2.8 THE RELATION BETWEEN SYMMETRY AND OPTICAL ACTIVITY Symmetry becomes a subject of interest to a chemist early in his study of organic chemistry because symmetry (or its absence) is a criterion of optical activity. A discussion of optical activity usually Fig. 2.14 Ethane in the almost-eclipsed, optically active conformation. immediately precedes the consideration of the carbohydrates. In part, perhaps, this is justified on historical grounds, since carbo- hydrate chemistry and optical activity were closely intertwined in Emil Fischer's brilliant development of the structure of carbohydrates in the later part of the nineteenth century. Today the use of optically active compounds provides a powerful tool for the elucidation of reaction mechanisms. The relationship between optical activity and the symmetry properties of a molecule thus merits some discussion. A compound is optically active if its mirror image is not super- imposable upon the original. In the application of this test, it must be realized that the atoms in a molecule are in constant motion with respect to each other. Let us consider ethane (Fig. 2.14) in a con- formation almost but not quite eclipsed. Now the mirror image of this conformation of ethane is not superimposable on the original one, and hence, by the above test, ethane in this conformation is optically active. If, indeed, all the molecules of ethane were frozen in this conformation, ethane would be optically active. We know, however, that rotation around single bonds, including the C—C bond, is relatively easy and requires only a small activation energy, and hence the conformation shown in Fig. 2.14 is only one of an infinite number of possible conformations. Furthermore, an extremely largenumber of molecules is present in any practical volume of ethane; for example, approximately 30,000,000,000,000,000 (3 x 10"*) in one cubic millimeter. Consequently for all molecules corresponding to the structure shown in Fig. 2.14, there is a statistically equal probability that a like number of molecules represented by its mirror image are also present. Hence, if the molecule of Fig. 2.14 is arbitrarily considered to rotate the plane of polarized light in a dextro direction, the practically equal number of molecules possessing AT ek Fig. 2.15. (a) One of the three possible staggered and (4) one of the three possible eclipsed conformations of ethane, the mirror-image structure will rotate the plane of polarized light an equal amount in the /evo direction, and hence the net optical activity will be zero; the mixture is a racemic modification. Although Fig. 2.14 represents a molecule of ethane which is nonsuperimposable on its mirror image, other conformations of ethane, six to be precise, have superimposable mirror images. These conformations are the three possible exactly eclipsed and the three possible exactly staggered conformations; one of each is shown in Fig. 2.15. As will be shown, the fact that (6) has a plane of symmetry and (a) in addition a center of symmetry immediately implies that the mirror iinage of (a) is superimposable on (a) and the mirror image of (©) superimposable on (5). Consequently we are spared the necessity of writing or drawing the mirror image and performing the super- positioning, although in this particular example the process is simple if not obvious. Ethane can be said to be optically inactive because,for every imaginable conformation, there exists another confor- mation which is the mirror image of the first and because these conformations are readily interconvertible and of equal energy, and accordingly present in equal proportions. Any activity of the first is canceled by that of the mirror image. In only six conformations is the mirror image equivalent and superimposable on the original. In order to be optically active, a molecule must not be readily able to assume any conformation whose mirror image is superimposable on the original. Hence it can be immediately concluded that ethane is inactive because it can readily assume a conformation [either (a) or (6)] which has a superimposable mirror image. The foregoing discussion indicates how useful it could be to deter- mine whether or not a molecule has a superimposable mirror image, that is, whether it is optically active. If the four groups or atoms attached to the carbon atom in Cabcd are all different, the mirror image of the molecule will not be superimposable on the original, and the carbon atom is called an asymmetric carbon atom. If the molecule is more complicated, it is sometimes difficult to decide whether the four groups attached to a particular carbon are “different.” Furthermore, many optically active molecules that contain no “asymmetric” carbon atoms are known. One single criterion is sufficient to determine whether or not a molecule is optically active: the existence of an S, axis in the molecule. I has an S, axis, even if p = 1, the molecule is inactive, that is, it is superimposable on its mirror image. In most examples it is common practice to search for a plane of symmetry or a center of symmetry simply because these symmetry elements are easier to spot than the S, and Sz axes to which they correspond, respectively. However, some molecules are known which do not possess either an S, or an ‘Sz axis but which are inactive, owing to an S, axis of order higher than twofold. Thus, the spiran shown in Fig. 2.16 has neither a plane nor a center of symmetry, but the vertical axis that bisects both rings and goes through the spiro nitrogen atom is an S, axis. Rotation by 90° around this axis followed by reflection in a plane perpendicular to the axis and passing through the nitrogen atom restores the molecule to the original configuration. Consequentlyitis not surprising that it has been impossible to resolve this molecule. It is important to note that a molecule may possess an element of symmetry and still be optically active. Thus if the only symmetry element present in a molecule is a C, axis, an ordinary axis of symmetry, the molecule will be optically active. Consider, for example, frans-1,2-dichlorocyclopropane (Fig. 2.17). The axis in the plane of the molecule bisecting the methylene group and the opposite C—C bond is a C, axis; rotation around it results in an orientation superimposable on the original one. However, the mirror image (6) of the molecule is not superimposable on (@) and hence (a) and (6) are enantiomorphs. Note also that the spiran of Fig. 2.16 has a C, axis coincident with the S, axis; but the presence of the S, and not of the C, axis is responsible for the lack of optical activity. Molecules such as trans-1,2-dichlorocyclopropane, which have a symmetry element but which are optically active, cannot correctly be said to be asymmetric because asymmetric means with- out symmetry. Such molecules are described as dissymmetric. An 16 A molecule Fig.2.17 (a) An optically active compound and which is optically in- (6) its mirror image. active because of the presence of an S, axis.optically active compound need not be asymmetric, but it must be dissymmetric. Thus dissymmetric compounds need not be asym- metric, but all asymmetric compounds are dissymmetric. It was stated earlier that if any readily accessible conformation of a molecule possesses an S, axis, the molecule will be inactive. Free rotation around single bonds in most acyclic compounds is possible. The barrier to free rotation would have to be about 15-20 keal/mole before individual conformers or rotamers could be isolated at room temperature. With cyclic compounds complete rotation around the bonds making up the ring is impossible. However, in the cyclo- hexane and other saturated ring systems a variety of conformations are interconvertible at room temperature. Thus, cyclohexane can exist in either of two (rigid) chair forms which interconvertible through a (flexible) boat form (Fig. 2.18). In going from one chair form to the other, all the C—C bonds must be partially rotated. The energy barrier for the conversion of a chair to a boat form is estimated to be about 10-11 kcal/mole. The free-energy difference between the more stable chair forms and the boat form is estimated to be about 4 kcal/mole, which is sufficient to insure that about 99.9 percent of the molecules at room temperature are in the chair form. The chair forms of cyclohexane have S;, Sz, and Sg axes, the S, axis going through the center of the molecule and perpendicular to the approximate plane of the molecule; this axis is also a C, axis. BP AS Fig. 2.18 The two interconvertible chair forms (a) and (c), and the boat form (6) of cyclohexane. If one of the hydrogens is replaced by another group, for example, chlorine (Fig. 2.19), the resulting molecule has an S, axis and there- fore a plane of symmetry. The plane of symmetry is perpendicular to the ring and includes the chlorine atom and carbons | and 4 and the hydrogens attached to these carbon atoms. The S, axis is I LA oe Noh, @ Fig. 2.19 The equatorial (a) and axial (6) forms of chlorocyclohexane.perpendicular to the plane and bisects the 2—3 and $—6 bonds. The same symmetry elements would be present were the chlorine in the axial position (Fig. 2.196). Neither conformation lacks an S, axis and hence neither is optically active, and chlorocyclohexane, which consists of a mixture of the equatorial and axial forms, although predominantly equatorial, is inactive. Let us now consider cis-1,2-dichlorocyclohexane (Fig. 2.20): In the 1,2-cis form, one chlorine is in an axial (a) position and the other chlorine is in an equatorial (e) position. The inverted form now has the former equatorial chlorine in an axial position, and the former axial in an equatorial. Since both forms are (a, e), they are of equal stability, and since the energy barrier to inversion is not large interconversion occurs readily at room temperature. Thus cis-1,2- dichlorethane consists of an equimolar mixture of both forms. Now, neither (a) nor (6) has an S, axis, and hence we may be tempted to conclude that the compound is optically active. However, close Ak By. @ oo Fig. 2.20 (a) The 1(a),2(e}-dichlorocyclohexane, and (6) the 1(e), 2(a)-form. examination will reveal that Figs. 2.20@ and 2.206 are, in fact, mirror images of each other and thus if (a) were dextrorotatory, any activity would be canceled by the equal population of the equivalently levorotatory enantiomorphic (5). Thus we may consider that cis-1,2-dichloro- cyclohexane is inactive because it is a racemic modification. If we were to con- St sider the cyclohexane ring as a com- pletely planar ring (Fig. 2.21), then the & possibility of optical activity would be ruled out on the basis of the existence of . a plane of symmetry (or S, axis); on this cyclohexane assuming @ basis we might conclude that the com- planar cyclohexane ring and - showing the S, axis perpen- Pound was a meso modification. Thus, dicular to the ring. whether we correctly rule out optical activity on the basis of a racemic modi- Fig. 2.21. cis-1,2-Dichloro-fication or on the less sophisticated basis of a meso modification, we end up with the same result. Fortunately it is true that for the purpose of determining optical activity the cyclohexane ring may be considered planar. Perhaps the theoretical justification for this is that in the ready interconversion of the two chair forms the “average conformation” is a planar ring. Finally, mention should be made of a special situation in which a molecule may possess no S, axis in any conformation and still be inactive. Such a molecule is (dextro)-menthyl-(/evo)-menthyl-2,6,2',- 6'-tetranitro-4,4’-diphenate (Fig. 2.22). The mirror image of this molecule is not superimposable on the original. However, if the 4,4’ bonds in the mirror image are rotated, then the new molecule is NOz i} i] (+) CigHig—C—0- ‘O—C—CioHis (-) NOg NOz Fig. 2.22 A dissymmetric compound that is inactive. superimposable on the original, because of the generation of a pseudo S, axis. Such rotations are possible under ordinary condi- tions, and these rotameric interconversions ensure statistically equal populations of enantiomeric conformations and thus account for the observed optical inactivity. REFERENCES Robert P. Bauman, Absorption Spectroscopy, John Wiley and Sons, New York, 1962, Chapter 10. Andrew Streitwieser, Jr., Molecular Orbital Theory for Organic Chemists, John Wiley and Sons, New York, 1961, Sections 3.5-3.6. Gerhard Herzberg, Molecular Spectra and Molecular Structure, Vol. 2, Infrared and Raman Spectra of Polyatomic Molecules, D. Yan Nostrand Co., Princeton, N.J. 1945, pp. 1-12. P. J. Wheatley, The Determination of Molecular Structure, Oxford University