Organic Chemistry

1
Organic Chemistry

• William H. Brown
• Christopher S. Foote
• Brent L. Iverson

2
Nuclear Magnetic Resonance

• Chapter 13

3
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
• hydrogen atoms using 1H-NMR spectroscopy
• carbon atoms using 13C-NMR spectroscopy
• phosphorus atoms using 31P-NMR spectroscopy

4
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 also has a spin and
  a resulting nuclear magnetic moment
• the allowed nuclear spin states are determined by
  the spin quantum number, I, of the nucleus

5
Nuclear Spin States

• a 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

6
Nuclear Spins in B0

• within a collection of 1H and 13C atoms, nuclear
  spins are completely random in orientation
• when placed in a strong external magnetic field
  of strength B0, 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

7
Nuclear Spins in B0

• for 1H and 13C, only two orientations are allowed

8
Nuclear Spins in B0

• In an applied field strength of 7.05T, which is
  readily available with present-day
  superconducting electromagnets, the difference in
  energy between nuclear spin states for
• 1H is approximately 0.120 J (0.0286 cal)/mol,
  which corresponds to electromagnetic radiation of
  300 MHz (300,000,000 Hz)
• 13C is approximately 0.030 J (0.00715 cal)/mol,
  which corresponds to electromagnetic radiation of
  75MHz (75,000,000 Hz)

9
Nuclear Spin in B0

• the energy difference between allowed spin states
  increases linearly with applied field strength
• values shown here are for 1H nuclei

10
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
  earths gravitational field
• we express the rate of precession as a frequency
  in hertz

11
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)

12
Nuclear Magnetic Resonance

• Figure 13.3 the origin of nuclear magnetic
  resonance

13
Nuclear Magnetic 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
• The instrument used to detect this coupling of
  precession frequency and electromagnetic
  radiation records it as a signal
• signal a recording in an NMR spectrum of a
  nuclear magnetic resonance

14
Nuclear Magnetic Resonance

• 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
• 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
• 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

15
Nuclear Magnetic Resonance

• 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

16
Nuclear Magnetic Resonance

• signals are measured relative to the signal of
  the reference compound tetramethylsilane (TMS)
• for a 1H-NMR spectrum, signals are reported by
  their shift from the 12 H signal in TMS
• for a 13C-NMR spectrum, signals are reported by
  their shift from the 4 C signal in TMS
• Chemical shift (?) the shift in ppm of an NMR
  signal from the signal of TMS

17
NMR Spectrometer
18
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 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

• 1H-NMR spectrum of methyl acetate
• 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
• a molecule with 1 set of equivalent hydrogens
  gives 1 NMR signal

21
Equivalent Hydrogens

• a molecule with 2 or more sets of equivalent
  hydrogens gives a different NMR signal for each
  set

22
Signal Areas

• 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

23
Chemical Shifts 1H-NMR
24
Chemical Shift - 1H-NMR
25
Chemical Shift

• Depends on (1) electronegativity of nearby atoms,
  (2) the hybridization of adjacent atoms, and (3)
  diamagnetic effects from adjacent pi bonds
• Electronegativity

26
Chemical Shift

• Hybridization of adjacent atoms

27
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

28
Chemical Shift

• magnetic induction in the pi bonds of a
  carbon-carbon triple bond (Fig 13.9)

29
Chemical Shift

• magnetic induction in the pi bond of a
  carbon-carbon double bond (Fig 13.10)

30
Chemical Shift

• magnetic induction of the pi electrons in an
  aromatic ring (Fig. 13.11)

31
Signal Splitting the (n 1) Rule

• Peak the units 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 if a hydrogen has n hydrogens
  nonequivalent to it but equivalent among
  themselves on the same or adjacent atom(s), its
  1H-NMR signal is split into (n 1) peaks

32
Signal Splitting (n 1)

• 1H-NMR spectrum of 1,1-dichloroethane

33
Signal Splitting (n 1)

• Problem predict the number of 1H-NMR signals
  and the splitting pattern of each

34
Origins of Signal Splitting

• 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) 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

35
Origins of Signal Splitting
36
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 certain signals in expanded
  form
• 1H-NMR spectrum of 3-pentanone scale expansion
  shows the triplet quartet pattern more clearly

37
Coupling Constants

• Coupling constant (J) the distance between peaks
  in a split signal, expressed in hertz
• the value is a quantitative measure of the
  magnetic interaction of nuclei whose spins are
  coupled

38
Origins of Signal Splitting
39
Signal Splitting

• Pascals Triangle
• as illustrated by the highlighted entries, each
  entry is the sum of the values immediately above
  it to the left and the right

40
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

41
Coupling Constants

• an important factor in vicinal coupling is the
  angle a between the C-H sigma bonds and whether
  or not it is fixed
• coupling is a maximum when a is 0 and 180 it
  is a minimum when a is 90

42
More Complex Splitting Patterns

• thus far, we have concentrated on 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 Hb is adjacent to
  nonequivalent Ha on one side and Hc on the other,
  the resulting coupling gives rise to a doublet of
  doublets

43
More Complex Splitting Patterns

• if Hc is a set of two equivalent H, then the
  observed splitting is a doublet of triplets

44
More Complex Splitting Patterns

• because the angle between C-H bond determines the
  extent of coupling, bond rotation is a key
  parameter
• in molecules with relatively free rotation about
  C-C sigma bonds, H atoms bonded to the same
  carbon in CH3 and CH2 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
• nonequivalent H on the same carbon will couple
  and cause signal splitting
• this type of coupling is called geminal coupling

45
More Complex Splitting Patterns

• in ethyl propenoate, an unsymmetrical terminal
  alkene, the three vinylic hydrogens are
  nonequivalent

46
More Complex Splitting Patterns

• a tree diagram for the complex coupling of the
  three vinylic hydrogens in ethyl propenoate

47
More Complex Splitting Patterns

• cyclic structures often have restricted rotation
  about their C-C bonds and have constrained
  conformations
• as a result, two H atoms on a CH2 group can be
  nonequivalent, leading to complex splitting

48
More Complex Splitting Patterns

• a tree diagram for the complex coupling in
  2-methyl-2-vinyloxirane

49
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 sp3 hybridized C atoms

50
More Complex Splitting Patterns

• simplification of signal splitting occurs when
  coupling constants are the same

51
More Complex Splitting Patterns

• an example of peak overlap occurs in the spectrum
  of 1-chloro-3-iodopropane
• the central CH2 has the possibility for 9 peaks
  (a triplet of triplets) but because Jab and Jbc
  are so similar, only 4 1 5 peaks are
  distinguishable

52
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

53
Stereochemistry Topicity

• Homotopic atoms or groups
• homotopic atoms or groups have identical chemical
  shifts under all conditions

H
H
H
H
C
C
C
C
D
D
H
H
Achiral
Achiral
54
Stereochemistry Topicity

• Enantiotopic groups
• enantiotopic atoms or groups have identical
  chemical shifts in achiral environments
• they have different chemical shifts in chiral
  environments

H
H
H
H
C
C
C
C
F
F
F
F
H
H
D
D
Chiral
Chiral
55
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

56
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

3-Methyl-2-butanol
57
Stereochemistry and Topicity

• 1H-NMR spectrum of 3-methyl-2-butanol
• the methyl groups on carbon 3 are diastereotopic
  and appear as two doublets

58
13C-NMR Spectroscopy

• Each nonequivalent 13C gives a different signal
• a 13C signal is split by the 1H bonded to it
  according to the (n 1) rule
• coupling constants of 100-250 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 13C-NMR
  spectrometer is a hydrogen-decoupled mode

59
13C-NMR Spectroscopy

• In a hydrogen-decoupled mode, a sample is
  irradiated with two different radio frequencies
• one to excite all 13C 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 13C-NMR spectrum, each
  hydrogen is in an average or effectively constant
  nuclear spin state, with the result that 1H-13C
  spin-spin interactions are not observed they are
  decoupled

60
13C-NMR Spectroscopy

• hydrogen-decoupled 13C-NMR spectrum of
  1-bromobutane

61
Chemical Shift - 13C-NMR
62
Chemical Shift - 13C-NMR
63
The DEPT Method

• In the hydrogen-decoupled mode, information on
  spin-spin coupling between 13C 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
  Transfer (DEPT) an NMR technique for
  distinguishing among 13C signals for CH3, CH2,
  CH, and quaternary carbons

64
The DEPT Method

• The DEPT methods uses a complex series of pulses
  in both the 1H and 13C ranges, with the result
  that CH3, CH2, and CH signals exhibit different
  phases
• signals for CH3 and CH carbons are recorded as
  positive signals
• signals for CH2 carbons are recorded as negative
  signals
• quaternary carbons give no signal in the DEPT
  method

65
Isopentyl acetate

• 13C-NMR (a) proton decoupled and (b) DEPT

66
Interpreting NMR Spectra

• Alkanes
• 1H-NMR signals appear in the range of ? 0.8-1.7
• 13C-NMR signals appear in the considerably wider
  range of ? 10-60
• Alkenes
• 1H-NMR signals appear in the range ? 4.6-5.7
• 1H-NMR coupling constants are generally larger
  for trans vinylic hydrogens (J 11-18 Hz)
  compared with cis vinylic hydrogens (J 5-10 Hz)
• 13C-NMR signals for sp2 hybridized carbons appear
  in the range ? 100-160, which is downfield from
  the signals of sp3 hybridized carbons

67
Interpreting NMR Spectra

• 1H-NMR spectrum of vinyl acetate (Fig 13.33)

68
Interpreting NMR Spectra

• Alcohols
• 1H-NMR O-H chemical shifts often appears in the
  range ? 3.0-4.0, but may be as low as ? 0.5.
• 1H-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 ? 3.0-4.0
• Ethers
• a distinctive feature in the 1H-MNR spectra of
  ethers is the chemical shift, ? 3.3-4.0, of
  hydrogens on carbon attached to the ether oxygen

69
Interpreting NMR Spectra

• 1H-NMR spectrum of 1-propanol (Fig. 13.34)

70
Interpreting NMR Spectra

• Aldehydes and ketones
• 1H-NMR aldehyde hydrogens appear at ? 9.5-10.1
• 1H-NMR a-hydrogens of aldehydes and ketones
  appear at ? 2.2-2.6
• 13C-NMR carbonyl carbons appear at ? 180-215
• Amines
• 1H-NMR amine hydrogens appear at ? 0.5-5.0
  depending on conditions

71
Interpreting NMR Spectra

• Carboxylic acids
• 1H-NMR carboxyl hydrogens appear at ? 10-13,
  lower than most any other hydrogens
• 13C-NMR carboxyl carbons in acids and esters
  appear at ? 160-180

72
Interpreting NMR Spectra

• Spectral Problem 1 molecular formula C5H10O

73
Interpreting NMR Spectra

• Spectral Problem 2 molecular formula C7H14O

74

• Nuclear
• Magnetic Resonance
• End Chapter 13