CHAPTER 7 STEREOCHEMISTRY he greek word stereos means"solid, " and stereochemistry refers to chemistry in three dimensions. The foundations of organic stereochemistry were laid by Jacobus vant Hoff and Joseph Achille Le Bel in 1874. Independently of each other, vant Hoff and Le Bel proposed that the four bonds to carbon were directed toward the cor- ners of a tetrahedron. One consequence of a tetrahedral arrangement of bonds to carbon is that two compounds may be different because the arrangement of their atoms in space is different. Isomers that have the same constitution but differ in the spatial arrangement of their atoms are called stereoisomers. We have already had considerable experience with certain types of stereoisomers--those involving cis and trans substitution patterns Our major objectives in this chapter are to develop a feeling for molecules as three- dimensional objects and to become familiar with stereochemical principles, terms, and notation. A full understanding of organic and biological chemistry requires an awareness of the spatial requirements for interactions between molecules; this chapter provides the 7.1 MOLECULAR CHIRALITY: ENANTIOMERS Everything has a mirror image, but not all things are superposable on their mirror images Mirror-image superposability characterizes many objects we use every day. Cups and saucers, forks and spoons, chairs and beds are all identical with their mirror images. Man other objects though-and this is the more interesting case--are not. Your left hand and your right hand, for example, are mirror images of each other but cant be made to coin- cide point for point, palm to palm, knuckle to knuckle, in three dimensions. In 1894, william "Vant Hoff was the recipient of the first Nobel Prize in chemistry in 1901 for his work in chemical dynam. ics and osmotic pressure--two topics far removed from stereochemistry. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
259 CHAPTER 7 STEREOCHEMISTRY The Greek word stereos means “solid,” and stereochemistry refers to chemistry in three dimensions. The foundations of organic stereochemistry were laid by Jacobus van’t Hoff* and Joseph Achille Le Bel in 1874. Independently of each other, van’t Hoff and Le Bel proposed that the four bonds to carbon were directed toward the corners of a tetrahedron. One consequence of a tetrahedral arrangement of bonds to carbon is that two compounds may be different because the arrangement of their atoms in space is different. Isomers that have the same constitution but differ in the spatial arrangement of their atoms are called stereoisomers. We have already had considerable experience with certain types of stereoisomers—those involving cis and trans substitution patterns in alkenes and in cycloalkanes. Our major objectives in this chapter are to develop a feeling for molecules as threedimensional objects and to become familiar with stereochemical principles, terms, and notation. A full understanding of organic and biological chemistry requires an awareness of the spatial requirements for interactions between molecules; this chapter provides the basis for that understanding. 7.1 MOLECULAR CHIRALITY: ENANTIOMERS Everything has a mirror image, but not all things are superposable on their mirror images. Mirror-image superposability characterizes many objects we use every day. Cups and saucers, forks and spoons, chairs and beds are all identical with their mirror images. Many other objects though—and this is the more interesting case—are not. Your left hand and your right hand, for example, are mirror images of each other but can’t be made to coincide point for point, palm to palm, knuckle to knuckle, in three dimensions. In 1894, William *Van’t Hoff was the recipient of the first Nobel Prize in chemistry in 1901 for his work in chemical dynamics and osmotic pressure—two topics far removed from stereochemistry. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SEVEN Stereochemistry Thomson (Lord Kelvin) coined a word for this property. He defined an object as chiral if It Is rposable on its mirror image. Applying Thomson's term to chemistry, we sa that a molecule is chiral if its two mirror-image forms are not superposable in three dimen sions. The ork"chiral"is derived from the Greek word cheir meaning "hand, and it is entirely appropriate to speak of the"handedness"of molecules. The opposite of chiral is achiral. A molecule that is superposable on its mirror image is achiral. In organic chemistry, chirality most often occurs in molecules that contain a car- bon that is attached to four different groups. An example is bromochlorofluoromethane (BrCIFCH). is a known compound, and H been described in the chemi- described a method for the on of brClfCh that Bromochlorofluoromethane predominantly one enan tiome As shown in Figure 7. 1. the two mirror images of bromochlorofluoromethane cannot be uperposed on each other. Since the two mirror images of bromochlorofuoromethane a not superposable, BrCIFCH is chiral The two mirror images of bromochlorofuoromethane have the same constitution that is, the atoms are connected in the same order. But they differ in the arrangement of their atoms in space; they are stereoisomers. Stereoisomers that are related as an object and its nonsuperposable mirror image are classified as enantiomers. The word"enantiomer describes a particular relationship between two objects. One cannot look at a single mole- cule in isolation and ask if it is an enantiomer any more than one can look at an individual human being and ask, "ls that person a cousin? "Furthermore, just as an object has one, and only one, mirror image, a chiral molecule can have one, and only one, enantiomer. Notice in Figure 7.1c, where the two enantiomers of bromochlorofuoromethane are similarly oriented, that the difference between them corresponds to an interchange of the positions of bromine and chlorine. It will generally be true for species of the type C(w x, y, z), where w, x, y, and z are different atoms or groups, that an exchange of two of them converts a structure to its enantiomer but an exchange of three returns the orig inal structure. albeit in a different orientation. Consider next a molecule such as chlorodifluoromethane(Cif,Ch). in which two of the atoms attached to carbon are the same. Figure 7.2 on page 262 shows two molecular models of CIF2CH drawn so as to be mirror images. As is evident from these drawings, it is a sim- ple matter to merge the two models so that all the atoms match. Since mirror-image repl sentations of chlorodifluoromethane are superposable on each other, CIF2 CH is achiral The surest test for chirality is a careful examination of mirror-image forms for superposability. Working with models provides the best practice in dealing with mole cules as three-dimensional objects and is strongly recommended. 7.2 THE STEREOGENIC CENTER As we' ve just seen, molecules of the general type Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Thomson (Lord Kelvin) coined a word for this property. He defined an object as chiral if it is not superposable on its mirror image. Applying Thomson’s term to chemistry, we say that a molecule is chiral if its two mirror-image forms are not superposable in three dimensions. The work “chiral” is derived from the Greek word cheir, meaning “hand,” and it is entirely appropriate to speak of the “handedness” of molecules. The opposite of chiral is achiral. A molecule that is superposable on its mirror image is achiral. In organic chemistry, chirality most often occurs in molecules that contain a carbon that is attached to four different groups. An example is bromochlorofluoromethane (BrClFCH). As shown in Figure 7.1, the two mirror images of bromochlorofluoromethane cannot be superposed on each other. Since the two mirror images of bromochlorofluoromethane are not superposable, BrClFCH is chiral. The two mirror images of bromochlorofluoromethane have the same constitution. That is, the atoms are connected in the same order. But they differ in the arrangement of their atoms in space; they are stereoisomers. Stereoisomers that are related as an object and its nonsuperposable mirror image are classified as enantiomers. The word “enantiomer” describes a particular relationship between two objects. One cannot look at a single molecule in isolation and ask if it is an enantiomer any more than one can look at an individual human being and ask, “Is that person a cousin?” Furthermore, just as an object has one, and only one, mirror image, a chiral molecule can have one, and only one, enantiomer. Notice in Figure 7.1c, where the two enantiomers of bromochlorofluoromethane are similarly oriented, that the difference between them corresponds to an interchange of the positions of bromine and chlorine. It will generally be true for species of the type C(w, x, y, z), where w, x, y, and z are different atoms or groups, that an exchange of two of them converts a structure to its enantiomer, but an exchange of three returns the original structure, albeit in a different orientation. Consider next a molecule such as chlorodifluoromethane (ClF2CH), in which two of the atoms attached to carbon are the same. Figure 7.2 on page 262 shows two molecular models of ClF2CH drawn so as to be mirror images. As is evident from these drawings, it is a simple matter to merge the two models so that all the atoms match. Since mirror-image representations of chlorodifluoromethane are superposable on each other, ClF2CH is achiral. The surest test for chirality is a careful examination of mirror-image forms for superposability. Working with models provides the best practice in dealing with molecules as three-dimensional objects and is strongly recommended. 7.2 THE STEREOGENIC CENTER As we’ve just seen, molecules of the general type x z w C y Cl±C±Br H W W F Bromochlorofluoromethane 260 CHAPTER SEVEN Stereochemistry Bromochlorofluoromethane is a known compound, and samples selectively enriched in each enantiomer have been described in the chemical literature. In 1989 two chemists at Polytechnic University (Brooklyn, New York) described a method for the preparation of BrClFCH that is predominantly one enantiomer. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
7.2 The Stereogenic Center (a) Structures A and B are mirror-image representations of bromochlorofluoromethane(BrCIFCH) (b) To test for superposability, reorient B by turning it 180 tumn180° B (c)C A and B. The two do not match. A and B cannot be superposed on each other. a chiral molecule. The two mirror-image forms are of each other two mirror-image forms are not superposable. groups FIGURE 7. 1 A molecule with four different groups attached to a single carbon is chiral. Its are chiral when w, x, v, and z are different substituents. a tetrahedral carbon atom that bears four different substituents is variously referred to as a chiral center, a chiral car- 1987 issue of the Joumal of bon atom, an asymmetric center, or an asymmetric carbon atom. A more modern term Chemical Education gives a is stereogenic center, and that is the term that we'll use (Stereocenter is synonymous horough discussion of molec- ar chirality and with stereogenic center:) past and present terminal- Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
are chiral when w, x, y, and z are different substituents. A tetrahedral carbon atom that bears four different substituents is variously referred to as a chiral center, a chiral carbon atom, an asymmetric center, or an asymmetric carbon atom. A more modern term is stereogenic center, and that is the term that we’ll use. (Stereocenter is synonymous with stereogenic center.) 7.2 The Stereogenic Center 261 (a) Structures A and B are mirror-image representations of bromochlorofluoromethane (BrClFCH). (b) To test for superposability, reorient B by turning it 180°. (c) Compare A and B. The two do not match. A and B cannot be superposed on each other. Bromochlorofluoromethane is therefore a chiral molecule. The two mirror-image forms are enantiomers of each other. B A A B Br Cl H F Br Cl H F Br Cl H F A Br Cl H F Br Cl H F B Br Cl H F turn 180° FIGURE 7.1 A molecule with four different groups attached to a single carbon is chiral. Its two mirror-image forms are not superposable. An article in the December 1987 issue of the Journal of Chemical Education gives a thorough discussion of molecular chirality and some of its past and present terminology. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SEVEN Stereochemistry FIGURE 7.2 Mirro image forms of chlorodifluo- romethane are superposable in each other. chlorodifluc eos● Noting the presence of one(but not more than one) stereogenic center in a mole cule is a simple, rapid way to determine that it is chiral. For example, C-2 is a stereo- genic center in 2-butanol; it bears a hydrogen atom and methyl, ethyl, and hydroxyl groups as its four different substituents. By way of contrast, none of the carbon atoms bear four different groups in the achiral alcohol 2-propanol H CH3C—CH2CH3 OH 2-Butanol Chiral: four different Achiral: two of the substituent substituents at C-2 at C-2 are the same PROBLEM 7.1 Examine the following for stereogenic centers: (a)2-Bromopentane (c)1-Bromo-2-methylbutane (b)3-Bromopentane d)2-Bromo-2-methylbutane SAMPLE SOLUTION erogenic carbon has four different substituents. (a)In 2-bromopentane, C-2 satisfies this requirement.(b) None of the carbons in 3 bromopentane have four different substituents, and so none of its atoms are stereogenIc centers. H3C—CH2CH2CH3CH3CH2-C—CH2CH3 2-Bromopentane 3-Bromop Molecules with stereogenic centers are very common, both as naturally occurring substances and as the products of chemical synthesis. Carbons that are part of a double bond or a triple bond can't be stereogenic centers. CH3CH, CH,-C-CH, CH,CH, CH3 (CH3)2C=CHCH, CH -C-CH=CH2 CH,CH 4-Ethyl-4-methyloctane Linalool (a chiral alkane) (a pleasa obtained fr Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Noting the presence of one (but not more than one) stereogenic center in a molecule is a simple, rapid way to determine that it is chiral. For example, C-2 is a stereogenic center in 2-butanol; it bears a hydrogen atom and methyl, ethyl, and hydroxyl groups as its four different substituents. By way of contrast, none of the carbon atoms bear four different groups in the achiral alcohol 2-propanol. PROBLEM 7.1 Examine the following for stereogenic centers: (a) 2-Bromopentane (c) 1-Bromo-2-methylbutane (b) 3-Bromopentane (d) 2-Bromo-2-methylbutane SAMPLE SOLUTION A stereogenic carbon has four different substituents. (a) In 2-bromopentane, C-2 satisfies this requirement. (b) None of the carbons in 3- bromopentane have four different substituents, and so none of its atoms are stereogenic centers. Molecules with stereogenic centers are very common, both as naturally occurring substances and as the products of chemical synthesis. (Carbons that are part of a double bond or a triple bond can’t be stereogenic centers.) 4-Ethyl-4-methyloctane (a chiral alkane) CH2CH3 CH3CH2CH2 C CH3 CH2CH2CH2CH3 Linalool (a pleasant-smelling oil obtained from orange flowers) OH (CH3)2C CHCH2CH2 C CH3 CH CH2 H Br CH3 C CH2CH2CH3 2-Bromopentane H Br CH3CH2 C CH2CH3 3-Bromopentane 2-Butanol Chiral; four different substituents at C-2 OH CH3 C H CH2CH3 2-Propanol Achiral; two of the substituents at C-2 are the same OH CH3 C H CH3 262 CHAPTER SEVEN Stereochemistry Cl Cl H H F F F F FIGURE 7.2 Mirrorimage forms of chlorodifluoromethane are superposable on each other. Chlorodifluoromethane is achiral. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
7.2 The Stereogenic Center A carbon atom in a ring can be a stereogenic center if it bears two different sub- stituents and the path traced around the ring from that carbon in one direction is differ ent from that traced in the other. The carbon atom that bears the methyl group in 1, 2 epoxypropane, for example, is a stereogenic center. The sequence of groups is O-CH2 as one proceeds clockwise around the ring from that atom, but is CH2-O in the anti- clockwise direction. Similarly, C-4 is a stereogenic center in limonene models of the H2C—CHCH3 g By Modeling and 1-2-Epoxypropane Limonene (product of epoxidation of propene) (a constituent of lemon oil) PROBLEM 7. 2 Identify the stereogenic centers, if any, in (a)2-Cyclopenten-1-ol and 3-cyclopenten-1-ol SAMPLE SOLUTION (a)The hydroxyl-bearing carbon in 2-cyclopenten-1-oI is a stereogenic center. There is no stereogenic center in 3-cyclopenten-1-ol, since the sequence of atoms1→2→3→4→5 is equivalent regardless of whether one proceeds clockwise or anticlockwis H OH 2-Cyclopenten-1-ol enten -1-ol Even isotopes qualify as different substituents at a stereogenic center. The stereo- chemistry of biological oxidation of a derivative of ethane that is chiral because of deu terium(d=2H)and tritium (T= H) atoms at carbon, has been studied and shown to proceed as follows: CH Biological oxidation HO The stereochemical relationship between the reactant and the product, revealed by the isotopic labeling, shows that oxygen becomes bonded to carbon on the same side from hich is lost One final, very important point about stereogenic centers. Everything we have said in this section concerns molecules that have one and only one stereogenic cen ter, molecules with more than one stereogenic center may or may not be chiral. Mol- ecules that have more than one stereogenic center will be discussed in Sections 7.10 through 7.13 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
A carbon atom in a ring can be a stereogenic center if it bears two different substituents and the path traced around the ring from that carbon in one direction is different from that traced in the other. The carbon atom that bears the methyl group in 1,2- epoxypropane, for example, is a stereogenic center. The sequence of groups is O±CH2 as one proceeds clockwise around the ring from that atom, but is CH2±O in the anticlockwise direction. Similarly, C-4 is a stereogenic center in limonene. PROBLEM 7.2 Identify the stereogenic centers, if any, in (a) 2-Cyclopenten-1-ol and 3-cyclopenten-1-ol (b) 1,1,2-Trimethylcyclobutane and 1,1,3-Trimethylcyclobutane SAMPLE SOLUTION (a) The hydroxyl-bearing carbon in 2-cyclopenten-1-ol is a stereogenic center. There is no stereogenic center in 3-cyclopenten-1-ol, since the sequence of atoms 1 → 2 → 3 → 4 → 5 is equivalent regardless of whether one proceeds clockwise or anticlockwise. Even isotopes qualify as different substituents at a stereogenic center. The stereochemistry of biological oxidation of a derivative of ethane that is chiral because of deuterium (D 2 H) and tritium (T 3 H) atoms at carbon, has been studied and shown to proceed as follows: The stereochemical relationship between the reactant and the product, revealed by the isotopic labeling, shows that oxygen becomes bonded to carbon on the same side from which H is lost. One final, very important point about stereogenic centers. Everything we have said in this section concerns molecules that have one and only one stereogenic center; molecules with more than one stereogenic center may or may not be chiral. Molecules that have more than one stereogenic center will be discussed in Sections 7.10 through 7.13. C T H D CH3 C T HO D CH3 biological oxidation H 4 OH 3 5 2 1 2-Cyclopenten-1-ol H 4 3 5 2 OH 3 4 2 5 1 3-Cyclopenten-1-ol (does not have a stereogenic carbon) H2C CHCH3 O 1-2-Epoxypropane (product of epoxidation of propene) CH3 H 3 C 6 2 5 4 1 CH3 CH2 Limonene (a constituent of lemon oil) 7.2 The Stereogenic Center 263 Examine the molecular models of the two enantiomers of 1,2-epoxypropane on Learning By Modeling and test them for superposability. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SEVEN Stereochemistry 7. 3 SYMMETRY IN ACHIRAL STRUCTURES Certain structural features can sometimes help us determine by inspection whether a mol ecule is chiral or achiral. For example, a molecule that has a plane of symmetry or a cen ter of symmetry is superposable on its mirror image and is achiral a plane of symmetry bisects a molecule so that one half of the molecule is the mirror image of the other half. The achiral molecule chlorodifluoromethane, for exam- ple, has the plane of symmetry shown in Figure 7.3 A point in a molecule is a center of symmetry if any line drawn from it to som element of the structure will, when extended an equal distance in the opposite direction encounter an identical element. The cyclobutane derivative in Figure 7. 4 lacks a plane of symmetry, yet is achiral because it possesses a center of symmetry. PROBLEM 7. 3 Locate any planes of symmetry or centers of symmetry in each of the following compounds. Which of the compounds are chiral? Which are achiral? (a)(Er-1, 2-Dichloroethen (c)cis-1, 2-Dichlorocyclopropane (b)(Z)-1, 2, Dichloroethene (d) trans-1, 2-Dichlorocyclopropane SAMPLE SOLUTION (a)(E)-1, 2-Dichloroethene is planar. The molecular plane is plane of syi Furthermore, (E)-1, 2-dichloroethene has a center of symmetry located at the mid point of the carbon-carbon double bond. It is achira FIGURE 7. 3 A plane f symmetry defined atoms H-C-Cl chlorodifluoromethane into Br Br FIGURE 7. 4(a)Struc tural formulas a and b are drawn as mirror images. (b) The two mirror images are superposable by rotating form b 180 about an axis passing through the center B≡A f the molecule. the center of the molecule is a center of (a) (b) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
7.3 SYMMETRY IN ACHIRAL STRUCTURES Certain structural features can sometimes help us determine by inspection whether a molecule is chiral or achiral. For example, a molecule that has a plane of symmetry or a center of symmetry is superposable on its mirror image and is achiral. A plane of symmetry bisects a molecule so that one half of the molecule is the mirror image of the other half. The achiral molecule chlorodifluoromethane, for example, has the plane of symmetry shown in Figure 7.3. A point in a molecule is a center of symmetry if any line drawn from it to some element of the structure will, when extended an equal distance in the opposite direction, encounter an identical element. The cyclobutane derivative in Figure 7.4 lacks a plane of symmetry, yet is achiral because it possesses a center of symmetry. PROBLEM 7.3 Locate any planes of symmetry or centers of symmetry in each of the following compounds. Which of the compounds are chiral? Which are achiral? (a) (E)-1,2-Dichloroethene (c) cis-1,2-Dichlorocyclopropane (b) (Z)-1,2,Dichloroethene (d) trans-1,2-Dichlorocyclopropane SAMPLE SOLUTION (a) (E)-1,2-Dichloroethene is planar. The molecular plane is a plane of symmetry. Furthermore, (E)-1,2-dichloroethene has a center of symmetry located at the midpoint of the carbon–carbon double bond. It is achiral. 264 CHAPTER SEVEN Stereochemistry F F Cl H Br Br Cl Cl Br Br Cl Cl A B (a) Br Br Cl Cl B (b) Br Br Cl Cl BPA FIGURE 7.4 (a) Structural formulas A and B are drawn as mirror images. (b) The two mirror images are superposable by rotating form B 180° about an axis passing through the center of the molecule. The center of the molecule is a center of symmetry. FIGURE 7.3 A plane of symmetry defined by the atoms H±C±Cl divides chlorodifluoromethane into two mirror-image halves. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
4 Properties of Chiral Molecules: Optical Activity Any molecule with a plane of symmetry or a center of symmetry is achiral, but their absence is not sufficient for a molecule to be chiral. a molecule lacking a center of symmetry or a plane of symmetry is likely to be chiral, but the superposability test should be applied to be certain 7. 4 PROPERTIES OF CHIRAL MOLECULES: OPTICAL ACTIVITY The experimental facts that led vant Hoff and Le bel to propose that molecules having The phenomenon of optical the same constitution could differ in the arrangement of their atoms in space concerned ctivity was discovered by the physical property of optical activity. Optical activity is the ability of a chiral sub- the French physicist Jean- stance to rotate the plane of plane-polarized light and is measured using an instrument Baptiste Biot in 1815 alled a polarimeter.( Figure 7.5) The light used to measure optical activity has two properties: it consists of a sin- le wavelength and it is plane-polarized. The wavelength used most often is 589 nm (called the D line ), which corresponds to the yellow light produced by a sodium lamp Except for giving off light of a single wavelength, a sodium lamp is like any other lamp in that its light is unpolarized, meaning that the plane of its electric field vector can have any orientation along the line of travel. A beam of unpolarized light is transformed to plane-polarized light by passing it through a polarizing filter, which removes all the waves except those that have their electric field vector in the same plane. This plane polarized light now passes through the sample tube containing the substance to be exam ined, either in the liquid phase or as a solution in a suitable solvent(usually water, ethanol, or chloroform). The sample is"optically active "if it rotates the plane of polar ized light. The direction and magnitude of rotation are measured using a second polar izing filter (the"analyzer")and cited as a, the observed rotation. To be optically active, the sample must contain a chiral substance and one enantiomer must be present in excess of the other: A substance that does not rotate the plane of polar ized light is said to be optically inactive. All achiral substances are optically inactive. What causes optical rotation? The plane of polarization of a light wave undergoes a minute rotation when it encounters a chiral molecule. enantiomeric forms of a chiral molecule cause a rotation of the plane of polarization in exactly equal amounts but in Sample tube with solution of optically Angle rotatIon ctive substance Analyzer light oscillates Plane-polarized 180° FIGURE 7.5 The mp emits light moving in all When the light passes through stance. The plan contains a solu econd polarizing filter(called the analyzer)is ed in degrees that is used to measure the angle of rotation (Adapted from M. Silberberg, Chemistry, 2d edition, McGraw-Hill Higher Education, New York, 1992,p.616) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Any molecule with a plane of symmetry or a center of symmetry is achiral, but their absence is not sufficient for a molecule to be chiral. A molecule lacking a center of symmetry or a plane of symmetry is likely to be chiral, but the superposability test should be applied to be certain. 7.4 PROPERTIES OF CHIRAL MOLECULES: OPTICAL ACTIVITY The experimental facts that led van’t Hoff and Le Bel to propose that molecules having the same constitution could differ in the arrangement of their atoms in space concerned the physical property of optical activity. Optical activity is the ability of a chiral substance to rotate the plane of plane-polarized light and is measured using an instrument called a polarimeter. (Figure 7.5). The light used to measure optical activity has two properties: it consists of a single wavelength and it is plane-polarized. The wavelength used most often is 589 nm (called the D line), which corresponds to the yellow light produced by a sodium lamp. Except for giving off light of a single wavelength, a sodium lamp is like any other lamp in that its light is unpolarized, meaning that the plane of its electric field vector can have any orientation along the line of travel. A beam of unpolarized light is transformed to plane-polarized light by passing it through a polarizing filter, which removes all the waves except those that have their electric field vector in the same plane. This planepolarized light now passes through the sample tube containing the substance to be examined, either in the liquid phase or as a solution in a suitable solvent (usually water, ethanol, or chloroform). The sample is “optically active” if it rotates the plane of polarized light. The direction and magnitude of rotation are measured using a second polarizing filter (the “analyzer”) and cited as , the observed rotation. To be optically active, the sample must contain a chiral substance and one enantiomer must be present in excess of the other. A substance that does not rotate the plane of polarized light is said to be optically inactive. All achiral substances are optically inactive. What causes optical rotation? The plane of polarization of a light wave undergoes a minute rotation when it encounters a chiral molecule. Enantiomeric forms of a chiral molecule cause a rotation of the plane of polarization in exactly equal amounts but in 7.4 Properties of Chiral Molecules: Optical Activity 265 The phenomenon of optical activity was discovered by the French physicist JeanBaptiste Biot in 1815. 0° 180° 270° 90° Analyzer Rotated polarized light Plane-polarized light oscillates in only one plane Sample tube with solution of optically active substance α Polarizing filter Unpolarized light oscillates in all planes Light source Angle of rotation FIGURE 7.5 The sodium lamp emits light moving in all planes. When the light passes through the first polarizing filter, only one plane emerges. The plane-polarized beam enters the sample compartment, which contains a solution enriched in one of the enantiomers of a chiral substance. The plane rotates as it passes through the solution. A second polarizing filter (called the analyzer) is attached to a movable ring calibrated in degrees that is used to measure the angle of rotation . (Adapted from M. Silberberg, Chemistry, 2d edition, McGraw-Hill Higher Education, New York, 1992, p. 616.) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SEVEN Stereochemistry pposite directions. A solution containing equal quantities of enantiomers therefore exhibits rotation because all the tiny increments of clockwise produced by molecules of one"handedness"are canceled by an equal number of increments of anticlockwise rotation produced by molecules of the opposite handedness Mixtures containing equal quantities of enantiomers are called racemic mixtures. Racemic mixtures are optically inactive. Conversely, when one enantiomer is present in excess, a net rotation of the plane of polarization is observed. At the limit, where all the molecules are of the same handedness, we say the substance is optically pure Optical purity, or percent enantiomeric excess, is defined Optical purity percent enantiomeric excess Thus, a material that is 50%o optically pure contains 75%o of one enantiomer and 25%o of Rotation of the plane of polarized light in the clockwise sense is taken as positive (+) and rotation in the anticlockwise sense is taken as a negative(-)rotation. The clas ical terms for positive and negative rotations are dextrorotatory and levorotatory, from the Latin prefixes dextro-("to the right")and levo-(to the left), respectively. At one time, the symbols d and l were used to distinguish between enantiomeric forms of a sub- stance. Thus the dextrorotatory enantiomer of 2-butanol was called d-2-butanol, and the levorotatory form 1-2-butanol; a racemic mixture of the two was referred to as dl-2- butanol. Current custom favors using algebraic signs instead, as in(+)-2-butanol, (-)-2-butanol, and(+)-2-butanol, respectively The observed rotation a of an optically pure substance depends on how many mol- ecules the light beam encounters. A filled polarimeter tube twice the length of another produces twice the observed rotation, as does a solution twice as concentrated. To account for the effects of path length and concentration, chemists have defined the term specific rotation, given the symbol [a]. Specific rotation is calculated from the observed rotation according to the expression ams per milliliter of so la lution instead of grams per where c is the concentration of the sample in grams per 100 mL of solution, and l is the length of the polarimeter tube in decimeters. (One decimeter is 10 cm Specific rotation is a physical property of a substance, just as melting point, boil ing point, density, and solubility are. For example, the lactic acid obtained from milk is exclusively a single enantiomer. We cite its specific rotation in the form [a]=+3.8% The temperature in degrees Celsius and the wavelength of light at which the measure ment was made are indicated as superscripts and subscripts, respectively PRoBLEM 7. 4 Cholesterol, when isolated from natural sources, is obtained as a single enantiomer. The observed rotation a of a 0.3-g sample of cholesterol in 15 L of chloroform solution contained in a 10-cm polarimeter tube is -0.78. Cal culate the specific rotation of cholesterol PROBLEM 7. 5 A sample of synthetic cholesterol was prepared consisting entirely of the enantiomer of natural cholesterol. a mixture of natural and synthetic cho- lesterol has a specific rotation [a] of -13. What fraction of the mixture is nat- ural cholesterol? Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
opposite directions. A solution containing equal quantities of enantiomers therefore exhibits no net rotation because all the tiny increments of clockwise rotation produced by molecules of one “handedness” are canceled by an equal number of increments of anticlockwise rotation produced by molecules of the opposite handedness. Mixtures containing equal quantities of enantiomers are called racemic mixtures. Racemic mixtures are optically inactive. Conversely, when one enantiomer is present in excess, a net rotation of the plane of polarization is observed. At the limit, where all the molecules are of the same handedness, we say the substance is optically pure. Optical purity, or percent enantiomeric excess, is defined as: Optical purity percent enantiomeric excess percent of one enantiomer percent of other enantiomer Thus, a material that is 50% optically pure contains 75% of one enantiomer and 25% of the other. Rotation of the plane of polarized light in the clockwise sense is taken as positive (), and rotation in the anticlockwise sense is taken as a negative () rotation. The classical terms for positive and negative rotations are dextrorotatory and levorotatory, from the Latin prefixes dextro- (“to the right”) and levo- (“to the left”), respectively. At one time, the symbols d and l were used to distinguish between enantiomeric forms of a substance. Thus the dextrorotatory enantiomer of 2-butanol was called d-2-butanol, and the levorotatory form l-2-butanol; a racemic mixture of the two was referred to as dl-2- butanol. Current custom favors using algebraic signs instead, as in ()-2-butanol, ()-2-butanol, and ()-2-butanol, respectively. The observed rotation of an optically pure substance depends on how many molecules the light beam encounters. A filled polarimeter tube twice the length of another produces twice the observed rotation, as does a solution twice as concentrated. To account for the effects of path length and concentration, chemists have defined the term specific rotation, given the symbol []. Specific rotation is calculated from the observed rotation according to the expression [] where c is the concentration of the sample in grams per 100 mL of solution, and l is the length of the polarimeter tube in decimeters. (One decimeter is 10 cm.) Specific rotation is a physical property of a substance, just as melting point, boiling point, density, and solubility are. For example, the lactic acid obtained from milk is exclusively a single enantiomer. We cite its specific rotation in the form [] D 25 3.8°. The temperature in degrees Celsius and the wavelength of light at which the measurement was made are indicated as superscripts and subscripts, respectively. PROBLEM 7.4 Cholesterol, when isolated from natural sources, is obtained as a single enantiomer. The observed rotation of a 0.3-g sample of cholesterol in 15 mL of chloroform solution contained in a 10-cm polarimeter tube is 0.78°. Calculate the specific rotation of cholesterol. PROBLEM 7.5 A sample of synthetic cholesterol was prepared consisting entirely of the enantiomer of natural cholesterol. A mixture of natural and synthetic cholesterol has a specific rotation [] D 20 of 13°. What fraction of the mixture is natural cholesterol? 100 cl 266 CHAPTER SEVEN Stereochemistry If concentration is expressed as grams per milliliter of solution instead of grams per 100 mL, an equivalent expression is [] cl Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
7.5 Absolute and Relative Configuration It is convenient to distinguish between enantiomers by prefixing the sign of rota- tion to the name of the substance. For example, we refer to one of the enantiomers of 2-butanol as (+)-2-butanol and the other as(-)-2-butanol. Optically pure(+)-2-butanol has a specific rotation [a]D of +13.5 optically pure (-)-2-butanol has an exactly oppo- site specific rotation [a]D of -13.59 7.5 ABSOLUTE AND RELATIVE CONFIGURATION The spatial arrangement of substituents at a stereogenic center is its absolute configu ration. Neither the sign nor the magnitude of rotation by itself can tell us the absolute configuration of a substance. Thus, one of the following structures is(+)-2-butanol and he other is(-)-2-butanol, but without additional information we can't tell which is which In several places throughout CH, CH H the chapter we will use red CH Although no absolute configuration was known for any substance before 1951 organic chemists had experimentally determined the configurations of thousands of com pounds relative to one another(their relative configurations)through chemical inter- conversion. To illustrate, consider (+)-3-buten-2-o1. Hydrogenation of this compound :lds(+)-2-butanol CH3 CHCH=CH2+ H2 CH3CHCH2CH3 Make a molecular model buten-2-ol and the 2-butanol 3-Buten-2-ol Hvdrogen 2-Butanol alb+135° Since hydrogenation of the double bond does not involve any of the bonds to the stereo- genic center, the spatial arrangement of substituents in(+)-3-buten-2-ol must be the same as that of the substituents in (+)-2-butanol. The fact that these two compounds have the same sign of rotation when they have the same relative configuration is established by the hydrogenation experiment; it could not have been predicted in advance of the experiment Sometimes compounds that have the same relative configuration have optical tions of opposite sign. For example, treatment of (-)-2-methyl-1-butanol with hydr bromide converts it to(+)-l-bromo-2-methylbutane of one of the enantiomers of 2. bromo-2-methylbutane formed CH3 CH,CHCH,OH HBr →CHCH2CHCH2Br+H2O from it lethyl-1-butane I-Bromo-2-methylbutane Water aB3-5.8° ab3+4.0° This reaction does not involve any of the bonds to the stereogenic center, and so both the starting alcohol (-)and the product bromide(+) have the same relative configura- Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
It is convenient to distinguish between enantiomers by prefixing the sign of rotation to the name of the substance. For example, we refer to one of the enantiomers of 2-butanol as ()-2-butanol and the other as ()-2-butanol. Optically pure ()-2-butanol has a specific rotation [] D 27 of 13.5°; optically pure ()-2-butanol has an exactly opposite specific rotation [] D 27 of 13.5°. 7.5 ABSOLUTE AND RELATIVE CONFIGURATION The spatial arrangement of substituents at a stereogenic center is its absolute configuration. Neither the sign nor the magnitude of rotation by itself can tell us the absolute configuration of a substance. Thus, one of the following structures is ()-2-butanol and the other is ()-2-butanol, but without additional information we can’t tell which is which. Although no absolute configuration was known for any substance before 1951, organic chemists had experimentally determined the configurations of thousands of compounds relative to one another (their relative configurations) through chemical interconversion. To illustrate, consider ()-3-buten-2-ol. Hydrogenation of this compound yields ()-2-butanol. Since hydrogenation of the double bond does not involve any of the bonds to the stereogenic center, the spatial arrangement of substituents in ()-3-buten-2-ol must be the same as that of the substituents in ()-2-butanol. The fact that these two compounds have the same sign of rotation when they have the same relative configuration is established by the hydrogenation experiment; it could not have been predicted in advance of the experiment. Sometimes compounds that have the same relative configuration have optical rotations of opposite sign. For example, treatment of ()-2-methyl-1-butanol with hydrogen bromide converts it to ()-1-bromo-2-methylbutane. This reaction does not involve any of the bonds to the stereogenic center, and so both the starting alcohol () and the product bromide () have the same relative configuration. 2-Methyl-1-butanol []D 25 5.8° CH3CH2CHCH2OH CH3 1-Bromo-2-methylbutane []D 25 4.0° CH3CH2CHCH2Br CH3 Hydrogen bromide HBr Water H2O 3-Buten-2-ol []D 27 33.2° OH CH3CHCH CH2 2-Butanol []D 27 13.5° OH CH3CHCH2CH3 Hydrogen H2 Pd C H H3C CH3CH2 OH H CH3 CH2CH3 HO C 7.5 Absolute and Relative Configuration 267 In several places throughout the chapter we will use red and blue frames to call attention to structures that are enantiomeric. Make a molecular model of one of the enantiomers of 3- buten-2-ol and the 2-butanol formed from it. Make a molecular model of one of the enantiomers of 2- methyl-1-1-butanol and the 1- bromo-2-methylbutane formed from it. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER SEVEN Stereochemistry An elaborate network connecting signs of rotation and relative configurations was developed that included the most important compounds of organic and biological chemist When, in 1951, the absolute configuration of a salt of (+)-tartaric acid was determined, the absolute configurations of all the compounds whose configurations had been related to (+)-tartaric acid stood revealed as well. Thus, returning to the pair of 2-butanol enantiomers that introduced this section, their absolute configurations are now known to be as shown CHaO CHCH OH CH (+)-2-Butano (一)2- Butanol PROBLEM 7.6 Does the molecular model shown represent (+)-2-butanol or ()-2-butanol? 7.6 THE CAHN-INGOLD-PRELOG R-S NOTATIONAL SYSTEM Just as it makes sense to have a nomenclature system by which we can specify the con stitution of a molecule in words rather than pictures, so too is it helpful to have one that lets us describe stereochemistry. We have already had some experience with this idea when we distinguished between E and Z stereoisomers of alkenes. In the E-Z system, substituents are ranked by atomic number according to a set of rules devised by R. S. Cahn, Sir Christopher Ingold, and Vladimir Prelog(Section 5.4) Actually, Cahn, Ingold, and Prelog first developed their ranking system to deal with the problem of the absolute configuration at a stereogenic center, and this is the systems major application. Table 7.1 shows how the Cahn-Ingold-Prelog system, called the sequence rules, is used to specify the absolute configuration at the stereogenic center in(+)-2-butanol The January 1994 issue of As outlined in Table 7.1,(+)-2-butanol has the S configuration. Its mirror image is(-)-2-butanol, which has the R configuration cation contains an article that describes how to your hands to assign R and S configurations. CH: CH H H CH,CH3 -OH Ho-C CH (S)-2-Butane (R)-2-Butano Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
An elaborate network connecting signs of rotation and relative configurations was developed that included the most important compounds of organic and biological chemistry. When, in 1951, the absolute configuration of a salt of ()-tartaric acid was determined, the absolute configurations of all the compounds whose configurations had been related to ()-tartaric acid stood revealed as well. Thus, returning to the pair of 2-butanol enantiomers that introduced this section, their absolute configurations are now known to be as shown. PROBLEM 7.6 Does the molecular model shown represent ()-2-butanol or ()-2-butanol? 7.6 THE CAHN–INGOLD–PRELOG R–S NOTATIONAL SYSTEM Just as it makes sense to have a nomenclature system by which we can specify the constitution of a molecule in words rather than pictures, so too is it helpful to have one that lets us describe stereochemistry. We have already had some experience with this idea when we distinguished between E and Z stereoisomers of alkenes. In the E–Z system, substituents are ranked by atomic number according to a set of rules devised by R. S. Cahn, Sir Christopher Ingold, and Vladimir Prelog (Section 5.4). Actually, Cahn, Ingold, and Prelog first developed their ranking system to deal with the problem of the absolute configuration at a stereogenic center, and this is the system’s major application. Table 7.1 shows how the Cahn–Ingold–Prelog system, called the sequence rules, is used to specify the absolute configuration at the stereogenic center in ()-2-butanol. As outlined in Table 7.1, ()-2-butanol has the S configuration. Its mirror image is ()-2-butanol, which has the R configuration. C H H3C CH3CH2 OH (S)-2-Butanol H CH3 CH2CH3 HO C (R)-2-Butanol and C H H3C CH3CH2 OH H CH3 CH2CH3 HO C ()-2-Butanol ()-2-Butanol 268 CHAPTER SEVEN Stereochemistry The January 1994 issue of the Journal of Chemical Education contains an article that describes how to use your hands to assign R and S configurations. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website