know about stereo chemistry
DESCRIPTION
coolTRANSCRIPT
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Hugo Meekes
Solid State Chemistry / IMM
Chirality and Stereochemistry
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Chiral molecules: Left and Right
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Chiral objects: Left and Right
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Chiral molecules: Left and Right
Two stereoisomers called enantiomers
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Chiral molecules: other stereoisomers
-bi-2-naphthol
Axial chirality
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Other stereoisomers: Non-chiral
Cis-trans isomers
Diastereoisomers
Conformational isomers (rotamers)
Not mirror images
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Chiral molecules: Nomenclature
Natural amino acid Alanine
Enantiomers: left- and right handed individuals
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Chiral molecules: Nomenclature
Alanine: projection along C*-H
7N < 6C < 1H
R(ectus) Alanine S(inister) Alanine
Cahn-Ingold-Prelog priority rules
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Chiral molecules: Nomenclature
D,L used for amino acids and sugars
D(extro) Alanine L(aevo) Alanine
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Chiral molecules: Nomenclature
+ (dextro) / - (laevo): optical rotation (optical activity)
+ Alanine - Alanine
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Chiral molecules: physical properties
Physical property D/L
Melting point equal
Boiling point equal
Solubility equal
equal
Optical activity (polarimetry) +/-
Circular dichroism +/-
Physisorption (chiral chromatography) +/-
Chiral molecules: chemical properties
Chemical property D/L
Reactivity for achiral reagents equal
Reactivity for chiral reagents +/-
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Chiral molecules: bioactivity
limonene
m
aspartame
m
Smell
Taste
L D
LL DD
R.H. Mazur, J. Med. Chem. 13 (1970) 1217
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Chiral molecules: bioactivity
morning sickness birth defects
(S)-thalidomide (R)-thalidomide
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Chiral molecules: physical properties
Physical property D/L
Melting point equal
Boiling point equal
Solubility equal
equal
Optical activity (polarimetry) +/-
Circular dichroism +/-
Physisorption (chiral chromatography) +/-
Chiral molecules: chemical properties
Chemical property D/L
Reactivity for achiral reagents equal
Reactivity for chiral reagents +/-
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Chiral characterization
Optical activity
(polarimetry)
Physisorption: (chiral) HPLC
(High-Performance Liquid Chromatography)
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Chiral characterization : optical activity
(g/mL)ion concentrat x (dm) elength tub
)(rotation
lc
TSpecific rotation
Polarimeter measures rotation of linearly polarized light
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Chiral characterization : chiral HPLC
HPLC measures the flow time of molecules through the column
In chiral HPLC the column is filled with a chiral adsorbent
different retention times for R and S enantiomers
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Chiral molecules: Separation
Separation
Synthesis
Crystallization
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Hugo Meekes
Solid State Chemistry / IMM
Abrasive Grinding as a Route
to Chiral Purity
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Classical resolution using crystallization
Racemic conglomerate
D-tartaric acid
L-tartaric acid
Louis Pasteur
1822-1895
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Crystal structure
Molecule
aspartame
Unit cell
aspartame
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Crystal Forms of Enantiomers
Right handed (R) molecule
Left handed (S) molecule
Racemic compound Solid solution Racemic conglomerate 88 % 10 % 2 %
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Crystal Forms of Enantiomers
Racemic compound Racemic conglomerate
DL-valine L-valine
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Crystal Forms of Enantiomers
DL-valine L-valine
Only racemic conglomerates are fit for chiral separation
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Chiral Separation: nucleation and attrition
Crystal Nucleation combined with Secondary Nucleation
Havinga, Egbert. Chem. Weekblad 38 (1941) 642; Kondepudi et al. Science 250 (1990) 975
Achiral solution but racemic conglomerate
NaClO3 solution
crystals
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The new players in the grinding approach
Cristobal Viedma and Wim Noorduin
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Chiral Separation using intense stirring (grinding)
Cristobal Viedma Phys. Rev. Lett. 94 (2005) 065504
Time (hours)
Intense stirring NaClO3
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NaClO3 without grinding
Ostwald ripening: Large crystals grow at the cost of smaller ones
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Ostwald Ripening
-END STATE: ONE SINGLE CRYSTAL, L or D
-Ostwald ripening takes a long time
-Small crystals are effective Ostwald ripeners!!
-Attrition helps but gives many L and D crystals !?!
-NEAR EQUILIBRIUM PROCESS: NO NUCLEATION
NaClO3
W. Noorduin et al., Crystal Growth & Design, 8 (2008) 1675
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Monte Carlo Simulation Monte Carlo Simulation
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Computer Simulation