Introduction to Organic Chemistry Chapter 6 - Chirality PDF

INTRODUCTION TO ORGANIC CHEMISTRY Sixth Edition William H. Brown Thomas Poon Chapter 6 Chirality: The Handedness of Molecules This slide deck contains...

INTRODUCTION TO ORGANIC CHEMISTRY Sixth Edition William H. Brown Thomas Poon Chapter 6 Chirality: The Handedness of Molecules This slide deck contains animations. Please disable animations if they cause issues with your device. Copyright ©2021 John Wiley & Sons, Inc. What Are Stereoisomers? Figure 6.1 Relationships among isomers. In this chapter, we study enantiomers and diastereomers. Copyright ©2021 John Wiley & Sons, 2 Inc. Enantiomers Enantiomers: Nonsuperposable mirror images. o As an example, consider 2-butanol a molecule that exists as a pair of enantiomers. The mirror image is not superposable on the original; they are different compounds. Copyright ©2021 John Wiley & Sons, 3 Inc. Enantiomers (Cont’d 1) o One way to see that the mirror image of 2- butanol is not superposable on the original is to rotate the mirror image and then compare it with the original. Copyright ©2021 John Wiley & Sons, 4 Inc. Enantiomers (Cont’d 2) o Now try to fit the mirror image on top of the mirror image so that all groups and bonds match exactly. o The original and mirror image are not superposable. o They are different molecules with different properties. Copyright ©2021 John Wiley & Sons, 5 o They are enantiomers Inc.(nonsuperposable mirror Enantiomers (Cont’d 3) Enantiomers: Stereoisomers that are nonsuperposable mirror images are chiral (from the Greek: cheir, hand). The term refers to relationship between pairs of objects. o They show handedness. The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it. o Stereocenter: A carbon with four different groups bonded to it. Copyright ©2021 John Wiley & Sons, Inc. 6 Achiral objects If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism. o Such an object is achiral (without chirality). As an example, consider 2-propanol. o Notice that this molecule has no stereocenter. Copyright ©2021 John Wiley & Sons, 7 Inc. Achiral Molecules and Their Mirror Images o To see the relationship between an achiral original and its mirror image, rotate the mirror image by 120°. o After this rotation, all atoms and bonds of the mirror image fit exactly on the original. o This means that the achiral original and its mirror image are the same molecule. o An achiral molecule has no handedness. Copyright ©2021 John Wiley & Sons, 8 Inc. Enantiomers (Cont’d 4) To summarize o An object that is nonsuperposable on its mirror image is chiral (it shows handedness). o The most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it. o A carbon with four different groups bonded to it is called a stereocenter. o An object that is superposable on its mirror image is achiral (without chirality). o Nonsuperposable mirror images are enantiomers. o Enantiomers, like gloves, always come in Copyright ©2021 John Wiley & Sons, 9 Inc. Drawing Chiral Molecules Following are four different representations for one of the enantiomers of 2-butanol. o Both (1) and (2) show all four groups bonded to the stereocenter and show the tetrahedral geometry. o (3) is a more abbreviated line-angle formula; although we show the H atom on the stereocenter, we do not normally show it in line-angle formulas. o (4) is the most abbreviated representation; you must remember that an H present on this stereocenter. Copyright ©2021 John Wiley & Sons, 10 Inc. Drawing Chiral Molecules (Cont’d) o On the left is one enantiomer of 2-butanol. o On the right are two representations for its mirror image. Copyright ©2021 John Wiley & Sons, 11 Inc. Naming Enantiomers - R,S Because enantiomers are different compounds, each must have a different name. o Here are the enantiomers of the over-the-counter drug Ibuprofen. o The R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other. Copyright ©2021 John Wiley & Sons, 12 Inc. The R,S System To assign an R or S configuration: o Assign a priority (Section 4.2C) from 1 (highest) to 4 (lowest) to each group on the stereocenter. o Orient the stereocenter so that the group of lowest priority is projecting away from you. o Read the three groups projecting toward you in order from (1) to (3). o If reading these three groups is clockwise, the configuration is R (Latin, rectus, straight, correct). o If reading these three groups is Copyright ©2021 John Wiley & Sons, Inc. 13 The R,S System (Cont’d 1) o Problem: Assign an R or S configuration to each stereocenter. Copyright ©2021 John Wiley & Sons, 14 Inc. The R,S System (Cont’d 2) o Problem: Assign an R or S configuration to the enantiomers of ibuprofen. Remember to add the H at the stereocenter. Copyright ©2021 John Wiley & Sons, 15 Inc. Enantiomers & Diastereomers For a molecule with 1 stereocenter, 21 = 2 stereoisomers are possible. For a molecule with 2 stereocenters, a maximum of 22 = 4 stereoisomers are possible. For a molecule with n stereocenters, a maximum of 2n stereoisomers are possible. Copyright ©2021 John Wiley & Sons, 16 Inc. Enantiomers & Diastereomers (Cont’d) 2,3,4- Trihydroxybutanal o Figure 6.4 Two stereocenters; 22 = 4 stereoisomers (two pairs of enantiomers) are possible. Copyright ©2021 John Wiley & Sons, 17 Inc. Meso Compounds Meso compound: an achiral compound possessing two or more stereocenters. o Tartaric acid contains two stereocenters. o Figure 6.5 Two stereocenters; 2n = 4, but only three stereoisomers exist, one meso compound and one pair of enantiomers. Copyright ©2021 John Wiley & Sons, 18 Inc. Planes of Symmetry Figure 6.2 Plane of Symmetry: An imaginary plane passing through an object and dividing it such that one half is the mirror image in of the other half. Copyright ©2021 John Wiley & Sons, 19 Inc. Chirality in Cyclic Molecules 2-Methylcyclopentanol o 2 stereocenters; according to the 2n rule, a maximum of 22 = 4 stereoisomers are possible. o How many actually exist? Answer four; two pairs of enantiomers. Copyright ©2021 John Wiley & Sons, 20 Inc. Chirality in Cyclic Molecules (Cont’d 1) 1,2-Cyclopentanediol o 2 stereocenters = a maximum of 4 stereoisomers. o How many exist? Answer: three, one meso compound (the cis isomer) and one pair of enantiomers (the trans isomer). Copyright ©2021 John Wiley & Sons, 21 Inc. Chirality in Cyclic Molecules (Cont’d 2) 4-Methylcyclohexanol o How many stereoisomers are possible? o Answer: Two. The cis isomer (achiral) and the trans isomer (also achiral). Copyright ©2021 John Wiley & Sons, 22 Inc. Chirality in Cyclic Molecules (Cont’d 3) 3-Methylcyclohexanol o 2 stereocenters = a maximum of 4 stereoisomers o How many exist? Answer: four, two pairs of enantiomers. Copyright ©2021 John Wiley & Sons, 23 Inc. Chirality in Cyclic Molecules (Cont’d 4) 2-Methylcyclohexanol o 2 stereocenters = a maximum of 4 stereoisomers o how many exist? Answer: four, two pairs of enantiomers. Copyright ©2021 John Wiley & Sons, 24 Inc. Chirality in Cyclic Molecules (Cont’d 5) 1,3-Cyclohexanediol o 2 stereocenters = a maximum of 4 stereoisomers o How many exist? Answer: three, the cis isomer (meso) and the trans isomer (a pair of enantiomers). Copyright ©2021 John Wiley & Sons, 25 Inc. Three Or More Stereocenters Problem: o How many stereocenters are present in the molecule on the left? o How many stereoisomers are possible? o One of the possible stereoisomers is menthol. o Assign an R or S configuration to each stereocenter in menthol. Copyright ©2021 John Wiley & Sons, 26 Inc. Three Or More Stereocenters (Cont’d) Problem: Cholesterol o On the left is the carbon skeleton of cholesterol. o Identify all stereocenters. o How many stereoisomers are possible? Copyright ©2021 John Wiley & Sons, 27 Inc. Optical Activity Ordinary light: Light waves vibrating in all planes perpendicular to its direction of propagation. Plane-polarized light: Light waves vibrating only in parallel planes. Polarimeter: An instrument for measuring the ability of a compound to rotate the plane of plane-polarized light. Optically active: Showing that a compound rotates the plane of plane- polarized light. Copyright ©2021 John Wiley & Sons, 28 Inc. Polarimeter Figure 6.6 Schematic diagram of a polarimeter. Copyright ©2021 John Wiley & Sons, 29 Inc. Optical Activity (Cont’d) o Dextrorotatory: Clockwise rotation of the plane of plane-polarized light. o Levorotatory: Counterclockwise rotation of the plane of plane-polarized light. o 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). Copyright ©2021 John Wiley & Sons, 30 Inc. Chirality in the Biomolecules Except for inorganic salts and a few low- molecular-weight organic substances, the molecules in living systems, both plant and animal, are chiral. o Although these molecules can exist as a number of stereoisomers, almost invariably only one stereoisomer is found in nature. o Instances do occur in which more than one stereoisomer is found in nature, but these rarely exist together in the same biological system. Copyright ©2021 John Wiley & Sons, 31 Inc. Chirality in Biomolecules (Cont’d 1) Enzymes (protein biocatalysts) all have many stereocenters. o An example is chymotrypsin, an enzyme in the intestines of animals, that catalyzes the digestion of proteins. o Chymotrypsin has 251 stereocenters. o The maximum number of stereoisomers possible is 2251! o Only one of these stereoisomers is produced and used by any given organism. o Because enzymes are chiral substances, most either produce or react with only substances that match their stereochemical requirements. Copyright ©2021 John Wiley & Sons, 32 Inc. Chirality in Biomolecules (Cont’d 2) Figure 6.7 Schematic diagram of the surface of an enzyme capable of distinguishing between enantiomers. Copyright ©2021 John Wiley & Sons, 33 Inc. Chirality in Biomolecules (Cont’d 3) o Because interactions between molecules in living systems take place in a chiral environment, a molecule and its enantiomer or one of its diastereomers elicit different physiological responses. o As we have seen, (S)-ibuprofen is active as a pain and fever reliever, whereas its R enantiomer is inactive. o The S enantiomer of naproxen is the active pain reliever, whereas its R enantiomer is a liver toxin! Copyright ©2021 John Wiley & Sons, 34 Inc. Resolution Racemic mixture: An equimolar mixture of two enantiomers. o Because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero. Resolution: The separation of a racemic mixture into its enantiomers. Copyright ©2021 John Wiley & Sons, 35 Inc. Resolution (Cont’d) Enzymes as resolving agents. Copyright ©2021 John Wiley & Sons, 36 Inc. Chirality Problem: In Chapter 5, we discussed the acid- catalyzed hydration of alkenes and its mechanism. Acid-catalyzed hydration of 1-butene, for example, gives 2-butanol. a) Is 1-butene chiral? b) Is 2-butanol chiral? c) How many stereoisomers are possible for 2-butanol? d) Account for the fact that 2-butanol synthesized by the acid-catalyzed hydration of 1-butene is produced as a racemic mixture and is therefore, optically inactive. Copyright ©2021 John Wiley & Sons, 37 Inc. Chirality and the Handedness of Molecules End Chapter 6 Copyright ©2021 John Wiley & Sons, 38 Inc. Copyright Copyright © 2021 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in Section 117 of the 1976 United States Act without the express written permission of the copyright owner is unlawful. Request for further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publisher assumes no responsibility for errors, omissions, or damages, caused by the use of these programs or from the use of the information contained herein. Copyright ©2021 John Wiley & Sons, 39 Inc.