Organic Chemistry

1. Organic Chemistry Jin Hongwei College of Chemical Engineering and Materials Science jhwei828@zjut.edu.cn

2. Chapter Six Stereochemistry • Introduction • Enantiomers and the Tetrehedral Carbon • Chirality and Chiral Molecules • Isomerism: Constitutional Isomers and Stereoisomers • Representation of Chiral Molecules • Nomenclature of Enantiomers: The R,S-System • Properties of Enantiomers: Optical Activity • Racemic Mixture and Meso Compounds

3. Introduction • Are you right-handed or left-handed? Though most of us don’t often think about it, handedness plays a surprisingly large role in our daily activities. • Our hands aren’t identical, they aremirror images. When you hold a right hand up to a mirror, the image you see looks like a left hand. • Handedness also plays a large role in organic chemistry as a direct consequence of the tetrahedral stereochemistry of sp3-hybridized carbon. Most drugs and most of the molecules in our bodies are handed.

4. Disaster ofThalidomide • BACK

5. Enantiomers and the Tetrehedral Carbon • Mirror-image molecules that are not superimposable are calledenantiomers.（对映异构） • Tetrahedral carbon atoms and their mirror images. • Molecules of the type CH3Xand CH2XY are identical to their mirror images, but a molecule of the type CHXYZis not. • A CHXYZmolecule is related to its mirror image in the same way that a right hand is related to a left hand. • BACK

6. Chirality and Chiral Molecules • Molecules that are not superimposable with their mirror images and thus exist in two enantiomeric forms are said to bechiral.（手性的） • How can we predict whether a given molecule is or is not chiral? A molecule is not chiral if it contains a plan of symmetry.（对称性） • Cause ofchiralityin an organic molecule is the presence of a carbon atom bonded to four different groups. For example: • Lactic acid BACK

7. Isomerism: Constitutional Isomers and Stereoisomers • There are two fundamental types of isomers: constitutional isomers and stereoisomers. • Constitutional isomers are compounds whose atoms are connected differently. Among the kinds of constitutional isomers we’ve seen are skeletal, functional, and positional isomers. For example:

8. Isomerism: Constitutional Isomers and Stereoisomers • Stereoisomers are compounds whose atoms are connected in the same order but with a different geometry. Among the kinds of stereoisomers are enantiomers, diastereomers, and cis-trans isomers. • Enantiomers （对映异构体） • (nonsuperimposable mirror-image • stereoisomers) • Diastereomers（非对映异构体） • (nonsuperimposable non-mirror-image • stereoisomers) • Configurational diastereomers • （构型非对映异构体） • Cis-trans diastereomers

9. Isomerism: Constitutional Isomers and Stereoisomers • A flow diagram summarizing the different kinds of isomers. BACK

10. Representations of Chiral Molecules(1) • In 1891, Emil Fischer(1852-1919, 1902 Nobel Prize winner) suggested a method based on the projection of a tetrahedral carbon atom onto a flat surface. TheseFischer projectionswere soon adopted and are now a standard means of depicting stereochemistry at chirality centers, particularly in carbohydrate chemistry. • A tetrahedral carbon atom is represented in a Fischer projection by two crossed lines. The horizontal lines represent bonds comingout of the page, and the vertical lines represent bonds goingintothe page.(横出竖进)

11. Representations of Chiral Molecules(2) • Because a given chiral molecule can be drawn in many different ways, it’s often necessary to compare two projections to see if they represent the same or different enantiomers. Only two kinds of motions are allowed: • 1. A Fischer projection can be rotated on the page by 180o, but not by 90o. • 2. A Fischer projection can have one group held steady while the other three rotate in either a clockwise or a counterclockwise direction.

12. Representations of Chiral Molecules(3) • Which of the following Fischer projections represent the same enantiomer? • Convert the following tetrahedral representation of (S)-2-Chlorobutane into a Fischer projection:

13. Nomenclature of Enantiomers: The R,S-System(1) • Although Fischer projection and tetrahedral representation can provide pictorial representations of stereochemistry, they are difficult to translate into words. Thus, a verbal method for indicating the three-dimensional arrangement of atoms, orconfiguration(构型), at a chirality center is necessary. • Step1 According to Cahn-Ingold-Prelog sequence rules, assign priorities the four atoms or groups attached to the chiral carbon center. • Step2 Describing the stereochemical configuration around the carbon by orienting the molecule so that the group of lowest priority(4) is pointing directly back, away from us. • Step3 Looking at the other three groups, which are appear to radiate toward us, draw a curved arrow from the highest to second-highest to third-highest-priority groups(1→2→ 3). • Step4 If the arrow is clockwise, we say that the chirality center has R configuration. If the arrow is counterclockwise, we say that the chirality center has S configuration.

14. Nomenclature of Enantiomers: The R,S-System(2) same as • Assign R or S configuration to the chirality center in each of the following molecules: R configuration same as S configuration BACK

15. Properties of Enantiomers: Optical Activity(1) • Optical Activity • The study of stereochemistry has its origins in the work of the nineteenth century French scientistJean Baptiste Biot, who was investigating the nature ofplane-polarizedlight. • Biot made the remarkable observation that, when a beam ofplane-polarized lightpasses through a solution of certain organic molecules such as sugar, the plane of polarization isrotated. Not all organic substances exhibit this property, but those that do are said to beoptically active. • The amount of rotation can be measured with an instrument known as a polarimeter, represented schematically in follow picture:

16. Properties of Enantiomers: Optical Activity(2) • Specific Rotation • The amount of rotation observed in a polarimeter depends on the number of optically active molecules that the light beam encounters. Thus, the amount of rotation depends on both sample concentration and sample pathlength. To express optical rotation data in a meaningful way so that comparisons can be made, we have to choose standard conditions. The specific rotation[α]D,of a compound is defined as the observed rotation when the sample pathlenghlis 1decimeter, the sample concentration C is 1g/ml. BACK

17. Racemic Mixture and Meso Compounds(1) • Let’s investigate the stereochemistry of addition of Br2 to alkenes: • 1.Start with cis-2-butene,Br2 can add to the double bond to generate a bromonium ion, which is attacked from the left (path a), can leads to (2S,3S)-dibromobutane, and attacked from the right (path b), leads to (2R,3R)-dibromobutane. Since both modes of attack on the bromonium ion are equally likely, a 50:50mixture (racemic mixture) of the two enantiomeric products is formed.

18. Racemic Mixture and Meso Compounds(2) • 2. What about the addition of Br2 to trans-2-butene? Is the same racemic product mixture formed? The answer is no. Although trans-2-butene react with Br2 to generate (2R,3S)-dibromobutane, (2S,3R)-dibromobutane. After close look at the two products, however, show that they are identical. Both structures represent meso-2,3-dibromobutane.