NMR spectroscopy of stereoisomers
Encyclopedia
NMR spectroscopy
techniques can determine the absolute configuration
of stereoisomers such as cis or trans alkene
s, R or S enantiomer
s, and R,R or R,S diastereomer
s.
In a mixture of enantiomers, these methods can help quantify the optical purity by integrating the area under the NMR peak corresponding to each stereoisomer. Accuracy of integration can be improved by inserting a chiral derivatizing agent with a nucleus other than hydrogen or carbon, then reading the heteronuclear NMR spectrum: for example fluorine-19 NMR
or phosphorus-31 NMR
. Mosher's acid
contains a -CF3 group, so if the adduct has no other fluorine atoms, the 19F NMR of a racemic mixture shows just two peaks, one for each stereoisomer.
As with NMR spectroscopy in general, good resolution requires a high signal-to-noise ratio
, clear separation between peaks for each stereoisomer, and narrow line width for each peak. Chiral lanthanide shift reagents cause a clear separation of chemical shift, but they must be used in low concentrations to avoid line broadening.
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
techniques can determine the absolute configuration
Absolute configuration
An absolute configuration in stereochemistry is the spatial arrangement of the atoms of a chiral molecular entity and its stereochemical description e.g. R or S....
of stereoisomers such as cis or trans alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s, R or S enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s, and R,R or R,S diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
s.
In a mixture of enantiomers, these methods can help quantify the optical purity by integrating the area under the NMR peak corresponding to each stereoisomer. Accuracy of integration can be improved by inserting a chiral derivatizing agent with a nucleus other than hydrogen or carbon, then reading the heteronuclear NMR spectrum: for example fluorine-19 NMR
Fluorine-19 NMR
Fluorine-19 nuclear magnetic resonance is an analytical technique. 19F has a spin of 1/2, and a relative abundance of 100 % and a high magnetogyric ratio, making measurements very fast . Integrals are reliable due to the lack of a nuclear Overhauser effect...
or phosphorus-31 NMR
Phosphorus-31 NMR
Phosphorus-31 NMR spectroscopy is an analytical technique. Solution 31P-NMR is one of the more routine NMR techniques because 31P has an isotopic abundance of 100% and a relatively high magnetogyric ratio. The 31P nucleus also has a spin of ½, making spectra relatively easy to interpret...
. Mosher's acid
Mosher's acid
Mosher's acid, or α-methoxy-α-trifluoromethylphenylacetic acid is a carboxylic acid which was first used by Harry Stone Mosher as a chiral derivatizing agent. It is a chiral molecule, consisting of R and S enantiomers.-Applications:...
contains a -CF3 group, so if the adduct has no other fluorine atoms, the 19F NMR of a racemic mixture shows just two peaks, one for each stereoisomer.
As with NMR spectroscopy in general, good resolution requires a high signal-to-noise ratio
Signal-to-noise ratio
Signal-to-noise ratio is a measure used in science and engineering that compares the level of a desired signal to the level of background noise. It is defined as the ratio of signal power to the noise power. A ratio higher than 1:1 indicates more signal than noise...
, clear separation between peaks for each stereoisomer, and narrow line width for each peak. Chiral lanthanide shift reagents cause a clear separation of chemical shift, but they must be used in low concentrations to avoid line broadening.
Methods
- Karplus equationKarplus equationThe Karplus equation, named after Martin Karplus, describes the correlation between 3J-coupling constants and dihedral torsion angles in nuclear magnetic resonance spectroscopy:J = A \cos^2 \phi + B \cos\,\phi + C...
- Chiral derivatizing agent
- Mosher's acidMosher's acidMosher's acid, or α-methoxy-α-trifluoromethylphenylacetic acid is a carboxylic acid which was first used by Harry Stone Mosher as a chiral derivatizing agent. It is a chiral molecule, consisting of R and S enantiomers.-Applications:...
- Chiral solvating agent
- Chiral lanthanide shift reagent (e.g. EufodEufodEuFOD is the chemical compound with the formula Eu3, also called Eu3. This coordination compound is used primarily as a shift reagent in NMR spectroscopy...
)
- Mosher's acid
- NMR database methodNMR database methodThe NMR database method enables identification of the stereochemistry of chiral molecules, especially polyols. It relies on the observation that NMR spectroscopy data depend only on the immediate environment near an asymmetric carbon, not on the entire molecular structure...