Lecture 3: 2D NMR Spectroscopy 2D NMR Spectroscopy: Chem 135

E.
Kwan Lecture 3: 2D NMR Spectroscopy Chem 135
2D NMR Spectroscopy between sites, which is very useful if you want to know the
structure of a molecule.
Eugene E. Kwan
Every 2D NMR experiment has the same general format:
preparation evolution mixing detection

xx x x
4 5
t1 t2
Scope of Lecture (1) Preparation: Some sequence of pulses is used to generate

two frequency states that are poised to interact in a useful way. This is
dimensions typically a 90° pulse that generates transverse magnetization.
problem absolute value vs.
solving phase-sensitive (2) Evolution: The resonances precess in the rotating frame
modes
according to their offsets. This means that magnetization is
two-dimensional NMR "frequency-labeled" as a function of t1.
structural spectroscopy COSY
elucidation (3) Mixing: Magnetization is transfered through bond (or
workflow (through space or chemical exchange).
HSQC
HMBC
(4) Detection: The magnetization that did not get transferred
during the mixing period will appear at the same frequency
Two Frequency Dimensions during the detection period. These are diagonal peaks of
frequency (A, A). Magnetization that was at frequency A
1D NMR spectra are called "1D" because they have one but moved to frequency B during the mixing period will
frequency dimension, but actually have an additional dimension, precess at an off-diagonal frequency (A, B).
intensity:
This is best illustrated by the basic COSY-90 sequence:
intensity
t2
t1
H channel
90x 90x
frequency
2D NMR means that there are two frequency dimensions. COSY stands for COrrelations SPectroscopy and is a method
1D peaks tell you something about a particular chemical site: for finding homonuclear, through-bond correlations. (There
what it's chemical environment is like, how many nuclei are are other methods for finding heteronuclear, through-bond
present, how many nuclei are near the site, etc. But there's no correlations.) Implicitly, the above diagram means that we run
mechanism for telling you anything about the the connections a series of experiments, with a fixed values of t1 every time.
E. Kwan Lecture 3: 2D NMR Spectroscopy Chem 135
t1 (1) As with 1D spectra, this may also involve intermediate
t2 zero-filling, apodization, or linear prediction.
experiment #1
(2) Quadrature detection, i.e., the discrimination of positive vs.
negative frequencies is possible and necessary, but is
t1 complicated and will not be considered in this lecture.
t2
experiment #2 (3) Recall that 1D spectra have a real and imaginary part and
that phase correction ensures that the real part has a purely
absorption lineshape. In 2D spectra, there are two real parts
t1
t2 and two imaginary parts (one for each dimension). In an
ideal world, the real part of both would be absorptive as well:
experiment #3
The entire experiment generates a 2D data matrix. Fourier

transformation of the rows, followed by the columns gives the
final 2D spectrum:
(Red = negative contour; black = positive countour)
If this is the case, we can present the data in a phase-sensitive

format. However, in some experiments, this is impossible, and
it is necessary to mix the real and imaginary parts to give an
absolute value format:
absolute value = Sqrt[real2 + imaginary2]
These partially absorptive/dispersive peaks do not have a
standard Lorentzian shape and instead appear as broader
phase-twisted shapes:
Flavors of COSY
The basic COSY-90 sequence is: (5) 1D Curves: These are not part of the 2D experiment. They do not have to be
drawn at all, but it is customary to add them to for reference. The curves
t2
t1 shown below are “projections” of the peaks onto the axes. Because
H channel increasing ni is very costly, resolution is poor. A better alternative is to place
90x 90x
the actual 1D spectra on these axes (acquired in separate experiments.)
In VNMR, this is requested with the "gCOSY"
command. Here is the COSY-90 spectrum for
ethyl acetate: O
O 0.5
1.0
(1) Cross-peaks: In ethyl acetate,
there’s an ethyl group, which means
that a methyl and a methylene share 1.5
a vicinal coupling.
F1 Chemical Shift (ppm)

2.0
(2) Isolated Peaks: Not everything
has large enough couplings to give 2.5
off-diagonal peaks (for example,
this acetate). In general, COSY
3.0
mostly shows 2J and 3J couplings.
3.5
(3) Diagonal: Of course, every proton is
coupled to itself. There’s nothing
4.0
interesting to see here.
(6) Symmetry: If A is coupled
to B, then B is coupled to A, 4.5
so there is reflection symmetry
(4) Shape: The spectrum is a square, about the diagonal.
since we are correlating a spectrum to
itself. 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
A detailed quantum-mechanical treatment, which is outside the (2) At sufficiently high resolution, crosspeaks are tilted.
scope of this course, shows that for an AX system, the Typically, geminal couplings will appear with positive slope,
crosspeaks have doubly absorptive lineshapes, but the diagonal while vicinal couplings will appear with negative slope.
peaks have doubly dispersive lineshapes: However, due to the variations in J, this is not always true.
(3) COSY-45 is slightly less sensitive than COSY-90 (by about

15%), but since COSY-90 is already a very sensitive
experiment, this is of no consequence. COSY-45 gives more
simplification than COSY-60, and is therefore preferred.
COSY-45 is the best absolute value COSY experiment for

routine use and should be used instead of COSY-90. The
PFG version can be requested in VNMR with "gCOSY45."
COSY-45 COSY-90
(source: Claridge, pg 140) The long tails from the dispersive

peaks can interfere with off-diagonal peaks. Therefore,
COSY-90 data are presented in absolute-value mode as
phase-twist lineshapes.
tilting
Just because something is popular doesn't necessarily mean it's
the best. A popular absolute-value version of COSY is called
COSY-. Here, the second 90° pulse is replaced by a smaller
pulse of tip angle . Typically,  is 45° or 60°.
diagonal
t2 is less
t1
H channel crowded
90x x
This has several important consequences:
(1) The diagonal is compressed. Since we don't care about the

diagonal, and it can interfere with nearby cross-peaks, this is
good.
Flavors of COSY Expansions clearly show the tilting effect:
The difference between the two COSY spectra is particularly
evident in this example from Reynolds and Enriquez:
COSY-90
geminal vicinal
One post-acquisition strategy that is sometimes used to

enhance S/N is called "symmetrization" and is based on the
idea that the spectrum should have reflection symmetry about
f1=f2 (VNMR: foldt). However, because f1 is usually digitized
better than f2, crosspeaks are usually more resolved on one
side of the diagonal. Therefore, peaks that appear more
strongly on one side of the diagonal may be long-range peaks.
In addition to losing this information, false crosspeaks may
COSY-45 appear from the coincidental symmetry of t1 noise:
Heteronuclear Correlation Spectroscopy where exc is the initially excited spin and obs is the observed
For heteronuclear experiments, one has the option to prepare, nucleus. In dual-band probes, there is always a coil on the
evolve, or mix the magnetization on either proton or carbon (the inside (more sensitive) and a coil on the outside (less sensitive).
X-nucleus). For inverse-detection probes, the proton coil is on the inside;
direct-detection probes have the carbon coil on the inside.
old strategy: "direct" detection of X-nucleus (less sensitive)
new strategy: "indirect" detection of H-nucleus (better) Regardless of the detection scheme, the goal of all of these
experiments is to connect protons with carbons. Unlike
From Claridge, page 191: proton-proton correlation experiments (COSY, TOCSY), we
have the possibility of protons being directly (one-bond) or
remotely (multiple-bond) connected.
For an inverse-detected experiment, we see carbons that

are directly or remotely attached to protons:
H H H H H H H H H H
C C C O C C C C C O C C
one-bond (direct) multiple-bond (remote)

(This means that quaternary carbons, which do not have any
attached protons, do not appear in inverse-detection
experiments.) Remote correlations can be transmitted through
heteroatoms, but this is by no means required.
Conversely, for a direct-detection experiment, we see protons

that are directly or remotely attached to carbons:
H H H H H H H H H H
C C C O C C C C C O C C
one-bond (direct) multiple-bond (remote)

In this case, quaternary carbons can appear:
H H
In reality, various experimental considerations mean that the C O C C
advantage is less than 32/4=8. In general,
S
  exc obs
3/2 However, directly-detected multiple-bond correlation
N experiments are insensitive and not in routine use.
HSQC - Heteronuclear Single Quantum Correlation Spectroscopy
This is a proton-detected experiment that shows directly attached carbons (one bond). CH and CH3 peaks are phased up (red)
while CH2 peaks are phased down (blue). 1D curves are useful, but not required. This is the spectrum for menthol:
Me Me
(1) Spreading Out: The 1D

HO spectrum is quite crowded,
Me but having the second
dimension spreads out the
peaks over a much larger
not diastereotopic
area.
(double height)
(2) DEPT: The additional APT
pulses are a kind of “extra
fanciness” that require more
time during which signal can
decay, so there is some
diastereotopic
sensitivity loss. However,
HSQC-APT sequences of this
type can be acquired more
quickly than edited DEPT
spectra.
(3) Methylenes: These appear
on the same horizontal line,
since they’re two protons on
the same carbon. This allows
one to distinguish 2J from 3J
(or >3J) in COSY spectra.
HMBC Spectra
This is a proton-detected experiment that shows carbons that are 2-3 bonds away from protons. It is absolute value.
(1) A common artifact is the appearance of one-bond correlations. HMBC is "tuned" to detect the small couplings arising from
long-range interactions, but this is not perfect. These one-bond artifacts appear as doublets in f2, with J=1JCH. Occasionally,
this splitting is itself useful information. However, most of the time, one should be wary of these artifacts.
(2) HMBC incorporates a delay which under ideal circumstances is 1/2JCH. Since long-range couplings occupy a relatively wide
range of 5-25 Hz, this delay is often set at a compromise value of 60 ms (8 Hz). This means that not all of the correlations will
appear, and certainly not with equal intensity. Additionally, note that three-bond couplings are often larger than two-bond ones.
1 2 3 4 5 6 7 8
16
24

32
40
48
56
arrows indicate
one-bond peaks 64
72
3.5 3.0 2.5 2.0 1.5 1.0 0.5

Summary of 2D NMR Experiments COSY
1. HSQC: 1-bond C,H - all experiments are proton-detected Next, use COSY to determine the composition of each spin system.
2. COSY: 2,3-bond H,H
3. HMBC: 2,3-bond C,H axes: proton, proton
correlations: off-diagonal peaks are 2-3 bond couplings between protons
HSQC purpose: assign protons to spin systems
By far the simplest spectrum to understand, begin here.
spin system: a set of protons sharing through-bond (J) couplings
axes: proton, carbon
correlations: 1-bond C,H couplings 1 4
purpose: number proton spectrum, match each proton with a carbon, identify O
2 A B C D
CH2 pairs 5 6
3
1 2 3 D
1-2-3, 4-5, 6
down (CH2)
C
proton
up (CH, CH3)
B carbon
B
A A
protons 2 and 3 are on the A-B-C, D
same carbon; i.e., 2/3 is
proton a methylene (CH2) pair proton
proton 1 is directly HMBC
attached to carbon A
axes: proton, carbon
correlations: 2-3 bond couplings between protons
Numbering the Spectrum purpose: connect spin systems
Even if the proton spectrum overlaps, HSQC will usually separate the peaks 1 2
enough so they can be numbered (convention: left to right).
one-bond artifact:
1 2,3 4 proton 2 is directly
- although 2 and 3 overlap in attached to carbon B
(look for doublets)
carbon
the 1D spectrum, they have
2 4 B
very different carbon shifts
C so the HSQC separates them
carbon
B - only give a number for each A

unique chemical shift (e.g.,
3 a methyl group only gets one
A
1 number) proton
proton 2 is 2 or 3 bonds
proton 1 is 2 or 3 bonds away from carbon A
proton away from carbon A
Structural Elucidation Workflow (2) Tabulate the Data.

(1) Start with the HSQC to label the proton spectrum. ID (1H) (13C) Hs type J (Hz) COSY HMBC
Here's a hypothetical proton spectrum, where peaks 2 and 3 1 5.76 145.23 1 d 5.1 2 152.12
are very close (peaks are labeled from left to right):
2 3.76 72.45 1 d 5.1 1,3 32.47
1 2 3 4 5
3 3.47 -- 1 br s -- -- 202.57
... etc ...
integrals: 1H 2H 1H 1H 
The HSQC spectrum is very simple because it spreads out the Quaternary Carbons: 35.57, 54.32, 202.57...
peaks over two dimensions has little multiplet structure: CH2 pairs: 4/5, ...
- peaks are listed by number from high to low chemical shift

- HSQC: connect each proton to its directly attached carbons;
13 find methylene pairs
xx - COSY: if 1 is coupled to 2, then check that 2 is coupled to 1;
C axis
2 however, both partners of a methylene pair may not show

xx couplings to a common partner (peak 3)
3 - exchangeable protons do not appear in the HSQC
1
H axis - quaternary carbons can be found from HMBC or the 1D
spectrum carbon
It will also identify methylene pairs, both by color (remember, - HMBC: watch for one-bond peaks; more intense peaks like
CH and CH3 are opposite to CH2) and by the fact that they methyl groups are more likely to show long-range
occur on the same line. In this case, 4/5 is apparently a correlations; sp2 systems: 2J is small, but 3J is large (bigger for
methylene pair. Methylene pairs will always share a geminal anti than syn)
coupling. With diastereotopic protons, these will give rise to a (3) Generate Spin Systems
COSY crosspeak, which the HSQC will first identify as being
geminal in nature. - Use COSY to build up spin systems. Each "component" of
the spin system is a methyl group, a methylene pair, or a
methine (from the HSQC). Double-headed arrows represent
(putative) vicinal couplings, with dashed lines for long-range
couplings:
4/5 8 1 2 H H H H H
xx xx 4/5 is a methylene pair. C C C O C C
4 5
long-range coupling
(You might not know which ones are long-range. Use your Vicinal COSY Key HMBC
chemical intuition and look at the peak intensities and Fragment Structures
Correlations Correlations
asymmetry about the diagonal. You might have to change 2, 25.82
your diagram if you find it to be inconsistent later.) 11-2 2-14 11-14
H H
H3C CH3 H3C CH3 H3C CH3
(4) Connect Spin Systems 11, 21.00 14, 16.07 2-8 14-8
11-2
Look for HMBC correlations that connect a proton in one X X X X X X
spin system to a carbon in another spin system: H H
8, 50.12
145.23 33.37
Key Evidence
- methyls 11, 14: COSY to 2 - HSQC: 2, 8 = CH
4/5 8 1 2 6 7 3 - 2: COSY to 8
- 11, 14: mutual HMBC
- 11, 14: HMBC to 2, 8
Curved arrows indicate HMBC correlations. If you find such
a connection, that tells you that the spin systems must be - HMBC: double-headed arrows to indicate mutual correlations;
adjacent in the head-to-tail sense shown. Note that these single-headed arrows to indicate a one-way correlation
do not have to be mutual like COSY couplings: - if you feel comfortable, you can write "11-2" instead of "11-
finding this H H H H 25.82" to speed things up, but remember, HMBC correlations
does not will be are from protons to carbons
HMBC C C C C C C
mean present
correlation - Xs represent non-protons
If that doesn't work, you can look for a carbon, possibly Write down your reasoning (even though it's boring). By
quaternary, that protons in both spin systems have common their nature, these problems are very complicated, and there's a
HMBC correlations to: 35.57 99.9% chance you will not remember what peak is at 16.07 ppm
several years from now. If you write down what you were
4/5 8 1 2 6 7 3 thinking, you and others will be able to follow your process later
on without repeating the entire analysis. It's also likely you will
make some mistakes, which will be easier to track down this way.
(5) Generate Fragments
(6) Entry Points
In many cases, complex, overlapping signals will prevent you
from drawing out all the spin systems of the molecule. In When you look at a COSY or HMBC spectrum, you will see a
particular, unknown structural elucidations will require you to lot of peaks. Where should you start generating fragments
generate and connect fragments, which are tied together by from? In general: clearly resolved peaks with unambiguous
what is visible in a spin system and HMBC. Here is how I put or characteristic chemical shifts. Here are some ideas:
together menthol, which has some overlapping signals and one
continuous spin system: - carbonyl region - aromatic rings and olefins
- methyl groups - quaternary carbons
(7) Expand and Connect Fragments
Don't bite off too much at a time. Make a small fragment with
correlations you feel confident in assigning. Then, move on
to another entry point and generate another fragment.
Fragments with uncertain correlations are hard to use. Once
you have exhausted all the easy data, work on what's left to
expand your existing fragments, and if possible, connect them.
HO X HO
5-13, 9-4
CH2X
6 4, 13, 34.51
CH3
12, 22.10 - COSY, HMBC correlations
connect termini
(8) List Full Assignments
This is self-explanatory:
14 2 11 16.07 21.00
25.82
7 HO 1 HO 50.12
8 5, 9 23.10
71.53
3, 10 6 4, 13 45.03 34.51
31.62
12 22.10
You should also file all the FIDs and your "good" notes of what
you've done in the same place. If you feel the compound will go
into your thesis, take the time to write it out in journal format.
Problem 1
Please assign the proton and carbon resonances of ethyl nipecotate. (500 MHz, CDCl3; spectra are courtesy of
Dr. Jeffrey Simpson, MIT. See Simpson, Chapter 9 for his treatment of this problem.)
N
H
2.0 1.0 1.0 1.0 1.1 1.1 1.0 2.0 1.1 2.8
4.0 3.5 3.0 2.5 2.0 1.5 1.0

Chemical Shift (ppm)
173.99
59.84
48.35
46.14
42.20
27.10
25.27
13.91
192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0
Problem 1
Please assign the proton and carbon resonances of ethyl nipecotate. (500 MHz, CDCl3; spectra are courtesy of
Dr. Jeffrey Simpson, MIT. See Simpson, Chapter 9 for his treatment of this problem.)
O ID  (1H)  (13C) Hs Type J (Hz) COSY

O 1
N
H 2
10
11
Quaternary Carbons:
Methylene Pairs:
Problem 1
This is the HMQC spectrum. Please number the protons. What are the methylene pairs in this
molecule? Are there any quaternary carbons?
O
N
H
10
15
20
25
30

35
40
45
50
55
60
4.0 3.5 3.0 2.5 2.0 1.5 1.0

Problem 1
This is the COSY spectrum. Try to label the off-diagonal peaks.
N
H
1.0
1.5
2.0

2.5
3.0
3.5
4.0
4.0 3.5 3.0 2.5 2.0 1.5 1.0

Problem 1
The numbering I get is shown below.
N
H
A multiplet analysis in ACD/NMR Processor gives: 10

11
1H NMR (500 MHz, CDCl3)  ppm 1.05 (t, J=7.16 Hz, 3 H), 1.25 15
(ddd, J=10.49, 3.70, 2.59 Hz, 1 H), 1.40 - 1.53 (m, 2 H), 1.72 - 1.83
(m, 1 H), 2.17 - 2.28 (m, 1 H), 2.38 - 2.49 (m, 1 H), 2.60 (dd,
20
J=12.34, 9.38 Hz, 1 H), 2.72 (dt, J=12.34, 3.70 Hz, 1 H), 2.95 (dd,
J=12.34, 3.46 Hz, 1 H), 3.86 - 3.98 (m, 2 H). 9 10
25
The methylene pairs are 1, 2/4, 3/5, 7/8, 9/10, and 11. This would
have been a lot easier with a better-resolved HSQC-DEPT! 7 8 30

The carbon at 173.99 is quaternary (the ester).
35
40
6
3 5 45
50
2 4
55
1
60
4.0 3.5 3.0 2.5 2.0 1.5 1.0

Problem 1
Here’s how I annotate COSY spectra. I have bolded the correlations that do not correspond to geminal
couplings (guessed for aliphatic region) and are clear. Parentheses indicate weak couplings.
O
N
H 1 2 3 4 5 6 7 8/9 10 11
1.0
8/9 10 11
1.5
10-
8/9(?)
7 7-
8/9(?) 2.0

6
6-
8/9(?) 5-10
3 4 5
2.5
4-6
3-10
3-5 (2-6)
2
3.0
2-4
3.5
1-11
1
4.0
4.0 3.5 3.0 2.5 2.0 1.5 1.0

Problem 1 Here’s my data table below. At this point, overlap makes the spin systems hard to get at. But we can
use some common sense.
O ID  (1H)  (13C) Hs Type J (Hz) COSY
O
1 3.92 59.84 2 m -- 11
N 2 2.95 48.35 1 dd 12.3, 3.5 4, 6 (w)

H
(1) Entry Points: Start with the obvious. The
ethyl group is 1 and 11, and there’s only one 3 2.72 46.14 1 dt 12.3, 3.7 5, 10
methine in this molecule:
O
4 2.60 48.35 1 dd 12.3, 9.4 2, 6
1
6
O 5 2.43 46.14 1 m -- 3, 10
11
6 2.22 42.20 1 m -- 4, 2 (w)

N
H
7 1.78 27.10 1 m --
(2) Amine: Two sets of downfield, diastereotopic
protons must be adjacent to the amine. These
must be 2/4 and 3/5. There is a clear COSY 8 1.46 27.10 1 m --
correlation between 2 and 6. Therefore, by
process of elimination: 9 1.46 25.27 1 m --
O
10 1.25 25.27 1 ddd 10.5, 3.7, 3, 5
6
2.6
O 11 1.05 13.91 3 t 7.2 1
3/5 2/4
N
H Quaternary Carbons: 173.99
Methylene Pairs: 1, 2/4, 3/5, 7/8, 9/10

Problem 1
N
H 1 2 3 4 5 6 7 8/9 10 11
(3) Aliphatics: We need to distinguish between
1.0
9/10 and 7/8. Note that 10 has COSY
correlations to 3 and 5. (Why is one
correlation stronger than the other?) Thus:
O 1.5
10-
7/8 173.99 8/9(?)
6 1 11
9/10 O 7-
8/9(?) 2.0
3/5 2/4

N 6-
H
(4) Check: Do these assignments make sense 8/9(?) 5-10
2.5
based on chemical shift? ChemDraw 4-6
predictions certainly seem to be congruent 3-10
with the assignments:
3-5 (2-6)
O 3.0
1.98;1.73 4.12 2-4

2.33
1.55;1.45 O 1.30
3.5
2.76;2.73 3.21;2.96
N
H
2.0 1-11
4.0
(5) Check: Do the overlapping correlations make
sense? Yes, they seem to actually be: 7-8
4.0 3.5 3.0 2.5 2.0 1.5 1.0
(geminal), 6/8 (vicinal), and (10-8 and 10-9). F2 Chemical Shift (ppm)
Problem 2
Please assign the proton and carbon resonances of sucrose (500 MHz, D2O).
HO
HO
OH
O
O O OH
HO
HO OH
OH
1.0 1.0 1.1 5.8 1.0 2.0 1.0 1.1
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2
103.74
92.24
81.44
76.39
74.02
72.62
72.45
71.13
69.26
62.43
61.35
60.14
104 102 100 98 96 94 92 90 88 86 84 82 80 78 76 74 72 70 68 66 64 62 60 58
Problem 2
58
60
inset
62
60
64
61
arrows: double 66
62
intensity 68
63
70
64

72
65
74
66
67 76
68 78
69 80
70 82
71
84
72
86
3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 88

90
HMQC 92
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2
Problem 2
COSY-90
3.3
3.4
3.5
3.6
3.7
3.8
3.9
4.0

4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
5.0
5.1
5.2
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3
Problem 2
Numbering the protons requires some careful bookkeeping.
58
8 60
inset
62
10
60 7 64
61
66
62
12 68
63
11 70
64
56

72
65
3
9 74
66
2 76
67
68 78
69 80
4
70 82
71
84
72
86
3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 88

90
1 HMQC 92
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2
Problem 2
COSY-90
4 5-8 9 10 11 12 1 2 3 4 5-8 9 10 11 12
3.3
3.4
9-11 9-12 3.5
3.6
4- 3.7
12-
5-8(?)
5-8(?) 3.8
3
3.9
3-4
4.0

2
2-3 4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
5.0
5.1
1-11
5.2
1
5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3
Problem 2
Here’s some space for your data table:
ID  (1H)  (13C) Hs Type J (Hz) COSY
1
10
11
12
Quaternary Carbons:
Methylene Pairs:
Problem 2
I get this data table:
1 5.22 92.24 1 d 3.9 11
2 4.02 76.39 1 d 8.8 3
3 3.86 74.02 1 t 8.6x2 2, 4
4 3.70 81.44 1 m -- 3
5 3.66 72.45 1 m --
6 3.64 72.45 1 m --
7 3.63 62.43 1 m --
8 3.62 60.14 2 m --
9 3.57 72.62 1 t 9.7x2 11, 12
10 3.48 61.35 2 s S
11 3.36 71.13 1 dd 10.0, 3.9 1, 9
12 3.28 69.26 1 t 9.5x2 9
Quaternary Carbons: 103.74
Methylene Pairs: 5/6, 8, 10

Problem 2
Spin Systems.
Based on chemical shift arguments, 1 is the anomeric proton. It may help if I re-draw sucrose:
HO
O H
HO OH
HO
O OH
OH
O
OH
HO
Because this is a disaccharide, there are two major spin systems (10 is on its own). Here is how I draw them out:
1 = anomeric 2d
The left-hand spin system can be drawn out:
11 dd 3t HO 1
O H
HO 12 OH
HO
11
9t 4m 9 O OH
OH
O
12 t 5/6, 7, or 8 OH
HO
Which of 5/6, 7, or 8 must 12 be connected to?

5/6, 7, or 8
Problem 2
Spin Systems.
1 = anomeric 2d (1) Number of Protons
Note that 12 is connected to a methine. Therefore, it cannot be connected to 5/6 or 8,

and by process of elimination, must be connected to 7.
11 dd 3t
(2) The Other Spin System
Note that proton 2 is a doublet. This can only occur one way in the other spin system
9t 4m
HO 1
7 O
HO 12 H OH
12 t 5/6, 7, or 8 HO
11
9 O OH
OH 4
O
5/6, 7, or 8 2 3 OH
HO
3.50 (3) What about 4?
We must decide if proton 4 is connected to 5/6 or 8. Looking closely at the COSY

3.55
spectrum, it certainly looks like 4 is coupling to the right-hand part of the overlapping
mess. That means we can make a reasonable guess (but not a firm conclusion)
3.60 that it's 8. What steps could you take to confirm this?
3.65
3.70
3.70 3.65 3.60 3.55

Problem 2
Spin Systems. (4) Final Assignments
1 = anomeric 2d HO 5/6 1
7 O
HO 12 H OH
HO
11 10
11 dd 3t 9 O OH
OH 4
O
103.74 2 3 OH
9t 4m 8
HO
It remains only to assign the quaternary carbon (of which there is only one) and the
12 t 5/6, 7, or 8 remaining methylene (also only one left).
Questions you should know the answers to:
5/6, 7, or 8 - Why do all the protons have large couplings except 1?
- Why aren't the hydroxyl protons visible?
- Why was this problem difficult, and what could you have done to make life easier
for yourself?
OH O
solvent: acetone-d6
HO O
OH
naringenin
Please assign this spectrum.
H2O
0.7 0.9 0.9 2.1 2.1 2.0 1.2 1.2 1.1
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
OH O
HO O
OH
naringenin
phenol OH
phenol OH
0.7 0.9 0.9 2.1 2.1 2.0 1.2 1.2 1.1
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
OH O
- number from left to right
HO O
- one number per unique chemical shift
OH
naringenin
5
1 6
4
3 8 9
2
7
0.7 0.9 0.9 2.1 2.1 2.0 1.2 1.2 1.1
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
gHSQC
35
OH O 40
45
HO O 50
OH 55
naringenin
60
65
70
75

80
85
90
95
100
105
110
115
120
125
130
135
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
35
OH O 40
blue = CH2 45
HO O 50
OH - two peaks, same horizontal 55

naringenin line = same carbon = CH2 60
65
70
75

80
85
90
95
100
105
110
115
120
125
130
135
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
35
OH O
integrates to 2H 40
45
HO O 50
OH 55
naringenin symmetry makes 60
these protons 65
equivalent 70
75

80
85
90
95
100
105
110
red = CH 115
120
125
130
135
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
35
OH O 40
45
HO O
integrates to 1H 50
OH 55
naringenin
60
65
integrates to 2H
70
75
red = CH

80
85
90
note: this is two peaks 95
100
105
110
115
120
125
130
135
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
35
OH O 40
x 45
HO O
9 10
50
OH 55
naringenin
60
65
70
8 75

80
85
90
6 95
7 100
105
110
red = CH 115
120
5
125
130
4 -re-numbering is necessary 135
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
OH O
HO O
OH
naringenin
- combine accurate 1D
13C shift data with HSQC
128.74
to generate table
115.88
79.65
43.20
130.50
96.51
196.96
165.01
95.54
115.80
164.09
158.40
102.94
167.00
208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24
OH O Naringenin (500 MHz, acetone-d6)
HO O
1 12.18 -- 1 s* --
2 9.56 -- 1 s* --
OH 3 8.51 -- 1 s* --
naringenin
4 7.40 128.74 2 m --
5 6.91 115.88 2 m --
6 5.97 95.54 1 m --
7 5.96 96.51 1 m --
8 5.46 79.65 1 dd 13.0, 3.0
9 3.19 43.20 1 dd 13.0, 17.1
10 2.74 43.20 1 dd 17.1, 3.0
Quaternary carbons: 196.96, 167.00, 165.01, 164.09, 158.40, 130.50, 102.94
CH2 pairs: 9/10
* exchangeable
5,6
1 7
4
3 9 10
2
8
0.7 0.9 0.9 2.1 2.1 2.0 1.2 1.2 1.1
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
gCOSY
4 5 6,7 8 9 10 2.5
10
3.0
9
9-10 3.5
4.0
- ignore peaks on 4.5

the diagonal
5.0
8
5.5
8-9 8-10
6,7
6.0
6.5
4-5
5
7.0
- number peaks on both axes

4
7.5
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
updated data
Naringenin (500 MHz, acetone-d6)

1 12.18 -- 1 s* -- --
2 9.56 -- 1 s* -- --
3 8.51 -- 1 s* -- --
4 7.40 128.74 2 m -- 5
5 6.91 115.88 2 m -- 4
6 5.97 95.54 1 m -- --
7 5.96 96.51 1 m -- --
8 5.46 79.65 1 dd 13.0, 3.0 9, 10
9 3.19 43.20 1 dd 13.0, 17.1 8, 10
10 2.74 43.20 1 dd 17.1, 3.0 8, 9
CH2 pairs: 9/10
* exchangeable
OH O
spin systems:
HO O
4 m – 5 m; 8 dd – 9/10 dd/dd
OH
naringenin
1 12.18 -- 1 s* --
2 9.56 -- 1 s* --
3 8.51 -- 1 s* --
4 7.40 128.74 2 m --
5 6.91 115.88 2 m --
6 5.97 95.54 1 m --
7 5.96 96.51 1 m --
8 5.46 79.65 1 dd 13.0, 3.0
9 3.19 43.20 1 dd 13.0, 17.1
10 2.74 43.20 1 dd 17.1, 3.0
CH2 pairs: 9/10
* exchangeable geminal = 17.1 196.96
OH O
vicinal = 13.0, 3.0
9,10
spin systems:
HO O
4 m – 5 m; 8 dd – 9/10 dd/dd
- 9/10 can be assigned immediately 8 OH
naringenin
(there’s only one CH2 in the molecule)
1 12.18 -- 1 s* --
2 9.56 -- 1 s* --
3 8.51 -- 1 s* --
4 7.40 128.74 2 m --
5 6.91 115.88 2 m --
6 5.97 95.54 1 m --
7 5.96 96.51 1 m --
8 5.46 79.65 1 dd 13.0, 3.0
9 3.19 43.20 1 dd 13.0, 17.1
10 2.74 43.20 1 dd 17.1, 3.0
CH2 pairs: 9/10
* exchangeable 196.96
OH O
9,10
spin systems: 6, 7
HO O
4 m – 5 m; 8 dd – 9/10 dd/dd 4, 5
- by elimination, 4 and 5 are on the mono-phenol 8 OH
naringenin
- however, order is unclear
- 6/7 must be on the bis-phenol
gHMBC
OH O OH O 40
1 1
H H 48
13
C 56
HO O HO O
13
C 1-bond 64
OH OH
one-bond peak three-bond peak
peak 72
80
88
1-bond and 96
n-bond peaks 104

indicates 112
symmetry 120
128
136
144
152
160
168
176
note: couplings to carbons are usually sp2 184
3-bond because 2JCH is small 192
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0
gHMBC:
carbonyl region
6,7 8 9 10 189
OH O 190
191
HO O
OH
192
193
194

195
196
196.96 197
198
long-range (>3 bond
correlations) OH O 199
13 1
C H
200
HO O
201
OH
6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5

4 5 6,7 8 9 10
71
OH O
72
HO O 73
OH
74
8 75
76

77
78
79
79.65 80
HSQC 81
82
8 4-79.65 83
84
85
86
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
4 5 6,7 8 9 10
71
OH O
72
HO O 73
OH
74
OH O OH O 75
76
1
H
13 1

13 C H
C 77
HO O HO O
4/5 4/5 78
OH OH
79
three bonds four bonds
79.65 80
OH O
4 81
H
5 82
H
HO O
83
OH 84
proton 4 must be ortho to 85

carbon at 79.65 ppm
86
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5
HMBC
1 2 3 4 5 111.5
112.0
112.5
113.0
OH O
113.5
114.0
HO O
114.5
OH 115.0

115.5
116.0
115.88 5
116.5
117.0
HSQC
117.5
118.0
5 118.5
119.0
119.5
120.0
- HMBC can be used to assign OH protons 120.5
12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0
HMBC
1 2 3 4 5 111.5
112.0
112.5
113.0
113.5
OH O 114.0
114.5
115.0

115.5
13
HO O C 116.0
115.88 1
H 116.5
O
3 3-115.88 117.0
117.5
118.0
118.5
119.0
119.5
120.0
120.5
12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0
HMBC
1 2 3 4 5 111.5
112.0
112.5
OH O 113.0
4 113.5
H 114.0
5
H 114.5
HO O 115.88
115.0

H 3
O 115.5
116.0
115.88 116.5
117.0
117.5
118.0
can you explain these correlations? 118.5
119.0
119.5
120.0
120.5
12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0
HMBC
1 2 3 4 5 111.5
OH O 112.0
H 112.5
5
H
HO O 113.0
OH O
4 OH 113.5
H
114.0
HO O 115.88
114.5
OH
115.0

115.5
116.0
115.88 116.5
117.0
OH O 117.5
H 118.0
5
H 118.5
HO O
119.0
OH
115.88 119.5
120.0
120.5
12.5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0
80
how can the 85

remaining ipso what are the relevant
90
carbons be assigned? correlations in this region?
95
100
105
110

115
OH O 120
4 125
H
5 130
H
HO O 135
3 140
? OH
145
150
? 155
160
8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7
3 4 5
8 80
OH O 85
4 90
H
5 95
H
HO O 8 100
105
3
OH 110

5 115
120
125
4
130.50 130
135
140
145
150
155
158.40 160
8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7
3 4 5
8 80
OH O 85
90
5
H
OH O HO O 95
130.50 OH
H4
100
3
HO O JCH is large
105
130.50 OH
110
2
JCH is small

5 115
120
125
4
130.50 OH O
130
correlation 135
HO O 3 missing 140
H
O 145
158.40
150
155
158.40 160
8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7
40
9 10
48
56
64
72
8 80
88
96
102.94 104

112
120
128
130.50 OH O 196.96
136
9/10 144
152
160
HO O 8 168
130.50 OH
176
184
192
196.96
3.45 3.40 3.35 3.30 3.25 3.20 3.15 3.10 3.05 3.00 2.95 2.90 2.85 2.80 2.75 2.70 2.65 2.60 2.55 2.50
40
9 10
48
56
64
72
8 80
88
96
102.94 104

112
102.94 120
128
130.50 OH O 196.96
136
H 144
9/10
152
HO O 8 160
168
130.50 OH 176
184
192
196.96
3.45 3.40 3.35 3.30 3.25 3.20 3.15 3.10 3.05 3.00 2.95 2.90 2.85 2.80 2.75 2.70 2.65 2.60 2.55 2.50
6, 7
95
100
105
110
115
6, 7 – 102.94
102.94 120

125
OH O
H 130
135
HO O 140
H 145
OH
150
confirmation of assignment 155
160
165
6.10 6.05 6.00 5.95 5.90 5.85 5.80

1 2
7 7/96.51 95
6 1
H 100
102.94 O O
7H 105
2-95.54
96.51 HO O 2-96.51 110
OH 115
120

OH O 96.51 OH O 125
7H
1-102.94 2H O O 2H O O
130
102.94 H6 135
H 95.54 OH OH
1 O O 140
145
HO O
150
OH
155
160
165
12.0 11.5 11.0 10.5 10.0 9.5

1 2
6 95
7 102.94 100
102.94 1
105
OH O
110
7
115
120
HO O

2 6 125
1-165.01 OH 130
three phenolic ipso 135
carbons remain unassigned: 140
167.00, 165.01, 164.09

145
150
-these correlations are
still difficult to interpret 155
160
1-167.00 (long-range?)
165
12.0 11.5 11.0 10.5 10.0 9.5

162.5
163.0
163.5
164.0
6-164.09
164.5
165.0

7-165.01 165.5
166.0
166.5
7-167.00 167.0
167.5
168.0
168.5
-raising contour level

169.0
deconvolutes peaks
6.01 6.00 5.99 5.98 5.97 5.96 5.95 5.94 5.93 5.92 5.91 5.90 5.89
102.94 162.5
1
OH O 163.0
from previous slide: 7 163.5
164.0
6-164.09 HO O
2 6 164.5
OH
165.0
1-165.01 three phenolic ipso

7-165.01 carbons remain unassigned: 165.5
167.00, 165.01, 164.09

166.0
166.5
1-167.00 (weak) 7-167.00 2-167.00 (weak) 167.0
167.5
168.0
raising contour level 168.5
shows this peak 169.0
6.01 6.00 5.99 5.98 5.97 5.96 5.95 5.94 5.93 5.92 5.91 5.90 5.89
162.5
1 102.94
163.0
165.01 H
O O
7
H 163.5
164.0
HO O
6-164.09 2 6
167.00 164.09 OH 164.5
165.0
1-165.01

7-165.01 165.5
166.0
166.5
1-167.00 (weak) 7-167.00 2-167.00 (weak) 167.0
167.5
168.0
168.5
169.0
6.01 6.00 5.99 5.98 5.97 5.96 5.95 5.94 5.93 5.92 5.91 5.90 5.89
Observed vs. Predicted Chemical Shifts – ACD/Labs NMR Predictor (v6)
8 ID Obsvd.  Calcd.  Obsvd.  Calcd. 
(1H, ppm) (1H, ppm) (13C, ppm) (13C ppm)
7 1 12.18 9.87 -- --
2 9.56 9.87 -- --
predicted chem ical shift (ppm )
3 8.51 9.87 -- --
6
4 7.40 7.38 128.74 128.58
5 6.91 6.90 115.88 115.68
5 6 5.97 6.20 95.54 95.63
7 5.96 6.19 96.51 96.31
4 8 5.46 5.44 79.65 79.26
9 3.19 3.18 43.20 42.81
10 2.74 2.72 43.20 42.81
3
y = 1.0153x - 0.0278 196.96 196.76
2
R = 0.9979 167.00 167.20
2 165.01 164.32
2 3 4 5 6 7 8
164.09 163.67
observed chemical shift (ppm)
158.40 158.18
200 130.50 129.85
180 102.94 102.39
predicted chemical shift (ppm)
160 Overall Assignments: -exchangeable peaks

140
1 102.94 not predicted well
196.96
120 165.01 H -otherwise, excellent
O O
100 7
H
agreement
9/10
4 -DFT methods can also
80
HO O 8 5 be used, but their
60 2 6 3
y = 1.0006x - 0.3724
OH
implementation can
2
R =0.99996 167.00 164.09
40 be tricky
40 60 80 100 120 140 160 180 200 130.50
observed chemical shift (ppm)
158.40
Molecular Modelling
B3LYP/6-31g(d)
- two possible ground-state conformers ID  (1H)  (13C) Hs Type J (Hz)
1 12.18 -- 1 s* --
OH O 2 9.56 -- 1 s* --
3 8.51 -- 1 s* --
9/10 4 7.40 128.74 2 m --
5 6.91 115.88 2 m --
HO O 8 6 5.97 96.51 1 m --
7 5.96 95.54 1 m --
OH 8 5.46 79.65 1 dd 13.0, 3.0
9 3.19 43.20 1 dd 13.0, 17.1
10 2.74 43.20 1 dd 17.1, 3.0
rel G: +2.7 kcal/mol rel G: +0.0 kcal/mol
observed coupling (Hz)
dihedral (8-C-C-9): 47.2 (13.0) dihedral (8-C-C-9): 177.8 (13.0)

dihedral (8-C-C-10): 71.0 (3.0) dihedral (8-C-C-10): 59.5 (3.0)
Problem 4
An unknown compound of molecular weight 348 has the spectral data shown below. A singlet near
3.2 ppm disappears on D2O addition. Please deduce its molecular formula, skeletal connectivity,
assignments, and relative stereochemistry (show key ROESY correlations).
ID  (1H)  (13C) Hs Type J (Hz) COSY Key HMBC Key ROESY

1 5.20 73.1 1 t 9.5x2 3, 2 170.4 4, 7
2 5.08 68.7 1 t 9.5x2 1, 7 169.6 3
3 4.96 71.6 1 dd 9.5, 8.0 4, 1 169.4 2
4 4.59 99.8 1 d 8.0 3 1, 7
5 4.26 62.3 1 dd 12.3, 4.9 6, 7 170.8 7
6 4.11 62.3 1 dd 12.3, 2.5 5, 7 170.8 7
7 3.68 71.8 1 m -- 2, 5, 6 1, 4, 5, 6
8 ~3.2 -- 1 br s -- --
9 2.08 20.95 3 s -- -- 170.8
10 2.05 20.90 3 s -- -- 169.4
11 2.02 20.79 3 s -- -- 169.6
12 2.00 20.83 3 s -- -- 170.4
Quaternary Carbons: 170.8, 170.4, 169.6, 169.4
Molecular formula:
Problem 4

1 5.20 73.1 1 t 9.5x2 3, 2 170.4 4, 7
2 5.08 68.7 1 t 9.5x2 1, 7 169.6 3
3 4.96 71.6 1 dd 9.5, 8.0 4, 1 169.4 2
4 4.59 99.8 1 d 8.0 3 1, 7
5 4.26 62.3 1 dd 12.3, 4.9 6, 7 170.8 7
6 4.11 62.3 1 dd 12.3, 2.5 5, 7 170.8 7
7 3.68 71.8 1 m -- 2, 5, 6 1, 4, 5, 6
8 ~3.2 -- 1 br s -- --
9 2.08 20.95 3 s -- -- 170.8
10 2.05 20.90 3 s -- -- 169.4
11 2.02 20.79 3 s -- -- 169.6
12 2.00 20.83 3 s -- -- 170.4
Molecular formula:
Hints
• Entry Point: Methyl Groups

Every methyl group has an HMBC correlation to a quaternary carbon. What functional group does this represent? What
do the chemical shifts of 9-12 signify?
(2) Spin Systems

What are the spin systems in this molecule?
Problem 4

1 5.20 73.1 1 t 9.5x2 3, 2 170.4 4, 7
2 5.08 68.7 1 t 9.5x2 1, 7 169.6 3
3 4.96 71.6 1 dd 9.5, 8.0 4, 1 169.4 2
4 4.59 99.8 1 d 8.0 3 1, 7
5 4.26 62.3 1 dd 12.3, 4.9 6, 7 170.8 7
6 4.11 62.3 1 dd 12.3, 2.5 5, 7 170.8 7
7 3.68 71.8 1 m -- 2, 5, 6 1, 4, 5, 6
8 ~3.2 -- 1 br s -- --
9 2.08 20.95 3 s -- -- 170.8
10 2.05 20.90 3 s -- -- 169.4
11 2.02 20.79 3 s -- -- 169.6
12 2.00 20.83 3 s -- -- 170.4
(2) Spin Systems

What are the spin systems in this molecule?
5 dd/6 dd 7m 2t 1t 3 dd 4d
Apart from 5/6, everything is a methine.
(3) Connect Fragments

From the HMBC, note that: 5 dd/6 dd 7m 2t 1t 3 dd 4d
HMBC
O O O O
170.8 169.6 170.4 169.4
X Me X Me X Me X Me
9 11 12 10
Problem 4

1 5.20 73.1 1 t 9.5x2 3, 2 170.4 4, 7
2 5.08 68.7 1 t 9.5x2 1, 7 169.6 3
3 4.96 71.6 1 dd 9.5, 8.0 4, 1 169.4 2
4 4.59 99.8 1 d 8.0 3 1, 7
5 4.26 62.3 1 dd 12.3, 4.9 6, 7 170.8 7
6 4.11 62.3 1 dd 12.3, 2.5 5, 7 170.8 7
7 3.68 71.8 1 m -- 2, 5, 6 1, 4, 5, 6
8 ~3.2 -- 1 br s -- --
9 2.08 20.95 3 s -- -- 170.8
10 2.05 20.90 3 s -- -- 169.4
11 2.02 20.79 3 s -- -- 169.6
12 2.00 20.83 3 s -- -- 170.4
(4) Esters: From chemical shift arguments, these are acetates, no methyl esters or methyl ketones. Also, every proton in
the major spin system is on an oxygen. Thus, we have:
169.6 169.4
OAc OAc
5 dd/6 dd 2t 3 dd
OR
AcO
7m 1t 4d
170.8
OR OAc X
170.4
This looks a lot like a sugar!

Problem 4

1 5.20 73.1 1 t 9.5x2 3, 2 170.4 4, 7
2 5.08 68.7 1 t 9.5x2 1, 7 169.6 3
3 4.96 71.6 1 dd 9.5, 8.0 4, 1 169.4 2
4 4.59 99.8 1 d 8.0 3 1, 7
5 4.26 62.3 1 dd 12.3, 4.9 6, 7 170.8 7
6 4.11 62.3 1 dd 12.3, 2.5 5, 7 170.8 7
7 3.68 71.8 1 m -- 2, 5, 6 1, 4, 5, 6
8 ~3.2 -- 1 br s -- --
9 2.08 20.95 3 s -- -- 170.8
10 2.05 20.90 3 s -- -- 169.4
11 2.02 20.79 3 s -- -- 169.6
12 2.00 20.83 3 s -- -- 170.4
In fact, it is acetylated glucose. Note the large trans di-axial couplings. Here are the assignments and key ROE correlations:
5/6 8 7 4
O OH
AcO 1
7 4
9 AcO
O OH
1
AcO 2 3 OAc AcO OAc
11 10
OAc OAc
12
2 3

Lecture 3: 2D NMR Spectroscopy 2D NMR Spectroscopy: Chem 135

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Lecture 3: 2D NMR Spectroscopy 2D NMR Spectroscopy: Chem 135

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E.

Kwan Lecture 3: 2D NMR Spectroscopy Chem 135

preparation evolution mixing detection

Scope of Lecture (1) Preparation: Some sequence of pulses is used to generate

The entire experiment generates a 2D data matrix. Fourier

(Red = negative contour; black = positive countour)

If this is the case, we can present the data in a phase-sensitive

F1 Chemical Shift (ppm)

(3) COSY-45 is slightly less sensitive than COSY-90 (by about

COSY-45 is the best absolute value COSY experiment for

(source: Claridge, pg 140) The long tails from the dispersive

This has several important consequences:

(1) The diagonal is compressed. Since we don't care about the

One post-acquisition strategy that is sometimes used to

For an inverse-detected experiment, we see carbons that

one-bond (direct) multiple-bond (remote)

Conversely, for a direct-detection experiment, we see protons

one-bond (direct) multiple-bond (remote)

(1) Spreading Out: The 1D

F1 Chemical Shift (ppm)

3.5 3.0 2.5 2.0 1.5 1.0 0.5

B - only give a number for each A

Structural Elucidation Workflow (2) Tabulate the Data.

- peaks are listed by number from high to low chemical shift

2 however, both partners of a methylene pair may not show

4.0 3.5 3.0 2.5 2.0 1.5 1.0

O ID  (1H)  (13C) Hs Type J (Hz) COSY

F1 Chemical Shift (ppm)

4.0 3.5 3.0 2.5 2.0 1.5 1.0

F1 Chemical Shift (ppm)

4.0 3.5 3.0 2.5 2.0 1.5 1.0

A multiplet analysis in ACD/NMR Processor gives: 10

F1 Chemical Shift (ppm)

4.0 3.5 3.0 2.5 2.0 1.5 1.0

F1 Chemical Shift (ppm)

4.0 3.5 3.0 2.5 2.0 1.5 1.0

N 2 2.95 48.35 1 dd 12.3, 3.5 4, 6 (w)

6 2.22 42.20 1 m -- 4, 2 (w)

Methylene Pairs: 1, 2/4, 3/5, 7/8, 9/10

F1 Chemical Shift (ppm)

1.98;1.73 4.12 2-4

1.0 1.0 1.1 5.8 1.0 2.0 1.0 1.1

F1 Chemical Shift (ppm)

F1 Chemical Shift (ppm)

3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 88

F1 Chemical Shift (ppm)

F1 Chemical Shift (ppm)

F1 Chemical Shift (ppm)

3.65 3.60 3.55 3.50 3.45 3.40 3.35 3.30 88

F1 Chemical Shift (ppm)

2 4.02 76.39 1 d 8.8 3

3 3.86 74.02 1 t 8.6x2 2, 4

9 3.57 72.62 1 t 9.7x2 11, 12

11 3.36 71.13 1 dd 10.0, 3.9 1, 9

12 3.28 69.26 1 t 9.5x2 9

Quaternary Carbons: 103.74

Methylene Pairs: 5/6, 8, 10

Which of 5/6, 7, or 8 must 12 be connected to?

Note that 12 is connected to a methine. Therefore, it cannot be connected to 5/6 or 8,

3.50 (3) What about 4?

We must decide if proton 4 is connected to 5/6 or 8. Looking closely at the COSY

3.70 3.65 3.60 3.55