Introduction to Organic Chemistry 2 ed William H. Brown

Chirality Chapter 4

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

Stereoisomers Are divided into enantiomers and diastereomers

Chirality Chiral: 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

Plane of Symmetry Plane of symmetry: an imaginary plane dividing an object such that one half is the mirror image of the other half

Plane of Symmetry

Chirality Lactic acid is chiral; that is it and its mirror image are nonsuperposable it and its mirror image are enantiomers

Stereocenter The most common (but not the only ) cause of chirality in organic molecules is the presence of a stereocenter Stereocenter: an atom in a molecule at which interchange of two atoms or groups of atoms bonded to it gives a stereoisomer the most common type of stereocenter is a tetrahedral carbon atom with four different groups bonded to it.

Stereocenter 2-Chlorobutane has one stereocenter and exists as a pair of enantiomers

R,S - Priority Rules Each atom bonded to the stereocenter is assigned a priority 1. Priority is based on atomic number; the higher the atomic number, the higher the priority

R,S - Priority Rules 2. If priority cannot be assigned on the basis of atoms bonded directly to the stereocenter, look to the next set of atoms and continue until priority is assigned

R,S - Priority Rules 3. Atoms participating in a double bond are considered to be bonded to an equivalent number of similar atoms by single bonds

R or S Configuration 1. Locate th stereocenter, identify its four substituent, and assign each a priority from 1 (highest) to 4 (lowest) 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, configuration is R (from the Latin rectus); if it is counterclockwise, configuration is S (from the Latin sinister)

R or S Configuration (S)-2-Chlorobutane

R or S Configuration (R)-3-Chlorocyclohexene

Two or More Stereocenters 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 etc.

Two or More Stereocenters 2,3,4-Trihydroxybutanal two stereocenters; 22 = 4 stereoisomers exist

Two or More Stereocenters 2,3-Dihydroxybutanedioic acid (tartaric acid) 2n = 4, but only three stereoisomers exist Meso compound: an achiral compound possessing two or more stereocenters

Two or More Stereocenters 2-Methylcyclopentanol

Two or More Stereocenters 1,2-Cyclopentanediol

Two or More Stereocenters cis-3-Methylcyclohexanol

Two or More Stereocenters trans-3-Methylcyclohexanol

Properties of Stereoisomers Enantiomers have identical physical and chemical properties in achiral environments Diastereomers are different compounds and have different physical and chemical properties Meso-tartaric acid, for example, has different physical and chemical properties from its enantiomers (see Table 4.1)

Plane Polarized Light 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

Optical Activity Specific rotation: observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dm in length and at a concentration of 1 g/mL

Optical Activity For a pair of enantiomers, the value of the specific rotation of each is the same, but opposite in sign

Resolution Racemic mixture: an equimolar mixture of two enantiomers because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero Resolution: the separation of a racemic mixture into its enantiomers

Resolution 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 enantiomerically pure acids are recovered

Resolution Examples of enantiomerically pure bases

Resolution Naproxen resolved by way of its ethyl ester

Resolution

Chirality in the Biological World Except for inorganic salts and a few low-molecular-weight organic substances, the molecules of living systems are chiral Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system It is a chiral world!

Chirality in the Biological World Consider chymotrypsin, a protein-digesting enzyme in the digestive system of animals chymotrypsin contains 251 stereocenters the maximum number of stereoisomers possible is 2251 There are only 238 stars in our galaxy!

Chirality in the Biological World Enzymes are like hands in a handshake the substrate fits into a binding site on the enzyme surface a left-handed molecule will only fit into a left-handed binding site and a right-handed molecule will only fit into a right-handed binding site enantiomers have different physiological properties because of the handedness of their interactions with other chiral molecules in living systems

Chiral Drugs Some chiral drugs are sold as racemic mixtures, others as a single enantiomer

Chiral Drugs

Chirality End of Chapter 4