1. Using 2D NMR
Strategy
Organic Structure Analysis, Crews, Rodriguez and Jaspars

2. THE PROCESS OF STRUCTURE ELUCIDATION
Organic Structure Analysis, Crews, Rodriguez and Jaspars

3. Organic Structure Analysis, Crews, Rodriguez and Jaspars

4. DEREPLICATION: The process of rapidly discovering whether
a compound has
previously been reported.
Organic Structure Analysis, Crews, Rodriguez and Jaspars

5. STRATEGY BASED ON C-C CONNECTIVITY
Organic Structure Analysis, Crews, Rodriguez and Jaspars

6. STRATEGY BASED ON C-C CONNECTIVITY PROBLEMS
Based on 13C-13C correlations – 1/ chance
Need large amounts of sample
Sample must have high solubility
Need long acquisition times (>24 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)
Organic Structure Analysis, Crews, Rodriguez and Jaspars

7. STRATEGY BASED ON C-C CONNECTIVITY
EXAMPLE
F-B
C-E
A-D
D-C
A-B
Organic Structure Analysis, Crews, Rodriguez and Jaspars

8. STRATEGY BASED ON C-C CONNECTIVITY
EXAMPLE F B A D C E
Gives topology of molecule
Chemical shift information gives:
Organic Structure Analysis, Crews, Rodriguez and Jaspars

9. 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
Organic Structure Analysis, Crews, Rodriguez and Jaspars

10. 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 I K A G D F B H C E N L M
Organic Structure Analysis, Crews, Rodriguez and Jaspars

11. STRATEGY BASED ON C-H CONNECTIVITY
&
&
HMBC data is ambiguous
(2 or 3 bond correlations – impossible to tell which)
Organic Structure Analysis, Crews, Rodriguez and Jaspars

12. STRATEGY BASED ON C-H CONNECTIVITY
Organic Structure Analysis, Crews, Rodriguez and Jaspars

13. STRATEGY BASED ON C-H CONNECTIVITY – DEPT DATA
Label from left
to right in capitals A B C D E F
Organic Structure Analysis, Crews, Rodriguez and Jaspars

14. 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
Organic Structure Analysis, Crews, Rodriguez and Jaspars

15. STRATEGY BASED ON C-H CONNECTIVITY – HSQC DATA
ATOM
dC (ppm)
DEPT
dH (ppm) A
131 CH
5.5 B
124
5.2 C 68
4.0 D 42
CH2
3.0
2.5 E 23
CH3
1.5 F 17
1.2
Organic Structure Analysis, Crews, Rodriguez and Jaspars

16. STRATEGY BASED ON C-H CONNECTIVITY – HSQC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

17. STRATEGY BASED ON C-H CONNECTIVITY – HSQC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

18. STRATEGY BASED ON C-H CONNECTIVITY – HSQC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

19. STRATEGY BASED ON C-H CONNECTIVITY – HSQC DATA
diastereotopic protons
Organic Structure Analysis, Crews, Rodriguez and Jaspars

20. STRATEGY BASED ON C-H CONNECTIVITY – COSY DATA
b-f
c-e
a-d/d’
a-b
And many more…
Organic Structure Analysis, Crews, Rodriguez and Jaspars

21. STRATEGY BASED ON C-H CONNECTIVITY – COSY DATA
ATOM
dC (ppm)
DEPT
dH (ppm)
COSY (HH) A
131 CH
5.5
b, c, d/d’, f B
124
5.2
a, d/d’, f C 68
4.0
a, d/d’, e D 42
CH2
3.0
2.5
a, b, c, d, e E 23
CH3
1.5
c, d/d’ F 17
1.2
a, b
Organic Structure Analysis, Crews, Rodriguez and Jaspars

22. STRATEGY BASED ON C-H CONNECTIVITY – COSY DATA
diagonal
Organic Structure Analysis, Crews, Rodriguez and Jaspars

23. STRATEGY BASED ON C-H CONNECTIVITY – COSY DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

24. STRATEGY BASED ON C-H CONNECTIVITY – COSY DATA
HSQC suggests diastereotopic protons:
3.08/2.44 ppm
1.86/2.07 ppm ? OK
Organic Structure Analysis, Crews, Rodriguez and Jaspars

25. STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA
D-c
A-b
B-a
C-a
And many more…
Organic Structure Analysis, Crews, Rodriguez and Jaspars

26. STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA
ATOM
dC (ppm)
DEPT
dH (ppm)
COSY (HH)
HMBC (CH) A
131 CH
5.5
b, c, d/d’, f
b, c, d, f B
124
5.2
a, d/d’, f
a, d, f C 68
4.0
a, d/d’, e
a, d, e D 42
CH2
3.0
2.5
a, b, c, d, e
a, b, c, e E 23
CH3
1.5
c, d/d’
c, d F 17
1.2
a, b
Organic Structure Analysis, Crews, Rodriguez and Jaspars

27. STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

28. STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

29. STRATEGY BASED ON C-H CONNECTIVITY – HMBC DATA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

30. Combinatorial explosion
STRATEGY BASED ON C-H CONNECTIVITY
RETROSPECTIVE CHECKING
Combinatorial
explosion
Pieces:
Possibilities:
Organic Structure Analysis, Crews, Rodriguez and Jaspars

31. 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
Organic Structure Analysis, Crews, Rodriguez and Jaspars

32. PROSPECTIVE CHECKING Pieces:
Organic Structure Analysis, Crews, Rodriguez and Jaspars

33. COMPARISON OF C-H AND C-C STRATEGIES
C-C Strategy
C-H Strategy
Experiment
Time
1H NMR
< 1 min
1 min
13C NMR
1 – 4 h
DEPT 135
HSQC nt=1, ni=256
15 min
HSQC nt=4, ni=256
1 h
HMBC nt=1, ni=512
HMBC nt=4, ni=512
NOESY nt=4, ni=256
INADEQUATE
24 h
COSY nt=1, ni=256
Total time
~26 h
6 – 12 h
Sample conc
6 M
10 – 100 mM
Organic Structure Analysis, Crews, Rodriguez and Jaspars

34. 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.
Atom
dC (ppm)
dH (ppm)
1H - 1H COSY
(3 bond only)
1H  13C Long range
(2 - 3 bonds) A
218 s -
A-b, A-c, A-d, A-e B
47 t
1.8 dd
b-d
B-c, B-d, B-e, B-f C
38 t
2.3 m
c-e
C-b, C-d, C-e D
32 d
1.5 m
d-b, d-e, d-f
D-b, D-c, D-e, D-f E
31 t
2.2 m
e-c, e-d
E-b, E-c, E-d, E-f F
20 q
1.1 d
f-d
F-b, F-d, F-e
Organic Structure Analysis, Crews, Rodriguez and Jaspars

35. An additional peak is present in the 1H NMR at 11.6 ppm (bs). Atom
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).
Atom
dC (ppm)
dH (ppm)
1H - 1H COSY
(3 bond only)
1H  13C Long range
(2 - 3 bonds) A
178 s -
A-d, A-b B
136 d
5.7 m
b-c, b-d
B-d, B-c, B-e C
118 d
5.5 m
c-b, c-e
C-b, C-d, C-e, C-f D t
3.0 d
d-b
D-b, D-c E t
2.1 m
e-c, e-f
E-b, E-c, E-f F
13 q
1.0 t
f-e
F-c, F-e
Organic Structure Analysis, Crews, Rodriguez and Jaspars

36. SELECTIVE 1D - TOCSY 90o (selective) Spin-lock Preparation Mixing
Detection
J. Mag. Res. 1989, 85, 1-14.
J. Mag. Res. 1989, 81,
Organic Structure Analysis, Crews, Rodriguez and Jaspars

37. SELECTIVE 1D – TOCSY SUBSPECTRA
Organic Structure Analysis, Crews, Rodriguez and Jaspars

38. Mystery Compound: Eunicellin
Organic Structure Analysis, Crews, Rodriguez and Jaspars

39. 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
Organic Structure Analysis, Crews, Rodriguez and Jaspars

40. STRATEGY BASED ON C-H CONNECTIVITY RETROSPECTIVE CHECKING
Pieces:
Possibilities:
Organic Structure Analysis, Crews, Rodriguez and Jaspars