Organic Chemistry: Enantiomers and Chirality

Introduction to Organic Chemistry, Chapter 6: Chirality

• Chirality refers to the "handedness" of molecules
• Isomers are different compounds with the same molecular formula
• Constitutional isomers have different connectivity of atoms
• Stereoisomers have the same connectivity, but different orientations in space
• Enantiomers are stereoisomers that are nonsuperposable mirror images
• Diastereomers are stereoisomers that are not mirror images
• 2-butanol exists as a pair of enantiomers, whose mirror images are not superposable

Stereoisomers

• Stereoisomers are isomers with the same connectivity of atoms but different spatial arrangements
• Enantiomers are nonsuperposable mirror images
• Diastereomers are stereoisomers that are not mirror images

Enantiomers

• They are nonsuperposable mirror images
• A molecule that exists as a pair of enantiomers; its mirror image is not superposable on the original
• 2-butanol is an example, with its mirror image not superposable
• Rotation of the mirror image by 180° about the C-O bond makes the CH₃-C-OH portion match the original. However, the H and CH₂CH₃ groups are not superposable, as they extend in different directions in space.

Enantiomers (Continued)

• Trying to fit the mirror image on top of the mirror image requires accounting for the orientations of all groups and bonds
• The original molecule and its mirror image are different molecules, with different properties.
• Enantiomers are nonsuperposable mirror images

Enantiomers (Continued 2)

• Stereoisomers that are nonsuperposable mirror images are chiral; this term refers to the relationship between pairs of objects
• Chirality is exemplified by a molecule's handedness
• The common cause of enantiomerism in organic molecules lies in a carbon bonded to four different groups.
• A carbon with four different groups bonded to it is a stereocenter

Achiral Objects

• Objects that are superposable on their mirror images are achiral
• Lacking chirality; they are not handed
• 2-propanol, for instance, lacks a stereocenter

Achiral Molecules and Their Mirror Images

• An achiral molecule and its mirror image are identical
• Rotation of the mirror image of an achiral molecule brings its atoms into precise alignment with the original molecule's atoms
• Achiral molecules possess no handedness.

Enantiomers (Cont'd 3)

• Summary of chiral molecules: nonsuperposable mirror images; show handedness
• The most common cause of enantiomerism is when a carbon is bonded to four different groups
• A stereocenter is a carbon atom with four different groups
• Enantiomers are different molecules, possessing distinct properties.

Drawing Chiral Molecules

• Four distinct representations of an enantiomer of 2-butanol are presented
• Representations (1) and (2) demonstrate the tetrahedral geometry and all four groups attached to the stereocenter.
• Representation (3) is a simplified line-angle formula, although the H atom on the stereocenter is displayed.
• Representation (4) provides the most concise representation—an H atom on the stereocenter is implicit
• The left-hand side shows one enantiomer of 2-butanol, while two representations of its mirror image are shown on the right

Naming Enantiomers - R,S

• Enantiomers require distinct names to differentiate them—this is exemplified by ibuprofen
• The R,S system provides a method for differentiating between enantiomers without needing to explicitly draw them or point to one particular enantiomer.

The R,S System

• The R,S system assigns priorities (1 through 4) to groups on the stereocenter
• Orient the stereocenter, so the group of lowest priority points away.
• Read the three groups in order (1 to 3)
• Clockwise reading indicates an R configuration; counterclockwise indicates an S.
• The R,S system dictates the distinction between enantiomers through the use of priority rules

The R,S System (Continued)

• This system offers a method to assign R or S configuration to each stereocenter
• Includes examples of assignments for chiral centers in chemical formulas.
• Provides an example to identify R or S configurations in ibuprofen
• Illustrates the use of the R, S nomenclature for organic molecules

Enantiomers & Diastereomers

• A molecule with one stereocenter has two stereoisomers.
• Molecules with two stereocenters can have up to four stereoisomers.
• Stereoisomers involving two or more chiral centers include two pairs of enantiomers, and one meso compound

Enantiomers & Diastereomers (Continued)

• Figure 6.4 illustrates two stereocenters, resulting in four stereoisomers: two pairs of enantiomers.
• The structures depict either a pair of enantiomers (e.g., Erythrose or Threose.)

Meso Compounds

• A meso compound is an achiral compound with two or more stereocenters.
• Tartaric acid contains two stereocenters; only three stereoisomers exist—one meso compound and one pair of enantiomers
• Figure 6.5 displays three stereoisomers of tartaric acid: one meso compound and one pair of enantiomers

Planes of Symmetry

• A plane of symmetry divides an object into two halves that are mirror images of each other
• This is exemplified in several molecular configurations, including a cylinder and several molecular structures; structures that don't have a plane of symmetry are chiral

Chirality in Cyclic Molecules

• For 2-methylcyclopentanol, two stereocenters exist, with up to 4 stereoisomers possible
• Two pairs of enantiomers exist
• A variety of other molecules are discussed in this category

Chirality in Cyclic Molecules (Continued)

• 1,2-Cyclopentanediol has two stereocenters, which yields 4 stereoisomers
• Three stereoisomers exist: one meso compound and one pair of enantiomers

Chirality in Cyclic Molecules (continued 2) and (continued 3) and (continued 4)

• Several examples are described
• Four stereocenters mean four possible stereoisomers
• Different molecules are described in these categories, including several pairs of enantiomers and a meso compound

Chirality in Cyclic Molecules (Continued 5)

• 1,3-cyclohexanediol, with two stereocenters, yields 4 stereoisomers
• Three stereoisomers occur; there is one meso compound, along with a pair of enantiomers

Three Or More Stereocenters

• The number of stereocenters present in a molecule is determined
• The number of possible stereoisomers for a molecule is determined
• Examples include menthol and cholesterol, which both have multiple stereocenters

Three Or More Stereocenters (Continued)

• Cholesterol's structure has 8 stereocenters, meaning 2⁸ = 256 stereoisomers are possible

Optical Activity

• Ordinary light waves vibrate in all planes perpendicular to the direction of propagation
• Plane-polarized is used to describe light waves that vibrate only in parallel planes.
• A polarimeter measures the ability of compounds to rotate plane-polarized light
• Optically active compounds rotate the plane of plane-polarized light

Polarimeter

• It's a device used to meticulously measure the rotation of plane-polarized light by a chemical sample.
• The components include a light source, polarizing filter, sample tube, and an analyzer

Optical Activity (Continued)

• Dextrorotatory molecules produce a clockwise rotation of light's plane of polarization
• Levorotatory molecules produce counter-clockwise rotation.
• Specific rotation is determined by the magnitude of rotation for a given concentration and tube length of optically active substance

Chirality in Biomolecules

• Most biomolecules are chiral, with few inorganic salts and low-molecular organic substances being exceptions
• Usually, only one stereoisomer is found in nature for a compound

Chirality in Biomolecules (Continued)

• Enzymes are chiral biocatalysts that have many stereocenters
• An example is chymotrypsin, which has 251 stereocenters
• The maximum number of stereoisomers for chymotrypsin is very high.
• Only one stereoisomer of any chiral compound is created and employed by an organism

Chirality in Biomolecules (Continued 2)

• Enzymes exhibit chiral behavior, reacting or producing only substances with stereochemical compatibility

Chirality in Biomolecules (Continued 3)

• Molecular interactions in chiral environments lead to distinct physiological responses by molecules and their enantiomers/diastereomers
• (S)-ibuprofen, for instance, is an active pain reliever. However, its R enantiomer is inactive
• Most drugs exist as enantiomers that can have dramatically differing physiological responses

Resolution

• A racemic mixture is an equimolar blend of two enantiomers
• The specific rotation of the racemic mixture is zero.
• Resolution is the procedure to separate enantiomers in a racemic mixture

Resolution (Continued)

• Enzymes can be used to resolve racemic mixtures
• It's a method for separating components of a racemic mixture

Chirality

• Discusses several problems or examples relating to chirality
• The discussion illustrates whether various molecules are chiral or achiral
• It elucidates the concepts of configurational isomers, stereoisomers, and enantiomers, and it involves the R/S configuration system.