7. What is ∆E in NMR? Nuclei
behave as tiny magnets (random
orientation).
In a magnetic field H0, they
organize with (α, lower energy) or
against (β, higher energy) the field.
∆E = hν0 resonance frequency:
The frequency that matches
exactly the energy difference.
8. Protons as Tiny Magnets Line Up With
and Against an External Magnetic
Filed
Ratio α:β ~ 1:1
19. Consider H+: No e, no shielding, peak
furthest to the left.
But:
When we add an e-withdrawing group:
e.g., CH3 Cl, causes deshielding (to left).
Chemical shift provides a finely tuned picture
of electronic environment around each H.
C HH
H
H
+ -
Electrons cause shielding:
Peak moves upfield (to right).
20. If we substitute with e-negative groups, shielding of
observed nucleus is diminished; or nucleus is
“deshielded” (relatively).
22. The Chemical Shift δ
The position of peak relative to an
internal standard. Most common is
Tetramethylsilane: (CH3)4Si or “TMS”,
the “zero” point in the spectrum.
=
ν (from TMS) Hz
RF (e.g., 300 MHz)
ppm,
is independent of machine (90, 300 MHz, etc.)
δ
23. Distance from
TMS in Hz/300
MHz in ppm
266 Hz
0.89 ppm
541 Hz
1.80 ppm
978 Hz
3.26 ppm
24. Application of δ
CH3 CH3 CH3CH2Br
Br2
hυ
+ CH3CHBr2 + BrCH2CH2Br
EPM of 1-bromopropane
2 signals
2 signals
1 signal
Most deshielded
of all
27. “Fast” processes, such as methyl
rotation, equilibrate Hs:
For calibration: A B
Ea
k
Ea ~ 20 kcal mol-1, k ~ 10-2 sec-1, t1/2 = 1 min
Ea ~ 25 kcal mol-1, k ~ 10-6 sec-1, t1/2 = 66 h
NMR time scale < 1 sec.
28. Recall: Ea = 10.8 kcal mol-1.
To “freeze” ring flip on the NMR time scale:
we need to cool to -90ºC (Jensen)
29. Integration
Area under peak = relative # of
associated Hs. Computer-automated.
e.g. (CH3)3CCH2OH 9:2:1
CH3OCH2CH2OCH3 3:2
Helps in peak assignments.
33. (N+1) Rule
N equivalent adjacent hydrogens
(i.e. on neighboring carbons) give
rise to (N+1) peaks.
e.g., doublet (d), triplet (t),
quartet (q), quintet (quin), etc.
34. Why ?
Hbα strengthens H0 around Ha : deshielding
Hbβ weakens H0 around Ha : shielding
Result: two lines (1:1 ratio, d) instead of one.
Distance between them in Hz is the
coupling constant J.
Cl C C O CH2 CH3
Ha
OCH2CH3Cl
Hb
d d
q t
Ha “sees” two types of Hb neighbors
(through bond): Hbα and Hbβ
In a magnetic field, all
Hs exist as Hα:Hβ ~ 1:1.
35.
36. Same value
Ha and Hb are said to “split” each other with a J of 7 Hz.
37. J is field independent: Same at
90, 300, etc. MHz
Range: 1-18 Hz.
For more than one neighbor : H “sees”
all α, β combinations of neighbors. Thus,
two neighboring Hs:
αα, αβ, βα , ββ: 1:2:1 triplet
ααα, ααβ, αβα, βαα , αββ, βαβ, ββα , βββ
1:3:3:1 quartet
Three neighboring Hs:
38.
39.
40.
41. Summary Points
1. Equivalent protons show no splitting.
2. J is independent of H0.
3. Nonadjacent Hs J ~ 0.
4. (N+1) Rule. Ratio from Pascal’s triangle.
5. Splitting is mutual. If there is one split peak,
there has to be (at least) one other.
C X C
HH
50. Problem:
3 H
2 H
1 H
4 H
3 H
3 H
2 H
1 H
1 H
The two butanols:
CH3CH2CH2CH2OH
CH3CH2CHCH3
Which is which?
OH
51. Complex Splitting Patterns
[N+1] rule holds strictly only when:
1. Js to all neighbors equal, and
2. ∆ν >> J : first order patterns.
3. Otherwise complex signals: non-first order
multiplets.
δ (Heq) > δ (Hax)
1
1
4
2
3
52. Multiplets are typical of alkyl chains: all δs similar.
e.g.,
One solution: stronger magnet higher field spectra
For example, what might be non-first-order
at 90 MHz, may resolve into a first-order
pattern at 300 or 500 MHz.
(Recall ν ~ H0 ), “spreads out” spectrum,
but Js stay same (field independent).
56. “Sequential” [N+1] Rule
1st Order patterns can be analyzed
for neighbors with differing Js.
Js should differ for non-equivalent
neighbors.
CH3 C C Cl
ClCl
Hb Ha
c
Jab = 3.6 Hz
Jbc = 6.8 Hz
Apply split sequentially
57.
58. CH3 C C Cl
ClCl
Hb Ha
c
Jab = 3.6 Hz
Jbc = 6.8 Hz
63. H Bonded/Acidic Protons:
OH, SH, N H
Recall CH2 O H
Why? Fast H+ exchange
(Hα and Hβ trade places)
“decouples” hydrogens.
Variable
s !
Variable (concentration and moisture-dependent)
and no coupling !
64. Coupling is restored on cooling, because proton
exchange is “frozen” (on the NMR time scale).
CH3OH
OH peak often broad; disappears on addition
of D2O to the sample (H/D exchange).
65. 13C NMR Spectroscopy
Only 1% 13C in nature: No 13C—13C
splitting, since chances of finding two
13C adjacent are small (~0.01%).
(For the same reason: No 13C—H seen in 1H NMR.
99% of sample is 12C).
Large Js 13C H J ~ 100-150 Hz
13C C H J ~ 5-10 Hz
But: 13C—H visible in 13C NMR.
72. Advanced Techniques
Distortionless polarization transfer
(“DEPT”) 13C NMR spectrum. Tells us
whether the carbon is attached to 3, 2,
1 or no hydrogen, i.e. CH3, CH2, CH, or C.
Requires running the spectrum in three
different ways (using specific laser
pulse sequences).
Example : Limonene.
79. MRI, median sagittal section: cervicodorsal syringomyelia. This
condition is characterized by the presence of fluid-filled cavities
in the spinal cord substance.
83. This spiral
represents the 23
stages occurring in
the first trimester
of pregnancy and
every two weeks of
the second and
third trimesters.
84. Stage 1
Fertilization
1 Oocyte, 300 Million
Sperm, 24 hours
0.1 - 0.15 mm
1 day post-ovulation
Fertilization begins
when a sperm
penetrates an oocyte
(an egg) and it ends with
the creation of the
zygote. The fertilization
process takes
about 24 hours.
Stage 5
Implantation
Complete,
Placental
Circulation
System Begins
0.1 – 0.2 mm
7-12 days post-
ovulation
Stage 2
Stage 10
Cleavage
First Cell Division,
Blastomeres,
Mitotic division
0.1-0.2 mm
1.5-3 days post-
ovulation
Neural Folds Begin
to Fuse, Heart
Tube Fuses
1.5-3.0 mm
21-23 days post-
ovulation
85. Cross Sections of 3-D
Image
… of a human
embryo, 44
days after
conception.
Roughly the
size of a navy bean, it still
has webbed fingers and
toes, but is already
developing a brain with two
hemispheres, the precursors
of vertebrae (dashlike
structures in right slice) and
internal organs.
86. Stage 15
Stage 23
(6 to 8 weeks post fertilization)
Lens vesicle, nasal pit, hand plate;
trunk widens; future cerebral
hemispheres distinct
Head and neck
(approximately 56-57
postovular days)
Essential external and
internal structures complete
