Chapter 6 Stereochemistry chapter 6 Isomer Organization Isomers Stereoisomers Enantiomers Geometric Cis/trans Constitutional isomers Diastereomers Conformational Isomers chapter 6 Meso compounds Epimers Stereoisomers • Same bonding sequence. • Different arrangement in space. • Example: HOOC-CH=CH-COOH has two geometric (cis-trans) isomers O H C OH C C HO C O HO C C OH C C H O o fumaric acid, mp 287 C essent ial met abolite O H H => o maleic acid, mp 138 C toxic irrit ant chapter 6 Chirality • “Handedness”: right glove doesn’t fit the left hand. • Mirror-image object is different from the original object chapter 6 Examples of Handed Objects • • • • • Your hands, from the previous slide Gloves Scissors Screws Golf clubs chapter 6 How about molecules? • Chemical substances can be handed • Handed substances are said to be chiral • Molecules, that are chiral are nonsuperimposable on their mirror image chapter 6 Chirality in Molecules • cis isomers are achiral (not chiral). chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. • Enantiomers: nonsuperimposable mirror images, different molecules. chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. • Enantiomers: nonsuperimposable mirror images, different molecules. • One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons. chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. • Enantiomers: nonsuperimposable mirror images, different molecules. • One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons. • The one enantiomer of carvone is the essence of caraway, and the other, the essence of spearmint. • Most molecules in the plant and animal world are chiral and usually only one form of then enantiomer is found. chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. • Enantiomers: nonsuperimposable mirror images, different molecules. • One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons. • The one enantiomer of carvone is the essence of caraway, and the other, the essence of spearmint. • Most molecules in the plant and animal world are chiral and usually only one form of then enantiomer is found. • Nineteen of the twenty known amino acids are chiral, and all of them are classified as left handed. chapter 6 Chirality in Molecules • The cis isomer is achiral. • The trans isomer is chiral. • Enantiomers: nonsuperimposable mirror images, different molecules. chapter 6 Stereocenters • Any atom at which the exchange of two groups yields a stereoisomer. • Examples: • Asymmetric carbons • Double-bonded carbons in cis-trans isomers => chapter 6 Mirror Planes of Symmetry • If two groups are the same, carbon is achiral. (animation) • A molecule with an internal mirror plane cannot be chiral.* Caution! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed. chapter 6 (R), (S) Nomenclature(Absolute Configuration) • Called the Cahn-Ingold-Prelog convention • Different molecules (enantiomers) must have different • names. • Usually only one enantiomer will be biologically active. • Configuration around the chiral carbon is specified with (R) and (S). chapter 6 Cahn-Ingold-Prelog Rules • Assign a priority number to each group attached to the chiral carbon. • Atom with highest atomic number assigned the highest priority #1. • In case of ties, look at the next atoms along the • chain. • Double and triple bonds are treated like bonds to • duplicate atoms. chapter 6 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) chapter 6 Properties of Enantiomers • • • • Same boiling point, melting point, density Same refractive index Different direction of rotation in polarimeter Different interaction with other chiral molecules – Enzymes – Taste buds, scent chapter 6 Plane-Polarized Light • Polarizing filter – calcite crystals or plastic sheet. • When two filters are used, the amount of light transmitted depends on the angle of the axes. chapter 6 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) chapter 6 Biological Discrimination chapter 6 Racemic Mixtures • Equal quantities of d- and l- enantiomers a 50/50 mixture. • Notation: (d,l) or () • No optical activity. • The mixture may have different b.p. and m.p. from the enantiomers! chapter 6 Fischer Projections • Flat drawing that represents a 3D molecule. • A chiral carbon is at the intersection of horizontal and vertical lines. • Horizontal lines are forward, out-of-plane. • Vertical lines are behind the plane. chapter 6 Fischer Rules • Carbon chain is on the vertical line. • Horizontal bonds pointing up with respect to the plane of the paper. • Vertical bonds pointing down with respect to the plane of the paper. • Highest oxidized carbon at top. • Rotation of 180 in plane doesn’t change molecule. • Do not rotate 90! • Do not turn over out of plane! chapter 6 Fischer Structures • Easy to draw, easy to find enantiomers, easy to find internal mirror planes. • Examples: CH3 CH3 CH3 H Cl Cl H H Cl Cl H H Cl H Cl CH3 CH3 CH3 A meso compound chapter 6 => Fischer (R) and (S) • Lowest priority (usually H) comes forward, so assignment rules are backwards! • Clockwise 1-2-3 is (S) and counterclockwise 12-3 is (R). • Example: (S) CH3 (S) H Cl Cl H CH3 chapter 6 Mirror image, both would be R Diastereomers • Stereoisomers that are not mirror images. • Molecules with 2 or more chiral carbons. • Geometric isomers (cis-trans), since they are not mirror images. H H H C C C C H3C CH3 CH3 cis-2-bu te n e H3C H trans-2-bu te n e chapter 6 Ring Compounds • Cis-trans isomers possible. • May also have enantiomers. • Example: trans-1,2-dimethylcyclopentane => chapter 6 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 is 2n, where n = the number of chiral carbons. chapter 6 Examples COOH COOH H HO * OH HO * H COOH H enantiomers (2R,3R)-tartaric aci d * H * OH COOH (2S,3S)-tartaric aci d COOH H * OH H * OH A meso compound, contains 2 or more stereocenters and a plane of symmetry COOH (2R,3S)-tartari c aci d chapter 6 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, we now know absolute configurations: D is (R) and L is (S). • No relationship to dextro- or levorotatory, meaning that some D enantiomers are (R) and some are (S). • Anyone who can look at a structure and determine which way it will rotate polarized light receives an automatic Noble Prize! There is a lot we do not know! chapter 6 D and L Assignments CHO * H OH CH2OH Penultimate carbon is the stereocenter farthest away from the carbonyl group. If the higher priority group is on the left, then (L), if on the right then (D) sugar. D-(+)-glyce ralde h yde COOH H2N * H CH2CH2COOH L-(+)-gl u tam i c aci d chapter 6 CHO H * OH HO * H H * OH H * OH CH2OH D-(+)-gl u cose 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 chapter 6 Resolution of Enantiomers • Pasteur was the first to resolve an enatiomeric mixture, using a magnifying glass and tweezers. • Animals can consume a racemate and metabolize on of the tow enantiomers, while the other is recovered in their waste products. • Chemical means, described on the next slide chapter 6 Chemical Resolution of Racemate • React a racemic mixture with a chiral compound to form diastereomers, which can chapter 6 Stereochemistry Review chapter 6 Compare the physical properties of enantiomers. a. Different physical properties. b.Same physical properties. c. Cannot determine. d.Same chemical properties. chapter 6 Answer a. Different physical properties. b.Same physical properties. c. Cannot determine. d.Same chemical properties. Enantiomers have the same physical properties, such as melting point or boiling point. chapter 6 Identify as R, S, or achiral. Br Cl C H a. b. c. d. R S Achiral Cannot be determined. chapter 6 CH3 Answer a. b. c. d. R S Achiral Cannot be determined. Br > Cl > CH3 > H chapter 6 Identify as R, S, or achiral. I H C CH2CH3 CH3 a. b. c. d. R S Achiral Cannot be determined. chapter 6 Answer a. b. c. d. R S Achiral Cannot be determined. I > CH3CH2 > CH3 > H chapter 6 Identify as R, S, or achiral. CH3CH2 a. b. c. d. CH2CH2CH3 CH3 C CH CH3 CH3 R S Achiral Cannot be determined. chapter 6 Answer a. b. c. d. R S Achiral Cannot be determined. CH(CH3)2 > CH2CH2CH3 > CH2CH3 > CH3 chapter 6 Identify as R, S, or achiral. CH2CH3 H3C C HC a. b. c. d. R S Achiral Cannot be determined. chapter 6 CH(CH3)2 CH2 Answer a. b. c. d. R S Achiral Cannot be determined. CH=CH2 > CH(CH3)2 > CH2CH3 > CH3 chapter 6 Identify as R, S, or achiral. CH3 H3C CH HC a. b. c. d. C R H C S Achiral Cannot be determined. 3 chapter 6 C CH3 CH3 Answer a. b. c. d. R S Achiral Cannot be determined. C6H5 > HC≡C > C(CH3)3 > CH(CH3)2 chapter 6 Identify the type isomer for (R) 2-pentanol. a. Dextrorotatory isomer. b.Levorotatory isomer. c. Has to be experimentally determined. d.Neither. chapter 6 Answer a. Dextrorotatory isomer. b.Levorotatory isomer. c. Has to be experimentally determined. d.Neither. Dextrorotatory and levorotatory isomers must be experimentally determined. chapter 6 Classify 2R,3S-2,3-dichloropentane and 2S,3S-2,3-dichloropentane. a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical chapter 6 Answer a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical Diastereomers are stereoisomers that are not mirror images. chapter 6 Classify 2S,3S-2,3-dichloropentane and 2R,3R-2,3-dichloropentane. a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical chapter 6 Answer a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical Enantiomers are mirror image isomers. chapter 6 Classify 2R,3S-2,3-dichlorobutane and 2S,3R-2,3-dichlorobutane. a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical chapter 6 Answer a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical The compounds are identical. chapter 6 Classify 2R,3R-2,3-dichlorobutane and 2S,3S-2,3-dichlorobutane. a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical chapter 6 Answer a. Enantiomers b.Diastereomers c. Conformational isomers d.Constitutional isomers e.Identical The compounds are enantiomers. chapter 6 Identify the number of stereoisomers for 3-bromo-2,4,5-trichlorohexane. a. 6 stereoisomers b.8 stereoisomers c. 12 stereoisomers d.16 stereoisomers e.24 stereoisomers chapter 6 Answer a. 6 stereoisomers b.8 stereoisomers c. 12 stereoisomers d.16 stereoisomers e.24 stereoisomers The number of stereoisomers is 24 or 16. chapter 6 Define meso compound. a. A meso compound is an achiral molecule. b.A meso compound has a plane of symmetry. c. A meso compound has chiral carbons. d.All of the above. chapter 6 Answer a. A meso compound is an achiral molecule. b. A meso compound has a plane of symmetry. c. A meso compound has chiral carbons. d. All of the above. A meso compound has chiral carbons, is achiral, and has a plane of symmetry. chapter 6 Identify a pair of diastereomers. a. A and B b.A and D c. B and C d.None H H H H Br C Cl Cl C Br Br C Cl Cl C Br Br C Cl Br C Cl Cl C Br Cl C Br H A H B H chapter 6 C H D Answer a. A and B b.A and D c. B and C d.None chapter 6 Identify a pair of enantiomers. a. A and B b.A and D c. B and C d.A and C H H H H Br C Cl Cl C Br Br C Cl Cl C Br Br C Cl Br C Cl Cl C Br Cl C Br H A H B H chapter 6 C H D Answer a. A and B b.A and D c. B and C d.A and C chapter 6 Identify a meso compound. a. A b.B c. C d.A and D H H H H Br C Cl Cl C Br Br C Cl Cl C Br Br C Cl Br C Cl Cl C Br Cl C Br H A H H B C chapter 6 H D Answer a. A b.B c. C d.A and D chapter 6 Compare the physical properties of diastereomers. a. Different physical properties. b.Same physical properties. c. Cannot determine. d.Same chemical properties. chapter 6 Answer a. Different physical properties. b.Same physical properties. c. Cannot determine. d.Same chemical properties. Diastereomers have different physical properties, such as melting point or boiling point. chapter 6 End of Chapter 6 chapter 6