Stereochemistry Constitution, conformation. Chirality, enantiomers and diastereomers. Absolute and relative configuration. Optical activity. Fischer- and Cahn-Ingold-Prelog-convention (CIP). Stereochemistry: Chemistry in three dimensions; the relationship of physical and chemical properties to the spatial arrangement of the atoms in a molecule. Stereochemistry refers to chemistry in three dimensions. 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. Isomer: Isomers are different compounds that have the same molecular formula. They may be either constitutional isomers or stereoisomers. OR One of a set of molecules that have the same molecular formula, but different structure. Constitutional isomer: (skeletal isomer; structural isomer):Constitutional isomers are isomers that differ in the order in which their atoms are connected. Stereoisomers: Stereoisomers are isomers that have the same constitution but differ in the arrangement of their atoms in space. Tautomer: Any molecule in a set of constitutional isomers that are conceptually related by the shift of a hydrogen atom and one or more p bonds. Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group. The keto and enol forms are constitutional isomers. Using older terminology they are referred to as tautomers of each other. Conformation: The shapes that a molecule can adopt due to rotation around one or more single bonds. OR Nonidentical representations of a molecule generated by rotation about single bonds. Conformational isomers (conformers): Isomers that have the same connectivity sequence and can be interconverted by rotation around one or more single (σ) bonds. OR Conformations of a single molecule. conformers configurational isomers Configuration: The three-dimensional arrangement of atoms or groups in a molecule, usually in reference to stereoisomers. Stereoisomer (configurational isomer): One molecule in a set of isomers that differ by the position of atoms in space, but are not constitutional isomers or conformational isomers. OR Isomers which have the same constitution but which differ in respect to the arrangement of their atoms in space. Stereoisomers may be either enantiomers or diastereomers. MOLECULAR CHIRALITY 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 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. snail Chiral: Term describing an object that is not superposable on its mirror image. Achiral: Opposite of chiral. An achiral object is superimposable on its mirror image. Enantiomers and Diastereomers A molecule is chiral if its two mirror-image forms are not superposable in three dimensions. The opposite of chiral is achiral. A molecule that is superposable on its mirror image is achiral. In organic chemistry, chirality most often Consider chloro-difluoromethane (ClF2CH), in occurs in molecules that contain a carbon that which two of the atoms attached to carbon is attached to four different groups. An are the same. As is evident from these example is bromochlorofluoromethane drawings, it is a simple matter to merge the (BrClFCH). two models so that all the atoms match. Since the two mirror images of bromo- Since mirror-image representations chlorofluoromethane are not superposable, of chlorodifluoromethane are superposable BrClFCH is chiral. on each other, ClF2CH is achiral. 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. Enantiomer (optical isomer): One of a pair of molecules that are non-superimposable mirror images. Every chiral molecule has an enantiomer pair. Always two molecules have enantiomer relationship – enantiomer pairs. Just as an object has one, and only one, mirror image, a chiral molecule can have one, and only one, enantiomer. Enantiomers: has same distances, angles between atoms which are not connected directly same chemical and physical properties (the usual physical properties such as density, melting point, and boiling point are identical within experimental error for both enantiomers of a chiral compound. They are indistinguishable in ACHIRAL ENVIROMENT. (Important: in a CHIRAL ENVIROMENT this equality breaks off, enantiomers are distinguishable, separable, e.g. optical activity!) Racemic mixture (racemate): Mixtures containing equal quantities of enantiomers are called racemic mixtures. (A 1:1 mixture of enantiomers.) Racemic mixtures are optically inactive. Stereoisomers that are not related as an object and its mirror image are called diastereomers; diastereomers are stereoisomers that are not enantiomers. More molecules can diastereomers not only two molecules. All together 26 = 128 stereoisomers (configurational isomer) – from these strychnine is just 1! + 1 enantiomer + 126 diastereomers Diastereomers: different distances, between atoms which are not connected directly different chemical and physical properties (they are distinguishable) in ACHIRAL ENVIROMENT (separable, different reactivity). Consequences: • every non conformer and non enantiomer stereoisomer is diastereomer • diastereomers are not mirror images chirality is not crucial (necessary) Example: geometric isomers: geometric isomers are a subtype of diastereomers 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 . A plane of symmetry defined by the atoms H-C-Cl divides chlorodifluoromethane into two mirror-image halves. 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 lacks a plane of symmetry, yet is achiral because it possesses a center of symmetry. (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. 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. Symmetry elements All molecules which have a plane of symmetry (or a rotary-reflection axis, symmetry element Sn) are achiral (and thus superimposable with their mirror images). Chiral Molecules Terms of chirality: in the molecule there IS NOT a plane of symmetry (mirror plane) or a center of symmetry axis of symmetry IS allowed!! Groups of chiral molecules: - asymmetrical molecules (is not any symmetry elements) - disymmetric molecules with axis of symmetry chiral achiral 1. THE STEREOGENIC CENTER Molecules of the general type 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.) Carbons that are part of a double bond or a triple bond can’t be stereogenic centers! 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. 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. One final, very important point about stereogenic centers. Molecules that have one and only one stereogenic center are chiral molecules. Molecules with more than one stereogenic center may or may not