Problem 1.

The addition of lithium dimethylcuprate to an alkyne produced a mixture of E and Z isomers which were
separated by HPLC. Please assign the resonances in the spectra below and determine which isomer is which.

4
Me 11
8 10 Si
3 5 O
9 12
2 6
N O Ph
1
O 7
O

5H 1H 2H 2H 2H 2H 1H 3H 4H 9H 6H

5H 1H 2H 3H 2H 2H 3H 4H 9H 6H

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
500 MHz, CDCl3
 4
Me 11
8 10 Si
3 5 O
9 12
2 6
N O Ph “normal” allylic
1
O 7 proton shift
O

E isomer
5H 1H 2H 2H 2H 2H 1H 3H 4H 9H 6H
allylic proton:
downfield due to
A(1,3) strain

Z isomer
5H 1H 2H 3H 2H 2H 3H 4H 9H 6H

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0
Chemical Shift (ppm)
500 MHz, CDCl3
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Types of Structural Determination Problems Here is a hypothetical spectrum:
(1) Spectral Assignment 1 2 3 4 5

- given a structure and a spectrum, verify that the spectrum

matches the compound and assign all of the peaks to integrals: 1H 2H 1H 1H 
atoms in the molecule
(a) Adopt the convention of labeling the peaks from left to right.
- real world scenario: reaction product analysis
This gives you a unique name for every resonance.
(2) Unknown Structural Elucidation
(b) Mass Balance: Are there the right number of protons and
carbons?
- given the spectra of an unknown compound, determine its
structure and then assign of its peaks
(c) Start with the HSQC: Sometimes, the peaks will overlap.
- real world scenario: novel natural product, unexpected
Use the HSQC to uniquely label every proton, as well as
outcome of a reaction
determine direct attachments between protons and carbons:
Workflow
These steps apply to both problems.

13
(0) Compound Purity xx

C axis
2
Has the compound been purified to the best of your ability? xx
Is the baseline of the proton spectrum clean? Dirty spectra 3
are hard to interpret and can make conclusions difficult to 1
H axis
draw. Consider semi-preparative HPLC or preparative TLC
prior to analysis. (Elemental analysis remains the gold Here, peaks 2 and 3 overlap in the proton spectrum, but the
standard of purity. A high resolution mass "hit" does not greater chemical shift range of the carbon axis disperses the
guarantee any level of purity.) peaks so that they can be distinguished.

(1) Data Acquisition (d) Multiplicity: HSQC phase gives DEPT information. Red/up=
CH or CH3; blue/down=CH2. Write down all the methylene
- 1D spectra: proton, carbon (optional) pairs for reference. These will help you distinguish geminal
- 2D spectra: COSY-45, HSQC, HMBC coupling from vicinal or long-range couplings in the COSY.
- of course, not all of these data will be necessary for
simpler compounds (e) Quaternary carbons: These do not appear in the HSQC, but
should appear in the carbon or HMBC. Isolated, but clearly
(2) Tabulate Data resolved peaks are often excellent "entry points" for analysis.
Make a list of these carbons.
- make it a habit to tabulate the data before analysis to avoid
confirmation bias (f) Be methodical and double-check everything.
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Workflow (3) Generate Spin Systems
(2) Tabulate Data - Use COSY to build up spin systems. Each "component" of
(d) Multiplicity 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 6 7
xx xx 4/5 is a methylene pair.
4 5 3
long-range coupling
(g) Bookkeeping: Here is the format I use. A similar format is (You might not know which ones are long-range. Use your
used in many natural products papers. chemical intuition and look at the peak intensities and
asymmetry about the diagonal. You might have to change
ID (1H) (13C) Hs type J (Hz) COSY HMBC your diagram if you find it to be inconsistent later.)
(4) Connect Spin Systems
1 5.76 145.23 1 d 5.1 2 152.12
Look for HMBC correlations that connect a proton in one
2 3.76 72.45 1 d 5.1 1,3 32.47 spin system to a carbon in another spin system:
145.23 33.37
3 3.47 -- 1 br s -- -- 202.57
... etc ...
4/5 8 1 2 6 7 3
Quaternary Carbons: 35.57, 54.32, 202.57...
CH2 pairs: 4/5, ...
Curved arrows indicate HMBC correlations. If you find such
a connection, that tells you that the spin systems must be
- peaks are listed by number from high to low chemical shift
adjacent in the head-to-tail sense shown. Note that these
- HSQC: connect each proton to its directly attached carbons;
do not have to be mutual like COSY couplings:
find methylene pairs
finding this H H H H
- COSY: if 1 is coupled to 2, then check that 2 is coupled to 1; does not will be
however, both partners of a methylene pair may not show HMBC C C C C C C
mean present
couplings to a common partner (peak 3) correlation
- exchangeable protons do not appear in the HSQC If that doesn't work, you can look for a carbon, possibly
- quaternary carbons can be found from HMBC or the 1D quaternary, that protons in both spin systems have common
spectrum carbon HMBC correlations to: 35.57
- HMBC: watch for one-bond peaks; more intense peaks like
methyl groups are more likely to show long-range correlations;
sp2 systems: 2J is small, but 3J is large (bigger for anti than syn) 4/5 8 1 2 6 7 3
 exchangeable

1 2 3 4 5 H2O 6 7 8 9-12 13 14

3.45 3.35 2.0 1.5 1.0

Chemical Shift (p... Chemical
Chemical Shift (ppm) Shift (ppm)
HSQC Spectrum

11 14
CH or CH3 16

(CH2)
2 (5) (9) 24
12
6

F1 Chemical Shift (ppm)

32
(4) (13)

40

(3) 8 (10)
48

56

64
1

3.5 3.0 2.5 2.0 1.5 1.0 0.5

F2 Chemical Shift (ppm)
HMBC

1 2 3 4 5 6 7 8

16

24

F1 Chemical Shift (ppm)

32

40

48

56

64

72

3.5 3.0 2.5 2.0 1.5 1.0 0.5

F2 Chemical Shift (ppm)

- arrows indicate one-bond peaks

- these artifacts appear as doublets in proton dimension
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Workflow (6) Entry Points
(5) Generate Fragments
When you look at a COSY or HMBC spectrum, you will see a
In many cases, complex, overlapping signals will prevent you lot of peaks. Where should you start generating fragments
from drawing out all the spin systems of the molecule. In from? In general: clearly resolved peaks with unambiguous
particular, unknown structural elucidations will require you to or characteristic chemical shifts. Here are some ideas:
generate and connect fragments, which are tied together by
what is visible in a spin system and HMBC. Here is how I put - carbonyl region - aromatic rings and olefins
together menthol, which has some overlapping signals and one - methyl groups - quaternary carbons
continuous spin system:
Vicinal COSY Key HMBC (7) Expand and Connect Fragments
Fragment Structures
Correlations Correlations
2, 25.82 Don't bite off too much at a time. Make a small fragment with
11-2 2-14 11-14
H H correlations you feel confident in assigning. Then, move on
H3C CH3 H3C CH3 H3C CH3
to another entry point and generate another fragment.
11, 21.00 14, 16.07 2-8 14-8
11-2 Fragments with uncertain correlations are hard to use. Once
X X X X X X you have exhausted all the easy data, work on what's left to
H H expand your existing fragments, and if possible, connect them.
8, 50.12
Key Evidence
- methyls 11, 14: COSY to 2 - HSQC: 2, 8 = CH HO X HO
- 2: COSY to 8 5-13, 9-4
- 11, 14: mutual HMBC CH2X
- 11, 14: HMBC to 2, 8 6 4, 13, 34.51
CH3
12, 22.10 - COSY, HMBC correlations
- HMBC: double-headed arrows to indicate mutual correlations; connect termini
single-headed arrows to indicate a one-way correlation (8) List Full Assignments
- if you feel comfortable, you can write "11-2" instead of "11- This is self-explanatory:
25.82" to speed things up, but remember, HMBC correlations
are from protons to carbons 14 2 11 16.07 21.00
25.82
- Xs represent non-protons HO 50.12
7 HO 1
8 5, 9 23.10
71.53
Write down your reasoning (even though it's boring). By 3, 10 6 4, 13 45.03 34.51
their nature, these problems are very complicated, and there's a 31.62
99.9% chance you will not remember what peak is at 16.07 ppm 12 22.10
several years from now. If you write down what you were
thinking, you and others will be able to follow your process later You should also file all the FIDs and your "good" notes of what
on without repeating the entire analysis. It's also likely you will you've done in the same place. If you feel the compound will go
make some mistakes, which will be easier to track down this way. into your thesis, take the time to write it out in journal format.
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Workflow My spectrum looks nice, but the peaks overlap.
(9) Check Answer
Are any multiplets or even parts of multiplets exposed? Try
- Is your flat structure consistent with all of the NMR data?
- Are there any other possibilities? changing the solvent (benzene titration?) first. Then, try
1D-TOCSY with a variety of mixing times to deconvolute the
(10) Interpret Relative Stereochemistry spectrum.

- H,H coupling constants I don't have a lot of sample.

- nOe/rOe correlations
- (C,H) coupling constants Did you set the experimental parameters correctly? Did you
- render structures in 3D and highlight diagnostic data tune the probe and calibrate the pulse widths? These will make
- details: see Lecture 9 a substantial difference.
Troubleshooting
Try a Shigemi tube. Tubes with plugs of different magnetic
My proton spectrum looks bad. susceptibilities are available. Samples in these expensive tubes
will be hard to shim, but have about double the S/N. These are
Do you have paramagnetic ions, particulates, or other nice for getting carbon-13 spectra. You can also try a smaller
impurities? Purify your compound by flash chromatography or diameter tube (but you have to have the right spinner and probe.)
HPLC, or at least filter it through some cotton. A very pure
0.5 mg is preferable to a dirty 5 mg. Desperate? Try a cryo-probe at higher field strengths.
Is the sample volume correct? Samples that are too short are My sample has a lot of solvent in it.
difficult to shim.
Did you use a deuterated solvent? (Duh.) Co-evaporation of
Is this a S/N issue? If you have <0.5 mg, a detailed 2D NMR your sample with (regular) chloroform helps. If that's not
analysis with standard equipment will be very difficult. You will enough, try heptane or toluene (may require higher vacuum).
save time by going back to make more sample first.
Remember, a lot of these experiments depend on the I have nice data, but I don't understand it.
observation of carbon-13 satellites, which are very small!
Did you check your data table? One mistake can make the data
Are you in the intermediate exchange regime? Try changing unintelligible or give a ridiculous answer. Is everything
the temperature or field strength (higher or lower). Try consistent?
changing from CDCl3 to d6-DMSO.
Try another angle. Have a coffee (or a beer) and start from a
Is this a shimming issue? Is your NMR tube bad? Try another new entry point. Try having someone else look at the data.
tube. Try recalling the default shims and manually shimming. Just don't try the same strategy over and over. Rethink your
Try using the gradient autoshim on deuterium-gradient-enabled assumptions. Above all, think about the chemistry. Where
spectrometers, followed by simplex autoshimming. Turn the did the compound come from? What is its reactivity?
spin off and adjust the XY shims as well.
courtesy Prof. Andy Phillips (Yale)
courtesy Prof. Andy Phillips (Yale)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
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
Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
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:
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
This is the HMQC spectrum. Please number the protons. What are the methylene pairs in this
O molecule? Are there any quaternary carbons?
O

N
H

10

15

20

25

30

F1 Chemical Shift (ppm)

35

40

45

50

55

60

4.0 3.5 3.0 2.5 2.0 1.5 1.0

F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
This is the COSY spectrum. Try to label the off-diagonal peaks.
O

N
H

1.0

1.5

2.0

F1 Chemical Shift (ppm)

2.5

3.0

3.5

4.0

4.0 3.5 3.0 2.5 2.0 1.5 1.0

F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
The numbering I get is shown below.
O

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

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
Here’s how I annotate COSY spectra. I have bolded the correlations that do not correspond to geminal
O 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

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2 Here’s my data table below. At this point, overlap makes the spin systems hard to get at. But we can
O use some common sense.
ID  (1H)  (13C) Hs Type J (Hz) COSY
O
1 3.92 59.84 2 m -- 11
N
H
2 2.95 48.35 1 dd 12.3, 3.5 4, 6 (w)
(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

E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 2
O

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

F1 Chemical Shift (ppm)

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)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
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
Chemical Shift (ppm)
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
Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
Please assign the proton and carbon resonances of sucrose (500 MHz, D2O).

58

60
inset
62

60
64
61
arrows: double 66
62
intensity 68
63
70
64

F1 Chemical Shift (ppm)

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
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
F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3

COSY-90

3.3

3.4

3.5

3.6

3.7

3.8

3.9

4.0

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
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

F1 Chemical Shift (ppm)

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
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
F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3

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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
Here’s some space for your data table:
ID  (1H)  (13C) Hs Type J (Hz) COSY
1

10

11

12

Quaternary Carbons:

Methylene Pairs:
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
I get this data table:
ID  (1H)  (13C) Hs Type J (Hz) COSY
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

E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
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
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
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
F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 3
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
Chemical Shift (ppm)
 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
Chemical Shift (ppm)
 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
Chemical Shift (ppm)
gHSQC

35

OH O 40

45

HO O 50

OH 55
naringenin
60

65

70

75

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 35

OH O
integrates to 2H 40

45

HO O 50

OH 55
naringenin symmetry makes 60
these protons 65

equivalent 70

75

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 35

OH O 40

45

HO O
integrates to 1H 50

OH 55
naringenin
60

65
integrates to 2H
70

75

red = CH

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 35

OH O 40
x 45

HO O
9 10
50

OH 55
naringenin
60

65

70

8 75

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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
Chemical Shift (ppm)
 OH O Naringenin (500 MHz, acetone-d6)
ID  (1H)  (13C) Hs Type J (Hz) COSY
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
Chemical Shift (ppm)
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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 updated data

Naringenin (500 MHz, acetone-d6)

ID  (1H)  (13C) Hs Type J (Hz) COSY
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
Quaternary carbons: 196.96, 167.00, 165.01, 164.09, 158.40, 130.50, 102.94
CH2 pairs: 9/10
* exchangeable
OH O

spin systems:
HO O
4 m – 5 m; 8 dd – 9/10 dd/dd
OH
naringenin
Naringenin (500 MHz, acetone-d6)
ID  (1H)  (13C) Hs Type J (Hz) COSY
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
Quaternary carbons: 196.96, 167.00, 165.01, 164.09, 158.40, 130.50, 102.94
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)
 Naringenin (500 MHz, acetone-d6)
ID  (1H)  (13C) Hs Type J (Hz) COSY
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
Quaternary carbons: 196.96, 167.00, 165.01, 164.09, 158.40, 130.50, 102.94
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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
gHMBC:
carbonyl region
6,7 8 9 10 189

OH O 190

191
HO O

OH
192

193

194

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
 4 5 6,7 8 9 10
71
OH O
72

HO O 73

OH
74

8 75

76

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
HMBC

1 2 3 4 5 111.5

112.0

112.5

113.0

113.5

OH O 114.0

114.5

115.0

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 80

how can the 85

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

100

105

110

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 3 4 5
8 80

OH O 85

4 90

H
5 95

H
HO O 8 100

105
3
OH 110

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 40
9 10
48

56

64

72

8 80

88

96

102.94 104

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 40
9 10
48

56

64

72

8 80

88

96

102.94 104

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 6, 7

95

100

105

110

115
6, 7 – 102.94
102.94 120

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
 1 2

6 95

7 102.94 100

102.94 1
105
OH O
110

7
115

120
HO O

F1 Chemical Shift (ppm)

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

F2 Chemical Shift (ppm)
 162.5

163.0

163.5

164.0
6-164.09
164.5

165.0

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
 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

F1 Chemical Shift (ppm)

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
F2 Chemical Shift (ppm)
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)
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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:
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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:

Hints

(1) 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?
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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

(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
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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

(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!

E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
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

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
E. Kwan Lecture 8: Solving Structural Determination Problems Chem 117
Problem 5
Me O O
KHMDS
O ?
O THF, rt
OTBS LR-ESI-MS: 389.2
O N O

Please deduce the flat structure of the byproduct.

NMR Data (500 MHz, 45% CDCl3 in C6D6)

ID  (1H)  (13C) Hs Type J (Hz) COSY-45 Key HMBC NOE
1 5.66 131.5 1 m -- 2, 3, 4
2 5.13 119.0 1 dd 17.1, 1.5 1, 3, 4
3 5.02 119.0 1 dd 10.5, 1.2 1, 2
4 4.39 66.1 2 m -- 1, 2 119.0, 131.5, 168.2
5 3.80 56.6 1 d 2.4 10 41.3, 43.9, 71.2, 168.2, 200.5 11
6 3.61 71.2 1 dd 9.0, 3.2 9, 11 56.6 10
7 3.10 63.2 1 t 2.9x2 9, 11 71.2, 200.5, 203.4
8 2.81 43.9 1 d 19.5 10 20.5, 41.3, 56.6, 203.4
9 1.94 34.2 1 ddd 14.6, 9.3, 2.9 6, 7, 11 63.2, 200.5
10 1.76 43.9 1 dd 19.5, 2.0 5, 8 20.5, 41.3, 56.6, 71.2, 203.4 6
11 1.52 34.2 1 dt 14.6, 2.9x2 6, 7, 9 71.2, 203.4 5
12 0.94 20.5 3 s -- -- 41.3, 43.9, 56.6, 71.2
13 0.81 25.9 9 s -- -- 25.7
14 -0.10 -4.5 6 d -- -- --
Quaternary Carbons: 200.5, 203.4, 168.2, 41.3, 25.7; IR: three carbonyls present