christopher J. Welch Department of Pharmaceutical Chemistry Uppsala Biomedical Centre, Uppsala University S-751 23 Uppsala, Sweden
Chemistry at the Art/Archaeology Interface A human head is a decorated two-dimensional surface with positive curvature in the third dimension, as with a model globe of the Earth. The Shroud of Turin (J. Chem. Educ. 1997, 74, 373) is a two-dimensional surface with zero curvature, as is paper used as a map. Elliptic (positive curvature), plane (zero curvature), and hyperbolic (negative curvature) spaces cannot be mapped one onto another without distortion. Triangles’ interior angles sum to more than, exactly, and less than 180 degrees respectively in each curved space. Euclid’s Fifth Postulate is different for each curved space. No flat map can represent the curved Earth without distortion. No flat cloth can receive the projected image of a human head without distortion. Either the Shroud of Turin is a scam, or all geometry starting with Euclid is invalid. Note that the published image is a photographic negative of the Shroud of Turin. One can duplicate the artifact at home by heating a bas relief sculpture to the char temperature of cloth followed by placing the cloth on the heated surface. Use a cellulose fiber—polyester melts and wool smells awful. Alan M. Schwartz Molecular Genesis Life Sciences Ltd. Vancouver, BC V6G 2L7 Canada
The author replies: The geometric observation made by Alan Schwartz regarding the undistorted face shown in Figure 6 (J. Chem. Educ. 1997, 74, 373) is a point well taken. I agree that no flat cloth can receive the projected image of a human head without distortion. However, the published image is that of the face on the Shroud as it exists. Schwartz’s point is one more factor to add to Walter McCrone’s amassed evidence regarding the inauthenticity of the Shroud as reported in his recent book, Judgement Day for the Turin Shroud (Microscope Publications: Chicago, IL, 1996). Mary Virginia Orna Department of Chemistry College of New Rochelle New Rochelle, NY 10801
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