1. Integration10-6 Integration reveals the number of hydrogens responsible for an NMR peak. The area under an NMR peak is proportional to the number of equivalent nuclei contributing to the peak. By comparing peak areas, it is possible to quantitatively estimate the relative numbers of contributing protons. The areas are obtained by the controlling computer and plotted on top of the regular spectrum by choosing integration mode. 30

3. Chemical shifts and peak integration can be used to determine structure. Consider the monochlorination of 1-chloropropane: NMR spectroscopy distinguishes all three isomers: 1,1-Dichloropropane: Three NMR signals in the ratio of 3:2:1. Δ = 5.93 ppm (CH), 2.34 pm (CH2), and 1.01 (CH 3 ). 1,2-Dichloropropane: Three NMR signals in the ratio of 3:2:1. δ = 4.17 ppm (CH), 3.68 ppm (CH 2 ), and 1.70 ppm (CH 3 ). 1,3-Dichloropropane: Two NMR signals in the ratio of 2:1. δ = 3.71 ppm (CH 2 Cl) and 2.25 ppm (CH 2 ). 32

4. Spin-Spin Coupling: The Effect of Non- Equivalent Neighboring Hydrogens 10-7 When non-equivalent hydrogen atoms are not separated by at least one carbon or oxygen atom, an additional phenomenon called “spin-spin splitting” or “spin-spin coupling” occurs. Instead of single peaks (singlets), more complex patterns occur called multiplets (doublets, triplets or quartets). The number and kind of hydrogen atoms directly adjacent to the absorbing nuclei can be deduced from the multiplicity of the peak.

5. One neighbor splits the signal of a resonating nucleus into a doublet. Consider two protons, H a and H b. The population of each of these protons is very close to 50%  and 50%  in the external magnetic field, H 0. This means that in 50% of the molecules, H a protons will have H b protons in the  state and in 50% of the molecules, H a protons will have H b protons in the  state. The total field seen by 50% of the H a protons will therefore be slightly greater than H 0 and slightly less than H 0 for the other 50 % of the H a protons. What would have been a singlet NMR peak is now split into a doublet of peaks, symmetrically displaced from the original peak. 34

7. The chemical shift of the H a nucleus is reported as the center of the doublet. The amount of mutual splitting is equal. The distance between the individual peaks making up the doublet is called the “coupling constant” (J). Here J is 7 Hz. Coupling constants are independent of the field strength of the NMR spectrometer being used. 36

8. Spin-spin splitting is usually observed only between hydrogen atoms bound to the same carbon (geminal coupling) or to adjacent carbons (vicinal coupling). Hydrogen nuclei separated by more than two carbon atoms (1,3 coupling) is usually negligible.

9. 38

10. Local-field contributions from more than one hydrogen are additive. Consider the triplet above. It corresponds to the methyl (CH 3 ) protons being split by the methylene protons. The methylene proton spins will statistically orient in the external magnetic field as , ,  and . Each methyl proton will see an increased field 25% of the time (), no change 50% of the time ( and ), and a decreased field 25% of the time ().

11. The integrated intensity of the triplet will be 6 since there are a total of 6 equivalent methyl protons. 40

12. Methylene (CH 2 ) protons, CH 3 proton spins will statistically distribute as , , , , , , , and . This will result in a 1:3:3:1 quartet of peaks. The integrated intensity of the quartet will be 4, corresponding to the 4 equivalent methylene protons.

13. In many cases, spin-spin splitting is given by the N+1 rule. A simple set of rules: Equivalent nuclei located adjacent to one neighboring hydrogen resonate as a doublet. Equivalent nuclei located adjacent to two hydrogens of a second set of equivalent nuclei resonate as a triplet. Equivalent nuclei located adjacent to a set of three equivalent hydrogens resonate as a quartet. 42

14. This table illustrates the N+1 rule: Nuclei having N adjacent equivalent neighbors split into N+1 peaks. The heights of the N+1 peaks follow Pascal’s triangle.

15. It needs to note that non-equivalent nuclei split each other. A split in one requires a split in the other. The coupling constants will be the same for each type of nuclei. 44

17. 46

18. Spin-Spin Splitting: Some Complications10-8 Complex multiplets sometimes occur when there is a relatively small difference in δ between two absorptions. The N+1 rule may not apply in a direct way if several neighboring hydrogens having fairly different coupling constants are coupled to the resonating nucleus. The hydroxy proton may appear as a singlet, even if coupled to vicinal hydrogens.

19. Close-lying peak patterns give non-first-order spectra. The intensity patterns in many NMR spectra do not follow the idealized pattern of Pascal’s triangle but instead are skewed towards each other. The intensities of the lines facing each other is slightly larger than expected. Perfectly symmetrical splittings are observed only when the resonant frequency difference of the two groups of protons is much larger than the coupling constant between them. When ν >> J, the spectra is said to be first-order. Non-first-order spectra assume more complex shapes and can only be analyzed with the help of computers. Since the resonant frequency difference increases with higher field strengths (J remains the same), a complicated spectrum can be made first order by measuring it at higher field strengths. 48

21. Coupling to non-equivalent neighbors may modify the simple N+1 rule. The spectrum of 1,1,2-trichloropropane illustrates the effects of two sets of non-equivalent neighbors. 50

22. The H a proton is split by the H b proton into a doublet as expected. This doublet is at low field due to the effect of two adjacent chlorine atoms. The methyl protons are also split by the H b proton into a doublet as expected. This doublet is at high field. The H b proton is split by both H a and the methyl protons. In this case eight lines are observed because H a and the methyl protons have different coupling constants to H b. The methyl group splits the H b resonance into a quartet (1,3,3,1). Each line of the quartet is then split into a doublet by the H a proton (1,1,3,3,3,3,1,1).

23. In the case of 1-bromopropane, the hydrogens on C2 are also coupled to two non-equivalent sets of neighbors. A theoretical analysis of this resonance would predict as many as 12 lines (a quartet of triplets). Because the coupling constants are very similar, however, many of the lines overlap, thus simplifying the pattern. 52

24. Fast proton exchange decouples hydroxy hydrogens. In the spectra of 2,2- dimethyl-a-propanol, the OH absorption appears as a single peak and is not split by the CH 2 protons. In addition, the CH 2 protons are not split by the OH. The OH proton is weakly acidic and is both between alcohol molecules and traces of water on the NMR time scale at room temperature.

25. This type of decoupling is called “fast proton exchange.” It may be slowed or removed by removal of traces of water or acid or by cooling.

26. Rapid magnetic exchange self-decouples chlorine, bromine, and iodine nuclei. Fluorine is the only halogen that exhibits spin-spin coupling to 1 H in a proton NMR spectra. Chlorine, bromine, and iodine exhibit a fast internal magnetic equilibration on the NMR time scale which precludes an adjacent proton from recognizing them as having different alignments in the external field. This is termed “self-decoupling” in contrast to exchange- decoupling, as exhibited by the hydroxy protons.

27. Carbon-13 Nuclear Magnetic Resonance10-9 The NMR spectroscopy of 13 C is of greater potential utility than that of 1 H NMR. The 13 C spectra of an organic compound is much simpler than the 1 H spectra because spin-spin coupling between adjacent carbon atoms and between carbon and hydrogen atoms can be avoided. 56

28. Carbon NMR utilizes an isotope in low natural abundance: 13 C. Carbon occurs as a mixture of two principle isotopes, 12 C (98.89%) and 13 C (1.11%). Of these, only 13 C is active in NMR. Because of the low abundance of 13 C and its weaker magnetic resonance (1/6000 as strong as 1 H), FT NMR is usually used for 13 C spectroscopy because multiple pulsing and signal averaging allows the accumulation of strong signals than would otherwise be possible. Carbon-carbon coupling is absent in 13 C spectra due to the very low probability of two 13 C nuclei being adjacent to each other in a single molecule (.0111 x.0111 ~.0001). 13 C- 1 H coupling is present, however, the chemical shift range of 13 C is much greater than the splittings due to 1 H, which precludes the overlapping of adjacent multiplets. The 13 C chemical shifts are reported relative to an internal standard, usually (CH 3 ) 4 Si.

29. The 13 C NMR spectra of bromoethane above exhibits 13 C splitting by the methyl and methylene protons. The 13 C peak due to C1 is first split by its own two hydrogens to produce a triplet. Each of the triplet peaks is then split into a quartet by the adjacent protons on the C2 carbon. The 13 C peak due to C2 is first split by its own three hydrogens to produce a quartet. Each of the quartet peaks is then split into a triplet by the adjacent protons on the C1 carbon. 58

30. Hydrogen decoupling give single lines. 13 C- 1 H coupling can be completely removed by a technique called “broad-band hydrogen (or proton) decoupling.” In this technique, a strong broad radio frequency signal covering the entire resonant frequency range for hydrogen is simultaneously applied at the same time as the 13 C signal. The broad-band hydrogen signal causes rapid - flips of the hydrogen nuclei, effectively averaging their local magnetic field contributions. Using this technique simplifies the spectra of bromoethane to two single lines.

31. Proton decoupling is particularly powerful when analyzing complex molecules because every magnetically distinct carbon gives only a single peak. The decoupled 13 C spectra of methylcyclohexane shows only five peaks, revealing the twofold symmetry in the structure. A limitation of FT 13 C NMR spectroscopy is that, due to difficulties in integration, peak intensities (areas) no longer correspond to the numbers of nuclei present. 60

32. Carbon, like hydrogen, has chemical shifts which depend upon its chemical environment. Electron withdrawing groups cause deshielding. The chemical shifts go up in order: primary < secondary < tertiary carbon.

33. The numbers of non-equivalent carbons in the isomers of C 7 H 14 are clearly demonstrated by the numbers of 13 C peaks in their NMR spectra. Advances: DEPT 13 C and 2D-NMR. Using sophisticated time-dependent pulse sequences (two- dimensional NMR), it is now possible to establish coupling (e.g. bonding) between close-lying hydrogens (homonuclear correlation) or connected carbon and hydrogen atoms (heteronuclear correlation). This, in effect, determines the molecular connectivity of a molecule by measuring the magnetic effect of neighboring atoms on one another along a carbon chain. 62

34. On such pulse sequence is the distortionless enhanced polarization transfer (DEPT) 13 C NMR spectrum. DEPT gives information specifying which type of carbon gives rise to a specific signal in the normal 13 C spectrum: CH 3, CH 2, CH, or C quaternary. A DEPT experiment consists of three spectra: Normal broad-band decoupled spectra; DEPT-90 pulse sequence spectra, which reveals signals only of carbons bound to one hydrogen; DEPT-135 pulse sequence spectra which produces normal CH 3 and CH signals, but negative absorptions for CH 2 and no peaks for quaternary carbons.

35. Limonene DEPT: A: All 10 lines – 6 alkyl C at high field, 4 alkenyl C at low field B: CH carbons C: CH carbons, positive signal CH 3 carbons, negative signal CH 2 carbons Spectrum A lines – Spectrum C lines: quaternary carbon 64

36. We can apply 13 C NMR spectroscopy to the problem of the monochlorination of 1-chloropropane. Both 1,1- and 1,2-dichloropropane should exhibit three carbon signals each. The groups of three signals would be spaced differently due to the different arrangement of chlorine substituents. 1,3-dichloropropane should exhibit only two carbon signals. The two deshielded chlorine bearing carbons assignments in 1,2- dichloropropane can be made using DEPT data. The signal at 49.5 ppm appears inverted in a DEPT-135 spectrum (CH 2 ). The signal at 55.8 ppm is the only absorption in a DEPT-90 spectrum

37. Important Concepts10 1.NMR – Most important spectroscopic tool for elucidating organic structures. 2.Spectroscopy – Based on lower energy forms of molecules being converted into higher energy forms by the absorption of electromagnetic radiation. 3.NMR – Based on alignment of the nuclei of certain nuclei (i.e.. 1 H and 13 C) with (  ) and against (  ) a strong magnetic field.  to  transition affected by radio-frequency radiation leading to resonance and characteristic absorption spectra. High magnetic fields lead to higher resonant frequencies. 4.High Resolution NMR – Allows differentiation of 1 H and 13 C nuclei in different environments. Spectral positions are measured as the chemical shift, δ, in ppm from an internal standard (TMS). 66

38. Important Concepts10 5.Chemical Shifts – Highly dependent on presence (shielding) or absence (deshielding) of electron density. Electron donor substituents shield. Electron withdrawing substituents deshield. Hydrogen bonding or proton exchange result in broad peaks. 6.Chemical Equivalency – Equivalent hydrogens or carbons have the same chemical shift. 7.Integration of peak area indicates number of contributing hydrogens. 8.Spin-Spin Splitting – Pattern determined by number of hydrogen neighbors (N+1 Rule). Equivalent hydrogens show no mutual splitting.

39. Important Concepts10 9.Non-First-Order Spectra – Complicated patterns created when chemical-shift difference between coupled hydrogens is comparable to their coupling constant. 10.Non-Equivalent Neighboring Hydrogens – (N + 1) rule is applied sequentially. 11.Carbon NMR – Utilizes low abundance 13 C nuclei. C-C coupling is not observed. C-H coupling can be removed by proton decoupling. 12.DEPT 13 C NMR – Allows peak assignment to CH 3, CH 2, CH, and quaternary carbons respectively. 68