nmr_1.ppt
- 2. Over the past fifty years nuclear magnetic resonance spectroscopy, commonly referred to as NMR, has become the preeminent technique for determining the structure of organic compounds. Of all the spectroscopic methods, it is the only one for which a complete analysis and interpretation of the entire spectrum is normally expected.
- 3. Background The nuclei of many elemental isotopes have a characteristic spin (I). Some nuclei have integral spins (e.g. I = 1, 2, 3 ....) Some have fractional spins (e.g. I = 1/2, 3/2, 5/2 ....) A few have no spin, I = 0 (e.g. 12C, 16O, 32S, ....)
- 4. Table of nuclear spin characteristics Isotope Natural % Abundance Spin (I) Magnetic Moment (μ)* Magnetogyric /Gyromagnetic Ratio (γ)† 1H 99.9844 1/2 2.7927 26.753 2H 0.0156 1 0.8574 4,107 11B 81.17 3/2 2.6880 -- 13C 1.108 1/2 0.7022 6,728 17O 0.037 5/2 -1.8930 -3,628 19F 100.0 1/2 2.6273 25,179 29Si 4.700 1/2 -0.5555 -5,319 31P 100.0 1/2 1.1305 10,840
- 5. Isotopes of particular interest and use to organic chemists are 1H, 13C, 19F and 31P, all of which have I = 1/2. Since the analysis of this spin state is fairly straightforward, our discussion of NMR will be limited to these and other I = 1/2 nuclei.
- 6. NMR phenomenon: A spinning charge generates a magnetic field. The resulting spin-magnet has a magnetic moment (μ) proportional to the spin. The frequency of precession is proportional to the strength of the magnetic field, as noted by the equation: ωo = γBo. The frequency ωo is called the Larmor frequency and has units of radians per second. γ is known as the gyromagnetic ratio and is proportional to the magnetic moment.
- 7. • In the presence of an external magnetic field (Bo), two spin states exist, +1/2 and -1/2. • The magnetic moment of the lower energy +1/2 state is alligned with the external field, but that of the higher energy -1/2 spin state is opposed to the external field.
- 8. Note that the arrow representing the external field points North. • If rf energy having a frequency matching the Larmor frequency is introduced at a right angle to the external field (e.g. along the x-axis), the precessing nucleus will absorb energy and the magnetic moment will flip to its I = -1/2 state.
- 9. The difference in energy between the two spin states is dependent on the external magnetic field strength, and is always very small. The following diagram illustrates that the two spin states have the same energy when the external field is zero, but diverge as the field increases. At a field equal to Bx a formula for the energy difference is given (remember I = 1/2 and μ is the magnetic moment of the nucleus in the field).
- 11. For spin 1/2 nuclei the energy difference between the two spin states at a given magnetic field strength will be proportional to their magnetic moments. For the four common nuclei noted above, the magnetic moments are: 1H μ = 2.7927, 19F μ = 2.6273, 31P μ = 1.1305 & 13C μ = 0.7022. These moments are in nuclear magnetons, which are 5.05078•10-27 JT-1. The following diagram gives the approximate frequencies that correspond to the spin state energy separations for each of these nuclei in an external magnetic field of 2.35 T. The formula in the colored box shows the direct correlation of frequency (energy difference) with magnetic moment (h = Planck's constant = 6.626069•10-34 Js).
- 12. Proton NMR Spectroscopy Since protons all have the same magnetic moment, we might expect all hydrogen atoms to give resonance signals at the same field / frequency values. Fortunately this is not true. Why should the proton nuclei in different compounds behave differently in the NMR experiment ? Since electrons are charged particles, they move in response to the external magnetic field (Bo) so as to generate a secondary field that opposes the much stronger applied field. This secondary field shields the nucleus from the applied field, so Bo must be increased in order to achieve resonance. Bo must be increased to compensate for the induced shielding field. Most organic compounds exhibit proton resonances that fall within a 12 ppm range, and it is therefore necessary to use very sensitive and precise spectrometers to resolve structurally distinct sets of hydrogen atoms within this narrow range.
- 13. Chemical Shift
- 14. Unlike infrared and uv-visible spectroscopy, where absorption peaks are uniquely located by a frequency or wavelength, the location of different NMR resonance signals is dependent on both the external magnetic field strength and the rf frequency. Since no two magnets will have exactly the same field, resonance frequencies will vary accordingly and an alternative method for characterizing and specifying the location of nmr signals is needed. This problem is illustrated in the diagram. Although the eleven resonance signals are distinct and well separated, an unambiguous numerical locator cannot be directly assigned to each. One method of solving this problem is to report the location of an nmr signal in a spectrum relative to a reference signal from a standard compound added to the sample. Such a reference standard should be chemically unreactive, and easily removed from the sample after the measurement. Also, it should give a single sharp nmr signal that does not interfere with the resonances normally observed for organic compounds. Tetramethylsilane, (CH3)4Si, usually referred to as TMS, meets all these characteristics, and has become the reference compound of choice for proton and carbon nmr.
- 16. Since the separation (or dispersion) of NMR signals is magnetic field dependent, one additional step must be taken in order to provide an unambiguous location unit. To correct these frequency differences for their field dependence, we divide them by the spectrometer frequency (100 or 500 MHz in the example). The resulting number would be very small, since we are dividing Hz by MHz, so it is multiplied by a million, as shown by the formula in the blue shaded box. Note that νref is the resonant frequency of the reference signal and νsamp is the frequency of the sample signal. This operation gives a locator number called the Chemical Shift, having units of parts-per-million (ppm), and designated by the symbol δ
- 19. Proton Chemical Shift Ranges
- 20. We can deduce that one factor contributing to chemical shift differences in proton resonance is the inductive effect. If the electron density about a proton nucleus is relatively high, the induced field due to electron motions will be stronger than if the electron density is relatively low. The shielding effect in such high electron density cases will therefore be larger, and a higher external field (Bo) will be needed for the rf energy to excite the nuclear spin. Since silicon is less electronegative than carbon, the electron density about the methyl hydrogens in tetramethylsilane is expected to be greater than the electron density about the methyl hydrogens in neopentane (2,2- dimethylpropane), and the characteristic resonance signal from the silane derivative does indeed lie at a higher magnetic field. Such nuclei are said to be shielded. Elements that are more electronegative than carbon should exert an opposite effect (reduce the electron density); and methyl groups bonded to such elements display lower field signals (they are deshielded). The deshielding effect of electron withdrawing groups is roughly proportional to their electronegativity. Furthermore, if more than one such group is present, the deshielding is additive, and proton resonance is shifted even further downfield.
- 21. Proton Chemical Shifts of Methyl Derivatives Proton Chemical Shifts (ppm) Compound (CH3)4C (CH3)3N (CH3)2O CH3F δ 0.9 2.1 3.2 4.1 Compound (CH3)4Si (CH3)3P (CH3)2S CH3Cl δ 0.0 0.9 2.1 3.0 Compound X=Cl X=Br X=I X=OR X=SR CH3X 3.0 2.7 2.1 3.1 2.1 CH2X2 5.3 5.0 3.9 4.4 3.7 CHX3 7.3 6.8 4.9 5.0
- 22. Signal Strength The magnitude or intensity of NMR resonance signals is proportional to the molar concentration of the sample. It is necessary to measure the relative strength as well as the chemical shift of the resonance signals that comprise an NMR spectrum. From the relative intensities, together with the noted chemical shift correlations, the reader should be able to assign the signals in these spectra to the set of hydrogens that generates each. Hint: When evaluating relative signal strengths, it is useful to set the smallest integration to unity and convert the other values proportionally.
- 25. Hydroxyl Proton Exchange Experimentally, one simply adds a drop of heavy water to a chloroform-d solution of the compound and runs the spectrum again. The result of this exchange is displayed below. R-O-H + D2O R-O-D + D-O-H
- 26. NMR Solvents and Solvent Effects Early studies used carbon tetrachloride for this purpose, since it has no hydrogen that could introduce an interfering signal. Unfortunately, CCl4 is a poor solvent for many polar compounds and is also toxic. Deuterium labeled compounds, such as deuterium oxide (D2O), chloroform-d (DCCl3), benzene-d6 (C6D6), acetone-d6 (CD3COCD3) and DMSO-d6 (CD3SOCD3) are now widely used as NMR solvents. Since the deuterium isotope of hydrogen has a different magnetic moment and spin, it is invisible in a spectrometer tuned to protons. Because some of these solvents have π-electron functions and/or may serve as hydrogen bonding partners, the chemical shifts of different groups of protons may change depending on the solvent being used.
- 27. Properties of Some Deuterated NMR Solvents Solvent B.P. °C Residual 1H signal (δ) Residual 13C signal (δ) acetone-d6 55.5 2.05 ppm 206 & 29.8 ppm acetonitrile-d3 80.7 1.95 ppm 118 & 1.3 ppm benzene-d6 79.1 7.16 ppm 128 ppm chloroform-d 60.9 7.27 ppm 26.4 ppm cyclohexane-d12 78.0 1.38 ppm 26.4 ppm dichloromethane-d2 40.0 5.32 ppm 53.8 ppm dimethylsulfoxide-d6 190 2.50 ppm 39.5 ppm nitromethane-d3 100 4.33 ppm 62.8 ppm pyridine-d5 114 7.19, 7.55 & 8.71 ppm 150, 135.5 & 123.5 ppm tetrahydrofuran-d8 65.0 1.73 & 3.58 ppm 67.4 & 25.2 ppm
- 29. The NMR spectrum of 1,1-dichloroethane (right) is more complicated than we might have expected from the previous examples. Unlike its 1,2-dichloro-isomer (left), which displays a single resonance signal from the four structurally equivalent hydrogens, the two signals from the different hydrogens are split into close groupings of two or more resonances. This is a common feature in the spectra of compounds having different sets of hydrogen atoms bonded to adjacent carbon atoms. The signal splitting in proton spectra is usually small, ranging from fractions of a Hz to as much as 18 Hz, and is designated as J (referred to as the coupling constant). In the 1,1-dichloroethane example all the coupling constants are 6.0 Hz.
- 30. The splitting patterns found in various spectra are easily recognized, provided the chemical shifts of the different sets of hydrogen that generate the signals differ by two or more ppm. The patterns are symmetrically distributed on both sides of the proton chemical shift, and the central lines are always stronger than the outer lines. The most commonly observed patterns have been given descriptive names, such as doublet (two equal intensity signals), triplet (three signals with an intensity ratio of 1:2:1) and quartet (a set of four signals with intensities of 1:3:3:1). Four such patterns are displayed in the following illustration. The line separation is always constant within a given multiplet, and is called the coupling constant (J). The magnitude of J, usually given in units of Hz, is magnetic field independent.
- 31. The splitting patterns shown above display the ideal or "First- Order" arrangement of lines. This is usually observed if the spin- coupled nuclei have very different chemical shifts (i.e. Δν is large compared to J). If the coupled nuclei have similar chemical shifts, the splitting patterns are distorted (second order behavior). In fact, signal splitting disappears if the chemical shifts are the same. Two examples that exhibit minor 2nd order distortion are shown below (both are taken at a frequency of 90 MHz). The ethyl acetate spectrum on the left displays the typical quartet and triplet of a substituted ethyl group. The spectrum of 1,3- dichloropropane on the right demonstrates that equivalent sets of hydrogens may combine their influence on a second, symmetrically located set.
- 33. Even though the chemical shift difference between the A and B protons in the 1,3-dichloroethane spectrum is fairly large (140 Hz) compared with the coupling constant (6.2 Hz), some distortion of the splitting patterns is evident. The line intensities closest to the chemical shift of the coupled partner are enhanced. Thus the B set triplet lines closest to A are increased, and the A quintet lines nearest B are likewise stronger. A smaller distortion of this kind is visible for the A and C couplings in the ethyl acetate spectrum.
- 34. What causes this signal splitting, and what useful information can be obtained from it ? If an atom is perturbed or influenced by a nearby nuclear spin the observed nucleus responds to such influences, and its response is manifested in its resonance signal. This spin- coupling is transmitted through the connecting bonds. When the perturbing nucleus becomes the observed nucleus, it also exhibits signal splitting with the same J. For spin-coupling to be observed, the sets of interacting nuclei must be bonded in relatively close proximity (e.g. vicinal and geminal locations). Some spectroscopists place a number before the symbol J to designate the number of bonds linking the coupled nuclei (colored orange below). Using this terminology, a vicinal coupling constant is 3J and a geminal constant is 2J.
- 35. Magnitude of Some Typical Coupling Constants
- 36. The following general rules summarize important requirements and characteristics for spin 1/2 nuclei : 1) Nuclei having the same chemical shift (isochronous) do not exhibit spin- splitting. They may actually be spin-coupled, but the splitting cannot be observed directly. 2) Nuclei separated by three or fewer bonds (e.g. vicinal and geminal nuclei) will usually be spin-coupled and will show mutual spin-splitting of the resonance signals, provided they have different chemical shifts. Longer-range coupling may be observed in molecules having rigid configurations of atoms. 3) The magnitude of the observed spin-splitting depends on many factors and is given by the coupling constant J (units of Hz). J is the same for both partners in a spin-splitting interaction and is independent of the external magnetic field strength. 4) The splitting pattern of a given nucleus (or set of equivalent nuclei) can be predicted by the n+1 rule, where n is the number of neighboring spin-coupled nuclei with the same (or very similar) Js. If there are 2 neighboring, spin-coupled, nuclei the observed signal is a triplet ( 2+1=3 ); if there are three spin-coupled neighbors the signal is a quartet ( 3+1=4 ). In all cases the central line(s) of the splitting pattern are stronger than those on the periphery. The intensity ratio of these lines is given by the numbers in Pascal's triangle. Thus a doublet has 1:1 or equal intensities, a triplet has an intensity ratio of 1:2:1, a quartet 1:3:3:1 etc.
- 39. If a given nucleus is spin-coupled to two or more sets of neighboring nuclei by different J values, the n+1 rule does not predict the entire splitting pattern. Instead, the splitting due to one J set is added to that expected from the other J sets. Bear in mind that there may be fortuitous coincidence of some lines if a smaller J is a factor of a larger J.
- 40. Spin 1/2 nuclei include 1H, 13C, 19F & 31P. The spin-coupling interactions described above may occur between similar or dissimilar nuclei. If, for example, a 19F is spin-coupled to a 1H, both nuclei will appear as doublets having the same J constant. Spin coupling with nuclei having spin other than 1/2 is more complex and will not be discussed here.
- 41. Carbon NMR Spectroscopy The power and usefulness of 1H NMR spectroscopy as a tool for structural analysis should be evident from the past discussion. Unfortunately, when significant portions of a molecule lack C-H bonds, no information is forthcoming. Examples:
- 42. Even when numerous C-H groups are present, an unambiguous interpretation of a proton nmr spectrum may not be possible. The following diagram depicts three pairs of isomers (A & B) which display similar proton nmr spectra.
- 43. Many obstacles needed to be overcome before carbon NMR emerged as a routine tool : i) As noted, the abundance of 13C in a sample is very low (1.1%), so higher sample concentrations are needed. ii) The 13C nucleus is over fifty times less sensitive than a proton in the NMR experiment, adding to the previous difficulty. iii) Hydrogen atoms bonded to a 13C atom split its NMR signal by 130 to 270 Hz, further complicating the NMR spectrum.
- 44. Unlike proton NMR spectroscopy, the relative strength of carbon NMR signals are not normally proportional to the number of atoms generating each one. Because of this, the number of discrete signals and their chemical shifts are the most important pieces of evidence delivered by a carbon spectrum.
- 45. Low Field Region High Field Region 13C Chemical Shift Ranges * For samples in CDCl3 solution. The δ scale is relative to TMS at δ=0.
- 46. Examples:
- 47. The isomeric pairs previously cited as giving very similar proton nmr spectra are now seen to be distinguished by carbon nmr. In the example (blue box), cyclohexane and 2,3-dimethyl-2-butene both give a single sharp resonance signal in the proton nmr spectrum (the former at δ 1.43 ppm and the latter at 1.64 ppm). However, in its carbon nmr spectrum cyclohexane displays a single signal at δ 27.1 ppm, generated by the equivalent ring carbon atoms (colored blue); whereas the isomeric alkene shows two signals, one at δ 20.4 ppm from the methyl carbons (colored brown), and the other at 123.5 ppm (typical of the green colored sp2 hybrid carbon atoms).
- 48. The C8H10 isomers in the red box have pairs of homotopic carbons and hydrogens, so symmetry should simplify their NMR spectra. The fulvene (isomer A) has five structurally different groups of carbon atoms (colored brown, magenta, orange, blue and green respectively) and should display five 13C NMR signals (one near 20 ppm and the other four greater than 100 ppm). Although ortho-xylene (isomer B) will have a proton NMR very similar to isomer A, it should only display four 13C NMR signals, originating from the four different groups of carbon atoms (colored brown, blue, orange and green). The methyl carbon signal will appear at high field (near 20 ppm), and the aromatic ring carbons will all give signals having δ > 100 ppm.
- 49. Finally, the last isomeric pair, quinones A & B in the green box, are easily distinguished by carbon NMR. Isomer A displays only four carbon NMR signals (δ 15.4, 133.4, 145.8 & 187.9 ppm); whereas, isomer B displays five signals (δ 15.9, 133.3, 145.8, 187.5 & 188.1 ppm), the additional signal coming from the non-identity of the two carbonyl carbon atoms (one colored orange and the other magenta).