1 Chapter 13: NMR Spectroscopy Learning Objectives: 1. Know how nuclear spins are affected by a magnetic field, and be able to explain what happens when radiofrequency radiation is absorbed. 2. Be able to predict the number of proton and carbon NMR signals expected from a compound given its structure. 3. Be able to predict the splitting pattern in the proton NMR spectrum of a compound given its structure. 4. With the aid of a chart of chemical shifts from 1H and 13C NMR, be able to assign peaks in an NMR spectrum to specific protons in a compound. 5. Be able to interpret integration of NMR spectra. 6. Be able to use NMR spectra to determine the structures of compounds, given other information such as a molecular formula. 7. Be able to calculate coupling constants from 1H NMR spectra, and utilize the coupling constants for determining compound structure.* 8. Be able to determine the compound structure based on information generated from mass spectrometry, IR, NMR, and elemental analysis.* * Supplemental material, not included in the textbook Sections: 13.1 An Introduction to NMR Spectroscopy 13.2 Fourier Transform NMR 13.3 Shielding Causes Different Hydrogens to Show Signals at Different Frequencies* 13.4 The Number of Signals in an 1H NMR Spectrum* 13.5 The Chemical Shift Tells How Far the Signals Is from the Reference Signal* 13.6 The Relative Position of 1H NMR Signals* 13.7 Characteristic Values of Chemical Shifts* 13.8 Diamagnetic Anisotropiy 13.9 Integration of NMR Signals Reveals the Relative Number of Protons Causing the Signal* 13.10 Splitting of the Signals Is Described by the N+1 Rule* 13.11 More Examples of 1H NMR Spectra* 13.12 Coupling Constants Identify Coupled Protons* 13.13 Splitting Diagrams Explain the Multiplicity of a Signal* 13.14 Diastereotopic Hydrogens Are Not Chemically Equivalent 13.15 The Time Dependence of NMR Spectroscopy 13.16 Protons Bonded to Oxygen and Nitrogen* 13.17 The Use of Deuterium in 1H NMR Spectroscopy# 13.18 Resolution of 1H NMR Spectra 13.19 13C NMR Spectroscopy* 13.20 DEPT 13C NMR Spectra# 13.21 Two-dimensional NMR Spectroscopy# 13.22 NMR Used in Medicines Is Called Magnetic Resonance Imaging2 * Sections that will be focused # Sections that will be skipped Recommended additional problems 43 – 63, 65 – 72 Class Note 13.1 An Introduction to NMR Spectroscopy and 13.2 Fourier Transform NMR 13.3 Shielding Causes Different Hydrogens to Show Signals at Different Frequencies* cap NMR tube sample Applied magnetic field H H H upfield downfield intensity Deshielded (low electron density) Shielded (high electron density)3 13.4 The Number of Signals in an 1H NMR Spectrum* *Judge the chemically equivalent of H by the symmetry of molecule H HHHHHHHH ClHHHHHHH HHHHHHClClHHHHHHHHHHHHCH3ClHHBrHHClHNO2HHHClHClHHHClNO2HHHHHHHBrHHHHHHHHClHHHHHHH4 13.5 The Chemical Shift Tells How Far the Signals Is from the Reference Signal*, 13.6 The Relative Position of 1H NMR Signals* and 13.8 Diamagnetic Anisotropiy Internal reference compound: CHCl3 (from CDCl3) and (CH3)4Si (TMS) *Signal of TMS = 0 ppm (CHCl3 = 7.27 ppm) *Chemical shift (δδδδ) A. Effect from electronegativity (inductive effect) H ClHHHHHHH HHHHHHCl5 B. Effect from resonance OOOO6.157.634.92OCH3HHHHHOCH3HHHHHOCH3HHHHHOCH3HHHHH6.887.266.92 C. Effect from structure OOOO2.544.732.723.751.853.521.516 D. Diamagnetic Anisotropiy (anisotropic effect) Happlied magnetic field (Bo)induced magnetic field (Bi)actual magnetic field (Bo + Bi)H7.3 13.7 Characteristic Values of Chemical Shifts* Table 13.1 13.9 Integration of NMR Signals Reveals the Relative Number of Protons Causing the Signal* * Diagnostic for 1H NMR but less accurate for 13C NMR * Ratio rather than exact number H ClHHHHHHH HHHHHHClHaHbHcHaHbHHHHHHHHHHOHaHaHbHbIIIIII7 13.10 Splitting of the Signals Is Described by the N+1 Rule* A. Multiplicity of Signal and Relative Intensities Ratio Multiplicity 1 : 1 doublet 1 : 2 : 1 triplet 1 : 3 : 3 : 1 quartet 1 : 4 : 6 : 4 : 1 quintet 1 : 5 : 10 : 10 : 5 : 1 sextet 1 : 6 : 15 : 20 : 15 : 6 : 1 septet 1st splitting2nd splitting3rd splitting4th splitting5th splitting6th splittingOriginal signal11111111111123346 45 1010 561520156 Two important criteria: * For I = 1/2 * For chemically equivalent nuclei8 B. Examples H ClHHHHHHH HHHHHHClHaHbHcHaHbHHHHHHHHHHOHaHaHbHbIIIIII9 13.11 More Examples of 1H NMR Spectra* A. More examples Br BrHHHHHHHbHaH3CHHHHO HCH3H3COHaHbHcHdIVVHbHe10 B. Difference between quartet (q) and doublet of doublet (dd) Cl BrClHOCH3HBrHHHHClHO HHHOHaHbVIVIIHaHbHcHc11 13.12 Coupling Constants Identify Coupled Protons* and 13.13 Splitting Diagrams Explain the Multiplicity of a Signal* A. Table 14.3 and handout B. Calculation of coupling constant (J value) 3.2 ppm3.3 ppm15 mm5 mm2.5 mm400 MHz 1H NMRintegral ratio of peaks:1:3:3:13.2 ppm3.3 ppm15 mm5 mm2.5 mm400 MHz 1H NMRintegral ratio of peaks:1:1:1:1pattern Apattern B12 C. Splitting diagrams and J values (1) HbHaHcJab = Jac(1)Jab > Jac(2) (2) long range coupling (4 bonds)13 D. Structure determination and J values (1) Example 1 COCH3HcHbHaJab = 2 HzJac = 15 HzJbc = 7 Hz (2) Example 2: determination of cis and trans isomers COCH3HbH3CHaJab = 15 Hz or 7 HzHbCOCH3H3CHatranscis14 (3) Example 3: determination of the regioisomers of di-substituted benzene derivatives BrNH2HHHHHNH2HBrHHHNH2BrHHH1,2-di-substituted(ortho)1,3-di-substituted(meta)1,4-di-substituted(para)15 13.14 Diastereotopic Hydrogens Are Not Chemically Equivalent HBrHHHHHH 13.15 The Time Dependence of NMR Spectroscopy Figure 13.29 HHHH16 13.16 Protons Bonded to Oxygen and Nitrogen* and 13.17 The Use of Deuterium in 1H NMR Spectroscopy# 13.18 Resolution of 1H NMR Spectra 60 MHz 90 MHz300 MHz 400 MHz600 MHz1H NMR17 13.19 13C NMR Spectroscopy* A. Table 13.4 Chemical shift and height (intensity) B. Proton-coupled and proton-decoupled 13C spectra18 13.22 NMR Used in Medicines Is Called Magnetic Resonance