CHEMICAL SHIFT AND COUPLING CONSTANTS

1. CHEMICAL SHIFT AND COUPLING CONSTANTS

2. Unpaired nuclear spins are of importance in NMR. An applied magnetic field B0, the strength of which is measured in tesla (T), and the frequency n of radiation used for resonance, measured in hertz (Hz), or megahertz (MHz)—(1 MHz = 106 Hz). The actual spectral data acquired by NMR is the free-induction decay, or FID. FID FT Frequency, Hz Time, sec

3. NMR Spectrometer • Schematic diagram of a nuclear magnetic resonance spectrometer.

4. 1H NMR—The Spectrum • An NMR spectrum is a plot of the intensity of a peak against its chemical shift, measured in parts per million (ppm). Protons in different environments absorb at slightly different frequencies, so they are distinguishable by NMR.

5. 1H-NMR spectrum of methyl acetate. • NMR absorptions generally appear as sharp peaks. • Increasing chemical shift is plotted from left to right. • Most protons absorb between 0-10 ppm. • The terms “upfield” and “downfield” describe the relative location of peaks. Upfield means to the right. Downfield means to the left. • NMR absorptions are measured relative to the position of a reference peak at 0 ppm on the d scale due to tetramethylsilane (TMS). TMS is a volatile inert compound that gives a single peak upfield from typical NMR absorptions. • High frequency:The shift of an NMR signal to the left on the chart paper. • Low frequency:The shift of an NMR signal to the right on the chart paper.

6. 1D 1H NMR Spectra of Skeletal Muscle Tissue

7. Chemical Shift When an atom is placed in a magnetic field, its electrons circulate about the direction of the applied magnetic field. This circulation causes a small magnetic field at the nucleus which opposes the externally applied field. The magnetic field at the nucleus (the effective field) is therefore generally less than the applied field by a fraction , B = Bo (1- ) The electron density around each nucleus in a molecule varies according to the types of nuclei and bonds in the molecule. The opposing field and therefore the effective field at each nucleus will vary. This is called the chemical shift phenomenon. n = (g/2p)Blocal = (gBo/2p)(1-s)

8. 1H NMR—Position of Signals • In the vicinity of the nucleus, the magnetic field generated by the circulating electron decreases the external magnetic field that the proton “feels”. • Since the electron experiences a lower magnetic field strength, it needs a lower frequency to achieve resonance. Lower frequency is to the right in an NMR spectrum, toward a lower chemical shift, so shielding shifts the absorption upfield.

9. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Position of Signals

10. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Position of Signals

11. 1H NMR—Position of Signals • The less shielded the nucleus becomes, the more of the applied magnetic field (B0) it feels. • This deshielded nucleus experiences a higher magnetic field strength, to it needs a higher frequency to achieve resonance. • Higher frequency is to the left in an NMR spectrum, toward higher chemical shift—so deshielding shifts an absorption downfield. • Protons near electronegative atoms are deshielded, so they absorb downfield.

12. Chemical Shift is field dependent The chemical shift of a nucleus is the difference between the resonance frequency of the nucleus and a standard, relative to the standard. This quantity is reported in ppm and given by the symbol delta, . Choice of Solvents: D2O, H2O, CDCl3, DMSO Reference Compounds: Aqueous solution: DSS (4,4-dimethyl-4-silapentane-1-sulfonic acid) (TSP) Trimethylsilyl propionate (CH3)4Si, usually referred to as TMS used in CDCl3, DMSO The magnitude of the screening depends on the atom. For example, carbon-13 chemical shifts are much greater than hydrogen-1 chemical shifts.

13. Protons in different environments absorb at slightly different frequencies, so they are distinguishable by NMR. • The frequency at which a particular proton absorbs is determined by its electronic environment. • The size of the magnetic field generated by the electrons around a proton determines where it absorbs. • Modern NMR spectrometers use a constant magnetic field strength B0, and then a narrow range of frequencies is applied to achieve the resonance of all protons. • Only nuclei that contain odd mass numbers (such as 1H, 13C, 19F and 31P) or odd atomic numbers (such as 2H and 14N) give rise to NMR signals.

14. The difference in resonance frequencies among the various hydrogen nuclei within a molecule due to shielding/deshielding is generally very small. • The difference in resonance frequencies for hydrogens in CH3Cl compared to CH3F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency.

15. Chemical Shifts 1H-NMR

16. Chemical shift depends on the • (1) electronegativity of nearby atoms, • (2) hybridization of adjacent atoms, and • (3) diamagnetic effects from adjacent pi bonds. • Electronegativity

17. Chemical Shift • Hybridization of adjacent atoms.

18. Chemical Shift • Diamagnetic effects of pi bonds • A carbon-carbon triple bond shields an acetylenic hydrogen and shifts its signal to lower frequency (to the right) to a smaller  value. • A carbon-carbon double bond deshields vinylic hydrogens and shifts their signal to higher frequency (to the left) to a larger  value.

19. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Chemical Shift Values • The chemical shift of a C—H bond increases with increasing alkyl substitution.

20. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Chemical Shift Values • Protons in a given environment absorb in a predictable region in an NMR spectrum.

21. Chemical Shift • Magnetic induction in the p bonds of a carbon-carbon triple bond shields an acetylenic hydrogen and shifts its signal lower frequency.

22. Chemical Shift • Magnetic induction in the p bond of a carbon-carbon double bond deshields vinylic hydrogens and shifts their signal higher frequency.

23. In some cases, such as the benzene molecule, the circulation of the electrons in the aromatic orbitals creates a magnetic field at the hydrogen nuclei which enhances the Bo field. This phenomenon is called deshielding. • In a magnetic field, the six  electrons in benzene circulate around the ring creating a ring current. • The magnetic field induced by these moving electrons reinforces the applied magnetic field in the vicinity of the protons. • The protons thus feel a stronger magnetic field and a higher frequency is needed for resonance. Thus they are deshielded and absorb downfield.

24. Four different features of a 1H NMR spectrum provide information about a compound’s structure: • Number of signals • Position of signals • Intensity of signals. • Spin-spin splitting of signals.

25. 1H NMR—Number of Signals • The number of NMR signals equals the number of different types of protons in a compound. • Protons in different environments give different NMR signals. • Equivalent protons give the same NMR signal. • To determine equivalent protons in cycloalkanes and alkenes, always draw all bonds to hydrogen.

26. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Number of Signals

27. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Number of Signals • In comparing two H atoms on a ring or double bond, two protons are equivalent only if they are cis (or trans) to the same groups.

28. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Number of Signals • Proton equivalency in cycloalkanes can be determined similarly.

29. 1H NMR—Position of Signals • Other Factors Affecting Chemical Shift • Solvent • Presence of electronegative atoms. • pH. • Temperature • Hydrogen bond • Conformational Changes • Presence of ligand

30. Nuclear Magnetic Resonance Spectroscopy Calculating 1H NMR—Chemical Shift Values • The chemical shift of a C—H can be calculated with a • high degree of precision if a chemical shift additivity table is used. • The additivity tables starts with a base chemical shift value depending on the structural type of hydrogen under consideration: 30

31. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Chemical Shift Values

32. Nuclear Magnetic Resonance Spectroscopy 1H NMR—Spin-Spin Splitting • Consider the spectrum below:

33. Ethyl Bromide

34. Spin-Spin Coupling

35. Spin-Spin Coupling (Splitting) Observation: A nucleus with a magnetic moment may interact with other nuclear spins resulting in mutual splitting of the NMR signal from each nucleus into multiplets.

36. The Origin of 1H NMR—Spin-Spin Splitting The frequency difference, measured in Hz, between two peaks of the doublet is called the coupling constant, J.

37. The Origin of 1H NMR—Spin-Spin Splitting • Spin-spin splitting occurs only between nonequivalent protons on the same carbon or adjacent carbons. Let us consider how the doublet due to the CH2 group on BrCH2CHBr2 occurs: • When placed in an applied field, (B0), the adjacent proton (CHBr2) can be aligned with () or against () B0. The likelihood of either case is about 50% (i.e., 1,000,006 vs 1,000,000). • Thus, the absorbing CH2 protons feel two slightly different magnetic fields—one slightly larger than B0, and one slightly smaller than B0. • Since the absorbing protons feel two different magnetic fields, they absorb at two different frequencies in the NMR spectrum, thus splitting a single absorption into a doublet, where the two peaks of the doublet have equalintensity.

38. The Origin of 1H NMR—Spin-Spin Splitting Let us now consider how a triplet arises: • When placed in an applied magnetic field (B0), the adjacent protons Ha and Hb can each be aligned with () or against () B0. • Thus, the absorbing proton feels three slightly different magnetic fields—one slightly larger than B0(ab). one slightly smaller than B0(ab) and one the same strength as B0 (ab).

39. When determining the spin-spin coupling, look at the number of protons on the adjacent carbon. For the methyl group, look at the methylene group. There are 2 protons, so using the N+1 rule tells us that the peak should be a triplet in a 1:2:1 ratio. CH2 b

40. The Origin of 1H NMR—Spin-Spin Splitting

41. For the methylene group, look at the methyl group. There are 3 protons, so using the N+1 rule tells us that the peak should be a quartet in a 1:3:3:1 ratio. CH3 a

42. 4. The Coupling Constant, J - theseparation between peaks in a multiplet measured in units of Hz. Jba a b Jba CH3CH2Br Jba CH2 b Jba = Jab = 7.3 Hz Jab Jab CH3 a

43. The energy of the interactions between two spins A and B can be found by the relationship: E = JAB * IA * IB • IAand IBare the nuclear spin vectors, and are proportional to • mAandmB, the magnetic moments of the two nuclei. JABis • the scalar coupling constant. So we see a very important • feature of couplings. It does not matter if we have a 60, a • 400, or an 800 MHz magnet,the coupling constants are • always the same!!!

44. Lets do a more detailed analysis in term of the energies. Lets think a two energy level system, and the transitions for nuclei A. When we have no coupling (J = 0), the energy involved in either transition (A1 or A2) is equal (no spin-spin interaction). A X J > 0 A X J = 0 E4 E3 E2 E1 A2 A2 Bo E A1 A1 • When J > 0, the energy levels of the spin system will be either stabilized or destabilized.Depending on the relative orientations of the nuclear moments, the energies for the A1 and A2 transition will change giving two different frequencies (two peaks for A).

45. J > 0 J < 0 J = 0 A2 A1 A2 A2 A1 A1 n A1n A2 n A1 = n A2 n A2n A1 • As mentioned before, the choice of positive or negative J is a • definition. However, we see that we won’t be able to tell if we have a positive or negative J, because the lines in the spectrum corresponding to the different transitions basically • change places. Unless we are interested in studying the • energies, this is not important for structure elucidation…

46. Spin-Spin Splitting Now look at some simple examples. Examine the size of the peaks in the splitting. Hb is augmenting external field causing a larger energy gap. Hb decrementing external field causing a smaller energy gap. Ha is being excited. Hb is causing spin-spin splitting by slightly increasing or decreasing the magnetic field experienced by Ha.

47. Two neighboring atoms assist external field. More energy needed to excite. Peak is “downfield”. Again Ha is flipping, resonating. The two Hb are causing spin-spin splitting by slightly changing the magnetic field experienced by Ha. One neighbor assists, one hinders. No effect. Both neighbors oppose. Less energy needed to excite, “upfield”. Recall that for the two Hb atoms the two states (helping and hindering the external field) are almost equally likely. This give us the 1 : 2 : 1 ratio. Figure 13.15b, p.512

48. Three neighboring Hb’s causing splitting when Ha is excited. All Hb augment Two augment, one decrement. One augment, two decrement. All decrement. Ha being excited. Three equivalent Hb causing spin spin splitting. Figure 13.15c, p.512

49. The Origin of 1H NMR—Spin-Spin Splitting

50. Spin-Spin Splitting in 1H NMR Spectra • Peaks are often split into multiple peaks due to magnetic interactions between nonequivalent protons on adjacent carbons, The process is called spin-spin splitting • The splitting is into one more peak than the number of H’s on the adjacent carbon(s), This is the “n+1 rule” • The relative intensities are in proportion of a binomial distribution given by Pascal’s Triangle • The set of peaks is a multiplet(2 = doublet, 3 = triplet, 4 = quartet, 5=pentet, 6=hextet, 7=heptet…..)