4 aromatic protons

1
Can we use 2D to assign this spectrum?
4 aromatic protons
Structure first determined by Woodward in 1948
(without NMR!)
2
HSQC
CH2
Identify CH, CH2 and CH3 peaks on HSQC (use DEPT
if necessary)
3
COSY
H-22 is a good place to start
22
23
4
HSQC
H-12 can be tentatively identified from C and H
shifts
23
12 ?
Transfer this information to the HSQC spectrum
22
5
COSY
13
8
We can identify 11 as a CH2 and 13 as a CH from
the HSQC H-8 can distinguished from H-14 by the
doublet multiplicity and shift 13-14 correlation
is weak, but is seen on one side of the diagonal
13, 14
11
13
12
6
HSQC
14
11
13
8
23
12
Note that have a number of dead ends as far as
COSY is concerned
22
7
COSY
The protons at C-15 can be identified by their
correlation to H-14
14
15
15
13
8
COSY
Having identified the C-15 protons, we can now
see the correlation to H-16
15
gem
16
15
16
9
HSQC
15
14
11
13
16
8
23
12
This leaves 3 CH2s, at C-17, C-18 and C-20
22
10
HSQC
The C-20 protons can be identified as a pair of
coupled (from COSY) doublets, not coupled to
anything else
11
COSY
The CH2s at C-17 and C-18 are left. The HSQC
shows an overlapping CH2 at 1.94 ppm. The
chemical shift indicates that this must be the
C-17 CH2. The CH2 at 2.92 and 3.35 ppm must be
C-18.
18
18
17 (diagonal)
12
HSQC
15
14
11
17
13
18
20
16
8
23
12
All protonated carbons have now been assigned
22
13
HMBC
We can now use HMBC to assign the non-protonated
carbons (and confirm other assignments, if
necessary)
C-10
H-12
H-11ax
H-11eq
14
HMBC
C-18
H-20
H-20
C-7
C-20
H-1
H-8
CH2-17
H-18
2 bond C-7 to H-16 correlation not observed?
H-15
15
COSY
TOCSY
12
11
8
13
15
14
16
15
(diagonal)
(diagonal)
17
16
NOESY
8
16
15
12
13
15
13
15
NOESY Avance 300 Degassed sample Degassing
removes oxygen (paramagnetic) from the sample
which would otherwise provide alternate
relaxation pathways.
gem
15
8
12
17
15N-HMBC
15N spectroscopy is very difficult! However, we
can measure 15N shifts and determine the location
of the nitrogens with HMBC (AMX 500, 10 mg
sample, overnight)
N-19
H-18
H-18
H-16
H-15
CH2-17
N-9
H-13
H-8
H-11