H Abstract Selective 1 H, 1 H decoupling Thematic use of ribavirin as an example to illustrate NMR...
-
Upload
hillary-atkinson -
Category
Documents
-
view
216 -
download
2
Transcript of H Abstract Selective 1 H, 1 H decoupling Thematic use of ribavirin as an example to illustrate NMR...
H
Abstract
Selective 1H,1H decoupling
Thematic use of ribavirin as an example to illustrate NMR principles and techniques
1. Williams, K. R.; King, R. W J. Chem. Educ. 1990, 67, A125-A137.
• UW Oshkosh Chemistry Department
• NSF-ILI Program (USE-9153034) for funds to purchase the JEOL GSX-270 NMR spectrometer
The molecule ribavirin serves as an excellent example for illustrating a variety of NMR principles and instrumental
techniques. Ribavirin was used in a thematic fashion as a recurring example throughout a semester-long interpretative
spectroscopy course. The goal was to provide a familiar molecular framework in which to introduce new concepts and techniques
of increasing complexity. Proton NMR spectra were acquired at 270 MHz (carbon at 67.5 MHz) in DMSO-d6
.
Unique protons & chemical shift
• Multiple functional groups with protons in diverse chemical environments
• Asymmetric structure with four contiguous stereogenic centers
• All protons are unique and give well-resolved 1H NMR signals
• All multiplets are first order, making splitting of analysis straightforward
• Interesting backstory (used clinically to treat serious viral infections)
• Commercially available (~$40/100 mg, TCI America, Aldrich, Acros, etc.)
d e f g h i j k l
Ribavirin serves as a good example to illustrate spin-spin splitting, including inverted splitting tree analysis.
Illustrating splitting and n+1 rule
D2O
+ D2O
a b c d e f g h i j k l H2O
HDO
Deuterium-proton exchange
Example: Irradiate proton g
Splitting in coupled protons k and l affected
g
k/l
ji
f
h
e
d
d e f g h i j k l
O
Hi Hh
HO OH
HdH
NO
N
NHa
CONH2Hg
O
H H
HO OH
HdH
NOH
N N
Ha
CONH21.4%
2.7%
9.2%
a b c d e f g h i j k l H2O
22 °C
40 °C
60 °C
70 °C
74 °C
80 °C
b/c
Coalescence Temperature = 74 °C
b c
AB
C D E F G H
160 140 120 100 80 60ppm
Proton decoupled13C NMR
DEPT 135
CH2CH CH
A/BC
CH3
CH
CH2
d e f gh i j k l
d
e
f
g
hi
j
kl
AB C D E F G H
kl
gf
ed
cb
a
ji
h
HETCOR example
Conformations and 1D NOE
Variable temperature NMR
13C NMR, DEPT
2D Homonuclear NMR1
2D Heteronuclear NMR
H2Oa b c d e f g h i j k l
H-Carbon
H-Oxygen
H-Nitrogen
*
*
*
*
1) Unique protons
2) Chemical shifts
3) Spin-spin splitting
4) H-D exchange
5) Selective decoupling
Hk ddd Hl dt
5.4 Hz
4.3 Hz
11.9 Hz
5.4 Hz
5.4 Hz
11.9 Hz
Ribavirin illustrates how asymmetry and restricted rotation can make protons inequivalent.
The aromatic ring and multiple heteroatoms also make ribavirin a good example for discussing deshielding effects and chemical shifts.
Rotation about ribavirin’s amide bond can be studied at experimentally accessible temperatures.
Ribavirin’s Properties Make it Useful in NMR Education
Brant L. Kedrowski and William F. Wacholtz, University of Wisconsin Oshkosh, Oshkosh, Wisconsin 54901
Summary
6) NOE & conformations
7) Variable temperature NMR
8) 13C NMR, DEPT
9) Homonuclear 2D NMR
10) Heteronuclear 2D NMRO
Hi Hh
HfO OHe
HdHj
NHgO N
NHa
O
N
Hb/c
Hb/c
Hk/lHk/l
doubletstriplet
quartets(approximate)
Ribavirin is useful in teaching the following NMR topics:Students can assign protons d-l definitively by selective decoupling.
Students can assign protons b, c, and e-g as OH or NH through exchange with D2O.
b/c
e/f/g
e/f/g
e/f/g
Conformations of ribavirin can be studied by NOE analysis. Homonuclear 2D techniques introduced with ribavirin.
COSY example
Heteronuclear 2D techniques introduced with ribavirin
Carbon NMR and DEPT techniques can be introduced with ribavirin
inequivalent methylene protons
inequivalent amide protons
Reference
Acknowledgements
O
Hi Hh
HfO OHe
HdHj
NHgO N
NHa
O
N
Hb/c
Hb/c
Hk/lHk/l
OH H
DO OD
HH
NDO N
NH
O
ND
D
HH
OH H
HO OH
HH
NHO N
NH
O
NH
H
HH
ppm
Ribavirin
The effect of temperature on chemical shifts of NH and OH protons is also clearly visible (only NH and OH signals shift upfield with increasing temps)