DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY
-
Upload
sagar-mudshinge -
Category
Documents
-
view
441 -
download
6
Transcript of DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY
![Page 1: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/1.jpg)
By:
Sagar Ravso Mudshinge
M.S.(Pharm.) IIIrd Sem
Dept. of Medicinal Chemistry
NIPER, S.A.S. Nagar. Punjab
DETERMINATION OF ABSOLUTE CONFIGURATION
BY NMR SPECTROSCOPY
![Page 2: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/2.jpg)
Flow of presentation
• Introduction
• Historical background
• Isomers
• Methods of determination of absolute configuration
• Principle and limitations of X-Ray Crystallography
• General approaches to determine the absolute configuration by
NMR
• Conclusions
![Page 3: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/3.jpg)
Introduction
• Stereoisomers with non-superimposible mirror images are
called as Enantiomers
• Diastereomers are non-mirror image stereoisomers
HOOC
COOH
OH
OH
HOOC
COOH
OH
OH
(2R ,3R)-2,3-dihydroxysuccinic acid(2S,3S)-2,3-dihydroxysuccinic acid
HOOC
COOH
OH
OH(2S,3S)-2,3-dihydroxysuccinic acid
HOOC
COOH
OH
OH(2R,3S)-2,3-dihydroxysuccinic acid
![Page 4: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/4.jpg)
HISTORICAL LANDMARKS IN THE FIELD OF
STEREOCHEMISTRY
Pasteur
Le Bel Vant Hoff
Fischer
1848- Pasteur achieves the first optical resolution of the
(+)- and (-)-enantiomers of tartaric acid.
1874 -van’t Hoff and Le Bel independently suggest
that tetravalent carbon is tetrahedral.
1900- Fischer develops the first systematic method for
depicting stereochemistry (Fischer
projections) and a notation for designating
configuration (D/L notation).
![Page 5: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/5.jpg)
Isomers
Are the structures symmetry related?
Can superimposed by translation
and/or rotation
Homomers
Enantiomers
Does structure have same
constitutionDiastereomers
Yes
No
Yes
Yes
No
![Page 6: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/6.jpg)
Different methods for determination of
absolute configuration
• Nuclear Magnetic Resonance(NMR)
• X-Ray Crystallography
• Optical Rotatory Dispersion(ORD)
• Circular Dichroism(CD)
![Page 7: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/7.jpg)
Principle of X- Ray Crystallography
Tetrahedron: Asymmetry .2009, 20,712–717
![Page 8: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/8.jpg)
Limitations of X- Ray Crystallography
• Need of good quality crystal
• Bulk sample should be enantiomerically pure
• Disorder is common problem
• Location of hydrogen can’t be detected
![Page 9: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/9.jpg)
General approaches to determine the
absolute configuration by NMR
Using chiral solvating agents
Derivatization by chiral auxillary reagents
Single
derivatization
Double
derivatization
Chem. Rev. 2004, 104, 17-117
![Page 10: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/10.jpg)
Characteristics of the auxiliary reagents
• A polar or bulky group to fix a particular conformation
• A functional group (e.g. carboxylic acid) that provides a site for
covalent attachment of the substrate
• A group that is able to produce an efficient and space-oriented
anisotropic effect
H3COOH
O
H
(R)-2-methoxy-2-phenylacetic acid
![Page 11: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/11.jpg)
![Page 12: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/12.jpg)
Chem. Rev., 2012, 112 (8), 4603–4641
![Page 13: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/13.jpg)
Conclusion
• NMR is Better alternative for these kind of assignments due to
its availability and easy handling and shorter duration of
experimentation
• Single and double derivatization methods are available for this
purpose but since it is evolving field there is need of lot of
work in this area tio widen its applicability
![Page 14: DETERMINATION OF ABSOLUTE CONFIGURATION BY NMR SPECTROSCOPY](https://reader034.fdocuments.net/reader034/viewer/2022042520/58ef20521a28abd8458b45df/html5/thumbnails/14.jpg)