Chapter 5 Stereochemistry Stereoisomers Same bonding sequence Different arrangement in space Example: OOC-C=C-COO has two geometric (cis-trans) isomers: COO COO COO COO Stereochemistry Slide 5-2 1
Chirality andedness : right glove doesn t fit the left hand. Mirror-image object is different from the original object. Stereochemistry Slide 5-3 Chirality in Molecules The cis isomer is achiral. The trans isomer is chiral. Enantiomers: nonsuperimposable mirror images, different molecules. Stereochemistry Slide 5-4 2
Stereocenters Any atom at which the exchange of two groups yields a stereoisomer. Examples: Asymmetric carbons Double-bonded carbons in cis-trans isomers Stereochemistry Slide 5-5 Chiral Carbons Tetrahedral carbons with 4 different attached groups are chiral (or stereogenic). If there is only one chiral carbon in a molecule, its mirror image will be a different compound (enantiomer). Stereochemistry Slide 5-6 3
Mirror Planes of Symmetry If two groups are the same, carbon is achiral. A molecule with an internal mirror (a sigma plane of symmetry) plane cannot be chiral, even if it has chiral carbons. These compounds are called meso. Caution! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed. Stereochemistry Slide 5-7 (R), (S) Nomenclature Different molecules must have different names Enantiomers, since they are different molecules, must have different names, since their structural names will be the same. Usually only one enantiomer will be biologically active. Configuration around the chiral carbon is specified with (R) and (S). Stereochemistry Slide 5-8 4
Cahn-Ingold-Prelog Rules Assign a priority number to each group attached to the chiral carbon. If more than one chiral carbon is present, do these steps for each chiral carbon one at a time, independent of the other chiral carbons. Atom with highest atomic number assigned the highest priority #1. In case of ties, look at the next atom(s) along the chain. Double and triple bonds are treated like bonds to duplicate atoms. Stereochemistry Slide 5-9 Dealing with Multiple Bonds Stereochemistry Slide 5-10 5
Assign Priorities O O O C C C C O maleic acid, mp 138 C toxic irritant 2 C C I C C CN Cl Stereochemistry Slide 5-11 Assign (R) or (S) Working in 3D, rotate molecule so that lowest priority group is in back. Draw an arrow from highest to lowest priority group. Clockwise = (R), Counterclockwise = (S) Stereochemistry Slide 5-12 6
Properties of Enantiomers Same boiling point, melting point, density Same refractive index Different direction of light rotation in polarimeter Different interaction with other chiral molecules Enzymes Taste buds, scent Stereochemistry Slide 5-13 Polarizing filter calcite crystals or plastic sheet. When two filters are used, the amount of light transmitted depends on the angle of the axes. Plane-Polarized Light Stereochemistry Slide 5-14 7
Polarimetry Use monochromatic light, usually sodium D Movable polarizing filter to measure angle Clockwise = dextrorotatory = d or (+) Counterclockwise = levorotatory = l or (-) Not related to (R) and (S) Stereochemistry Slide 5-15 Specific Rotation Observed rotation depends on the length of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light. [α] = α (observed) c l c is concentration in g/ml l is length of path in decimeters. Stereochemistry Slide 5-16 8
Calculate [α] D A 1.00-g sample is dissolved in 20.0 ml ethanol. 5.00 ml of this solution is placed in a 20.0-cm polarimeter tube at 25 C. The observed rotation is 1.25 counterclockwise. Stereochemistry Slide 5-17 Biological Discrimination Stereochemistry Slide 5-18 9
Racemic Mixtures Equal quantities of d- and l-enantiomers. Notation: (d,l) or (±) No optical activity. The mixture may have different b.p. and m.p. from the enantiomers! Stereochemistry Slide 5-19 Racemic Products If optically inactive reagents combine to form a chiral molecule, a racemic mixture of enantiomers is formed. Stereochemistry Slide 5-20 10
Optical Purity Also called enantiomeric excess (or ee). Amount of pure enantiomer in excess of the racemic mixture. If o.p. = 50%, then the observed rotation will be only 50% of the rotation of the pure enantiomer. Mixture composition would be 75-25. Stereochemistry Slide 5-21 Calculate % Composition The specific rotation of (S)-2-iodobutane is +15.90. Determine the % composition of a mixture of (R)- and (S)-2-iodobutane if the specific rotation of the mixture is -3.18. Stereochemistry Slide 5-22 11
Chirality of Conformers If equilibrium exists between two chiral conformers, molecule is not chiral. Judge chirality by looking at the most symmetrical conformer. Cyclohexane can be considered to be planar, on average. Stereochemistry Slide 5-23 Mobile Conformers Nonsuperimposable mirror images, but equal energy and interconvertible. Use planar approximation. Stereochemistry Slide 5-24 12
Nonmobile Conformers If the conformer is sterically hindered, it may exist as enantiomers. No R, S designation possible! Stereochemistry Slide 5-25 Allenes Chiral compounds with no chiral carbon Contains sp hybridized carbon with adjacent double bonds: - C=C=C- End carbons must have different groups. Allene is achiral. Stereochemistry Slide 5-26 13
Fischer Projections Flat drawing that represents a 3D molecule. A chiral carbon is at the intersection of horizontal and vertical lines. orizontal lines are forward, out-of-plane. Vertical lines are behind the plane. Stereochemistry Slide 5-27 Fischer Rules Carbon chain is on the vertical line. ighest oxidized carbon at top. Rotation of 180 in plane doesn t change 3D relationships in molecule; other rotations do!. Do not rotate 90! Do not turn over out of plane! Stereochemistry Slide 5-28 14
(S)-Lactic Acid Stereochemistry Slide 5-29 Manipulations of Fischer Projections Stereochemistry Slide 5-30 15
Fischer Mirror Images Easy to draw, easy to find enantiomers, easy to find internal mirror planes. Examples: CO 2 CO 2 CO 2 Br Br Br Br Br Br CO 2 CO 2 CO 2 Stereochemistry Slide 5-31 Fischer (R) and (S) Lowest priority (usually ) comes forward, so assignment rules are will be used backwards! ONLY works with correct Fischer projections. Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R). Example: Stereochemistry Slide 5-32 16
Diastereomers Stereoisomers that are not mirror images. Geometric isomers (cis-trans). Molecules with 2 or more chiral carbons. Stereochemistry Slide 5-33 Stereochemistry Slide 5-34 17
Alkenes Cis-trans isomers are not mirror images, so these are diastereomers. Special; called geometric isomers. Stereochemistry Slide 5-35 Ring Compounds Cis-trans isomers possible. May also have enantiomers. Example: trans-1,2-dimethylcyclopentane. Stereochemistry Slide 5-36 18
Two or More Chiral Carbons Enantiomer? Diastereomer? Meso? Assign (R) or (S) to each chiral carbon. Enantiomers have opposite configurations at each corresponding chiral carbon. Diastereomers have some matching, some opposite configurations. Meso compounds have internal mirror plane. Maximum number of all stereoisomers is 2 n, where n = the number of chiral carbons. Maximum number of diastereomers is (2 n )/2, where n = the number of chiral carbons. Stereochemistry Slide 5-37 Examples Stereochemistry Slide 5-38 19
Fischer-Rosanoff Convention Before 1951, only relative configurations could be known. Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were assigned D and same as (-)- glyceraldehyde were assigned L. With X-ray crystallography, now know absolute configurations: D is (R) and L is (S) but only for cases where the absolute configuration can be correlated. No relationship to dextro- or levorotatory. Stereochemistry Slide 5-39 D and L Assignments CO O O CO O CO O O O O C 2 O C 2 O C 2 O D-(+)-glucose D-(+)-(R)-glyceraldehyde D-(-)-threose Stereochemistry Slide 5-40 20
Properties of Diastereomers Diastereomers have different physical properties: m.p., b.p. They can be separated easily. Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated. Enantiomers are difficult to separate. Stereochemistry Slide 5-41 Resolution of Enantiomers React a racemic mixture with a chiral compound to form diastereomers, which can be separated. Stereochemistry Slide 5-42 21
Chromatographic Resolution of Enantiomers Stereochemistry Slide 5-43 Chapter 5 omework: 26, 27-30, 31c, 31e, 31f, 31h, 34, 36, 37, 39 (models will help) Stereochemistry Slide 5-44 22