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612 CHAPTER 13 • NUCLEAR MAGNETIC SPECTROSCOPY

PROBLEMS 13.22 The d 1.2–1.5 region of the 300-MHz NMR spectrum of 1-chlorohexane, given in Fig. 13.12, is complex and not first-order. Assuming you could synthesize the needed com- pounds, explain how to use deuterium substitution to determine the chemical shifts of the protons that absorb in this region of the spectrum. Explain what you would see and how you would interpret the results. 13.23. Explain how the NMR spectra of (a) 3-methyl-2-buten-2-ol and (b) 1,2,2-trimethyl-1-

propanol would change following a D2O shake.

CHARACTERISTIC FUNCTIONAL-GROUP 13.7 NMR ABSORPTIONS

This section surveys the important NMR absorptions of the major functional groups that we’ve already studied. The NMR spectra of other functional groups will be considered in the chapters devoted to those groups. A summary table of chemical shift information is given in Appendix III.

A. NMR Spectra of Two characteristic proton NMR absorptions for alkenes are the absorptions for the protons on the double bond, called vinylic protons (red in the following structures), and the protons on carbons adjacent to the double bond, called allylic protons (blue in the following structures). Don’t confuse these two types of protons. Typical chemical shifts are illustrated in the following structures and are summarized in Fig. 13.4. vinylic proton allylic protons

d 4.92 d 1.99 d 0.88 H d 5.58 terminal H CH2 CH2 CH3 vinylic Ld 1.32 L M protons $CCA ) (13.12) y d 4.88 HH) $ d 5.68 "H d 1.97 internal vinylic proton allylic proton In these structures, allylic protons have greater chemical shifts than ordinary alkyl protons, but considerably smaller chemical shifts than vinylic protons. Additionally, the chemical shifts of internal vinylic protons are greater than those of terminal vinylic protons. Recall from Sec. 13.3C that the same trend of chemical shift with branching is evident in the relative shifts of methyl, methylene, and methine protons on saturated carbon atoms. The chemical shifts of vinylic protons are much greater than would be predicted from the of the alkene functional group and can be understood in the following way. Imagine that an alkene in an NMR spectrometer is oriented with respect to the exter-

nal applied field B0 as shown in Figure 13.14. The applied field induces a circulation of the p electrons in closed loops above and below the plane of the alkene. This electron circulation

gives rise to an induced magnetic field Bi that opposes the applied field B0 at the center of the 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 613

13.7 CHARACTERISTIC FUNCTIONAL-GROUP NMR ABSORPTIONS 613

induced field Bi opposes B0 at the p bond

Bi (induced field) induced p-electron circulation

H H induced field Bi reinforces C C B0 at the vinylic proton H H

B0 (external applied field)

Figure 13.14 In an alkene,the induced field Bi (red) of the circulating p electrons augments the external applied field at the vinylic protons.As a result,vinylic protons have NMR absorptions at relatively large chemical shift (high frequency).

loop. This induced field can be described as contours of closed circles. Although the induced

field opposes the applied field B0 in the region of the p bond, the curvature of the induced field causes it to lie in the same direction as B0 at the vinylic protons. The induced field, therefore, augments the local field at the vinylic protons. As a result, the vinylic protons are subjected to a greater local field. This means that a greater frequency is required to bring them into reso- nance (Eq. 13.4). Consequently, their NMR absorptions occur at relatively high chemical shift. Because in solution are constantly in motion and tumbling wildly, at any given time only a small fraction of the alkene molecules are oriented with respect to the external applied field as shown in Fig. 13.14. The chemical shift of a vinylic proton is an average over all orientations of the molecule. However, this particular orientation makes such a large contribution that it dominates the chemical shift. Splitting between vinylic protons in alkenes depends strongly on the geometrical relation- ship of the coupled protons. Typical coupling constants are given in Table 13.3 on p. 614. The spectra shown in Fig. 13.15 on p. 615, illustrate the very important observation that vinylic protons of cis-alkenes have smaller coupling constants than those of their trans isomers. (The same point is evident in the coupling constants of cis and trans protons shown in Figs. 13.9 and 13.10.) These coupling constants, along with the characteristic AC H bending bands from IR spectroscopy (Sec. 12.4C), provide important ways to determineL alkene stereochemistry. The very weak geminal splitting between vinylic protons on the same carbon stands in con- trast to the much larger cis and trans splittings. Geminal splitting is also illustrated in Figs. 13.9 and 13.10. The last two entries in Table 13.3 show that small splitting in alkenes is sometimes ob- served between protons separated by more than three bonds. Recall that splitting over these distances is usually not observed in saturated compounds. These long-distance interactions between protons are transmitted by the p electrons. 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 614

614 CHAPTER 13 • NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

TABLE 13.3 Coupling Constants for Proton Splitting in Alkenes

Relationship of protons Name of relationship Coupling constant J, Hz HH

$CCA ) cis 6–14 ) $ H

$CCA ) trans 11–18 ) $H

H

$CCA ) geminal 0–3.5 ) $H

H

$CCA ) vicinal 4–10

) H ) "$C

% $ $

$C A C $ four-bond (allylic) 0–3.0 H C H % % (double bond$ can be

cis or trans)

$ %

H C L $C A C $ five-bond 0–1.5 H $ $C % % (double bond can$ be cis or trans)

In many spectra, geminal, four-bond, and five-bond splittings are not readily discernible as clearly separated lines, but instead are manifested as perceptibly broadened peaks. Such is the case, for example, in the NMR spectrum in Fig. 13.16 (Problem 13.24).

PROBLEM 13.24 Propose a structure for a compound with the formula C7H14 with the NMR spectrum shown in Fig. 13.16. Explain in detail how you arrived at your structure.

B. NMR Spectra of Alkanes and Cycloalkanes Because all of the protons in a typical alkane are in very similar chemical environments, the NMR spectra of alkanes and cycloalkanes cover a very narrow range of chemical shifts, typi- cally d 0.7–1.7. Because of this narrow range, the splitting in many of these spectra shows extensive non-first-order behavior. One interesting exception to these generalizations is the chemical shifts of protons on a cy- clopropane ring, which are unusual for alkanes; they absorb at unusually low chemical shifts, 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 615

13.7 CHARACTERISTIC FUNCTIONAL-GROUP NMR ABSORPTIONS 615

Ha Hb Ha Hb

J 8.3 Hz J 13.5 Hz = =

Ha Hb Cl Hb $CCA ) $CCA ) a Cl) $CO2H H) $CO2H cis trans

d 6.86 d 6.25 d 7.51 d 6.26 (a) (b)

Figure 13.15 The NMR spectra of the vinylic protons (color) of cis-trans isomers. The coupling constants are larger for the trans protons.

chemical shift, Hz 2400 2100 1800 1500 1200 900 600 300 0

21459 0.07 ppm C7H14

7202 2219 2451

8 7 6543210 chemical shift, ppm (d)

Figure 13.16 The NMR spectrum for Problem 13.24. The red number above each resonance is its relative inte- gral in arbitrary units.

typically d 0–0.5. Some even have at smaller chemical shifts than TMS (that is, negative d values). For example, the chemical shifts of the ring protons of cis-1,2-dimethylcy- clopropane shown in red are d ( 0.11). - d ( 0.11) - H H

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616 CHAPTER 13 • NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

The cause of this unusual chemical shift is an induced electron current in the cyclopropane ring that is oriented so as to shield the cyclopropane protons from the applied field. As a result, these protons are subjected to a smaller local field, and their chemical shifts are decreased.

C. NMR Spectra of Alkyl Halides and Ethers Several NMR spectra of alkyl halides and ethers were presented in developing the principles of NMR earlier in this chapter. The chemical shifts caused by the halogens are usually in pro- portion to their . For the most part, chloro groups and ether oxygens have about the same chemical-shift effect on neighboring protons (Fig. 13.4). However, epoxides, like cyclopropanes, have considerably smaller chemical shifts than their open-chain analogs.

d 3.65 d 2.95 d 2.4, 2.7

$ $

H3C CH O CH CH3 H3C CH CH2 L L LL LLO "CH3 "CH3

An interesting type of splitting is observed in the NMR spectra of compounds containing fluorine. The common of fluorine (19F) has a nuclear . Proton resonances are split by neighboring fluorine in the same general way that they are split by neighboring protons; the

same n 1 splitting rule applies. For example, the proton in HCCl2F appears as a doublet cen- tered at+ d 7.43 with a large coupling constant JHF of 54 Hz. This is not the NMR spectrum of the fluorine; it is the splitting of the proton spectrum caused by the fluorine. (It is also possi- ble to do fluorine NMR, but this requires, for the same magnetic field, a different operating frequency; the spectra of 1H and 19F do not overlap.) Values of H–F coupling constants are

larger than H–H coupling constants. The JHF value in (CH3)3C—F is 20 Hz; a typical JHH value over the same number of bonds is 6–8 Hz. Because JHF values are so large, coupling between protons and fluorines can sometimes be observed over as many as four single bonds.

PROBLEMS 13.25 Suggest structures for compounds with the following proton NMR spectra.

(a) C4H10O: d 1.13 (3H, t, J 7 Hz); d 3.38 (2H, q, J 7 Hz) (b) C3H5F2Cl: d 1.75 (3H, t, =J 17.5 Hz); d 3.63 (2H,= t, J 13 Hz) 13.26 How would the NMR spectrum= of ethyl fluoride differ from= that of ethyl chloride?

D. NMR Spectra of Alcohols Protons on the a-carbons of primary and secondary alcohols generally have chemical shifts in the same range as ethers, from d 3.2 to d 4.2 (see Fig. 13.4). Because tertiary alcohols have no a-protons, the observation of an O H stretching absorption in the IR spectrum accompanied L by the absence of the "CH O absorption in the NMR is good evidence for a tertiary alco- hol (or a phenol; see Sec.L 16.3B).L

H3C OH H3CCH2 OH (CH3)2CH OH (CH3)3C OH L L L L no protonL absorption in d 3.5 d 3.6 d 4.0 d 3–4 region 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 617

13.7 CHARACTERISTIC FUNCTIONAL-GROUP NMR ABSORPTIONS 617

The chemical shift of the OH proton in an alcohol is difficult to predict because it depends on the degree to which the alcohol is involved in hydrogen bonding under the conditions used to determine the spectrum. For example, in pure ethanol, in which the alcohol molecules are extensively hydrogen-bonded, the chemical shift of the OH proton is d 5.3. When a small

amount of ethanol is dissolved in CCl4, the ethanol molecules are more dilute and less exten- sively hydrogen bonded, and the OH absorption occurs at d 2–3. In the gas phase, there is al- most no hydrogen bonding, and the OH resonance of ethanol occurs at d 0.8.

The chemical shift of the O H proton in the gas phase is not as large as might be expected for a pro- ton bound to an electronegativeL atom such as oxygen. The surprisingly small chemical shift of unas- sociated OH protons is probably due to the induced field caused by circulation of the unshared elec- tron pairs on oxygen. This field shields the OH proton from the external applied field (Sec. 13.3A). Hydrogen-bonded protons, on the other hand, have greater chemical shifts because they bear less electron density and more positive charge (Sec. 8.3C).

The splitting between the OH proton and the a-protons of alcohols is interesting. For ex- ample, the n 1 splitting rule predicts that the OH resonance of ethanol should be a triplet,

and the CH2 resonance+ should be split by both the adjacent CH3 and OH protons, and should therefore consist of as many as (4 2) or eight lines (multiplicative splitting; Sec. 13.5A). X H3C CH2 OH L L triplet4 2 8 lines triplet X = The NMR spectrum of very dry ethanol, shown in Fig. 13.17a on p. 618, is as expected; note

the complexity of the d-proton (CH2) resonance at d 3.7. However, when a trace of water, acid, or base is added to the ethanol, the spectrum changes, as shown in Fig. 13.17b. The presence of water, acid, or base causes collapse of the O H resonance to a single line and obliterates

all splitting associated with this proton. Thus, Lthe CH2 proton resonance becomes a quartet, apparently split only by the CH3 protons. This type of behavior is quite general for alcohols, amines, and other compounds with a proton bonded to an electronegative atom. This effect on splitting is caused by a phenomenon called chemical exchange: an equilib- rium involving chemical reactions that take place very rapidly as the NMR spectrum is being determined. In this case, the chemical reaction is proton exchange between the protons of the alcohol and those of water (or other alcohol molecules). For example, acid-catalyzed proton exchange occurs as follows:

| | RO H OH2 ROH OH2 (13.13a)

LL223 + LL2 + 3 2 "H 2 "H

| | ROH ROH H OH2 (13.13b) LL2 LL2 + L 2 "H OH2 3 2 This exchange is nothing more than two successive acid–base reactions. (Write the mecha-

nism for _OH-catalyzed exchange.) For reasons that are discussed in Sec. 13.8, rapidly ex- changing protons do not show spin–spin splitting with neighboring protons. Acid and base catalyze this exchange reaction, accelerating it enough that splitting is obliterated. In the ab- sence of acid or base, this exchange is much slower, and splitting of the OH proton and neigh- boring protons is observed. 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 618

618 CHAPTER 13 • NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

chemical shift, Hz 2400 2100 1800 1500 1200 900 600 300 0

7.1 Hz 7.1 Hz CH3

dry ethanol 5.1 Hz

5.1 Hz

CH2 OH

8 7 6543210 (a) chemical shift, ppm (d)

chemical shift, Hz 2400 2100 1800 1500 1200 900 600 300 0

CH3 7.1 Hz wet ethanol OH 7.1 Hz

CH2

8 7 6543210 (b) chemical shift, ppm (d)

Figure 13.17 The NMR spectra of ethanol. (a) Absolute, or very dry, ethanol.The CH2 resonance is split by both the CH3 and OH protons. (b) Wet acidified ethanol.The CH2 resonance is split only by the CH3 protons. Notice also the shift of the OH resonance under wet and dry conditions. The more extensive hydrogen bonding under wet conditions causes a larger chemical shift.

As a practical matter, you have to be alert to the possibility of either fast or slow exchange when dealing with an NMR spectrum of an unknown that might be an alcohol. An intermedi- ate situation is also common, in which the OH proton resonance is broadened but the a-pro- tons show the splitting characteristic of fast exchange. The assignment of the OH proton can be confirmed in either of two ways. The first is by addition of a trace of acid to the NMR tube. 13_BRCLoudon_pgs5-0.qxd 12/9/08 1:13 PM Page 619

13.8 NMR SPECTROSCOPY OF DYNAMIC SYSTEMS 619

If the a- and O H protons are involved in splitting, the acid will obliterate this splitting and

will simplify theL resonances for these two protons. The second way is to use the “D2O shake,” discussed in Sec. 13.6. If a drop of D2O is added to the NMR sample tube and the tube is shaken, the OH protons rapidly exchange with the protons of D2O to form OD groups on the alcohol. As a result, the O H resonance disappears when the spectrum is rerun. Any split- ting of the a-proton causedL by the O H proton will also be obliterated because the O H proton is no longer present. L L

PROBLEM 13.27 Suggest structures for each of the following compounds.

(a) C4H10O; d 1.27 (9H, s); d 1.92 (1H, broad s; disappears after D2O shake) (b) C5H10O: d 1.78 (3H, s); d 1.83 (3H, s); d 2.18 (1H, broad s; disappears after D2O shake); d 4.10 (2H, d, J 7 Hz); d 5.40 (1H, t, J 7 Hz) = =

13.8 NMR SPECTROSCOPY OF DYNAMIC SYSTEMS

The NMR spectrum of cyclohexane consists of a singlet at d 1.4. Yet cyclohexane has two di- astereotopic, and therefore chemically nonequivalent, sets of hydrogens: the axial hydrogens and the equatorial hydrogens. Why shouldn’t cyclohexane have two resonances, one for each type of hydrogen? Recall that cyclohexane undergoes a rapid conformational equilibrium, the chair interconversion from Sec. 7.2B. The reason that the NMR spectrum of cyclohexane shows only one resonance has to do with the rate of the chair interconversion, which is so rapid that the NMR instrument detects only the average of the two conformations. Because the chair interconversion interchanges the positions of axial and equatorial protons (Eq. 7.6), only one proton resonance is observed. This is the resonance of the “average” proton in cyclo- hexane—one that is axial half the time and equatorial half the time. This example illustrates an important aspect of NMR spectroscopy: the spectrum of a compound involved in a rapid equilibrium is a single spectrum that is the time-average of all species involved in the equilib- rium. In other words, the NMR spectrometer is intrinsically limited to resolve events in time.

Although some equations describe this phenomenon exactly, it can be understood by the use of an analogy from common experience. Imagine looking at a three-blade fan or propeller that is rotating at a speed of about 100 times per second (see Fig. 13.18 on p. 620). Our eyes do not see the individ- ual blades, but only a blur. The appearance of the blur is a time-average of the blades and the empty space between them. If we photograph the fan using a shutter speed of about 0.1 second, the fan ap- pears as a blur in the resulting picture for the same reason: during the time the camera shutter is open (0.1 s) the blades make 10 full revolutions (Fig. 13.18a). Now imagine that we slow the fan to about 1 rotation per second. While the shutter is open, the fan blades make only 0.1 revolution—about 36 . The fan blades are more distinct, but still somewhat blurred (Fig. 13.18b). Finally, imagine that the° fan is rotating very slowly, say, one rotation every hundred seconds. While the shutter is open, the fan 1 ᎏᎏ blades traverse only 1000 of a circle—about 0.36 . In the resulting picture the individual blades are vis- ible and in relatively sharp focus (Fig. 13.18c). °The rapid conformational equilibrium of cyclohexane is to the NMR spectrometer roughly what the rapidly rotating propeller is to the slow camera shutter. Both types of cyclohexane protons can be observed if the rate of the chair interconversion is reduced by lowering the temperature. Imagine cooling a sample of cyclohexane in which all protons but one have been replaced by deuterium. (The use of deuterium virtually eliminates splitting with neighboring protons, because splitting between H and D is very small; Sec. 13.6.)