Chapter 26 Stereoisomerism The mirror image of this children’s ballet class is not superimposable on the class. Introduction to General, Organic, and Biochemistry, 10e John Wiley & Sons, Inc Morris Hein, Scott Pattison, and Susan Arena 1

Course Outline 26.1 Review of Isomerism 26.2 Plane-Polarized Light 26.3 Optical Activity 26.4 Fischer Projection Formulas 26.5 Enantiomers 26.6 Racemic Mixtures 26.7 Diastereomers and Meso Compounds Chapter 26 Summary 2 2

Review of Isomerism 1. Isomers are molecules that have the same chemical formula but differ in either: (a) how the atoms are connected or, (b) how the connected atoms are arranged in space. 2. Isomers that differ only in their connectivity are called structural isomers while those that differ in the spatial arrangement of their atoms are called stereoisomers. 3

Review of Isomerism The difference between structural isomers is due to different structural arrangements of the atoms that form the molecules. Examples of structural isomers are shown below. 4

Review of Isomerism Compounds that have the same structural formulas but differ in their spatial arrangement are called stereoisomers. There are two types of stereoisomers. Cis–trans or geometric isomers, which we have already considered. Optical isomers, the subject of this chapter. One feature of optical isomers is that they have the ability to rotate the plane of plane-polarized light . . . 5

Plane-Polarized Light Plane-polarized light is light that is vibrating in only one plane. Ordinary (unpolarized) light consists of electromagnetic waves vibrating in all directions (planes) perpendicular to the direction in which the light is traveling. 6

Plane-Polarized Light When ordinary light passes through a polarizer, it emerges vibrating in only one plane and is called plane-polarized light. 7

Plane-Polarized Light The rotation of plane-polarized light is quantitatively measured with an instrument called a polarimeter. When the sample tube in the polarimeter contains a solution of a material that is not optically active the plane of polarized light has been rotated zero degrees. When the sample tube in the polarimeter contains a solution of a material that is optically active the plane of polarized light has been rotated a specific number of degrees. 8

Plane-Polarized Light A schematic diagram of a polarimeter measuring an optically active sample is shown below. 9

Plane-Polarized Light The specific rotation [α] of an optically active sample can be calculated using the following formula using the observed rotation in degrees measured by the polarimter. 10

Optical Activity Optical activity is the ability of a substance to rotate plane-polarized light to the right or left. A substance that rotates polarized light to the right (clockwise) is said to be dextrorotatory (designated (+) in the name). A substance that rotates polarized light to the left (counterclockwise) is said to be levorotatory (designated (−) in the name). 11

Optical Activity A substance that can rotate plane-polarized light is optically active. A necessary condition for optical activity is the property chirality. Chirality is a property present in an object that cannot be superimposed on its mirror image. Chiral objects or chiral molecules do not have a plane of symmetry. They are asymmetric. 12

Optical Activity Your right hand and your left hand are mirror images of each other. Your left hand and right hand are not superimposable. Therefore your right hand and your left hand are chiral objects. Superimposable means that, when we lay one object upon another, all parts of both objects coincide exactly. 13

Optical Activity Chirality is typically seen in molecules that have a chiral or asymmetric carbon atom. Chiral or asymmetric carbon atoms have four different atoms or four different group attached to it. 14

Optical Activity A molecule that is not superimposable on its mirror image is said to be chiral. Chiral molecules relate to each other in the same manner as the right and left hands. They are not superimposable on their mirror images. Molecules or objects that are superimposable on each other are achiral. A molecule is achiral if it has a plane of symmetry. 15

Your Turn! Draw the mirror-image isomers for the following compounds that can exist as stereoisomers. CH3CHOHCH2CH2OH CH3CHBrCH(CH3)2 16

Your Turn! Draw the mirror-image isomers for the following compounds that can exist as stereoisomers. CH3CHOHCH2CH2OH This molecule has a chiral atom and exists as two stereoisomers. The carbon atom in red is connected to four different groups. 17

Your Turn! Draw the mirror-image isomers for the following compounds that can exist as enantiomers. 2) CH3CHBrCH(CH3)2 This molecule has a chiral atom and exists as two stereoisomers. The carbon atom in red is connected to four different groups. 18

Your Turn! Draw all the structural formulas for the butyl alcohols, C4H9OH, and indicate which molecules have optical activity. 19

Your Turn! Draw all the structural formulas for the butyl alcohols, C4H9OH, and indicate which molecules have optical activity. There are the four structural isomers. 20

Your Turn! Draw all the structural formulas for the butyl alcohols, C4H9OH, and indicate which molecules have optical activity. Only one of these has a chiral atom and is optically active. This atom is connected to four different groups. 21

Fischer Projection Formulas A Fischer projection is a two-dimensional structural formula used to represent a three-dimensional structure on paper. Figure I is a three-dimensional representation of lactic acid. Figures II and III are two Fischer projections of the molecule. 22

Fischer Projection Formulas In the Fischer Projections II and III: The horizontal bonds represent the bonds that project in front of the paper or toward the viewer. The vertical bonds represent the bonds that project behind the paper or away from the viewer. 23

Fischer Projection Formulas It is important to be careful when comparing projection formulas. Two rules apply: Projection formulas must not be turned 90°. Projection formulas must not be lifted or flipped out of the plane of the paper. Projection formulas may be turned 180° in the plane of the paper without changing the spatial arrangement of the molecule. 24

Fischer Projection Formulas Formulas I, II, III, IV, and V represent the same molecule. Formula IV was obtained by turning formula III 180°. Formula V is formula IV drawn in a three-dimensional representation. 25

Fischer Projection Formulas If formula III is turned 90°, the other stereoisomer of lactic acid is represented, as shown in formulas VI and VII. 26

Your Turn! Are molecules A and B the same molecule? 27

Your Turn! To answer this question you would perform an in-plane 180 rotation and then determine if the rotated molecule is superimposable on the other molecule. 28

Your Turn! A and B are not the same molecules because they are nonsuperimposable mirror images. 29

Your Turn! Redraw this Fischer Projection as a three-dimensional formula. 30

Your Turn! Redraw this Fischer Projection as a three-dimensional formula. Horizontal lines project toward the viewer, vertical lines project away from the viewer, and the circle represents the chiral carbon atom. 31

Enantiomers Enantiomers are optically active, non-superimposable mirror image molecules that have the property of chirality. A molecule that has a nonsuperimposable mirror image is chiral. 32

Enantiomers Most chiral molecules consist of enantiomer pairs where: (+) is assigned to the enantiomer that rotates polarized light to the right like (+)-lactic acid. (−) is assigned to the enantiomer that rotates polarized light to the left like (−)-lactic acid. 33

Figure 26. 8 These molecules are enantiomers Figure 26.8 These molecules are enantiomers. They are non-superimposable mirror images of each other. (−)-Lactic acid rotates plane-polarized light to the left while (+)-lactic acid rotates plane-polarized light to the right. 34

Enantiomers The Fisher Projections of (−)-lactic acid and (+)-lactic acid are shown on the right. 35

Your Turn! Draw mirror-image isomers for any of the compounds than can exist as enantiomers. CH3CH2CH2CHBrCH2CH2CH3 CH2BrCH2CHBrCH2CH3 CH3CH2CBr2CH2CH2CH3 36

Your Turn! Draw mirror-image isomers for any of the compounds than can exist as enantiomers. First determine if the molecules have chiral carbon atoms and can exist as enantiomers. CH3CH2CH2CHBrCH2CH2CH3 No chiral atoms CH2BrCH2CHBrCH2CH3 One chiral atom. CH3CH2CBr2CH2CH2CH3 No chiral atoms 37

Your Turn! Draw mirror-image isomers for any of the compounds than can exist as enantiomers. Draw the mirrror-images of molecule b). These molecules are enantiomers. b) CH2BrCH2CHBrCH2CH3 38

Enantiomers Enantiomers ordinarily have the same chemical properties, and other than optical rotation, they also have the same physical properties. Enantiomers rotate plane-polarized light the same number of degrees, but in opposite directions. Enantiomers usually differ in their biochemical properties. In fact, most living cells are able to use only one enantiomer of an enantiomeric pair. 39

Enantiomers The key factors of enantiomers and optical isomerism can be summarized as follows. 1. A carbon atom that has four different groups bonded to it is called an asymmetric or a chiral carbon atom. 2. A compound with one chiral carbon atom can exist in two stereoisomeric forms called enantiomers. 3. Enantiomers are nonsuperimposable mirror-image isomers. 40

Enantiomers 4. Enantiomers are optically active. They rotate plane-polarized light. 5. One isomer of an enantiomeric pair rotates polarized light to the left (counterclockwise). The other isomer rotates polarized light to the right (clockwise). The degree of rotation is the same but in opposite directions. 6. Rotation of polarized light to the right is indicated by (+) placed in front of the name of the compound, and rotation to the left is indicated by a (−) in the name. 41

Racemic Mixtures A mixture containing equal amounts of a pair of enantiomers is known as a racemic mixture. These mixtures are optically inactive. The mixtures have no observed rotation in a polarimeter because each enantiomer rotates the plane of polarized light an equal amount but in opposite directions so that each rotation cancels out. 42

Racemic Mixtures The (±) symbol is often used to designate racemic mixtures. For example, a racemic mixture of lactic acid is written as (±)-lactic acid because this mixture contains equal molar amounts of (+)-lactic acid and (−)-lactic acid. 43

Racemic Mixtures Racemic mixtures are usually obtained in laboratory syntheses of compounds in which a chiral carbon atom is formed. For example the catalytic reduction of pyruvic acid (an achiral compound) to lactic acid produces a racemic mixture containing equal amounts of (+)- and (−)-lactic acid: 44

Racemic Mixtures As a general rule, only one of the isomers is produced in the biological synthesis of optically active compounds. For example, only (+)-lactic acid is produced by reactions occurring in muscle tissue, and only (−)-lactic acid is produced by lactic acid bacteria in the souring of milk. 45

Racemic Mixtures Many pharmaceuticals are synthesized as racemic mixtures since organic syntheses are often not stereospecific. Typically, only one half of these racemic mixtures is medically active. Examples of this are shown Figure 26.9 on the next slide . . . 46

Racemic Mixtures Figure 26.9 Some examples of common chiral drugs. 47

Diastereomers and Meso Compounds The enantiomers are stereoisomers that differ only in the spatial arrangement of the atoms and groups within the molecule. The number of stereoisomers increases as the number of chiral carbon atoms increases. The maximum number of stereoisomers for a given compound is obtained by the formula 2n, where n is the number of chiral carbon atoms in the molecules. 48

Diastereomers and Meso Compounds A substance with two nonidentical chiral carbon atoms, such as 2-bromo-3-chlorobutane, four stereoisomers are possible (22 = 4). Formulas XVIII and XIX and formulas XX and XXI are enantiomers. All four compounds are optically active. 49

Diastereomers and Meso Compounds Enantiomers XVIII and XIX and enantiomers XX and XXI are not mirror-image isomers of each other. Stereoisomers that are not enantiomers (not mirror images of each other) are called diastereomers. 50

Diastereomers and Meso Compounds There are four different pairs of diastereomers of 2-bromo-3-chlorobutane: XVIII and XX, XVIII and XXI, XIX and XX, and XIX and XXI. 51

Diastereomers and Meso Compounds Look at another example. The 2n formula indicates that four stereoisomers of tartaric acid are possible. Formulas XXII and XXIII represent nonsuperimposable mirror-image isomers and are enantiomers. 52

Diastereomers and Meso Compounds Formulas XXIV and XXV are also mirror images but they are superimposable. Formula XXIV and XXV represent the same compound. Only three stereoisomers of tartaric acid exist. 53

Diastereomers and Meso Compounds Compound XXIV is achiral and does not rotate polarized light. A plane of symmetry can be passed between carbons 2 and 3 so that the top and bottom halves of the molecule are mirror images. 54

Diastereomers and Meso Compounds Stereoisomers that contain chiral carbon atoms and are superimposable on their own mirror images are called meso compounds, or meso structures. All meso compounds are optically inactive. 55

Diastereomers and Meso Compounds The three stereoisomers of tartaric acid are represented and designated in this fashion. 56

Diastereomers and Meso Compounds The (+) and (-) isomers are enantiomers. The meso compound is a diastereomer of the (+) and (-) isomers. The physical properties of these three isomers are shown on the next slide . . . 57

Diastereomers and Meso Compounds The enantomers have identical properties except for the specific rotation. The diastereomers differ in other physical properties. 58

Your Turn! How many stereoisomers exist for the following compound? 59

Your Turn! How many stereoisomers exist for the following compound? There are four stereoisomers. None of these structures are meso structures. 60

Your Turn! How many stereoisomers exist for the following compound? 61

Your Turn! How many stereoisomers exist for the following compound? There are three stereoisomers. The first two structures have a plane of symmetry and are identical. The last two structures are enantiomers. 62

Chapter 26 Summary Isomerism is the phenomenon of two or more compounds having the same number and kind of atoms. In stereoisomerism the isomers have the same structural formula but differ in the spatial arrangement of atoms. Stereoisomers have the same structural formula but differ in their spatial arrangement. 63 63

Chapter 26 Summary A polarimeter uses two polarizers to measure the rotation of plane-polarized light caused by a solution that contains an optically active compound. Compounds that are able to rotate polarized light are said to be optically active. Optical activity is commonly associated with asymmetric carbon atoms. A compound with an asymmetric carbon atom is not superimposable on its mirror image. 64 64

Chapter 26 Summary A molecule that is not superimposable on its mirror image is said to be chiral. A molecule with one chiral carbon atom can be in two optically active isomeric forms. Fischer projection formulas depict a three-dimensional molecule as a flat, two-dimensional drawing. Chiral molecules that are mirror images of each other are stereoisomers and are called enantiomers. 65 65

Chapter 26 Summary A mixture containing equal amounts of a pair of enantiomers is known as a racemic mixture. The maximum number of stereoisomers for a given chiral compound is equal to 2n, where n equals the number of chiral carbon atoms in the molecule. Stereoisomers that are not mirror images (enantiomers) are called diastereomers. 66 66

Chapter 26 Summary Stereoisomers that contain chiral carbon atoms and are superimposable on their mirror images are called meso compounds or meso structures. Meso compounds are not optically active and are achiral compounds. 67 67