NMR problems 1st part

1. The 1H NMR spectrum of the borohydride ion (BH4-) is given below. The element boron has two isotopes, both of which are NMR active: 10B (I=3, 20%) and 11B (I=3/2, 80%). Rationalize the appearance of the observed 1H spectrum.

Answer The BH4- ion has a tetrahedral shape so all 4 hydrogens are equivalent. There will be only one resonance in the 1H NMR spectrum and this will be split by coupling to the boron nucleus. Boron has 2 isotopes 10B (I=3, 20%) and 11B (I=3/2, 80%). So for the 20% of molecules that contain 10B, the 1H resonance will be split into a 7-line multiplet by coupling to 10B (using the rule that multiplicity = 2nI +1 where n = 1and I=3). For the 80% of molecules that contain 11B, the 1H resonance will be split into a 4-line multiplet by coupling to 11B (using the rule that multiplicity = 2nI +1 where n = 1and I=3/2). The observed spectrum will be the superposition of these two contributing sub-spectra.

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Note that if you could integrate the 7 lines from the spectrum arising from the molecules containing 10B and then the 4 lines the spectra arising from the molecules containing 11B, the relative intensities should be 1:4 (reflecting the ratio of the natural abundances of the 10B and 11B). If you measure the coupling constants from the spectra, you would find that 1JH-11B is approximately 80 Hz and that 1JH-10B is approximately 27 Hz. The ratio between these is 80/27=3 reflecting the fact that the magnetogyric ratio of 11B (11B) is approximately 3 times larger than the magnetogyric ratio and 10B (10B) and that coupling is proportional to the product of the magnetogyric ratios of the nuclei which are coupled
(Jij i.j).

2.The 1H NMR spectrum of methane (CH4) consists of a single resonance and because the four protons have exactly the same chemical shift, no H-H couplings appear in the spectrum so it is not possible to measure 2JH-H from the spectrum. The 1H NMR spectrum of dideuteromethane (CD2H2) is given below. Rationalise the splitting pattern and explain how you could estimate 2JH-H using this spectrum.

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Answer The CH2D2 molecule is tetrahedral and the two protons are equivalent. They have the same chemical shift and will be split by coupling to the two deuterium nuclei. Deuterium has a spin of 1. You would expect the proton signal to be split into 5 lines (using the rule that multiplicity = 2nI +1 where n = 2 and I=1) and 5 lines can be clearly seen in the spectrum with a splitting 2J1H-2H = 2.0 Hz. Given the fact that coupling is proportional to the product of the magnetogyric ratios of the nuclei which are coupled (Jij i.j), if we know 2J1H-2H (and this is proportional to 1H.2H) then we should be able to estimate 2J1H-1H in the same molecule. It should be fairly apparent that 2J1H-1H / 2J1H-2H = 1H / 2H and from the table in your hand-out material. 1H / 2H is approximately 6.5 so 2J1H-1H is approximately 6.5 x 2J1H-2H = 6.5 x 2.0 = 13.0
Hz.

3. The 1H NMR spectrum of propane consists of two signals ( 0.90 and 1.30) with areas in the ratio 3:1 respectively. Sketch the 1H spectrum of propane (to scale) for three different spectrometers with proton frequencies of 60 MHz, 300 MHz and 600 MHz. Answer The important thing to note is that the resonance frequency of a nucleus (expressed in Hz) depends on the strength of the magnetic field whereas the coupling constants (in Hz) are magnetic field independent. As the magnetic field is increased the signals get further apart (in Hz) but the widths of the multiplets remain the same.

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4. The 1H NMR spectrum of dipropylether, (CH3CH2CH2)2O, is given below. The spectrum consists of 3 distinct resonances at 3.4 (2H, triplet), 1.6 (2H, multiplet) and 1.0 (3H, triplet). Assign the spectrum and clearly describe the spectra which would be obtained while applying a strong Rf field at: 1 3.4 ppm. 2 1.6 ppm. 3 1.0 ppm.

Answer The signals in the spectrum can be readily assigned ( 3.4 is due to the CH2 group adjacent to the oxygen; 1.6 is due to the remaining CH2 group and 1.0 is due to the CH3 group). The assignment is based on (i) the relative intensities of the signals; (ii) the observed splitting pattern; (iii) the fact that the CH2 group adjacent to the oxygen must be the low field resonance. The resonance at 3.4 is a triplet because it is coupled to 2 protons on the adjacent carbon. The resonance at 1.6 is a triplet of quartets because it is coupled to the 2 protons at 3.4 (triplet splitting) and the 3 protons at 1.0 (quartet splitting).
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The effect of irradiation at each of these frequencies is to decouple the nuclei which have signals at these frequencies. Decoupling effectively removes the nucleus from the spin system. 1 With irradiation at 3.4, the multiplicity of the CH2 resonance at 1.6 is simplified from a triplet of quartets to a quartet. The CH3 resonance at 1.0 remains unchanged. 2 With irradiation at 1.6, the multiplicity of the CH2 resonance at 3.4 is simplified from a triplet to a singlet. The CH3 resonance at 1.0 is simplified from a triplet to a singlet. 3 With irradiation at 1.0, the multiplicity of the CH2 resonance at 1.6 is simplified from a triplet of quartets to a triplet. The CH2 resonance at 3.4 remains unchanged. 5. The 1H NMR spectrum of isovaleraldehyde, (CH3)2CHCH2CHO, is given below. The spectrum consists of 4 distinct resonances: 9.2 (1H, narrow triplet), 2.2 (2H, doublet of doublets), 1.6 (1H, multiplet) and 0.9 (6H, doublet). Assign the spectrum then sketch and clearly describe the spectra which would be obtained while applying a strong Rf field at: 1 9.2 ppm. 2 2.2 ppm. 3 1.6 ppm. 4 0.9 ppm.

Answer The signals in the spectrum can be readily assigned: 9.2 is due to the proton of the aldehyde group, 2.2 is due to the CH2 group adjacent to the aldehyde; 1.6 is due to the CH of the isopropyl group and 0.9 is due to the CH3 groups). The resonance at 9.2 is a triplet because it is coupled to 2 protons on the adjacent carbon. The resonance at 2.2 is a doublet of doublets because it is coupled to the aldehyde proton as well as the methine proton of the isopropyl group. The resonance at 1.6 is a triplet of septets because it is coupled to the 2 protons at 2.2 as well as the 6 equivalent
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protons in the isopropyl group. The resonance at 0.9 is a doublet due to coupling with the methine proton at 1.6. The effect of irradiation at each of these frequencies is to decouple the nuclei which have signals at these frequencies. Decoupling effectively removes the nucleus from the spin system. 1 With irradiation at 9.2, the multiplicity of the CH2 resonance at 2.2 is simplified from doublet of doublets to a doublet. The remaining resonances are unchanged. 2 With irradiation at 2.2, the multiplicity of the aldehyde resonance at 9.2 is simplified to a singlet and the methine resonance at 1.6 is simplified to a septet. The remaining resonance at 0.9 is unchanged. 3 With irradiation at 1.6, the multiplicity of the CH2 resonance at 2.2 is simplified from a doublet of doublets to a doublet. The methyl resonances at 0.9 collapse from a doublet to a singlet. The remaining resonances are unchanged. 4 With irradiation at 0.9, the methine resonance at 1.6 is simplified to a doublet. 6. The 13C(proton coupled) and 1H NMR spectra of trimethyl phosphate [(CH3O)3P=O] are given below. 1 Rationalise the multiplicity of signals in each spectrum. 2 What would happen to the appearance of the 13C spectrum if the 1H spectrum was irradiated with strong broad-band irradiation? 3 What would happen to the appearance of the 1H spectrum if the 31P spectrum was irradiated with strong broad-band irradiation? 4 What would happen to the appearance of the 13C spectrum if the 31P spectrum was irradiated with strong broad-band irradiation? 5 What would happen to the appearance of the 1H spectrum if the 13C spectrum was irradiated with strong broad-band irradiation?

Answer

The geometry of trimethyl phosphite is tetrahedral at phosphorus. All three

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of the CH3O groups are equivalent. There would be 1 resonance in the 13C NMR spectrum, 1 resonance in the 1H NMR spectrum and 1 resonance in the 31P NMR spectrum. Note that 31P is spin and 100% abundant, 1H is spin and effectively 100% abundant and 13C is spin but only about 1% abundant. 1 The 13C NMR spectrum is a doublet of quartets. The quartet splitting arises from the 3 protons directly attached to the carbon. The doublet splitting must arise from the 2-bond coupling between C and P. The 1H NMR spectrum is a doublet and the splitting must arise from the 3-bond coupling between the protons and phosphorus. 2 If the 1H NMR spectrum was irradiated with strong Rf radiation (ie decoupled), the quartet splitting would disappear in the 13C spectrum so the 13C spectrum would appear as a doublet. 3 If the 31P NMR spectrum was irradiated with strong Rf radiation (ie decoupled), the doublet splitting would disappear in the 1H spectrum so the 1H resonance would appear as a singlet. 4 If the 31P NMR spectrum was irradiated with strong Rf radiation (ie decoupled), the doublet splitting would disappear in the 13C spectrum so the 13C spectrum would appear as a quartet. 5 If the 13C NMR spectrum was irradiated with strong Rf radiation (ie decoupled), there would be almost no effect on the 1H NMR spectrum. Almost all of the protons in the sample would be attached to the NMR-silent nucleus 12C (not 13C) because the natural abundance of 13C is only about 1%. If you could see the (small) 13 C-satellites in the spectrum, the 13C splitting in these would be removed. 7. The element lead (Pb) has several naturally occuring isotopes including 204Pb (1.5%), 206Pb (24%), 207Pb (22%) and 208Pb (52%). Of these isotopes only 207Pb has a non-zero nuclear spin (207Pb, I=1/2). What would you expect to observe for the 1H NMR spectrum of tetramethyllead [(CH3)4Pb] given that 2J207Pb-H= 60Hz ? Answer Tetramethyllead [Me4Pb] is a tetrahedral molecule so all 4 of the methyl groups are equivalent. There will be only one resonance in the 1H NMR spectrum and this will be split by coupling to the Pb nucleus. Lead has 4 isotopes 204Pb (I=0, 1.5%), 206 Pb (I=0, 24%), 207Pb (I=1/2, 22%) and 208Pb (I= 0, 52%). So for the 22% of molecules that contain 207Pb, the 1H resonance will be split into a doublet by coupling to 207Pb. For the remainder of the molecules that contain 204Pb, 206Pb and 208Pb the 1H resonance will not be split by coupling to the Pb nuclei and so will occur as a singlet. The observed spectrum will be the superposition of the contributing sub-spectra - one singlet (about 76%) and one doublet (splitting 60 Hz and about 24% of the signal intensity).

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8.The 13C NMR spectrum of toluene (CH3C6H5) is given below. The spectrum was the result of 1024 acquisitions added together and was obtained with continuous broad-band proton decoupling. 1 The intensities of the signals are all different; what factors may be responsible for this ? 2 What measures could you take in order to accurately integrate the spectrum ?

Answer 13 1 The signal intensities in C spectra cannot usually be integrated (unless the spectra are recorded carefully under conditions that ensure that they can be properly integrated). Firstly you would expect the spectrum to contain 5 resonances - 4 for the aromatic carbons and one for the methyl carbon. The aromatic carbons should have two signals of intensity 2 (corresponding to the ortho and meta carbons and two signals of intensity 1 corresponding to the ipso and the para carbons. So ideally there should be 5 signals, 3 with intensity 1 and 2 with intensity 2. One of the factors which may be responsible for the differing signal intensity is the different relaxation times for the different carbons - the ipso carbon is not protonated and so it may well have a longer relaxation time than the other carbons. We have no indication of the time between acquisitions in this spectrum so the intensities of all signals may be underestimated (by differing amounts for each signal). If the carbons are not fully relaxed between acquisitions, then the signals in the resulting spectrum will not correctly reflect the relative numbers of nuclei giving rise to
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each signal. To accurately measure the integrals in the spectrum you need to ensure that all nuclei are fully relaxed between acquisitions. This can be achieved by simply waiting sufficient time between acquisitions such that the slowest relaxing nucleus is fully relaxed (usually to be safe we wait 500 approximately seconds). This can be a slow process if many acquisitions are required to obtain adequate signal. Alternatively it is common to add a small measured amount of a soluble paramagnetic salt to the sample before acquisition. The amount is critical - just sufficient to decrease relaxation times to convenient levels without broadening signals so much that the signals are difficult to observe.

9. The compound 2-bromo-2,3-dimethylsuccinic anhydride can exist as one of two isomers - one with methyl groups cis and one with methyl groups trans. The 1H NMR spectrum of one of the isomers of 2-bromo-2,3-dimethylsuccinic anhydride is given below. The spectrum consists of a quartet (1 proton) at 2.8, a doublet (3 protons) at 0.9 and a singlet (3 protons) at 1.6 ppm. Describe in detail experiments which you could use to establish which of the isomers gives rise to the spectrum.

Answer The NOE is a powerful method for establishing the three-dimensional proximity of nuclei (or groups of nuclei) in space and is used extensively in mapping and establishing the conformations, configurations and stereochemistry of molecules in solution. The magnitude of the NOE depends on the distance between the interacting nuclei. The NOE diminishes dramatically (
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1 / r 6 ) as the distance between saturated and observed nuclei (r) increases. It would be difficult to establish which of the isomers gives rise to spectrum presented - at least by inspection. Both isomers would be expected to give rise to a spectrum with 3 resonances - one methyl group which is not coupled to any other protons; one methyl group coupled to a vicinal proton (giving a doublet splitting, and one proton coupled to a methyl group (hence with a quartet splitting). Using NOE experiments, you would irradiate each of the signals in the spectrum (one by one) and observe the remaining resonances to assess whether there was an observable enhancement. In the cis isomer, irradiation of the singlet CH3 group would be expected to provide an enhancement of the doublet CH3. Irradiation of the doublet CH3 would provide an enhancement of the singlet CH3 as well as enhancing the methine (CH) proton. Irradiation of the methine proton would provide an enhancement of the doublet CH3. In the trans isomer, irradiation of the singlet CH3 group would be expected to provide an enhancement of the methine proton. Irradiation of the doublet CH3 would provide an enhancement of the methine (CH) proton. Irradiation of the methine proton would provide an enhancement of the doublet CH3 as well enhancing the singlet CH3 group. So the cis and trans isomers have different "signatures" in the NOE experiment and could be readily distinguished. In principle, one conclusive NOE result could establish the stereochemistry of the compound, however, in practice, NOE enhancements can be quite small and difficult to quantify and it is better to perform as many NOE experiments as possible and ensure that all of the observed NOE enhancements are consistent and reinforce the assignment of stereochemistry. 10. The compound 1-bromo-2,3-dimethyl-2-pentene can exist as either an (E) or a (Z)
stereoisomer. The 1H spectrum of one of the isomers of 1-bromo-2,3-dimethyl-2-pentene is given below. The spectrum consists of a quartet (2 protons) at 2.8, a triplet (3 protons) at 0.9 a singlet at 3.5 for the -CH2-Br group and two singlets at 2.1 and 2.5 for the -CH3 groups.Describe in

detail experiments which you could use to establish which of the isomers gives rise to the spectrum.

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Answer As in question 1, the steps in answering this question involve firstly assigning the NMR spectrum then performing one (or preferably more) NOE experiments to establish which groups are close together in space and hence establish the stereochemistry. The spectrum is easily assigned by inspection and some of the assignments are given in the question. It would be difficult to establish which of the isomers gives rise to spectrum presented - at least by inspection. Both isomers would be expected to give rise to a spectrum with 5 resonances - two methyl groups (3 proton singlets) a CH2Br group (2 proton singlet) and two resonances from the ethyl substituent - one two proton quartet and one three proton triplet. Using NOE experiments, you would irradiate key signals in the spectrum (one by one) and observe the remaining resonances to assess whether there was an observable enhancement. In the E isomer, irradiation of the singlet CH2 group (belonging to CH2Br) would be expected to provide an enhancement of both singlet CH3 groups. In the Z isomer, irradiation of the singlet CH2 group (belonging to CH2Br) would be expected to provide an enhancement of only one singlet CH3 group and the CH2 group (quartet) of the ethyl group. Similarly in the E isomer, irradiation of the quartet CH2 group (belonging to the ethyl substituent) would be expected to provide an enhancement of both singlet CH3 groups. In the Z isomer, irradiation of the quartet CH2 group (belonging to the ethyl substituent) would be expected to provide an enhancement of only one singlet CH3 group and the CH2 group (singlet) of the CH2Br group. Again the E and Z isomers have different "signatures" in the NOE experiment and could be readily distinguished and although in principle, one conclusive NOE result would be sufficient to establish the stereochemistry, in practice, it is better to perform as many NOE experiments as possible and ensure that all of the observed NOE enhancements are consistent and reinforce the assignment of stereochemistry. 11. Given below is the basic spectrum and two difference NOE experiments on the
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cephalosporin molecule [1]. The large arrows indicate positions of saturation. Describe how the two difference spectra were obtained and what information can be obtained from the spectra. The numbers (in %) on the structure are the results from a number of NOE experiments. Are these values consistent with the structure as drawn ?

Answer This question requires only a qualitative answer. The broad answer is that the NOE enhancements observed are consistent with the structure. You should note that NOE's are observed between all geminal protons (ie attached to the same carbon) as well as between vicinal protons (attached to adjacent carbons) providing the vicinal protons are cis ie. on the same face of the ring. The observation of NOE between protons which are on the same face of a ring structure is often a powerful method for establishing the position and stereochemistry of substitution around the ring.
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The unexpected NOE is that observed between the proton at C7 and C4 because in the diagram provided these are a long way apart. The occurrence of this NOE indicates that the structure of the molecule must be such that the molecule is folded so that the C7 and C4 protons are brought close together. 12. The 13C free induction decay (FID) was acquired following a single 30o pulse to a sample of iodomethane. The spectrum following Fourier transformation (FT) is given on the right.

Describe what would happen to the FID and to the spectrum obtained following FT when : 1 The pulse angle was increased by a factor of 3. 2 The pulse angle was increased by a factor of 6. 3 The pulse angle was increased by a factor of 12? 4 100 FIDs were accumulated and added together before FT. 5 The sample was dissolved in a viscous solvent before acquisition of the FID. 6 The proton spectrum was saturated for several seconds immediately before (but not during) the acquisition of the FID. 7 The 13C spectrum was saturated for several seconds immediately before acquisition of the FID. 8 The 1H spectrum was irradiated continuously with strong Rf radiation before and during the acquisition of the FID. Answer The 13C FID and spectrum are derived from a sample of CH3I. The spectrum is a quartet so it is clear that the spectrum is accumulated with no proton decoupling.
1

The pulse angle is 30o so increasing this by a factor of 3 will mean that a 90o pulse is delivered to the sample. The response of the sample is a sinusoidal function of the pulse angle. Sin(30) = and Sin(90) = 1 so the intensity of the signal in the FID and in the spectrum will be increased by a factor of 2. The pulse angle is 30o so increasing this by a factor of 6 will mean that a 180o pulse is delivered to the sample. The response of the sample is a sinusoidal function of the pulse angle. Sin(180) = 0 so the intensity of the signal in the FID and in the spectrum will be zero. Both the FID and the spectrum would contain only noise.
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The pulse angle is 30o so increasing this by a factor of 12 will mean that a 360o pulse is delivered to the sample. The response of the sample is a sinusoidal function of the pulse angle. Sin(360) = Sin(0) = 0 so the intensity of the signal in the FID and in the spectrum will be zero. Both the FID and the spectrum would contain only noise. The signal-to-noise ratio (S/N) of the spectrum increases as the square root of the number of acquisitions that are added together. If 100 acquisitions are added the S/N increases by a factor of 100 = 10. A viscous solvent will slow the rate of molecular tumbling and this in turn increases the efficiency of relaxation. Nuclei would be expected to relax more quickly and this would be reflected in a change in the appearance of the FID and the spectrum. The signal in the FID would decay to zero more rapidly (ie in less time); signals in the spectrum would be broader. Irradiation of the proton spectrum before (but not during) the acquisition would provide an NOE enhancement to the carbon spectrum (without decoupling carbon from protons). So the intensity of both the FID and the spectrum would be increased. Saturation of the 13C spectrum would mean that the 13C spectrum would not be observable, providing there was no significant delay between the saturation and recording the FID. Nuclei take several T1's to recover following saturation. Irradiation of the proton spectrum before and during the acquisition would provide an NOE enhancement to the carbon spectrum as well as decoupling the protons from carbon. Both the FID and spectrum would be increased in intensity due to the NOE. In addition the spectrum would no longer show a quartet splitting (due to proton coupling) but it would appear as a singlet. The shape of the FID would also be changed because rather than 4 lines contributing frequency components to the FID, there would be only one. The shape of the FID would be considerably simplified to a single decaying sine wave.

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