Chapter 6 Stereochemistry

Enantiomers and the Tetrahedral Carbon Stereoisomers: Have the same molecular formula and the same order of attachment of their atoms (the same connectivity), but different three-dimensional orientations of their atoms in space. example: the cis-trans isomers of cycloalkanes

Constitutional isomers Different compounds with the same molecular formula Constitutional isomers Isomers with a different order of attachment of atoms in their molecules Stereoisomers Isomers with the same order of attachment of atoms in their molecules, but a different orientation of their atoms in space Enantiomers Stereoisomers whose molecules are mirror images of each other Diastereomers Stereoisomers whose molecules are not mirror images of each other

Molecules of the type CH3X and CH2XY are identical to their mirror images, but a molecule of the type CHXYZ is not.

The Reason for Handedness in Molecules: Chirality molecules that are not identical to their mirror forms objects that are not superposable on their mirror images are said to be chiral; that is, they show handedness Achiral: objects that are superposable on their mirror images are said to be achiral; that is, they do not show handedness. an object is achiral if it possesses a plane of symmetry

Chirality centers (stereocenters): The most common (but not the only ) cause of chirality in an organic molecules is the presence of a stereocenter The most common type of stereocenter is a tetrahedral carbon atom with four different groups bonded to it.

Propanoic acid has a plane of symmetry that makes one side of the molecule a mirror image of the other side. Lactic acid has no such symmetry plane.

Optical Activity Ordinary light: consists of waves vibrating in all planes perpendicular to its direction of propagation Plane polarized light: consists of waves vibrating only in parallel planes Polarimeter: a device for measuring the extent of rotation of plane polarized light Observed rotation: the number of degrees, a, through which a compound rotates the plane of polarized light Dextrorotatory (+): rotation of the plane of polarized light to the right Levorotatory (-): rotation of the plane of polarized light to the left

FIGURE 6. 5 Schematic representation of a polarimeter FIGURE 6.5 Schematic representation of a polarimeter. Plane-polarized light passes through a solution of optically active molecules, which rotate plane of polarization.

Specific Rotation Specific rotation, [a]D: observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dm (=10 cm) in length and at a concentration of 1 g/mL observed rotation, a (degrees) Path length, l (dm) x concentration, c (g/mL) [a]D =

[ a ] = -13.52 = +13.52 (R)-(-)-2-Butanol (S)-(+)-2-Butanol C OH CH H 25 D = -13.52 = +13.52 (R)-(-)-2-Butanol (S)-(+)-2-Butanol C OH CH 3 2 H HO

FIGURE 6.6 Crystals of sodium ammonium tartrate, taken from Pasteur’s original sketches. One of the crystals is dextrorotatory in solution, and other is levorotatory.

Sequence Rules for Specifying Configuration The configuration of a stereocenter: R configuration S configuration R,S - Priority Rules Each atom bonded to the stereocenter is assigned a priority Priority is based on atomic number; the higher the atomic number, the higher the priority If a decision can’t be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until priority is assigned

Assignment of configuration to a chirality center 1. Look at the four atoms directly attached to the chirality center, and rank them according to atomic number, and assign a priority from 1st (highest) to 4th (lowest) to each substituent 2. Orient the molecule so that the group of lowest priority (4) is directed away from you 3. Read the three groups projecting toward you in order from highest (1) to lowest priority (3) 4. If reading is clockwise (right turn), configuration is R (from the Latin rectus); if it is counterclockwise (left turn), configuration is S (from the Latin sinister)

FIGURE 6.8 Assignment of configuration to (a) (R)-(－)-lactic acid and (b) (S)-(＋)-lactic acid.

Enantiomers and Diastereomers For a molecule with n stereocenters, a maximum of 2n stereoisomers are possible with 1 stereocenter, 21 = 2 stereoisomers are possible with 2 stereocenters, a maximum of 22 = 4 stereoisomers are possible Diastereomers are stereoisomers that are not mirror images

The four stereoisomers of 2-amino-3-hydroxybutanoic acid (threonine)

Molecules with More Than Two Stereocenters 28 =256 stereoisomers 28-1=128 pairs enantiomers Only one is produced in nature

Meso Compounds

Meso Compounds Meso compounds has a plane of symmetry A symmetry plane cutting through the C2-C3 bond of meso-tartaric acid makes the molecule achiral.

Physical Properties of Stereomers Enantiomers have identical physical and chemical properties in achiral environments Differ only in specific rotation Diastereomers are different compounds and have different physical and chemical properties Meso compound has different physical and chemical properties from its diastereomers

Racemic Mixtures and the Resolution of Enantiomers Racemic mixture (racemate): an equimolar mixture of two enantiomers because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero (optical inactive, )

Resolution of enantiomers One means of resolution is to convert the pair of enantiomers into two diastereomers diastereomers are different compounds and have different physical properties, which can be used to separate them A common reaction for chemical resolution is salt formation after separation of the diastereomers, the enantiomer are recovered

FIGURE 6.13 Reaction of a racemic lactic acid with optically pure (R)-1-phenylethanamine leads to a mixture of diastereomeric salts, which have different properties and can, in principle, be separated.

A Brief Review of Isomerism

Constitutional isomers are compounds whose atoms are connected differently Stereomers are compounds whose atoms are connected in the same way but with a different spatial arrangement

Chirality in Nature Although the different enantiomers of a chiral molecule have the same physical properties, they almost always have different biological properties

Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system

(a) One enantiomer fits easily into a chiral receptor site to exert its biological effect, but (b) the other enantiomer can’t fit into the same receptor

Chiral drugs

The S enantiomer of ibuprofen soothes the aches and pains of athletic injuries. The R enantiomer has no effect.