solving unknown structures using nmr organic structure analysis, crews, rodriguez and jaspars
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Solving Unknown Structures Using NMR
Organic Structure Analysis, Crews, Rodriguez and Jaspars
Six Simple Steps for Successful Structure Solution
• Get molecular formula. Use combustion analysis, mass spectrum and/or 13C NMR spectrum. Calculate double bond equivalents.
• Determine functional groups from IR, 1H and 13C NMR • Compare 1H integrals to number of H’s in the MF. • Determine coupling constants (J’s) for all multiplets. • Use information from 3. and 4. to construct spin systems
(substructures) • Assemble substructures in all possible ways, taking account of
dbe and functional groups. Make sure the integrals and coupling patterns agree with the proposed structure.
Organic Structure Analysis, Crews, Rodriguez and Jaspars
Organic Structure Analysis, Crews, Rodriguez and Jaspars
USING 1H NMR DATAUNKNOWN B
• A compound shows an M+. in the EIMS at 154 m/z• Further fragments are at 121, 93, 71, 55 and 39 m/z• The IR shows bands at 3400 cm-1 (broad) & 1450 cm-1
Use the 1H and 13C data to determine the structure of the compound
Organic Structure Analysis, Crews, Rodriguez and Jaspars
d
s
d
t
s
tq
q
t
q
13C NMR DATAUNKNOWN B
A B C D E F GHI J
Organic Structure Analysis, Crews, Rodriguez and Jaspars
MOLECULAR FORMULA DETERMINATIONUNKNOWN B
(C)2 + (CH)2 + (CH2)3 + (CH3)3 = C10H17
s d t q
BE
AC
DFI
GHJ
= 137 Da
The M+. appears at 154 m/z, so there isa mass difference of 17 Da (= OH)
Therefore molecular formula = C10H18O (2 dbe)
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H NMR DATAUNKNOWN B
Integrals:
H
3H 2H3H 3H
5HONLY 17 H!
Organic Structure Analysis, Crews, Rodriguez and Jaspars
SUBSTRUCTURESUNKNOWN B
H3C
H
CH3
A
C 125 d, 132 sH 5.05 t&Me groups at H 1.5
H
H
H
B
C 112 t, 146 dH 5.00 dd, 5.15 dd, 5.85 dd
H3C OH
C
C 73 sH 1.05 s
H H H H
D'D
MF = C10H18O !
Organic Structure Analysis, Crews, Rodriguez and Jaspars
WORKING STRUCTURESUNKNOWN B
OH
Ha
Ha
Ha
OH
OH
A – Ha should be ddt
B – Ha should be ddt
C – Ha should be dd
Organic Structure Analysis, Crews, Rodriguez and Jaspars
MASS SPECTRAL FRAGMENTATIONUNKNOWN B
OH
Ha
O+mass spectral fragmentation
1m/z 99
H
HaOH
+O
O+
mass spectral fragmentation
2
m/z 113
m/z 85
H
H
Ha
OH +O
mass spectral fragmentation
m/z 71H
3
Fragments at: 121, 93, 71, 55 and 39 m/z
Organic Structure Analysis, Crews, Rodriguez and Jaspars
USING MASS SPECTRAL DATAUNKNOWN G
• A compound shows an M+. in the EIMS at 128 m/z• Further fragments are at 99, 83, 72 and 57 m/z• The IR shows bands at 1680 cm-1 (strong) &
bands at 1400 - 1500 cm-1
Use the 1H and 13C NMR and MS data to determine the structure of the compound
Organic Structure Analysis, Crews, Rodriguez and Jaspars
13C NMR DATAUNKNOWN G
A B C D E FG
d dd t
t t q
Organic Structure Analysis, Crews, Rodriguez and Jaspars
MOLECULAR FORMULA DETERMINATIONUNKNOWN G
(C)0 + (CH)3 + (CH2)3 + (CH3)1 = C7H12
s d t qABC
DEF
G
= 96 Da
The M+. appears at 128 m/z, so there isa mass difference of 32 Da (= O2)
Therefore molecular formula = C7H12O2 (2 dbe)
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H NMR DATAUNKNOWN G
Integrals:
HH
H H
3H
H H2H
H
12 H Total
Organic Structure Analysis, Crews, Rodriguez and Jaspars
SUBSTRUCTURES UNKNOWN G
C 140 d, 101 dH 6.15 d, 4.70 m
C 96 dH 4.9 tO
H
H
O
O
H
O
H H
C 64 tMe
4 Oxygens in substructures but only 2 in MF
MF = C7H12O2 !
Organic Structure Analysis, Crews, Rodriguez and Jaspars
WORKING STRUCTURES UNKNOWN G
O
O
O OO O
36*
62 20*
15
64
26
10*64
15
O O O
O O+.
+
m/z 83
m/z 99
+.O O
O O
m/z 72m/z 56
+.
13C Shift additivity data
MS Fragmentation
Retro Diels-Alder
Fragments are at 99, 83, 72 and 57 m/z
Organic Structure Analysis, Crews, Rodriguez and Jaspars
USING COSY DATAUNKNOWN H
• A compound shows an [M + H]+ in the FAB MS at 132 m/z• MW = 131 (Odd) therefore odd number of nitrogens• A further fragment is at 86 m/z• The IR shows bands at 3400cm-1 (broad) & 1640 cm-1 (broad)
Use the NMR data to determine the structure of the compound
Organic Structure Analysis, Crews, Rodriguez and Jaspars
d
s
d
t
t
13C NMR DATAUNKNOWN H
A B C D E
Organic Structure Analysis, Crews, Rodriguez and Jaspars
MOLECULAR FORMULA DETERMINATIONUNKNOWN H
(C)1 + (CH)2 + (CH2)2 + (CH3)0 = C5H6
s d t q
A BC
DE
= 66 Da
The MW is 131, so there isa mass difference of 65 Da (= NO3H3)
Therefore molecular formula = C6H9NO3 (2 dbe)
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H NMR DATAUNKNOWN H
Integrals:
HONLY 6 H!
H2H H H
D2O so noXH (OH, NH)
b c d d’ e e’
Organic Structure Analysis, Crews, Rodriguez and Jaspars
SUBSTRUCTURESUNKNOWN H
C 176 sIR band at 3400
C 70 dH 4.6 m
C 60 dH 3.9 m
MF = C5H9NO3 !
OH
O
A
OH
B
C
HN
ED
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H – 1H COSY NMR SPECTRUMUNKNOWN H
b c d d’ e e’
b-e/e’
c-e/e’
d-d’
d-e’
e-e’
b-d/d’
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H – 1H COSY NMR DATAUNKNOWN H
c
c-e/e’
e e'
b-e/e’
OHb
b-d/d’
d d'
Also 4-bond correlation d-e’Diastereotopic pairs d-d’ and e-e’
Organic Structure Analysis, Crews, Rodriguez and Jaspars
SUBTRUCTURESUNKNOWN H
c
e e'
OHb
d d'
HN
OH
O
MF = C5H9NO3
HN COOH
HO
Hc
Hb
HN COOH
HO Hb
Hc
1 2
Working structures:
12 % NOENO NOE
Organic Structure Analysis, Crews, Rodriguez and Jaspars
ASSIGNING NMR DATA TO A KNOWN STRUCTUREGUAIAZULENE
10 12
3
4
56
8
9
11
12
1314
15
7
MF = C15H18
Expect:(C)5
(CH)6
(CH2)0
(CH3)4
Organic Structure Analysis, Crews, Rodriguez and Jaspars
13C NMR DATAGUAIAZULENE
sA
sB
dJ
sD
dddEFG
sC
dH
dK
qqLM
qN
qO
sI
(C)5 + (CH)6 + (CH2)0 + (CH3)4 = C15H18
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HSQC NMR DATAGUAIAZULENE
KK
k
LMLM
lm
NN
n
OO
o
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HSQC NMR DATAGUAIAZULENE
EE
e
FF
f
GG
g
HH
h
JJ
j
Organic Structure Analysis, Crews, Rodriguez and Jaspars
1H NMR DATAGUAIAZULENE
Hg
He
Hf
Hj
Hh
Hk
3Hn
3Ho
3Hl
3Hm
Label spectrum according to HSQC:
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
We will need expansions:
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
g e f j h
HI
GFCDEB
A
C-gF-g
I-g
D-e
A-f
G-fD-j
I-j
B-h
C-h
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
g e f j h
O
NLM
KK-g K-f
N-h
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
n o lm
LM-lmK-lm
B-lm
I-oH-n
D-oC-n
A-n
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
Carbon Proton
A f, n
B h, l/m
C g, h, n
D e, j, o
E
F g
G f
H n
I g, j, o
J
K f, g, l/m
L m
M l
N h
O
1H-1H COSY data indicates that e and j are adjacent (J(e-j) = 4 Hz) as are f and h (J(f-h) = 11 Hz)
‘Obvious’ assignments:
KL
M
N/O
O/N
E/J
J/E F/H
H/F
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
Carbon Proton
A f, n
B h, l/m
C g, h, n
D e, j, o
E
F g
G f
H n
I g, j, o
J
K f, g, l/m
L m
M l
N h
O
KL
M
N/O
O/N
E/J
J/E H
F
G
Signal for f is a ddlong-range couplingto remaining proton g
Organic Structure Analysis, Crews, Rodriguez and Jaspars
HMBC NMR DATAGUAIAZULENE
Carbon Proton
A f, n
B h, l/m
C g, h, n
D e, j, o
E
F g
G f
H n
I g, j, o
J
K f, g, l/m
L m
M l
N h
O
KL
M
E/J
J/E H
F
G B
A
N
O
C
HMBC data can’t decide positions of E, JHMBC data can’t decide positions of D, I
How do we decide?
Organic Structure Analysis, Crews, Rodriguez and Jaspars
FINALISING THE ASSIGNMENTSGUAIAZULENE
KL
M
E
J H
F
G B
A
O
C
NNOE
Placing D (134 ppm) here
D
puts it in a similar environment to C (136 ppm)
This puts I (125 ppm) here
I