hapter 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 is-trans isomers result from restricted rotation 6.2 A chiral object has a nonsuperimposable mirror image 6.3 An asymmetric center is the cause of chirality in a molecule 6.4 Isomers with one asymmetric center 6.5 ow to draw enantiomers 6.6 Naming enantiomers by the R,S system 6.7 hiral compounds are optically active 6.8 ow specific rotation is measured 6.9 Isomers with more than one asymmetric center 6.10 Meso compounds have asymmetric centers but are optically inactive 6.11 ow enantiomers can be separated 6.12 Receptors 6.13 The stereochemistry of reactions 6.14 The stereochemistry of enzyme-catalyzed reactions # Sections that will be skipped Recommended additional problems 30, 32, 34, 35, 36, 42, 49, 55 1
6.1 is-trans isomers result from restricted rotation Alkenes and cycloalkanes 3 3 3 3 3 3 I II III 3 3 3 3 IV V 6.2 A chiral object has a nonsuperimposable mirror image 2
6.3 An asymmetric center is the cause of chirality in a molecule 6.4 Isomers with one asymmetric center 6.5 ow to draw enantiomers A. What Are Enantiomers? Isomers onstitutional Isomer (Structural Isomer) Stereoisomer Enantiomer Diastereomer Enantiomers (a pair of enantiomers): mirror image but not superimposable Br 3 2 3 3
Important Terminologies: achiral, chiral, plane of symmetry, mirror image and stereocenter B. Drawing Enantiomers: riteria of being chiral: four different substituents (SP 3 hybridization) and no plane of symmetry. Examples: O Br 3 2 4
6.6 Naming enantiomers by the R,S system (i) Locate the stereocenter and prioritize its four substitutents from 1 (highest) to 4 (lowest). (ii) Rotate in the order from 1 to 2 to 3. (iii) If the 4 (lowest) substituent is pointing away from you, clockwise rotation will be R and counterclockwise rotation will be S. (iv) If the 4 (lowest) substituent is pointing toward you, clockwise rotation will be S and counterclockwise rotation will be R. (v) Examples O l O O l O 2 3 l 5
6.7 hiral compounds are optically active 6.8 ow specific rotation is measured 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). hiral compounds with clockwise rotation is designated as (+).hiral compounds with counterclockwise rotation is designated as (-). (+) and (-) have no correlation with R and S assignment. 6
6.9 Isomers with more than one asymmetric center Know the difference between enantiomers and diastereomers O O O O A. Assign R and S for identification: O O O O O O O O O O O O 2 O I 2 O II 2 O III 2 O IV Enantiomers: Diastereomers: B. Racemic Mixtures: a pair of enantiomers in 1/1 ratio Optical property is canceled intermolecularly. 7
6.10 Meso compounds have asymmetric centers but are optically inactive Meso ompounds (the presence of plane of symmetry) Optical property is canceled intramolecularly. O O O O O O 2 O 2 O O O A. Assign R and S for identification and check the presence of plane of symmetry: O 2 O 2 O 2 O 2 O O O O O O O O O 2 I O 2 II O 2 III O 2 IV B. More examples: (i) O O 2 3 O (ii) Br O 2 O 2 O 8
(iii) 3 3 3 3 3 O O O I II III IV O V 3 (iv) O 3 O 3 O O I 3 II 3 III IV O 3 V 9
. Molecules with three or ore stereocenters O Menthol O Number of possible stereoisomers: 2 n, n = number of stereocenters O O 6.11 ow enantiomers can be separated A. 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. 10
B. 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] 6.12 Receptors The Significance of hirality in the Biological World 3 3 O 2 O 2 (S)-Ibuprofen (S)-Naproxen O 3 11
6.13 The stereochemistry of reactions 6.14 The stereochemistry of enzyme-catalyzed reactions O 2 - O 2 - + 2 O fumarase O - O 2 fumurate O 2 - malate 12