Stereochemistry: Chiral Molecules PDF

Chapter 5 Stereochemistry: Chiral Molecules Chapter 5 1 t Isomerism: Constitutional Isomers and Stereoisomers l Stereoisomers are isomers with the same molecular formula and same connectivity of atoms but different arrangement of atoms in space...

Chapter 5 Stereochemistry: Chiral Molecules Chapter 5 1 t Isomerism: Constitutional Isomers and Stereoisomers l Stereoisomers are isomers with the same molecular formula and same connectivity of atoms but different arrangement of atoms in space Chapter 5 2 l Enantiomers: stereoisomers whose molecules are nonsuperposable mirror images l Diastereomers: stereoisomers whose molecules are not mirror images of each other ! Example: cis and trans double bond isomers ! Example: cis and trans cycloalkane isomers Chapter 5 3 t Enantiomers and Chiral Molecules !Chiral molecule ! Not superposable on its mirror image ! Can exist as a pair of enantiomers !Pair of enantiomers ! A chiral molecule and its mirror image !Achiral molecule ! Superposable on its mirror image Chapter 5 4 !Example: 2-butanol ! I and II are mirror images of each other (figures a and b) ! I and II are not superposable and so are enantiomers (figure c) ! 2-butanol is a chiral molecule ! Example: 2-propanol ! Not chiral Chapter 5 5 !Chiral molecule ! A molecule with a single tetrahedral carbon bonded to four different groups will always be chiral ! A molecule with more than one tetrahedral carbon bonded to four different groups is not always chiral ! Switching two groups at the tetrahedral center leads to the enantiomeric molecule in a molecule with one tetrahedral carbon !Stereogenic center ! An atom bearing groups of such nature that an interchange of any two groups will produce a stereoisomer ! Carbons at a tetrahedral stereogenic center are designated with an asterisk (*) ! Example: 2-butanol Chapter 5 6 t The Biological Importance of Chirality l The origin of biological properties relating to chirality is often likened to the specificity of our hands for their respective gloves; the binding specificity for a chiral molecule (like a hand) at a chiral receptor site (a glove) is only favorable in one way. l If either the molecule or the biological receptor site had the wrong handedness, the natural physiological response (e.g., neural impulse, reaction catalysis) would not occur. Chapter 5 7 t The Biological Importance of Chirality l A diagram showing how only one amino acid in a pair of enantiomers can interact in an optimal way with a hypothetical binding site (e.g., in an enzyme). Because of the chirality center of the amino acid, three-point binding can occur with proper alignment for only one of the two enantiomers. Chapter 5 8 t Tests for Chirality: Planes of Symmetry ! Plane of symmetry ! An imaginary plane that bisects a molecule in such a way that the two halves of the molecule are mirror images of each other ! A molecule with a plane of symmetry cannot be chiral ! Example ! 2-Chloropropane (a) has a plane of symmetry but 2-chlorobutane (b) does not Chapter 5 9 t Nomenclature of Enantiomers: The R,S System l Also called the Cahn-Ingold-Prelog system l The four groups attached to the stereogenic carbon are assigned priorities from highest (a) to lowest (d) l Priorities are assigned as follows ! Atoms directly attached to the stereogenic center are compared ! Atoms with higher atomic number are given higher priority ! If priority cannot be assigned based on directly attached atoms, the next layer of atoms is examined ! Example Chapter 5 10 l The molecule is rotated to put the lowest priority group back ! If the groups descend in priority (a,b then c) in clockwise direction the enantiomer is R ! If the groups descend in priority in counterclockwise direction the enantiomer is S Chapter 5 11 l Groups with double or triple bonds are assigned priorities as if their atoms were duplicated or triplicated Chapter 5 12 l Problem: Are A and B identical or enantiomers? ! Manipulate B to see if it will become superposable with A ! Exchange 2 groups to try to convert B into A ! One exchange of groups leads to the enantiomer of B ! Two exchanges of groups leads back to B Chapter 5 13 t Properties of Enantiomers: Optical Activity l Enantiomers have almost all identical physical properties (melting point, boiling point, density) l However, enantiomers rotate the plane of plane-polarized light in equal but opposite directions l Plane polarized light ! Oscillation of the electric field of ordinary light occurs in all possible planes perpendicular to the direction of propagation ! If the light is passed through a polarizer only one plane emerges Chapter 5 14 l The Polarimeter Chapter 5 15 l Specific Rotation ! An empty sample tube or one containing an achiral molecule will not rotate the plane- polarized light ! An optically active substance (e.g. one pure enantiomer ) will rotate the plane-polarized light ! The amount the analyzer needs to be turned to permit light through is called the observed rotation a ! The standard value specific rotation [a] can be calculated ! If the analyzer is rotated clockwise the rotation is (+) and the molecule is dextrorotatory ! If the analyzer is rotated counterclockwise the rotation is (-) and the molecule is levorotatory Chapter 5 16 l The specific rotation of the two pure enantiomers of 2-butanol are equal but opposite l There is no straightforward correlation between the R,S designation of an enantiomer and the direction [(+) or (-)]in which it rotates plane polarized light l Racemic mixture ! A 1:1 mixture of enantiomers ! No net optical rotation ! Often designated as (+) Chapter 5 17 t Racemic Forms and Enantiomeric Excess l Often a mixture of enantiomers will be enriched in one enantiomer ! One can measure the enantiomeric excess (ee) l Example: The optical rotation of a sample of 2-butanol is +6.76o. What is the enantiomeric excess? Chapter 5 18 t The Synthesis of Chiral Molecules l Most chemical reactions which produce chiral molecules produce them in racemic form Chapter 5 19 t Molecules with More than One Stereogenic Center l The maximum number of stereoisomers available will not exceed 2n, where n is equal to the number of tetrahedral stereogenic centers Chapter 5 20 l There are two pairs of enantiomers (1, 2) and (3,4) ! Enantiomers are not easily separable so 1 and 2 cannot be separated from each other l Diastereomers: stereoisomers which are not mirror images of each other ! For instance 1 and 3 or 1 and 4 ! Have different physical properties and can be separated Chapter 5 21 t Meso Compounds l Sometimes molecules with 2 or more stereogenic centers will have less than the maximum amount of stereoisomers Chapter 5 22 l Meso compound: Achiral despite the presence of stereogenic centers ! Not optically active ! Superposable on its mirror image ! Has a plane of symmetry Chapter 5 23 t Naming Compounds with More than One Stereogenic Center l The molecule is manipulated to allow assignment of each stereogenic center separately " This compound is (2R, 3R)-2,3-dibromobutane Chapter 5 24 t Fischer Projection Formulas l A 2-dimensional representation of chiral molecules ! Vertical lines represent bonds that project behind the plane of the paper ! Horizontal lines represent bonds that project out of the plane of the paper Chapter 5 25 t Stereoisomerism of Cyclic Compounds l 1,4-dimethylcyclohexane ! Neither the cis not trans isomers is optically active ! Each has a plane of symmetry Chapter 5 26 l 1,3-Dimethylcyclohexane ! The trans and cis compounds each have two stereogenic centers ! The cis compound has a plane of symmetry and is meso ! The trans compound exists as a pair of enantiomers Chapter 5 27 t Relating Configurations through Reactions in which No Bonds to the Stereogenic Carbon are Broken !A reaction which takes place in a way that no bonds to the stereogenic carbon are broken is said to proceed with retention of configuration Chapter 5 28 l Relative configuration: the relationship between comparable stereogenic centers in two different molecules ! (R)-1-Bromo-2-butanol and (S)-2-butanol have the same relative configuration l Absolute configuration: the actual 3-dimensional orientation of the atoms in a chiral molecule ! Can be determined by x-ray crystallography Chapter 5 29 t Chiral Molecules that Do Not Possess a Tetrahedral Atom with Four Different Groups l Atropoisomer: conformational isomers that are stable l Allenes: contain two consecutive double bonds Chapter 5 30