Chemistry
William Organic H. Brown Christopher S. Foote Brent L. Iverson
13-1
Nuclear Magnetic Resonance
Chapter 13
13-2
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
13-3
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
13-4
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
Element Nuclear spin quantum number ( I ) Number of spi n states
1
H
2
H
12
C
13
C
14
N
16
O
31
P
32
S
1/2 2
1 3
0 1
1/2 2
1 3
0 1
1/2 2
0 1
13-5
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
13-6
Nuclear Spins in B0
for 1H and 13C, only two orientations are allowed
13-7
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)
13-8
Nuclear Spin in B0
the energy difference between allowed spin states increases linearly with applied field strength values shown here are for 1H nuclei
13-9
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 coneshaped 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
Figure 13.3 the origin of nuclear magnetic "resonance
13-12
Nuclear Magnetic 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
Resonance:
13-13
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
13-14
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
360 Hz 6 300 x 10 Hz = 1.2 106 = 1.2 ppm
13-15
Nuclear Magnetic Resonance
signals are measured relative to the signal of the reference compound tetramethylsilane (TMS)
CH3 Si CH 3 CH3 Tetrameth yls ilane (TMS) CH3
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
13-16
NMR Spectrometer
13-17
NMR Spectrometer 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
Essentials
13-18
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 13-19
Equivalent Hydrogens
Equivalent
hydrogens: have the same chemical environment
a molecule with 1 set of equivalent hydrogens gives 1 NMR signal
O CH3 CCH3 Propanone (Acetone) H3 C ClCH 2 CH2 Cl H3 C 1,2-Di chloroethane Cyclopentane C C CH3 CH3
2,3-Di methyl 2-butene
13-20
Equivalent Hydrogens
a molecule with 2 or more sets of equivalent hydrogens gives a different NMR signal for each set
Cl CH3 CHCl 1,1-D ich loroeth ane (2 signals ) O Cyclop entan on e (2 s ign als) Cl C C H H (Z)-1-Ch loroprop ene (3 signals) Cyclohexen e (3 signals) CH3
13-21
Signal Areas
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
Relative
13-22
Chemical Shifts 1H-NMR
Typ e of Hyd rogen (CH3 ) 4 Si RCH3 RCH2 R R3 CH R2 C=CRCHR2 RC CH ArCH3 ArCH2 R ROH RCH2 OH RCH2 OR R2 NH O RCCH 3 O RCCH 2 R
Ch emical Shift () 0 (by definition) 0.8-1.0 1.2-1.4 1.4-1.7 1.6-2.6 2.0-3.0 2.2-2.5 2.3-2.8 0.5-6.0 3.4-4.0 3.3-4.0 0.5-5.0 2.1-2.3 2.2-2.6
Typ e of Hyd rogen O RCOCH3 O RCOCH2 R RCH2 I RCH2 Br RCH2 Cl RCH2 F ArOH R2 C=CH2 R2 C=CHR ArH O RCH O RCOH
Ch emical Shift () 3.7-3.9 4.1-4.7 3.1-3.3 3.4-3.6 3.6-3.8 4.4-4.5 4.5-4.7 4.6-5.0 5.0-5.7 6.5-8.5 9.5-10.1 10-13
13-23
Chemical Shift - 1H-NMR
13-24
Chemical Shift
Depends on (1) electronegativity of nearby atoms, (2) the hybridization of adjacent atoms, and (3) diamagnetic effects from adjacent pi bonds Electronegativity
CH3 -X CH3 F CH3 OH CH3 Cl CH3 Br CH3 I (CH3 ) 4 C (CH3 ) 4 Si Electron egativity of X 4.0 3.5 3.1 2.8 2.5 2.1 1.8 Chemical Shift () 4.26 3.47 3.05 2.68 2.16 0.86 0.00
13-25
Chemical Shift
Hybridization
of adjacent atoms
N ame of Hydrogen Alk yl Allylic Acetylen ic Vin ylic Ald ehydic Chemical Sh ift () 0.8 - 1.7 1.6 - 2.6 2.0 - 3.0 4.6 - 5.7 9.5-10.1
Type of Hydrogen (R = alkyl) RCH3 , R2 CH2 , R3 CH R2 C=C(R)CHR2 RC CH R2 C=CHR, R2 C=CH2 RCHO
13-26
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
Type of H RCH3 RC CH R2 C=CH2 N ame Alk yl Acetylenic Vin ylic Chemical Shift () 0.8- 1.0 2.0 - 3.0 4.6 - 5.7
13-27
Chemical Shift
magnetic induction in the pi bonds of a carbon-carbon triple bond (Fig 13.9)
13-28
Chemical Shift
magnetic induction in the pi bond of a carbon-carbon double bond (Fig 13.10)
13-29
Chemical Shift
magnetic induction of the pi electrons in an aromatic ring (Fig. 13.11)
13-30
Signal Splitting; the (n + 1) Rule
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
Peak:
13-31
Signal Splitting (n + 1)
1H-NMR spectrum of 1,1-dichloroethane
For thes e hyd rogens, n = 1; their signal is s plit into (1 + 1) = 2 p eaks; a d ou blet
CH3 -CH-Cl Cl
For this h yd rogen, n = 3; its s ignal is split into (3 + 1) = 4 p eaks; a q uartet
13-32
Signal Splitting (n + 1)
Problem: predict the number of 1H-NMR signals and the splitting pattern of each
O (a) CH3 CCH2 CH 3 O (b) CH3 CH2 CCH2 CH3 O (c) CH3 CCH( CH3 ) 2
13-33
Origins of Signal Splitting
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
Signal
13-34
Origins of Signal Splitting
13-35
Origins of Signal Splitting
because splitting patterns from spectra taken 300 at 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
13-36
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
Ha Hb C C Ha Ha Hb Hb 8-14 Hz Ha C C Hb 11-18 Hz 5-10 Hz C C Hb C C Hb 0-5 Hz Hb 8-11 Hz 0-5 Hz Ha 0-5 Hz Ha H Hb a
6-8 Hz Ha
13-37
Origins of Signal Splitting
13-38
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
13-39
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
13-40
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
13-41
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
13-42
More Complex Splitting Patterns
if Hc is a set of two equivalent H, then the observed splitting is a doublet of triplets
13-43
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
13-44
More Complex Splitting Patterns
in ethyl propenoate, an unsymmetrical terminal alkene, the three vinylic hydrogens are nonequivalent
13-45
More Complex Splitting Patterns
a tree diagram for the complex coupling of the three vinylic hydrogens in ethyl propenoate
13-46
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
13-47
More Complex Splitting Patterns
a tree diagram for the complex coupling in 2-methyl-2vinyloxirane
13-48
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
13-49
More Complex Splitting Patterns
simplification of signal splitting occurs when coupling constants are the same
13-50
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
13-51
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
13-52
Stereochemistry & Topicity
Homotopic
H
atoms or groups
Substitute one H by D
C
H
Cl Cl
H
Dichloromethane (achiral)
Substitution does not produce a stereocenter; C Cl therefore hydrogens D are homotopic. Achiral Cl
homotopic atoms or groups have identical chemical shifts under all conditions
13-53
Stereochemistry & Topicity
Enantiotopic
H C
H
groups
Substitute one H by D
Cl F
Chlorofluoromethane (achiral)
Substitution produces a H stereocenter; Cl therefore, hydrogens are C F enantiotopic. Both hydrogens are prochiral; D one is pro-R-chiral, the Chiral other is pro-S-chiral.
enantiotopic atoms or groups have identical chemical shifts in achiral environments they have different chemical shifts in chiral environments
13-54
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
H OH Substi tute one H on CH 2 by D H OH
H H 2-Butanol (chi ral)
H D Chiral
diastereotopic hydrogens have different chemical shifts under all conditions
13-55
Stereochemistry & Topicity
The
methyl groups on carbon 3 of 3-methyl-2butanol 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
OH
3-Methyl-2-butanol
protons of the methyl groups on carbon 3 have different chemical shifts
13-56
Stereochemistry and Topicity
1H-NMR
spectrum of 3-methyl-2-butanol
the methyl groups on carbon 3 are diastereotopic and appear as two doublets
13-57
13C-NMR
Each
Spectroscopy
13C
nonequivalent
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 13CNMR spectrometer is a hydrogen-decoupled mode
13-58
13C-NMR
In
Spectroscopy
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
13-59
13C-NMR
Spectroscopy
hydrogen-decoupled 13C-NMR spectrum of 1bromobutane
13-60
Chemical Shift - 13C-NMR
Typ e of Carbon RCH3 RCH2 R R3 CH RCH2 I RCH2 Br RCH2 Cl R3 COH R3 COR RC CR R2 C=CR2 Chemical S hift () 10-40 15-55 20-60 0-40 25-65 35-80 40-80 40-80 65-85 100-150 Type of Carb on C R O RCOR O RCNR2 O RCCOH O O RCH, RCR Chemical Sh ift () 110-160
160 - 180 165 - 180 165 - 185 180 - 215
13-61
Chemical Shift - 13C-NMR
13-62
The DEPT Method
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 CH , CH , CH, and quaternary carbons 3 2
In
13-63
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
13-64
Isopentyl acetate
13C-NMR: (a) proton decoupled and (b) DEPT
13-65
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
13-66
Interpreting NMR Spectra
1H-NMR spectrum of vinyl acetate (Fig 13.33)
13-67
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 electronwithdrawing 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
13-68
Interpreting NMR Spectra
1H-NMR spectrum of 1-propanol (Fig. 13.34)
13-69
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
13-70
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
13-71
Interpreting NMR Spectra
Spectral
Problem 1; molecular formula C5H10O
13-72
Interpreting NMR Spectra
Spectral
Problem 2; molecular formula C7H14O
13-73
Nuclear Magnetic Resonance
End Chapter 13
13-74