Chapter 5 Stereochemistry

Stereochemistry The Two Major Classes of Isomers constitutional (structural) isomers and stereoisomers. Constitutional/structural isomers have different connectivity : different IUPAC names, different physical and chemical properties. Stereoisomers have the same connectivity but different oriention in space : identical IUPAC names (except for a prefix like cis or trans). Configuration : A particular three-dimensional arrangement. Stereoisomers differ in configuration.

Stereochemistry

Importance of the stereochemistry Example Starch : glucose polymer, a food source to provide energy for growth. It is a major component of human diet: when cereals (barley, rice, wheat etc) and vegetables (potato, sweet potato, etc) are eaten, enzymes break down the starch molecules to glucose Cellulose : glucose polymer, gives rigidity to tree trunks, plant stems and leaves and it is resistant to hydrolysis by chemical or biological agents. It is indigestible to humans.

Stereochemistry

Stereochemistry Chiral and Achiral Molecules Although everything has a mirror image, mirror images may or may not be superimposable. Some molecules are like hands. Left and right hands are mirror images, but they are not identical, or superimposable.

So, we say right-handed /left-handed molecules Stereochemistry Achiral Molecules A molecule or object that is superimposable on its mirror image is said to be achiral. Two socks from a pair are mirror images that are superimposable. A sock and its mirror image are identical. Chiral : hand in Greek So, we say right-handed /left-handed molecules But which one is which?

Stereochemistry Chiral and Achiral Molecules Chirality check

Stereochemistry Chiral and Achiral Molecules

Stereochemistry Chiral and Achiral Molecules A and B are stereoisomers—specifically, they are enantiomers. A carbon atom with four different groups is a tetrahedral stereogenic center (chiral center).

Stereochemistry Chiral and Achiral Molecules With one stereogenic center, a molecule will always be chiral. With two or more stereogenic centers, a molecule may or may not be chiral. In general, a molecule with no stereogenic centers will not be chiral. There are exceptions to this. Achiral molecules usually contain a plane of symmetry but chiral molecules do not. A plane of symmetry : a mirror plane that cuts the molecule in half, so that one half of the molecule is a reflection of the other half.

Stereochemistry Stereogenic Centers locate a stereogenic center: examine each tetrahedral carbon atom in a molecule, and look at the four groups—not the four atoms—bonded to it. Always omit from consideration all C atoms that cannot be tetrahedral stereogenic centers. These include CH2 and CH3 groups Any sp or sp2 hybridized C

Stereochemistry Stereogenic Centers Larger organic molecules can have two, three or even hundreds of stereogenic centers.

Stereochemistry Stereogenic Centers To draw both enantiomers

Stereochemistry Stereogenic Centers

Stereochemistry Stereogenic Centers in Cyclic Compounds

Stereochemistry Stereogenic Centers

Stereochemistry Importance of Stereogenic Centers

Stereochemistry Labeling Stereogenic Centers with R or S Enantiomers are distinguished by adding the prefix R or S to the IUPAC name of the enantiomer. This is called the Cahn-Ingold-Prelog system. How to designate enantiomers as R or S: priorities must be assigned to each group bonded to the stereogenic center, in order of decreasing atomic number. The atom of highest atomic number gets the highest priority (1).

Stereochemistry Labeling Stereogenic Centers with R or S If two atoms on a stereogenic center are the same assign priority based on the atomic number of the atoms bonded to these atoms. One atom of higher atomic number determines the higher priority.

Stereochemistry Labeling Stereogenic Centers with R or S Among isotopes: assign priorities in order of decreasing mass number.

Stereochemistry Labeling Stereogenic Centers with R or S Assigning a priority to an atom that is part of a multiple bond: treat a multiply bonded atom as an equivalent number of singly bonded atoms.

Stereochemistry Labeling Stereogenic Centers with R or S

Stereochemistry Labeling Stereogenic Centers with R or S

Stereochemistry Labeling Stereogenic Centers with R or S

Stereochemistry Labeling Stereogenic Centers with R or S

Stereochemistry Labeling Stereogenic Centers with R or S Figure 5.7 Examples: Orienting the lowest priority group in back

Stereochemistry Labeling Stereogenic Centers with R or S

Stereochemistry Labeling Stereogenic Centers with R or S S S more examples S S

Stereochemistry Labeling Stereogenic Centers with R or S R S more examples R S

Stereochemistry Labeling Stereogenic Centers with R or S more examples 3 3 3 3 2 2 3 3 1 1 3 3 2 2 3 3 3 3

Stereochemistry Diastereomers For a molecule with n stereogenic centers, the maximum number of stereoisomers is 2n. possible stereoisomers of 2,3-dibromopentane. Diastereomers are stereoisomers that are not mirror images of each other.

Stereochemistry Meso Compounds stereoisomers of 2,3-dibromobutane. the maximum number of stereoisomers is 4.

Stereochemistry Meso Compounds Compound C contains a plane of symmetry, and is achiral. Meso compounds generally contain a plane of symmetry so that they possess two identical halves. or center of symmetry

Stereochemistry Meso Compounds

Stereochemistry When a compound has more than one stereogenic center, R and S configurations must be assigned to each of them. One stereoisomer of 2,3-dibromopentane The complete name is (2S,3R)-2,3-dibromopentane

Stereochemistry

Stereochemistry Disubstituted Cycloalkanes 1,3-dibromocyclopentane.

Stereochemistry Summary—Types of isomers

Stereochemistry Determining the relationship between two nonidentical molecules

Stereochemistry Physical Properties of Stereoisomers enantiomers have identical chemical and physical properties except in their interaction with chiral substances and plane-polarized light. Plane-polarized (polarized) light : light that has an electric vector that oscillates in a single plane. Plane-polarized light arises from passing ordinary light through a polarizer. A polarimeter : measures of the degree to which an organic compound rotates plane-polarized light.

Stereochemistry Physical Properties of Stereoisomers—Optical Activity achiral compounds : optically inactive --- the light that exits the sample tube remains unchanged.

Stereochemistry Physical Properties of Stereoisomers—Optical Activity chiral compounds: optically active --- rotates the plane of the polarized light through an angle . The angle  is measured in degrees (°), and is called the observed rotation.

Stereochemistry Physical Properties of Stereoisomers—Optical Activity If the rotation is clockwise – dextrorotatory -- d or (+). If the rotation is counterclockwise – levorotatory -- l or (-). Two enantiomers rotate plane-polarized light to an equal extent but in opposite directions. Thus, if enantiomer A rotates polarized light +5°, the same concentration of enantiomer B rotates it –5°. No relationship exists between R and S prefixes and the d (+) and l (-) designations that indicate optical rotation.

Stereochemistry Physical Properties of Stereoisomers—Racemic Mixtures racemic mixture (racemate) : mixture of an equal amount of two enantiomers. A racemic mixture is optically inactive -- the rotations cancel, and no rotation is observed.

Stereochemistry Physical Properties of Stereoisomers optical rotation : concentration, length of the path, temperature dependent Specific rotation : a standardized optical rotation denoted by the symbol [] defined using a specific sample tube length (l, in dm), concentration (c in g/mL), temperature (250C) , wavelength (589 nm). optical rotation v.s. specific rotation – ratio of two enantiomers, purity of one

Stereochemistry Physical Properties of Stereoisomers Since enantiomers have identical physical properties, they cannot be separated by common physical techniques like distillation. Diastereomers and constitutional isomers have different physical properties, and therefore can be separated by common physical techniques.

Stereochemistry Separation of enantiomers Recognition of enationmers differently Figure 9.13: Reaction of racemic lactic acid with (R)-1-phenylethylamine yields a mixture of diastereomeric ammonium salts. Fig. 9-13, p. 308

Stereochemistry Chemical Properties of Enantiomers Two enantiomers have exactly the same chemical properties except for their reaction with chiral non-racemic reagents. Many drugs are chiral and often must react with a chiral receptor or chiral enzyme to be effective. One enantiomer of a drug may effectively treat a disease whereas its mirror image may be ineffective or toxic.

Stereochemistry Physical Properties of Stereoisomers—Optical Purity Enantiomeric excess (optical purity) : a measurement of how much one enantiomer is present in excess of the racemic mixture. It is denoted by the symbol ee. cf. enantiomeric ratio ee = % of one enantiomer - % of the other enantiomer. Example—If a mixture contains 75% of one enantiomer and 25% of the other, the enantiomeric excess is 75% - 25% = 50%. Thus, there is a 50% excess of one enantiomer over the racemic mixture. The enantiomeric excess can also be calculated if the specific rotation [] of a mixture and the specific rotation [] of a pure enantiomer are known. ee = ([] mixture/[] pure enantiomer) x 100.

Stereochemistry Physical Properties of Stereoisomers—Optical Purity Enantiomeric excess (optical purity) : a measurement of how much one enantiomer is present in excess of the racemic mixture. It is denoted by the symbol ee. cf. enantiomeric ratio

Homework 5.31, 5.36, 5.37, 5.43, 5.47, 5.49, 5.51, 5.58, 5.60, 5.62, 5.64

Understanding organic reactions Preview of Chapter 6 Understanding organic reactions 1. What is substitution reaction ? 2. What is elimination reaction ? 3. What is addition reaction ? 4. What reactive intermediates can be generated from bond cleavage ? 5. What are the factors that affect reaction rate?