We have already covered two kinds of isomerism I Isomers (structural isomers CHAPTER 5 Stereoisomers n-suDer HC 5-1 Chiral Molecules HC HC HB HC . ct.cn. a5aeeachsmers 1
1 CHAPTER 5 Stereoisomers We have already covered two kinds of isomerism: •Constitutional Isomers (structural isomers) •Stereoisomers Examples of Constitutional Isomers: Examples of Stereoisomers: Another type of stereoisomerism is called mirror-image stereoisomerism. Mirror-image related stereoisomers are said to be left-handed and right-handed and occur when a molecule and its mirror image are non-superimposable. 5-1 Chiral Molecules The radical bromination of butane to form 2-bromobutane appears to yield a single product: Chiral molecules cannot be superimposed on their mirror images. The two 2-bromobutane molecules formed by the radical bromination of butane are actually nonsuperimposable and are therefore not identical. A molecule that is not superimposible on its mirror image is said to be chiral. In this case each isomer is called an enantiomer
Examples of chiral and achiral molecules: abseacec8pfecwe&mottstrchMays 人 hlor r个DD八 netrare 5-2 Optical Activity Optical rotation is measured with a polarimeter. enantiomer is dextrorotary (+ :enanti Theegrees)the 0A Temperature 2
2 Compounds whose mirror images are superimposable are called achiral. Examples of chiral and achiral molecules: Above all, the chiral examples contain an atom that is connected to 4 different substituent groups. This atom is called an asymmetric atom or a stereocenter. Often, asymmetric atoms are marked with an asterisk. Molecules having one stereocenter are always chiral. The symmetry in molecules helps to distinguish chiral structures from achiral ones. For most organic molecules, a sufficient test for chirality is absence of a plane of symmetry (mirror plane). A mirror plane is one that bisects the molecule in such a way that the half of the molecule on one side of the plane is the mirror image of the half on the other side of the plane. Methane has 6 planes of symmetry, chloromethane has 3, dichloromethane 2, bromochloromethane 1, and bromochlorofluoromethane none: 5-2 Optical Activity Enantiomers cannot be distinguished on the basis of their physical properties, such as boiling points, melting points, and densities. Enantiomers can be distinguished by the way they interact with plane-polarized light. When plane-polarized light is passed through a sample of one of the enantiomers, the plane of polarization is rotated either clockwise or counterclockwise. When the experiment is repeated with the other enantiomer, the plane-polarized light is rotated an equal amount, but in the opposite direction. If facing the light source: •Clockwise rotation: enantiomer is dextrorotary (+) •Counterclockwise rotation: enantiomer is levorotary (-) This interaction with light is called optical activity and enantiomers are often called optical isomers. Optical rotation is measured with a polarimeter. Light is electromagnetic radiation that oscillates perpendicular to its direction of motion. The oscillation of light can be resolved into two perpendicular components. When light is passed through a polarizer, only one of the two perpendicular components of light is passed through. This light is referred to as plane-polarized light. When plane-polarized light interacts with a chiral molecule, the plane of polarization of the light is rotated to the left or right. This effect is called optical rotation and the molecule is said to be optically active. Optical activity is measured using a polarimeter. This device contains a light source, a polarizer to produce the plane-polarized light, a sample cell, and an analyzer to determine the amount of rotation. The measured rotation (in degrees) is the observed optical rotation, α, of the sample. The value of α depends upon: •Structure of the chiral molecule •Concentration of the chiral molecule •Length of the sample cell •Wavelength of the light •Solvent used •Temperature
mfor chral pcific Retations ofris Chiral Cempeds o CI. 高Ca5马06 5-3 Absolute Configuration:R-S Sequence Rules canestablish the absolute oe0sgggaitiomerequlbrateswthsmirorlmage,he 5o8ae832 enters are labeledRorS. 时Ra2g3 .. arentheses to the name of th (R)-2-bromobutane hane (a racemie mixture) d lo R(+2,3-d ed in eit 3
3 The specific rotation [α] of a sample is defined for each chiral molecule (the value is solvent dependent): [ ] where [ ] = specific rotation t = temperature in degrees Celsius = wavelength of incident light (D = 589 nm, the yellow D line from Na) o t l c λ α α α λ = × = observed optical rotation in degres l = sample container length in dm c = concentration (g/ml) α Specific rotation is a physical constant for a substance, as is melting point, boiling point, density, etc. Examples of specific rotations: Optical rotation indicates enantiomeric composition. A racemic mixture is a mixture of equal amounts of the + and – enantiomers of a chiral compound. It shows no net rotation of plane-polarized light. When one enantiomer equilibrates with its mirror image, the process is called racemization. When one of the two enantiomers of a chiral compound is present in a mixture in excess over the other, there will be a net rotation of plane-polarized light. A 50% enantiomer excess would be defined as a mixture of 75% one enantiomer and 25% of the other (50%+ with 25%+ and 25%-). The mixture would be called 50% optically pure. The optical purity of an enantiomer is defined: [ ] [ ] % optical purity 100 enantiomer excess observed α α ⎛ ⎞ = ×= ⎜ ⎟ ⎝ ⎠ 5-3 Absolute Configuration: R-S Sequence Rules X-ray diffraction can establish the absolute configuration. The absolute configuration of an enantiomer is the actual spatial arrangement of the substituent groups around the chiral centers. There is no straightforward correlation between the absolute configuration of an enantiomer and the sign of rotation of the molecule. The absolute configuration of an enantiomer can be determined through single crystal X-ray diffraction analysis or through chemical correlation to a molecule whose absolute configuration has already been determined. Stereocenters are labeled R or S. The convention for naming enantiomers unambiguously was developed by R.S. Cahn, C. Ingold, and V. Prelog. The four substituents around the chiral carbon must be first ranked in order of decreasing priority. •a highest priority •b second-highest priority •c third-highest priority •d lowest priority When the molecule is positioned with the lowest-priority substituent away from the viewer, the remaining three substituents will be arranged in either a clockwise or counterclockwise direction. If the progression from a to b to c is clockwise, the configuration at the stereocenter is named S (sinister) otherwise the configuration is named R (rectus) The R or S is added as a prefix in parentheses to the name of the chiral compound. (R)-2-bromobutane (S)-2,3-dihydroxypropanal (R,S)-bromochlorofluoromethane (a racemic mixture) If known, the sign of rotation of plane-polarized light may also be added, however, there is no correlation between R,S and +,-: (R)-(+)-2,3-dihydroxypropanal
Sequence rules assign priorities to substituents. ule 1 k firet at the at ly attached to the st 8csgneanagdtg2etatemcnumter.hdrogen HH W)-I-Bro Rule 3: Verify these two example I a C(CHha 的 Verify thes -2 (8)3-Etky-2.2.4-trmcthyipentae CH-ct 5-4 Fischer Projections Theresmore than ne corretwaytodrawaFheprojecio e s d a0H 4
4 Sequence rules assign priorities to substituents. Rule 1: Look first at the atoms directly attached to the stereocenter. Precedence is in order of highest atomic number. Hydrogen is always the lowest precedence. A higher-mass isotope takes precedence over a lower-mass isotope. Rule 2: If two atoms are of the same precedence using rule 1, proceed along the two respective substituent chains until you reach a point of difference. Verify these two examples: Rule 3: Double and triple bonds are treated as if they are single and the atoms in them are duplicated or triplicated at each end by the respective atoms at the other end of the multiple bond. Verify these assignments: 5-4 Fischer Projections Fischer projection formulas represent 3-D tetrahedral carbon atoms and their substituents in two dimensions. The molecule is drawn in the form of a cross. •The tetrahedral carbon is in the plane of the paper at the center of the cross. •Atoms connected to the tetrahedral carbon by horizontal bonds are behind the plane of the paper. •Atoms connected to the tetrahedral carbon by vertical bonds are in front of the plane of the paper. There is more than one correct way to draw a Fischer projection:
Rotatinga Fischer projection may or may not KSgagasoit6aonio6nrproectoma5o nbhataetnenergPnehow2Ce8eghvheptud Ths then tus the 说器 H CHCH, cprojections tell us the absolute Ii8ntt6o58t56amo2teaei8oisomers CH.CCH.CH, oa A8aoesetroienmea H CI CH.C-SCCH, The possible combinations are RR,RS,R,and SS. o otaeorntcraecamn2aohe9geR (53EH2-Bm The center under scrutiny is5. 5
5 Rotating a Fischer projection may or may not change the absolute configuration. Rotating a Fisher projection formula by 90o converts the structure into that of the enantiomer of the molecule originally represented. Rotating a Fisher projection formula by 180o keeps the same enantiomer. Exchanging substituents in a Fischer projection also changes the absolute configuration. To compare a Fischer projection to another in a different orientation in order to see if they represent the same enantiomer: •Exchange any two substituents. This turns the molecule into its mirror image. •Exchange another two substituents. This then turns the molecule back into the original enantiomer. •Using a series of exchanges, convert one Fisher formula into the other. •If an odd number of exchanges are required, the two projection formulas represent different enantiomers. •If an even number of exchanges are required, the two projection formulas represent the same enantiomer. Fischer projections tell us the absolute configuration. •Draw any correct Fischer projection formula of a chiral center. •Assign priorities to all of the substituents. •Using two consecutive substituent exchanges (to preserve the chirality of the Fischer formula), place group d (lowest priority) on the top. •If the a,b,c groups are now arranged in a clockwise order, the enantiomer is R: if in a counterclockwise order, the enantiomer is S. Molecules Incorporating Several Stereocenters: Diastereomers 5-5 Two stereocenters can give four stereoisomers: chlorination of 2-bromobutane at C3. Consider the chlorination of 2- bromobutane. Several products are formed, but consider only the 2- bromo-3-chlorobutane. A second stereocenter is formed by the addition of the chlorine atom. The possible combinations are RR, RS, SR, and SS. Because all of the horizontal bonds in a Fischer projection formula point towards the viewer and all vertical bonds away from the viewer, a Fischer projection formula represents the molecule in its eclipsed conformation. In order to convert a Newman or dashed-wedged representation into a Fischer representation, first rotate the molecule to form an eclipsed rotomer. Treat each stereocenter separately and regard the group containing the other stereocenter as a simple substituent