Introduction to Organic Chemistry 2 ed William H. Brown

1. Introduction to Organic Chemistry2 edWilliam H. Brown

2. Nuclear Magnetic Resonance Chapter 21

3. Electromagnetic Radiation • Electromagnetic radiation: light and other forms of radiant energy • Wavelength (l): the distance between two consecutive identical points on a wave • Frequency (n): the number of full cycles of a wave that pass a point in a second • Hertz (Hz): the unit in which radiation frequency is reported; s-1 (read “per second”)

4. Electromagnetic Radiation • Wavelength

5. Molecular Spectroscopy • Molecular spectroscopy: the study of which frequencies of electromagnetic radiation are absorbed or emitted by substances and then correlating these frequencies with specific types of molecular structure

6. Molecular Spectroscopy • We study two types of molecular spectroscopy

7. Molecular Spectroscopy • Nuclear magnetic resonance (NMR) spectroscopy: a spectroscopic technique that gives us information about the number and types of atoms in a molecule, for example, about the number and types of • hydrogens using 1H-NMR spectroscopy • carbons using 13C-NMR spectroscopy • phosphorus using 31P-NMR spectroscopy

8. Nuclear Spin States • Nuclei of 1H and 13C, isotopes of the two elements most common to organic compounds, have a spin and behave as if they are tiny bar magnets • 12C and 16O do not have a nuclear spin and do not behave as tiny bar magnets • thus, nuclei of 1H and 13C are quite different from those of 12C and 16O

9. Nuclear Spins • within a collection of 1H and 13C atoms, nuclear spins are completely random in orientation • when placed in a strong external magnetic field, interactions between their nuclear spins and the applied magnetic field are quantized, and only two orientations are allowed • by convention, nuclei with spin +1/2 are aligned with the applied field and in the lower energy state; nuclei with spin -1/2 are aligned against it and in the higher energy state

10. Nuclear Spins • For 1H and 13C nuclei in an applied field.

11. Nuclear Spins • In an applied field strength of 7.05T (present-day superconducting electromagnets) the difference in energy between nuclear spin states for • 1H is approximately 0.0286 cal/mol, which corresponds to electromagnetic radiation of 300 MHz • 13C is approximately 0.00715 cal/mol, which corresponds to electromagnetic radiation of 75 MHz

12. Nuclear Magnetic Resonance • when nuclei in the lower energy state are irradiated with radio frequency of the appropriate energy, energy is absorbed and the nuclear spin is “flipped”

13. Nuclear Magnetic Resonance • Resonance: the absorption of electromagnetic radiation by a nucleus and the flip of its nuclear spin from a lower energy state to a higher energy state • the instrument used to detect this flip of nuclear spin records it as a signal • If we were dealing with 1H nuclei isolated from all other atoms and electrons, any combination of applied field and radiation that produces a signal for one 1H would produce a signal for all 1H • the same is true of 13C nuclei

14. Nuclear Magnetic Resonance • But hydrogens in organic molecules are not isolated from all other atoms; they are surrounded by electrons • electrons have spin and thereby create local magnetic fields; these local magnetic fields are several orders of magnitude weaker than the applied field • at the molecular level, the local magnetic fields shield hydrogens from the applied field • the effective magnetic field experienced by a 1H nucleus is the applied field less the local magnetic field

15. Nuclear Magnetic Resonance • The differences in resonance frequency among 1H in organic molecules are 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

16. Nuclear Magnetic Resonance • It is customary to measure the resonance frequency (signal) of individual nuclei relative to the 1H and 13C resonance frequencies (signals) of tetramethylsilane (TMS)

17. Nuclear Magnetic Resonance • Chemical shift (d): the shift in ppm of an NMR signal from the signal of TMS • for a 1H-NMR spectrum, signals are reported by how far they are shifted from the resonance signal of the 12 equivalent hydrogens in TMS • for a 13C-NMR spectrum, signals are reported by how far they are shifted from the resonance signal of the one carbon in TMS

18. NMR Spectrometer • Essentials of an NMR spectrometer are a powerful magnet, a radio-frequency generator, a radio-frequency detector, and a sample tube • The sample is dissolved in a solvent, most commonly CDCl3 or D2O, and placed in a sample tube which is then suspended in the magnetic field and set spinning • Using a Fourier transform NMR (FT-NMR) spectrometer, a spectrum can be recorded in about 2 seconds

19. NMR Spectrum • Downfield: the shift of an NMR signal to the left on the chart paper • Upfield: the shift of an NMR signal to the right on the chart paper

20. Equivalent Hydrogens • Equivalent hydrogens: have the same chemical environment • Molecules with • 1 set of equivalent hydrogens give 1 NMR signal • 2 or more sets of equivalent hydrogens give a different NMR signal for each set

21. Signal Areas • Relative areas of signals are proportional to the number of hydrogens giving rise to each signal • all modern NMR spectrometers electronically integrate and record the area of each signal

22. Chemical Shift - 1H-NMR

23. Chemical Shift - 1H-NMR

24. Signal Splitting (n + 1) • Peak: a unit into which an NMR signal is split; doublet, triplet, quartet, etc. • Signal splitting: splitting of an NMR signal into a set of peaks by the influence of neighboring nonequivalent hydrogens • (n + 1) rule: the 1H-NMR signal of a hydrogen or set of equivalent hydrogens is split into (n + 1) peaks by a nonequivalent set of n equivalent neighboring hydrogens

25. Signal Splitting (n + 1) • Problem: predict the number of 1H-NMR signals and the splitting pattern of each

26. 13C-NMR Spectroscopy • Each nonequivalent 13C gives a different signal • A 13C signal is split by an 1H bonded to it according to the (n + 1) rule • In the most common mode of recording a 13C spectrum, called the hydrogen-decoupled mode, this signal splitting is eliminated in order to simplify the spectrum • in the hydrogen-decoupled mode, all 13C signals appear as singlets

27. Chemical Shift - 13C-NMR

28. Interpreting NMR Spectra • Alkanes: • all 1H-NMR signals fall in the narrow range of d 0.8 - 1.7 • 13C signals fall in the considerably wider range of d 0 - 60 • Alkenes: • vinylic hydrogens typically fall in the range d 4.6 - 5.7 • the sp2 hybridized carbons of alkenes give 13C-NMR signals in the range d 100 - 150, which is downfield from the signals of sp3 hybridized carbons

29. Interpreting NMR Spectra • Alcohols: • the chemical shift of the hydroxyl hydrogen is variable. It normally falls in the range d 3.0 - 4.5, but may be as low as d 0.5. • hydrogens on an sp3 hybridized carbon adjacent to the -OH group are deshielded by the electron-withdawing inductive effect of the oxygen and their signals appear in the range d 3.4 - 4.0

30. Interpreting NMR Spectra • Benzene and its derivatives • all six hydrogens of benzene are equivalent and their 1H-NMR signal appears as a sharp singlet at d 7.27 • hydrogens attached to a substituted benzene ring appear in the region d 6.5 - 8.5 • in 13C-NMR spectroscopy, carbon signals of aromatic rings appear in the range d 110 - 160

31. Interpreting NMR Spectra • Amines • the chemical shift of amine hydrogens, like those of hydroxyl hydrogens, is variable and may be found in the region d 0.5 - 5.0 • because of rapid exchange of amine hydrogens, spin-spin splitting between amine hydrogens and hydrogens on the adjacent a-carbon are prevented, and amine hydrogens generally appear as singlets

32. Interpreting NMR Spectra • Aldehydes and ketones • aldehyde hydrogens give an 1H-NMR signal in the range d 9.5 - 10.1 • hydrogens in the alpha-carbon to an aldehyde or ketone carbonyl group typically appear in the region d 2.1 - 2.6 • the carbonyl carbon of aldehydes and ketones are readily identifiable in 13C-NMR spectroscopy by the position of their signals between d 190 - 210

33. Interpreting NMR Spectra • Carboxylic acids • the chemical shift of the carboxyl hydrogen is so large (d 10 - 13), even large than that of the aldehyde hydrogen (d 9.4 - 9.8) that it serves to distinguish carboxyl hydrogens from most other types of hydrogens • the carbonyl carbon of carboxylic acids appears in an 13C-NMR spectrum in the region d 175 - 185

34. Interpreting NMR Spectra • Esters • hydrogens on the alpha-carbon to the carbonyl group of an ester are slightly deshielded and give signals at d 2.0 - 2.6 • hydrogens on carbon attached to the carbon of the ester oxygen are more strongly deshielded and give signals at d 3.7 - 4.7 • the carbonyl carbon of an ester appears in a 13C-NMR spectrum in the region d 160 - 170

35. Index of H Deficiency • Index of hydrogen deficiency (IHD): the sum of the number of rings and pi bonds in a molecule • To determine IHD, compare the number of hydrogens in an unknown compound with the number in a reference hydrocarbon of the same number of carbons and with no rings or pi bonds • the molecular formula of the reference hydrocarbon is CnH2n+2

36. Index of H Deficiency • for each atom of a Group VII element (F, Cl, Br, I) added to the reference hydrocarbon, subtract one H • no correction is necessary for the addition of atoms of Group VI elements (O,S) to the reference hydrocarbon • for each atom of a Group V element (N, P) added to the reference hydrocarbon, add one hydrogen

37. Nuclear Magnetic Resonance End Chapter 21