Chapter 6. Isomers and Stereochemistry Learning objectives: 1. Differentiate chiral and achiral molecules. 2. Recognize and draw structural isomers (constitutional isomers), stereoisomers including enantiomers and diastereomers, racemic mixture, and meso compounds. 3. Identify the stereocenters in a molecule and assign the configuration as R or S. 4. Know the relationship between enantiomers and their specific rotations. Sections to be covered (in the order of delivery): 6.1 Stereoisomers 6.2 Chiral Molecules 6.3 Enantiomers and Diastereomers 6.4 Properties of Chiral Molecules 6.1 Stereoisomers Important Terminologies: achiral, chiral, plane of symmetry, mirror image and superimposable A. Classification of Isomers 1
Examples: B. Cis-trans (E/Z) Isomers are Diastereomers of Restricted C-C Bond Rotation I II III 3 C IV V 2
C. A chiral object has a nonsuperimposable mirror image D. Drawing Mirror Image (Enantiomers) Examples: Br C 2 3
E. Self-assessment Questions Can you identify stereoisomer and same molecule using mirror image? Can you draw the mirror image of a given compound? Can you describe the definition of structural isomer, conformer (conformational isomer), stereoisomer, enantiomer and diastereomer? 4
6.2 Chiral Molecules Chiral molecules: molecules without plane of symmetry! Enantiomers: chiral molecules that are mirror image to each other Diastereomers: chiral molecules that are not mirror image to each other A. Criteria of Being Chiral Molecule (i) Universal definition Know stereocenter (chiral center, chiral atom) Not superimposable with its mirror image. or No plane of symmetry. (ii) Simplified criteria but may have exception The presence of stereocenter (chiral center, chiral atom): four different substituents for an sp 3 hybridized atom. Chiral molecules may have no stereocenter. aving sterocenters may not be chiral. (iii) Stereocenter and chiral center (chiral atom) B. Find Plane of Symmetry 5
C. Stereocenters (chiral atoms) For molecules that are hard to find plane of symmetry, find stereocenter (atom). sp 3 hybridized C and N 6
S and P Examples: D. Identify Chiral Molecules Using Stereocenter (i) Molecules with odd number of stereocenters: (ii) Molecules with even number of stereocenters: Look for plane of symmetry or assign R and S 7
E. Assign R and S for Stereocenters Know racemic mixture and meso compounds 8
(i) Useful for molecules that have multiple stereocenters (ii) ow to Assign R and S for Stereocenters? 1. Prioritize (atomic number) four substituents (groups) attached to a stereocenter. 2. Place the less prioritized one (4) away from you and then rotate from 1-2-3. Examples: 9
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F. Self-assessment Questions Can you identify stereoisomer(s)? Can you explain the relationship among stereocenter, chiral molecule, enantiomer and diastereomer? Can you assign R and S of stereocenter (atom)? Can you explain what are racemic mixture and meso compound? 6.3 Enantiomers and Diastereomers Know the difference between enantiomers and diastereomers Mirror image to each other: enantiomers Not mirror image to each other: diastereomers (commonly have multiple stereocenters) Both enentiomers and diastereomers are stereoisomers Example: Threonine 11
A. Assign R and S for identification: Enantiomers: Diastereomers: B. Racemic Mixtures: a pair of enantiomers in 1/1 ratio Optical property is canceled intermolecularly. 12
C. Meso Compounds (the presence of plane of symmetry) Meso compounds have asymmetric centers but are optically inactive Optical property is canceled intramolecularly. O O C C O 2 C CO 2 O O O (i) Assign R and S for identification and check the presence of plane of symmetry: D. More examples Racemic Mixture and Meso Compounds (i) O 2 C O 13
(ii) I II III IV V (iii) 3 C I II III IV V 14
E. Molecules with Three or More Stereocenters Menthol Number of possible stereoisomers: 2 n, n = number of stereocenters O O F. Self-assessment Questions Can you identify a pair of enantiomers and diastereomers? Can you explain racemic mixture and meso compound? Can you calculate the possible stereoisomers for molecules with three or more stereocenters? 15
6.4 Properties of Chiral Molecules Important Terminologies: plane-polarized light, optically active, optical activity. A. Plane-Polarized Light B. A Polarimeter Light source 1 Light filter with grid 2 Sample tube with chiral compound 3 Rotatable filter with grid 4 Specific rotation: the observed rotation of an optically active substance at a concentration of 1 g/100 ml in a sample tube 10 cm long; for a pure liquid, concentration is in g/ml (density) C. Chiral compounds with clockwise rotation is designated as (+).Chiral compounds with counterclockwise rotation is designated as (-). (+) and (-) have no correlation with R and S assignment. 16
D. Racemic Mixture and Meso Compounds Are Optically Inactive E. Properties of stereoisomers Enantiomers: same chemical properties (reactivity), same physical properties (ex. boiling point, melting point, density and pka) except for the specific rotation (a pair of Enantiomers has the exact opposite direction in rotation). Diastereomers: different chemical and physical properties. (i) Separation of Enantiomers: Resolution [R] [R] [S] [S] [R] [R] [S] [S] [S] [R] [S] [R] a racemic mixture a pair of enantiomers ([R] and [S]) Addition of optically pure reagent [R*] [R,R*] [S,R*] [R,R*] [S,R*] [R,R*] [S,R*] [R,R*] [R,R*] [S,R*] [S,R*] a mixture of diastereomers ([R,R*] and [S,R*]) [R,R*] separation of diastereomers [S,R*] Removal of optically pure reagent [R*] Removal of optically pure reagent [R*] [R] [R] [R] [R] [R] [S] [S] [S] [S] [S] 17
(ii) The Significance of Chirality in the Biological World 3 C 3 C O 2 C O 2 C (S)-Ibuprofen (S)-Naproxen O F. Stereoselectivity: Selection Between Stereoisomers (i) reactions for alkenes 18
(ii) The stereochemistry of enzyme-catalyzed reactions CO 2 - CO 2 - C C + 2 O fumarase O C C - O 2 C fumurate CO 2 - malate G. Self-assessment Questions Do you know the relationship of chemical and physical properties between a pair of enantiomers and diastereomers? Can you explain why racemic mixture and meso compound are optically inactive? Can you explain the process of separating a pair of enantiomers (resolution)? Can you identify a stereoselective reaction? 19