Organic Chemistry Nuclear Magnetic Resonance H. D. Roth. Chemistry 307 Chapter 13 Nuclear Magnetic Resonance

Transcription

1 Chemistry 307 Chapter 13 Nuclear Magnetic Resonance Nuclear magnetic resonance (NMR) spectroscopy is one of three spectroscopic techniques that are useful tools for determining the structures of organic compounds. [You will learn about infrared (IR) spectroscopy in chapter 13 and about ultraviolet/visible (UVVis) spectroscopy in chapter 15.] Spectroscopic techniques probe the energy differences between two states in a molecule by irradiating it with electromagnetic radiation of known frequency. We can observe transitions, i.e., signals, when the incident radiation has the exact frequency, ν (that is a Greek nu) for which the energy of the photon, hν, matches the energy difference, E, between the two states, E = hν (p. 562). Spectroscopic techniques are non-destructive; the excited molecules decay back to the ground state without decomposition. Photons of different energies can probe different types of transitions. Different spectroscopic methods use different units to characterize the energies of the photons applied. The units are all related to the general equation, linking energy ( E) to frequency, ν (unit: s 1 or z, named after the German physicist ertz). E = h ν 1

2 UVVis spectroscopy uses wavelength, λ (unit: nm, nanometer, 10 9 m), to characterize the energy of the photon. Wavelength is related to frequency by ν = c / λ, therefore: E = h c / λ IR spectroscopy uses wave number, 1/λ (unit: cm 1 ) E = h c ~ ν Nuclear magnetic transitions are probed with radio waves. Compared to other spectroscopic techniques NMR has an additional complication: the energy differences between nuclear states and the resonance frequency are not constant, but depend on the magnetic field, 0, at which the spectrometer operates i.e., E, ν α B 0. At a magnetic field, B 0 = 14, 47, or 70 kgauss, 1 nuclei resonate at 60, 200, or 300 Mz. E ν α B Magnetic Field Strength, B [kgauss] Therefore, it is not sufficient to give the frequency at which an NMR transition occurs; in addition to the photon frequency we have to specify the magnetic field strength to describe our results unambiguously. Instead of denoting these two parameters for each NMR transition, we define chemical 2

3 shift as the ratio, δ, of the response frequency relative to that of a standard (TMS) divided by the resonance frequency: δ = shift from TMS (in z) spectrometer frequency (in Mz) Since the resonance frequency is proportional to the magnetic field strength, this is equivalent to denoting the frequency of the signal and the magnetic field strength. This ratio is given in ppm (parts per million, 10 6 ); it has no dimension. Different nuclei have different ranges of chemical shifts, e.g., Nucleus Range Standard 1 (10 ppm) Si(C3 ) 4 (TMS) 13 C (200 ppm) Si(C3 ) 4 19 F (400 ppm) CF3 COO 31 P (700 ppm) 85 % 3 PO 4 Because of the very small energy difference between the two nuclear spin levels transitions between them are very fast: both levels are in equilibrium (see Chapter 2). G = RTlnK or lnk = G /RT The energy difference, E, between 1 nuclear levels at 70 kgauss is only ~3x10 5kcal mol 1. Because of this very low energy difference the equilibrium populations of the nuclear spin levels are almost identical; typically they differ by much less than 1%. 3

4 We will focus our discussion on the magnetic resonance of 1 and 13C nuclei. owever many other nuclei also show magnetic resonance effects. The ability to show such effects is determined by the number of protons (Z) and neutrons (N) in the nucleus. Very significantly, nuclei with even Z and even N have no magnetic moment, i.e., they show no magnetic resonance. Unfortunately, this group includes two of the key elements of organic chemistry: 12C (Z = 6, N = 6) and 16O (Z = 8, N = 8). On the other hand nuclei with an odd number of protons or neutrons have magnetic moments and, thus, show magnetic resonance. Two features determine how easy it is to record the spectrum of a magnetic nucleus, its natural abundance and its relative sensitivity. The magnetic nucleus of hydrogen, 1, has a high natural abundance while the magnetic 13C is only a minor component of carbon. The relative sensitivity is related to the energy difference between the nuclear spin levels. It is high for 1 and 19F, but much lower for most other nuclei. Remember that a change in G affects K and the equilibrium populations exponentially. Nucleus Z N Abundance Relative Sensitivity C C N O

5 19F Si P In principle, we could record all magnetic nuclei if we had an instrument probing the wide range of frequencies required for this purpose. = 70 kg 15 N 13 C 1 19 F Resonance Frequency, ν [Mz] 300 In such a wide-band instrument chlorofluoromethane would show six signals, due to the nuclei 1, 19F, 13C, 2, 35, and F 1 ( 2 ) 1 C F ( 37 ) C Frequency (Mz) 0 5

6 owever, the significant value of NMR lies in the fact that nuclei of the same element, particularly 1 or 13C, resonate at slightly different frequencies, depending on their chemical environment. When we use an NMR spectrometer with a limited range of frequencies and expand the narrow range of the 1, and 13C spectrum, the different responses will give us an insight into different chemical environments. We call this type of spectroscopy high-resolution magnetic resonance F F 2 C O C 3 13 C ppm 0 ppm 200 ppm 0 ppm We will learn about high resolution 1 NMR; its value lies in three features, each of which provides us important information: 1) The different response frequencies of individual nuclei are called their chemical shift; they identify the number of different types of nuclei and the chemical environment of a nucleus or group of nuclei; 2) The intensity of the response signal, obtained by integration, provides a measure for the relative number of nuclei giving rise to this signal; 6

7 3) Adjacent non-equivalent nuclei cause a splitting (spin spin splitting, J coupling) of the signal into multiple lines, called multiplets; these multiplets identify the number of adjacent nuclei. Typical information gained from examining an NMR spectrum include: i) The number of different chemical shifts identifies the number of different types of groups present in the molecule. Typically, because of overlap, there are fewer signals than groups; however, for the simple spectra we will discuss the number of signals likely matches the number of groups. ii) The position of signals in the spectrum, the chemical shift, identifies the chemical environment of a group of nuclei; iii) The signal intensity identifies the relative number of nuclei represented by the signal; iv) The multiplicity (the number of lines in a signal) identifies the number of nearby nuclei interacting with the nucleus/i considered. Let us recall that the energy difference between the two nuclear spin levels, α (in the direction of the magnetic field, 0 ) and β [oriented antiparallel (opposite) to 0 ] are very minor. At a field of 70 kgauss E = hν = kcal mol 1 G = RTln K = RT log K [α] [β] n(α β) = 1 in 10,000 We now turn to the details of the three key features identified above. 1) Chemical Shift 7

8 Different chemical shifts are caused by different electronic environment of the corresponding 1 nucleus (or group of nuclei). This effect has its root in two physical principles: a) a magnetic field causes charged particles (electrons, such as the lone pairs at electronegative atoms, and magnetic nuclei) to move in circular fashion; and b) a moving charged particle (electron) induces a (small) magnetic field, hlocal. The induced field, hlocal, enhances or reduces the external magnetic field 0 by a small amount. We call a nucleus experiencing a higher field, 0 + hlocal deshielded. Its resonance is shifted to the left (to lower field or downfield). Nuclei experiencing the opposite effect are called shielded; they experience a smaller field, 0 hlocal. Their resonance is shifted to the right (to higher field or upfield). Different functional groups near a nucleus cause characteristic chemical shifts (Table 13.3). Electronegative atoms have a deshielding effect; the magnitude of the inductive effect correlates with the 8

9 electronegativity of the heteroatom. These effects decrease along an alkane chain, Br C 2 C 2 C ppm Empirical 1 Chemical Shift Benchmarks high field alkane, cycloalkane shielded allylic, benzylic alkyl next to electronegative atoms alkenes benzene and aromatics 10.0 aldehydes low field 12.0 carboxylic acids deshielded The question whether a group of nuclei are magnetically equivalent or nonequivalent is of great significance. 1 nuclei, which are chemically equivalent, have identical chemical shifts. 1 nuclei, which are magnetically equivalent have identical chemical shifts and couple to other nuclei in identical fashion. Chemical equivalence may be due to symmetry or to a molecular motion causing equivalence. Rapid rotation of a methyl group or conformational interconversion of two cyclohexane chair conformers will render nuclei equivalent. Be sure to check carefully for equivalence models will help. 2) Integration The intensity of a magnetic resonance signal is proportional to the number of equivalent nuclei represented by that signal. The intensity can be 9

10 obtained by integration, performed by a computer, which measures the area under the peak. The integrals provide the numerical ratio of the nuclei represented by the signal. The spectrum of methyl t-butyl ether has two signals in the ratio of 2 : 6 reflecting the presence of 1 and 3 C 3 groups. The three dichloropropanes have different chemical shifts and different ratios of 1 nuclei. C 3 three 1 signals 1 : 2 : 3 5.9, 2.35, 1.0 ppm C 3 two 1 signals 4 : 2 3.7, 2.25 ppm four 1 signals 1 : 1 : 1 : , 3.55, 4.15, 1.6 ppm 1,2-Dichloropropane has four different shifts because the two 1 nuclei on carbon 1 next to the chiral carbon are diastereotopic (see below). 10

11 3) Spin-spin coupling The few spectra discussed so far showed only single lines (singlets). Such signals are observed for groups of 1 nuclei without any 1 nuclei on an adjacent carbon. For compounds containing a nucleus or group of nuclei on an adjacent carbon the resonances appear as multiplets, groups of lines separated by identical distances. Such multiplets reveal significant information about the connectivity of individual groups in a molecule. The number of lines representing a nucleus (or group of equivalent nuclei) is determined by the number of nearby nuclei. This effect is caused by the alignment of nuclear magnets parallel or antiparallel to 0. A nucleus aligned parallel to 0 increases the field and deshields the neighboring nucleus; nuclei aligned antiparallel to 0 shield adjacent nuclei. Empirically signals with n neighboring nuclei are split into an n + 1 multiplet; if a is coupled to (b)n, its signal has (n + 1) lines. This relationship is called the n + 1 rule. Example: 3 C O C C 2 C ppm 1.0 ppm 3 C3 interacting with C2: (n + 1) triplet 2.2 ppm 3 C3 not coupled: (n + 1) singlet 2.4 ppm 2 C2 interacting with C3: (n + 1) quartet 3 C C C ppm 11

12 1.6 ppm 6 (C3)2 interacting with C: (n + 1) doublet 3.7 ppm 1 C interacting with (C3)2: (n + 1) septet Note that the J coupling is a mutual interaction. The strength of the interaction (the magnitude of J) is a function of a) the distance between the nuclei and b) the magnetic moments of these nuclei. For any two nuclei, these parameters must be identical, e.g., J a -C C- b = J b -C C- a ow do these interactions arise? When placed in a magnetic field magnetic nuclei align themselves either parallel or anti-parallel to the field. As a result nuclei in their vicinity experience either a slightly larger or a slightly smaller magnetic field than the nominal field, 0. We can explain the number of lines in a multiplet and their intensities by simple statistic considerations. The intensities of multiplet lines are determined by the probabilities of having the nuclei up (α) or down (β). For example, a nucleus, B, can have two orientations, parallel ( up, α) or anti-parallel ( down, β). The signal of the neighboring nucleus, A, is split into two lines; because of the miniscule energy difference between α and β spins, their levels are populated essentially equally: the two lines of A have 12

13 identical intensities (1 : 1). Two equivalent nuclei, B, have four probabilities: αα, αβ, βα, and ββ. Because αβ and βα are equivalent, there are three energy levels and three signals in the ratio of 1 : 2 : 1. Three equivalent nuclei, B, have eight probabilities: ααα - ααβ, αβα, and βαα - αββ, βαβ, and ββα - and ββ. Because the arrays with 13

14 2 αs are equivalent, and so are those with 2 βs, A has four signals in the ratio of 1 : 3 : 3 : 1. The multiplet intensities are given by Pascal's Triangle (p. 580). Note that each new term (number) is the sum of the two terms (numbers) above; this means that you can construct the triangle yourself readily. Number of neighboring nuclei n singlet Normalized Signal Intensities 1 0 doublet triplet quartet quintet sextet septet ) Spin-spin coupling complications The simple rules for multiplets given by Pascal s triangle are idealized and do not always apply. We will consider several such cases. i) Coupling to nuclei with very similar chemical shifts. 14

15 The NMR spectra of compounds having several groups with closelying chemical shifts have distorted spectra; we call these non-first-order spectra. In some spectra no clear multiplet pattern is discernible; in others, the multiplet intensities are slightly to seriously distorted. Recording the spectra at higher magnetic fields will improve the separation of the peaks and change the spectrum in the direction of the idealized pattern. ii) Coupling to non-equivalent nuclei In the majority of compounds hydrogens are coupled to two or three sets of neighboring 1 nuclei. In some compounds these neighbors have identical couplings, giving rise to a normal multiplet, cf., the hydrogens at C-2 of 1-bromopropane. In other cases, however, non-equivalent nuclei have different coupling constants, resulting in more complicated splitting patterns, cf., 1-iodopropane. ere, the n + 1 rule has to be applied sequentially for the sets of non-equivalent neighbors. It is convenient to begin with the largest coupling. 5) Enantiotopic and diastereotopic hydrogens (or groups) In some cases the two hydrogens of a C 2 group are nonequivalent. Typically, this is the case for a C 2 group next to a chiral center, e.g., the C 2 of 1,2-dichloropropane (see above). We call such hydrogens diastereotopic, because replacing one ( a ) or the other ( b ) by another function (e.g., Br) would generate diastereomers (bottom line, below). Diastereotopic hydrogens are nonequivalent; they have different chemical shifts and split each other, resulting in more complicated spectra. When a methylene group (C 2 ) has no adjacent chiral center, the two 1 nuclei are said to be enantiotopic, i.e., replacement of one ( a ) or the other ( b ) by 15

16 another group, such as, generates enantiomers (top line, below); the two 1 nuclei are magnetically equivalent. These nuclei are magnetically equivalent and have identical chemical shifts. a enantiotopic O b a O enantiomers O b COO COO COO a O b O b a O C 3 COO diastereotopic C 3 COO diastereomers C 3 COO 6) Fast exchange and consequences The signals of O functions often show no coupling to the hydrogens at the adjacent carbon. This observation is related to hydrogen bonding (remember?); the coupling is voided by a rapid exchange of the proton with other O groups and with traces of water; any remains in place (attached to the same O) for less than 10 5 s. Therefore, the NMR spectrum 16

17 shows only an average peak. The fast exchange can be slowed by cooling, causing the splitting to be observed. 7) 13C nuclear magnetic resonance You have learned that NMR spectroscopy is not limited to 1 nuclei. In particular, 13C NMR significantly aids structure elucidation. owever, the observation of 13C spectra faces major problems; we have learned earlier about the low natural abundance of 13C and the significantly lower sensitivity (the resonance frequency of 13C is only 1/4 that of 1. Furthermore 13C spectra have complex splitting patterns. Although we need not consider 13C 13C splittings (at the 1.1% natural abundance of 13C the probability of adjacent 13C nuclei is little more than 0.01%), 1 13C splittings are common and would further diminish the poor 13C intensities. In order to facility the recording of 13C spectra, all 1 splittings are removed by broad-band decoupling. This is achieved by applying a strong radiofrequency signal, covering the entire range of 1 frequencies, to the sample while the 13C spectrum is recorded. The resulting spectra show single lines for each magnetically distinct type of carbon. Like 1 spectra 13C spectra also have characteristic chemical shifts reflecting the chemical environment. The range of 13C shifts is much greater (~200 ppm) than that of 1 (10 ppm); 13C chemical shifts show similar trends to those of 1. Because of their low natural abundance, their low sensitivity, and because of the need to apply broad-band decoupling, 13C spectra are usually recorded by a special technique that allows ready accumulation. 17

18 Methods of Recording NMR Spectra There are two principal modes how NMR spectra, or any other spectra are recorded: a) Continuous Wave mode, CW Spectra recorded under conditions where the excitation frequency is changed continuously or, as in the case of NMR, where the magnetic field is changed continuously, are called continuous wave (CW) spectra. There will be spectral responses at a few frequencies, but at all other frequencies random noise is recorded. Multiple scans of the same sample can be accumulated to increase S/N, the signal to noise ratio. S/N increases with the square root of the number of scans; you need 100 scans to increase S/N tenfold. b) Fourier Transform mode, FT If we apply an energy pulse of frequency F to a sample for a very short time, t (turn excitation ON and OFF rapidly), we sample all frequencies in the range (F 1/t) < F < (F + 1/t) We then record the decay of the changes induced by the energy pulse; the result is called a free-induction decay (FID). Fourier transform is a mathematical procedure that converts the time record (FID) into a frequency record, the NMR spectrum. Multiple scans of the same sample can be accumulated increasing the signal to noise ratio, S/N. S/N increases with the square root of the number of scans; 100 scans will increase S/N tenfold. The FT method can be applied in NMR, IR, and MS. 9) Off-Resonance Decoupling Advanced Topic Broad-band decoupling simplifies the 13C spectra, but it also causes the loss of any information concerning nearby protons. For organic structure 18

19 determination it is of interest to know how many 1 nuclei are attached to a particular carbon. We have two methods that can provide that information and we will mention them briefly. The first, off-resonance decoupling, simplifies the 13C spectrum by eliminating all splittings but that due to 1 nuclei directly attached to the 13C in question. For example, the three signals in the 13C spectrum of 1,2,2-trichloromethane (shown below) can be assigned unambiguously. NOTE: you need not remember off-resonance decoupling for the coming exam. 10) DEPT (Distortionless Enhanced Polarization Transfer) Advanced The second method that identifies how many 1 nuclei are attached to a particular carbon is DEPT. A DEPT experiment separately identifies C 3, C 2, and C functions. It supplies the same information as off-resonance decoupling, but is easier to use with modern, computer controlled FT spectrometers. 19

20 Typically, a DEPT spectrum consists of three scans: the top trace has all, broad-band decoupled 13 C signals; the second, called DEPT-90, contains all methine carbons, bearing to a single1 nucleus; the third trace, called DEPT-135, has C and C 3 groups in absorption and C 2 groups in emission. Signals of quaternary carbons appear only in the top trace. The data can be manipulated further so that the top trace has all 13 C signals and the second, third and fourth traces have the C 3, C 2, and C groups, respectively. Computers have no problems sorting the signals for you. 11) 2D NMR COSY and ETCOR Advanced Topic 2D NMR spectroscopy records a spectrum as a function of two characteristic times. The resulting array of data is subjected to two Fourier transformations, yielding a spectrum as a function of two frequencies. We can plot a spectrum correlating two 1 frequencies (COSY); This gives 20

21 detailed insight into connectivity. Alternatively, we can correlate 1 with 13C frequencies; the resulting spectra reveal which 13C atom is connected to which group of protons. 21