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1. |
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 ( µ 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. |
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2. |
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. |
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3. |
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. 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. |