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Chapter 6: Chirality 153 Chapter 6: Chirality 153 Chapter 6: Chirality Problems 6.1 Each molecule has one stereocenter. Identify the stereocenter in each and draw stereorepresentations of the enantiomers of each. HO H H OH HO H H OH (a) ** (b) ** * * (c) 6.2 Assign an R or S configuration to each stereocenter: 1 1 4 S (a) H OH H OH (b) H OH 4 2 COH 2 C S 3 CH3 H CH3CH2 CH3 CH3 CH3CH2 CH3 3 CH3 CH3 view down C–H bond 2 When determining R,S configuration, the (c) HC O HC O R group of lowest priority must be pointing 4 towards the back. Your molecular model 1 C H COH H kit would be of great assistance – simply HO CH2OH build the molecule and place #4 in the CH2OH 3 back. view down C–H bond 154 Chapter 6: Chirality 6.3 Following are stereorepresentations of the four stereoisomers of 3-chloro-2-butanol: CH3 CH3 CH3 CH3 H C OH H C OH HO C H HO C H Cl C H H C Cl H C Cl Cl C H CH3 CH3 CH3 CH3 (1) (2) (3) (4) (a) Whichcompounds are enantiomers? Enantiomers are mirror images of one another. The chiral centers in one enantiomer are all opposite of those in the other enantiomer. There are two pairs of enantiomers, (1) and (3), and (2) and (4). (b) Which compounds are diastereomers? Diastereomers are compounds that are stereoisomers of each other, but they are not enantiomers. As a result, diastereomers must have one at least one stereocenter of the same configuration and at least one stereocenter of different configuration. There are four pairs of diastereomers, (1) and (2), (1) and (4), (2) and (3), and (3) and (4). 6.4 Following are four Newman projection formulas for tartaric acid: COOH COOH COOH COOH H OH HO H H COOH H COOH H OH H OH H OH HO H COOH COOH OH OH (1) (2) (3) (4) COOH COOH HO H HO H H OH HO H COOH COOH Chapter 6: Chirality 155 (a) Which represent the same compound? When comparing Newman projections, it is often helpful to rotate the carbon-carbon bond to obtain a useful reference point. In the structures above, (3) and (4) have been rotated so that the two −COOH groups are anti to each other, as in (1) and (2). This allows us to immediately notice that (2) and (3) are identical. COOH COOH (b) Which represent enantiomers? H OH HO H When compounds (1) and (4) are lined up side- by-side, they are mirror images of each other, H OH HO H so they are enantiomers. COOH COOH (c) Which represent(s) meso tartaric acid? (2) and (3), which are the same, are meso because they have an internal plane of symmetry. It is helpful to draw an eclipsed conformation; in meso compounds, the substituents that are eclipsing each other are identical. The internal plane of symmetry lies parallel to the page and is between the front and rear carbon atoms of the Newman projection. Drawing the structure using the representation used in Problem 6.3 also reveals an internal plane of symmetry. COOH H COOH HO H HO H HO HO C H H OH HO C H COOH COOH COOH COOH 6.5 How many stereoisomers are possible for 1,3-cyclopentanediol? Because 1,3-cyclopentanediol has two stereocenters, a maximum of four stereoisomers are possible. The two −OH groups can be configured up/up, up/down, down/down, and down/up. However, the up/up and down/down configurations represent the same meso compound, so there are only three possible stereoisomers. HO OH HO OH trans-1,3-cyclopentanediol (pair of enantiomers) HO OH HO OH cis-1,3-cyclopentanediol (meso) 156 Chapter 6: Chirality This problem reiterates an important point: the name trans-1,3-cyclopentanediol does not distinguish between the two trans enantiomers. The trans designation just means that the two groups are on opposite sides, relative to each other. Thus, there are only two cis- trans isomers of 1,3-cyclopentanediol, but there are a total of three stereoisomers. 6.6 How many stereoisomers are possible for 1,4-cyclohexanediol? The compound is achiral because it has an internal plane of symmetry, and it does not have any stereocenters. However, the cyclohexane ring allows for cis-trans isomerism. HO OH HO OH cis-1,4-cyclohexanediol trans-1,4-cyclohexanediol Chemical Connections 6A. Draw all possible stereoisomers of Captopril and determine the relationship between each. Following are structural formulas for three other angiotensin-converting enzyme (ACE) inhibitors, all members of the "pril" family. Which are chiral? For each that is chiral, determine the number of stereoisomers possible for it. List the similarities in structure among each of these four drugs. Four stereoisomers are possible for Captopril. There are two pairs of enantiomers (indicated by solid arrows) and four pairs of diastereomers (indicated by dotted arrows). O O CH SH CH SH N C 2 N C 2 H CH3 CH3 H H COOH H COOH O O CH SH CH SH N C 2 N C 2 H H CH CH H 3 H 3 HOOC HOOC Quinapril, Ramipril, and Enalapril each contain three chiral centers, giving rise to 23 = 8 possible stereoisomers for each compound. These drugs share structural similarities Chapter 6: Chirality 157 (indicated in bold) with Captopril, which is redrawn below. The indicated similarities are likely essential for the angiotensin-converting enzyme to bind to these drugs. CH3 O O CH3 CH3 HS N N * N * * H O COOH O COOH Captopril Quinapril (Accupril) CH3 O O CH3 O O CH3 CH3 N * N * **N **N H H O COOH O COOH Ramipril (Altace) Enalapril (Vasotec) Quick Quiz 1. Enantiomers are always chiral. True. In order for an object or a molecule to be chiral, it cannot have an internal plane of symmetry. As a result, the object or molecule would not be superimposable on its mirror image. 2. An unmarked cube is chiral. False. An unmarked cube has a plane of symmetry – in fact, it has three planes of symmetry! 3. Stereocenters can be designated using E and Z. False. The E/Z system is used to identify cis-trans isomers of alkenes. Stereocenters are designated using R and S. 4. A chiral molecule will always have a diastereomer. False. A chiral molecule will always have an enantiomer, but not necessarily a diastereomer. Molecules with two or more stereocenters may have diastereomers. 5. Every object in nature has a mirror image. True. It is possible to have a mirror image of every object – it’s a matter of if the mirror images are the same or different! 6. A molecule that possesses an internal plane of symmetry can never be chiral. True. The mirror image of such a molecule would be superimposable and thus identical. 7. Pairs of enantiomers have the same connectivity. True. Stereoisomers have the same connectivity but different, noninterconverting spatial positionings of the atoms and groups. Compounds that are stereoisomers must all be of the same constitutional isomer. 158 Chapter 6: Chirality 8. Enantiomers, like gloves, occur in pairs. True. Enantiomers are always mirror images of each other, so they can only exist as pairs. 9. A cyclic molecule with two stereocenters will always have only three stereoisomers. False. The number of possible stereoisomers will depend on whether the substituents bonded to the ring are identical or not. For example, 1-chloro-2-fluorocyclohexane has four stereosiomers, but 1,2-dichlorocyclohexane has only three stereoisomers. 10. An achiral molecule will always have a diastereomer. False. Only achiral molecules that have two or more stereocenters (meso compounds) will have a diastereomer. 11. The cis and trans isomers of 2-butene are chiral. False. Although cis-trans isomerism is a type of stereoisomerism, it is not the same as chirality. The cis-trans isomers of 2-butene are not mirror images of each other. 12. A human foot is chiral. True. Your left and right feet are mirror images of each other, and this is why we need left and right shoes. Those shoes are also mirror images! Also recall enantiomers behave differently in a chiral environment – this is why your left foot does not properly fit in your right shoe. 13. A compound with n stereocenters will always have 2n stereoisomers. False. It is incorrect that it will always have 2n stereoisomers. This number is simply a mathematical maximum of the number of stereoisomers that may exist. 14. A molecule with three or more stereocenters cannot be meso. False. As long as a molecule has at least two stereocenters and an internal plane of symmetry, it is meso. 15. A molecule with three or more stereocenters must be chiral. False. Meso compounds, which are achiral, may have three or more stereocenters. 16. Each member of a pair of enantiomers will have the same boiling point. True. Enantiomers have the same physical properties, which includes boiling point. 17. If a molecule is not superposable on its mirror image, it is chiral. True. Chiral objects have nonsuperimposable mirror images. 18. For a molecule with two tetrahedral stereocenters, four stereoisomers are possible. True. Keep in mind that this is the maximum number that is possible and that it can be reduced if a meso stereoisomer exists. 19. Constitutional isomers have the same connectivity. False. Constitutional isomers have the same molecular formula, but they have different connectivity. 20. Enantiomers can be separated by interacting them with the same chiral environment or chemical agent.
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