13-1 Nuclear Magnetic Resonance Chapter 13

13-2 Molecular Spectroscopy  Nuclear magnetic resonance (NMR) spectroscopy:  Nuclear magnetic resonance (NMR) spectroscopy: a spectroscopic technique that gives us information about the number of certain types of atoms and their environment in a molecule.  Most commonly, about the number and types of: hydrogen atoms using 1 H-NMR spectroscopy carbon atoms using 13 C-NMR spectroscopy  The NMR study in Chem 3020 will be restricted to these two types of atoms.

Nuclear Spin States  An electron has a spin quantum number of 1/2 with allowed values of +1/2 and -1/2. This spinning charge creates an associated magnetic field, in effect, an electron behaves as if it is a tiny bar magnet and has what is called a magnetic moment.  The same effect holds for certain atomic nuclei. Any atomic nucleus that has an odd mass number, an odd atomic number, or both has a net nuclear spin and a resulting nuclear magnetic moment. The allowed nuclear spin states are determined by the spin quantum number, I, of the nucleus.

13-4 Nuclear Spin States, Table 13.1 I2I + 1A nucleus with spin quantum number I has 2I + 1 spin states; if I = 1/2, there are two allowed spin states. Table 13.1 gives the spin quantum numbers and allowed nuclear spin states for selected isotopes of elements common to organic compounds.

Nuclear Spins in B 0 Within a collection of 1 H and 13 C atoms, nuclear spins are completely random in orientation. When placed in a strong external magnetic field of strength B o (or H o ), however, interaction between nuclear spins and the applied magnetic field is quantized, with the result that only certain orientations of nuclear magnetic moments are allowed.

13-6 Nuclear Spins in B 0 for 1 H and 13 C, only two orientations are allowed (Fig 13.1) B0B0B0B0

13-7 Nuclear Spins in B 0  In an applied field strength of 7.05T (Tesla), which is readily available with present-day superconducting electromagnets, the difference in energy between nuclear spin states for: 1 H is approximately J ( cal)/mol, which corresponds to electromagnetic radiation of 300 MHz (300,000,000 Hz). 13 C is approximately J ( cal)/mol, which corresponds to electromagnetic radiation of 75MHz (75,000,000 Hz).

13-8 Nuclear Spin in B 0 The energy difference between allowed spin states increases linearly with applied field strength. Values shown here are for 1 H nuclei (Fig 13.2) B0B0B0B0 300 MHz 60 MHz

Nuclear Magnetic Resonance When nuclei with a spin quantum number of 1/2 are placed in an applied field, a small majority of nuclear spins are aligned with the applied field in the lower energy state. The nucleus begins to precess and traces out a cone-shaped surface, in much the same way a spinning top or gyroscope traces out a cone- shaped surface as it precesses in the earth’s gravitational field. We express the rate of precession as a frequency in hertz.

13-10 Nuclear Magnetic Resonance  If the precessing nucleus is irradiated with electromagnetic radiation of the same frequency as the rate of precession: the two frequencies couple, energy is absorbed, and the nuclear spin is flipped from spin state +1/2 (with the applied field) to -1/2 (against the applied field).

13-11 Nuclear Magnetic Resonance The origin of nuclear magnetic “resonance” (Fig 13.3)

13-12 Nuclear Magnetic Resonance  Resonance:  Resonance: in NMR spectroscopy, resonance is the absorption of electromagnetic radiation by a precessing nucleus and the resulting “flip” of its nuclear spin from a lower energy state to a higher energy state.  Relaxation:  Relaxation: a loss of energy when the higher energy state returns to the lower energy state.  The instrument used to detect this coupling of precession frequency and electromagnetic radiation records it as a signal. Signal:Signal: A recording in an NMR spectrum of a nuclear magnetic resonance.

NMR Spectrometer (Fig 13.4)

13-14 NMR Spectrometer  Essentials of an NMR spectrometer are a powerful magnet, a radio-frequency generator, and a radio-frequency detector  The sample is dissolved in a solvent, most commonly CDCl 3 or D 2 O, 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

13-15 Nuclear Magnetic Resonance If we were dealing with 1 H nuclei isolated from all other atoms and electrons, any combination of applied field and radiation that produces a signal for one 1 H would produce a signal for all 1 H. The same is true of 13 C nuclei. But hydrogens in organic molecules are not isolated from all other atoms; they are surrounded by electrons, which are caused to circulate by the presence of the applied field. diamagneticcurrent diamagnetic shielding.The circulation of electrons around a nucleus in an applied field is called diamagnetic current and the nuclear shielding resulting from it is called diamagnetic shielding.

13-16 NMR Spectrum  1 H-NMR spectrum of methyl acetate (Fig 13.5) Downfield:Downfield: the shift of an NMR signal to the left on the chart paper; downfield requires lower energy. Upfield:Upfield: the shift of an NMR signal to the right on the chart paper; upfield requires higher energy.

13-17 NMR: cycles/sec (Hertz) vs ppm (  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 CH 3 Cl compared to CH 3 F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency (ppm is also called 

13-18 NMR Reference Signal Signals are measured relative to the signal of the reference compound tetramethylsilane (TMS). For a 1 H-NMR spectrum, signals are reported by their shift from the 12 H signal in TMS. For a 13 C-NMR spectrum, signals are reported by their shift from the 4 C signal in TMS. Chemical shift (  ):Chemical shift (  ): the shift in ppm of an NMR signal from the signal of TMS.

Equivalent Hydrogens  Equivalent hydrogens:  Equivalent hydrogens: These have the same chemical environment. A molecule with 1 set of equivalent hydrogens gives 1 NMR signal.

13-20 Equivalent Hydrogens A molecule with 2 or more sets of equivalent hydrogens gives a different NMR signal for each set.

Signal Areas (integration)  Relative areas of signals are proportional to the number of H giving rise to each signal.  Modern NMR spectrometers electronically integrate and record the relative area of each signal (Fig 13.7).

13-22 ChemicalShifts 1 H-NMR RCH 2 OR (CH 3 ) 4 Si ArCH 3 RCH 3 RCCH RCCH 3 ROH RCH 2 OH ArCH 2 R O O RCH 2 R R 3 CH R 2 NH RCCH 2 R R 2 C=CRCHR 2 R 2 C=CHR RCH O RCOH O RCH 2 Cl RCH 2 Br RCH 2 I RCH 2 F ArH O O R 2 C=CH 2 RCOCH 3 RCOCH 2 R ArOH Type of Hydrogen 0 (by definition) Type of Hydrogen Chemical Shift (  ) Chemical Shift (  ) Chemical Shift - 1 H-NMR

13-23 Chemical Shift - 1 H-NMR, Fig (Fig 13.8)

13-24 A. Chemical Shift, Table 13.2  Depends on (1) electronegativity of nearby atoms, (2) the hybridization of adjacent atoms, and (3) diamagnetic effects from adjacent pi bonds.  Electronegativity: inductive effect deshields

13-25 B. Chemical Shift, Table 13.3  Hybridization of adjacent atoms: Greater “s” character in the hybrid holds shared electrons closer to carbon

13-26 C. Chemical Shift  Diamagnetic effects of pi bonds: A carbon-carbon triple bond shields an acetylenic hydrogen and shifts its signal upfield (to the right) to a smaller  value. A carbon-carbon double bond deshields vinylic hydrogens and shifts their signal downfield (to the left) to a larger  value.

13-27 Chemical Shift Magnetic induction in the pi bond of a carbon- carbon double bond (Fig 13.10):

13-28 Chemical Shift Magnetic induction of the pi electrons in an aromatic ring (Fig ).

13-29 Chemical Shift Magnetic induction in the pi bonds of a carbon- carbon triple bond (Fig 13.9):

13-30 Chemical Shift and Integration

Signal Splitting; the (n + 1) Rule  NMR Signals:  NMR Signals: not all appear as a single peak.  Peak:  Peak: The units into which an NMR signal appears: singlet, doublet, triplet, quartet, etc.  Signal splitting:  Signal splitting: Splitting of an NMR signal into a set of peaks by the influence of neighboring nonequivalent hydrogens.  (n + 1) rule:  (n + 1) rule: If a hydrogen has n hydrogens nonequivalent to it but equivalent among themselves on the same or adjacent atom(s), its 1 H-NMR signal is split into (n + 1) peaks.

13-32 Signal Splitting (n + 1) 1 H-NMR spectrum of 1,1-dichloroethane (Fig 13.12)

Origins of Signal Splitting  Signal coupling:  Signal coupling: An interaction in which the nuclear spins of adjacent atoms influence each other and lead to the splitting of NMR signals.  Coupling constant (J):  Coupling constant (J): The separation on an NMR spectrum (in hertz) between adjacent peaks in a multiplet. A quantitative measure of the influence of the spin-spin coupling with adjacent nuclei.

13-34 Origins of Signal Splitting (Fig 13.13) H a and H b are non-equivalent

13-35 Origins of Signal Splitting Because splitting patterns from spectra taken at 300 MHz and higher are often difficult to see, it is common to retrace and expand certain signals. 1 H-NMR spectrum of 3-pentanone; expansion more clearly shows the triplet/quartet (Fig 13.14).

13-36 Signal Splitting (n + 1) Problem Problem: Predict the number of 1 H-NMR signals and the splitting pattern of each.

13-37 Coupling Constants, Table 13.4  Coupling constant (J):  Coupling constant (J): the distance between peaks in a split signal, expressed in hertz. J is a quantitative measure of the magnetic interaction of nuclei whose spins are coupled.

13-38 A. Origins of Signal Splitting (Fig 13.15)

13-39 Signal Splitting  Pascal’s Triangle: As illustrated by the highlighted entries, each entry is the sum of the values immediately above it to the left and the right (Fig 13.16).

13-40 B. Physical Basis for (n + 1) Rule  Coupling of nuclear spins is mediated through intervening bonds. H atoms with more than three bonds between them generally do not exhibit noticeable coupling. For H atoms three bonds apart, the coupling is referred to as vicinal coupling (Fig 13.17).

13-41 Signal Splitting (n + 1) example

13-42 Coupling Constants An important factor in vicinal coupling is the angle  between the C-H sigma bonds and whether or not it is fixed. Coupling is a maximum when  is 0° and 180°; it is a minimum when  is 90° (Fig 13.18).

13-43 C. More Complex Splitting Patterns Thus far, we have observed spin-spin coupling with only one other nonequivalent set of H atoms. More complex splittings arise when a set of H atoms couples to more than one set H atoms. A tree diagram shows that when H b is adjacent to nonequivalent H a on one side and H c on the other, coupling gives rise to a doublet of doublets. (Fig 13.19)

13-44 More Complex Splitting Patterns If H c is a set of two equivalent H, then the observed splitting is a doublet of triplets. (Fig 13.20)

13-45 More Complex Splitting Patterns

13-46 D. More Complex Splitting Patterns Because the angle between C-H bond determines the extent of coupling, bond rotation is a factor. In molecules with relatively free rotation about C-C sigma bonds, H atoms bonded to the same carbon in CH 3 and CH 2 groups generally are equivalent. If there is restricted rotation, as in alkenes and cyclic structures, H atoms bonded to the same carbon may not be equivalent. geminal coupling.Nonequivalent H on the same carbon will couple and cause signal splitting, this type of coupling is called geminal coupling. (Fig 13.21)

13-47 More Complex Splitting Patterns In ethyl propenoate, an unsymmetrical terminal alkene, the three vinylic hydrogens are nonequivalent (Fig 13.22).

13-48 More Complex Splitting Patterns A tree diagram for the complex coupling of the three vinylic hydrogens in ethyl propenoate. (Fig 13.23)

13-49 More Complex Splitting Patterns Cyclic structures often have restricted rotation about their C-C bonds and have constrained conformations (Fig 13.24). As a result, two H atoms on a CH 2 group can be nonequivalent, leading to complex splitting.

13-50 More Complex Splitting Patterns A tree diagram for the complex coupling in 2- methyl-2-vinyloxirane (Fig 13.25).

13-51 F. More Complex Splitting Patterns  Complex coupling in flexible molecules: Coupling in molecules with unrestricted bond rotation often gives only m + n + I peaks. That is, the number of peaks for a signal is the number of adjacent hydrogens + 1, no matter how many different sets of equivalent H atoms that represents. The explanation is that bond rotation averages the coupling constants throughout molecules with freely rotation bonds and tends to make them similar; for example in the 6- to 8-Hz range for H atoms on freely rotating sp 3 hybridized C atoms.

13-52 More Complex Splitting Patterns simplification of signal splitting occurs when coupling constants are the same (Fig 13.26).

13-53 More Complex Splitting Patterns An example of peak overlap occurs in the spectrum of 1-chloropropane. The central CH 2 has the possibility for 12 peaks (a quartet of triplets) but because J ab and J bc are so similar, only = 6 peaks are distinguishable. (Fig 13.28)

Stereochemistry & Topicity  Depending on the symmetry of a molecule, otherwise equivalent hydrogens may be: homotopic enantiotopic diastereotopic  The simplest way to visualize topicity is to substitute an atom or group by an isotope; is the resulting compound: the same as its mirror image different from its mirror image are diastereomers possible

13-55 Stereochemistry & Topicity  Homotopic atoms or groups: Homotopic atoms or groups have identical chemical shifts under all conditions. Achiral H C H Cl Cl H C D Cl Cl Dichloro- methane (achiral) Substitution does not produce a stereocenter; therefore hydrogens are homotopic. Substitute one H by D Achiral H C H Cl Cl H C D Cl Cl Dichloro- methane (achiral) Substitution does not produce a stereocenter; therefore hydrogens are homotopic. Substitute one H by D

13-56 Stereochemistry & Topicity  Enantiotopic groups: Enantiotopic atoms or groups have identical chemical shifts in achiral environments. They have different chemical shifts in chiral environments. Chiral H C H Cl F H C D Cl F Chlorofluoro- methane (achiral) Substitute one H by D Substitution produces a stereocenter; therefore, hydrogens are enantiotopic. Both hydrogens are prochiral; one is pro-R-chiral, the other is pro-S-chiral. Chiral H C H Cl F H C D Cl F Chlorofluoro- methane (achiral) Substitute one H by D Substitution produces a stereocenter; therefore, hydrogens are enantiotopic. Both hydrogens are prochiral; one is pro-R-chiral, the other is pro-S-chiral.

13-57 Stereochemistry & Topicity  Diastereotopic groups: H atoms on C-3 of 2-butanol are diastereotopic. Substitution by deuterium creates a chiral center. Because there is already a chiral center in the molecule, diastereomers are now possible. Diastereotopic hydrogens have different chemical shifts under all conditions.

13-58 Stereochemistry & Topicity  The methyl groups on carbon 3 of 3-methyl-2- butanol are diastereotopic.  If a methyl hydrogen of carbon 4 is substituted by deuterium, a new chiral center is created. Because there is already one chiral center, diastereomers are now possible. Protons of the methyl groups on carbon 3 have different chemical shifts. OH 3-Methyl-2-butanol

13-59 Stereochemistry and Topicity  1 H-NMR spectrum of 3-methyl-2-butanol: The methyl groups on carbon 3 are diastereotopic and appear as two doublets (Fig 13.29).

C-NMR Spectroscopy  Each nonequivalent 13 C gives a different signal. A 13 C signal is split by the 1 H bonded to it according to the (n + 1) rule. Coupling constants of Hz are common, which means that there is often significant overlap between signals, and splitting patterns can be very difficult to determine.  The most common mode of operation of a 13 C- NMR spectrometer is a hydrogen-decoupled mode.

C-NMR Spectroscopy  In a hydrogen-decoupled mode, a sample is irradiated with two different radio frequencies. One to excite all 13 C nuclei. A second broad spectrum of frequencies to cause all hydrogens in the molecule to undergo rapid transitions between their nuclear spin states.  On the time scale of a 13 C-NMR spectrum, each hydrogen is in an average or effectively constant nuclear spin state, with the result that 1 H- 13 C spin-spin interactions are not observed; they are decoupled.

C-NMR: 1 H coupled and decoupled

C-NMR Spectroscopy Hydrogen-decoupled 13 C-NMR spectrum of 1- bromobutane:

13-64 Chemical Shift - 13 C-NMR

13-65 (Fig 13.31)

The DEPT Method  In the hydrogen-decoupled mode, information on spin-spin coupling between 13 C and hydrogens bonded to it is lost.  The DEPT method is an instrumental mode that provides a way to acquire this information. Distortionless Enhancement by Polarization TransferDEPT):Distortionless Enhancement by Polarization Transfer (DEPT): An NMR technique for distinguishing among 13 C signals for CH 3, CH 2, CH, and quaternary carbons.

13-67 The DEPT Method  The DEPT methods uses a complex series of pulses in both the 1 H and 13 C ranges, with the result that CH 3, CH 2, and CH signals exhibit different phases: Signals for CH 3 and CH carbons are recorded as positive signals. Signals for CH 2 carbons are recorded as negative signals. Quaternary carbons give no signal in the DEPT method.

13-68 Isopentyl acetate 13C-NMR: (a) proton decoupled and (b) DEPT (Fig 13.32)

Interpreting NMR Spectra  A. Alkanes 1 H-NMR signals appear in the range of  C-NMR signals appear in the considerably wider range of   B. Alkenes 1 H-NMR signals appear in the range  H-NMR coupling constants are generally larger for trans vinylic hydrogens (J= Hz) compared with cis vinylic hydrogens (J= 5-10 Hz) 13 C-NMR signals for sp 2 hybridized carbons. appear in the range  , which is downfield from the signals of sp 3 hybridized carbons.

13-70 Interpreting NMR Spectra 1 H-NMR spectrum of vinyl acetate (Fig 13.33)

13-71 Interpreting NMR Spectra  C. Alcohols  1 H-NMR O-H chemical shifts often appears in the range  , but may be as high as  H-NMR chemical shifts of hydrogens on the carbon bearing the -OH group are deshielded by the electron-withdrawing inductive effect of the oxygen and appear in the range   D. Ethers A distinctive feature in the 1 H-MNR spectra of ethers is the chemical shift,  , of hydrogens on carbon attached to the ether oxygen.

13-72 Interpreting NMR Spectra 1 H-NMR spectrum of 1-propanol (Fig )

13-73 Interpreting NMR Spectra  E. Aldehydes and ketones 1 H-NMR: Aldehyde hydrogens appear at  H-NMR:  -hydrogens of aldehydes and ketones appear at  C-NMR: Carbonyl carbons appear at   G. Amines 1 H-NMR: Amine hydrogens appear at  depending on conditions.

13-74 Interpreting NMR Spectra  F. Carboxylic acids 1 H-NMR: Carboxyl hydrogens appear at  10-13, lower than most any other hydrogens. 13 C-NMR: Carboxyl carbons in acids and esters appear at  (Fig 13.35).

13-75 Interpreting NMR Spectra  Spectral Problem 1; molecular formula C 5 H 10 O

13-76 Spectral Problem 1 molecular formula C 5 H 10 O molecular formula C 5 H 10 O

13-77 Interpreting NMR Spectra  Spectral Problem 2; molecular formula C 7 H 14 O

13-78 Spectral Problem 2  molecular formula C 7 H 14 O

13-79 Nuclear Magnetic Resonance End Chapter 13