Using 2D NMR

1
Using 2D NMR

• Strategy

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THE PROCESS OF STRUCTURE ELUCIDATION
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DEREPLICATION The process of rapidly discovering
whether a compound has previously been reported.
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STRATEGY BASED ON C-C CONNECTIVITY
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STRATEGY BASED ON C-C CONNECTIVITY PROBLEMS

• Based on 13C-13C correlations 1/10 000 chance
• Need large amounts of sample
• Sample must have high solubility
• Need long acquisition times (gt24 h)
• Correlations across heteroatoms not possible
  these must be determined using HMBC data
• Gives no information about C-H correlations
  need to get HSQC data to assign protons
• BUT If possible to use INADEQUATE, connectivity
  information is unambiguous (unlike HMBC)

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STRATEGY BASED ON C-C CONNECTIVITY EXAMPLE
F-B
C-E
A-D
D-C
A-B
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STRATEGY BASED ON C-C CONNECTIVITY EXAMPLE
E
B
A
D
C
F
Gives topology of molecule
Chemical shift information gives
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STRATEGY BASED ON C-C CONNECTIVITY REAL EXAMPLE
G-O
H-N
I-J
E-M E-L
G-H
C-N
D-J
D-G F-D
A-K
B-F
E-C
B-E
D-C
A-I
A-B
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STRATEGY BASED ON C-C CONNECTIVITY REAL EXAMPLE
Data A-B, A-I, A-K, B-E, B-F, E-C, E-L, E-M,
C-D, C-N, N-H, H-G, G-D, G-O, D-F, D-J, J-I
O
J
K
I
A
G
D
F
B
H
C
E
N
M
L
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STRATEGY BASED ON C-H CONNECTIVITY


HMBC data is ambiguous (2 or 3 bond correlations
impossible to tell which)
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STRATEGY BASED ON C-H CONNECTIVITY
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STRATEGY BASED ON C-H CONNECTIVITY DEPT DATA
CH3
CH3
CH
CH
CH
CH2
Label from left to right in capitals
A
B
C
D
E
F
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
A B C D
E F dC
f
e
d
diastereotopic protons
d
c
b
a
label protons in lower case letters
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HSQC DATA
diastereotopic protons
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STRATEGY BASED ON C-H CONNECTIVITY COSY DATA
b-f
c-e
a-d/d
a-b
And many more
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STRATEGY BASED ON C-H CONNECTIVITY COSY DATA
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STRATEGY BASED ON C-H CONNECTIVITY COSY DATA
r
r
diagonal
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STRATEGY BASED ON C-H CONNECTIVITY COSY DATA
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STRATEGY BASED ON C-H CONNECTIVITY COSY DATA
HSQC suggests diastereotopic protons 3.08/2.44
ppm 1.86/2.07 ppm
?
OK
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STRATEGY BASED ON C-H CONNECTIVITY HMBC DATA
D-c
A-b
B-a
C-a
And many more
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STRATEGY BASED ON C-H CONNECTIVITY HMBC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HMBC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HMBC DATA
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STRATEGY BASED ON C-H CONNECTIVITY HMBC DATA
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STRATEGY BASED ON C-H CONNECTIVITY RETROSPECTIVE
CHECKING
Combinatorial explosion
Pieces
Possibilities
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STRATEGY BASED ON C-H CONNECTIVITY RETROSPECTIVE
CHECKING
HMBC data (C-C-H C-C-C-H) from C ? H
And similarly for COSY data
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PROSPECTIVE CHECKING
Pieces
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COMPARISON OF C-H AND C-C STRATEGIES
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EXERCISE 1. For a simple organic compound the
mass spectrum shows a molecular ion at m/z 98.
The following data has been obtained from various
1D and 2D NMR experiments. Using this
information determine the structure of the
molecule in question and rationalise the 2D NMR
data given.
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EXERCISE 2. For a simple organic compound the
mass spectrum shows a molecular ion at m/z 114.
The following data has been obtained from various
1D and 2D NMR experiments. Using this information
determine the structure of the molecule in
question and rationalise the 2D NMR data given.
An additional peak is present in the 1H NMR at
11.6 ppm (bs).
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SELECTIVE 1D - TOCSY
90o (selective)
Spin-lock
Preparation
Detection
Mixing
J. Mag. Res. 1989, 85, 1-14. J. Mag. Res. 1989,
81, 186-190
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SELECTIVE 1D TOCSY SUBSPECTRA
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Mystery Compound
Eunicellin
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STRATEGY BASED ON C-C CONNECTIVITY REAL EXAMPLE
Data A-B, A-I, A-K, B-E, B-F, E-C, E-L, E-M,
C-D, C-N, N-H, H-G, G-D, G-O, D-F, D-J, J-I
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STRATEGY BASED ON C-H CONNECTIVITY RETROSPECTIVE
CHECKING
Pieces
Possibilities
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