Stereochemistry Chapter 5: Isomers

• Stereochemistry is covered in Chapter 5.

Isomers

• Isomers are different compounds sharing the same formula.
• There are two general types of isomers: constitutional and stereoisomers.

Constitutional Isomers

• Share the same molecular formula but possess a different constitution, or order of connectivity of atoms.

Stereoisomers

• Share the same molecular formula and constitution with different spatial arrangements of atoms.
• Geometric and optical isomers represent subcategories.

Chiral Carbon Atoms

• Chiral carbon atoms are also called asymmetric carbon atoms.
• A carbon atom bonded to four different groups defines a chiral center.
• The mirror image of a molecule with a chiral center results in a different compound, an enantiomer.

Enantiomers

• Enantiomers are stereoisomers.
• Enantiomers are mirror images but are not superimposable and are not identical.
• Only chiral compounds have enantiomers.
• An easier way to draw the enantiomer of a chiral compound is to invert the dashes and wedges of a chiral center.

Designating R vs. S Configuration

• Enantiomers are different compounds and therefore require different names.
• Enantiomers have an opposite configuration at their chiral center(s)
• The Cahn-Ingold-Prelog system designates each chiral center as having either "R" or "S" configuration.
• The enantiomer will possess the "S" configuration if a compound has the "R" configuration at a chiral center.

Designating R or S Configuration: Stepwise Procedure

• Using atomic numbers, prioritize the four groups attached to the chiral center, labeled 1, 2, 3, and 4.
• Arrange the molecule in space so that the lowest priority group (4) faces away.
• Determine whether the group priorities 1...2...3 progress in a clockwise or counterclockwise direction.
• Clockwise = R.
• Counterclockwise = S.
• Double bonds count as two single bonds when prioritizing for the Cahn, Ingold, and Prelog system.

Helpful Tricks

• Switching two groups on a chiral center produces its opposite configuration.
• Switching two of the groups twice returns the original configuration while allowing for priority 4 group pointing away.

R and S in IUPAC Nomenclature

• The (R) or (S) configuration is used in the IUPAC name to distinguish a compound from its enantiomer.

Optical Activity

• Enantiomers possess structures differing in the same way. Because of this, they have the same physical properties.
• Enantiomers differ in how they interact with other chiral compounds and differ in their optical activity.

Determining Configuration

• Enantiomers possess opposite configurations (R vs. S).
• Enantiomers rotate plane-polarized light in opposite directions.
• Plane-polarized light is passed through a sample of a chiral compound, which rotates the plane of light.
• Compounds able to rotate plane-polarized light are optically active. Only chiral compounds are optically active.
• A polarimeter is used to measure the rotation of polarized light by chiral compounds.

Specific Rotation

• Enantiomers rotate the plane of light to equal degrees but in opposite directions.
• The degree to which light is rotated depends on the sample concentration and the path length of the light.
• Standard optical rotation measurements are taken with 1 gram of compound dissolved in 1 mL of solution and a path length of 1 dm for the light.

Temperature and Wavelength of Light

• Temperature and wavelength of light affect rotation.
• They must be reported with measurements that are taken.

R and S Chiral Configuration

• (R) and (S) refer to the configuration of the chiral center.
• (+) and (-) signs refer to the direction that the plane of light is rotated.
• (+) rotation is called dextrorotary, and (-) is levorotatory.
• There is no correlation between R/S and +/-.
• The rotation of a racemic mixture consists of 50/50 mixture of two enantiomers and is equal to 0°.
• If one enantiomer is present in excess, the mixture will exhibit optical rotation that is less than a pure enantiomer.

Enantiomers and Diastereomers: Definitions

• Categories of isomers include constitutional isomers and stereoisomers.
• Enantiomers are stereoisomers that are mirror images.
• Diastereomers are stereoisomers that are not mirror images.
• Enantiomers have identical physical properties, while diastereomers have different physical properties.

Stereoisomeric Relationships

• The number of possible stereoisomers for a compound depends on the number of chiral centers (n) in the compound.
• Maximum number of stereoisomers = 2^n

Symmetry and Chirality- Introduction

• Any compound with only one chiral center will be a chiral compound.
• In compounds with more than one chiral center, it may not be chiral due to the presence of a plane of symmetry.
• The trans isomer is chiral, but the cis isomer is not (it is achiral).
• If a molecule has a plane of symmetry, it will be achiral.

Symmetry

• A compound that lacks a plane of symmetry may still be an achiral compound if it has reflectional symmetry through inversion about a central point in the molecule.
• The presence or absence of rotational symmetry is irrelevant to chirality.
• A compound with a plane of symmetry is achiral.
• A compound without a plane of symmetry is usually chiral, but there are exceptions, such as a compound with an inversion center.

Meso Compounds

• A compound with chiral centers, but is achiral because of symmetry, is called a meso compound.
• meso compounds have less stereoisomers than predicted by the 2^n formula.

Fischer Projections

• Fischer projections can also be used to represent molecules with chiral centers.
• Horizontal lines represent attachments coming out of the page.
• Vertical lines represent attachments going back into the page.
• Fischer projections are most useful when drawing molecules having multiple chiral centers, such as sugars.

Resolution of Enantiomers: Challenge

• Most methods of separating compounds from one another utilize the compounds' different physical properties.
• Distillation separates compounds with different boiling points.
• Recrystallization separates compounds with different solubilities.
• Such methods are ineffective in separating one enantiomer from its racemate due to their identical physical properties.

Pasteur's Method

• Pasteur performed the first resolution of enantiomers from a racemic mixture of tartaric acid salts by separating different shaped crystals by hand, using tweezers.
• The different enantiomers formed crystals with different shapes.
• This method is not applicable to most pairs of enantiomers.
• The differing physical properties of diastereomers allow easier separation.
• Affinity chromatography is often used to separate compounds.
• A glass column, or tube, is packed with a solid substance that acts as an adsorbent and through which a mixture is passed.
• Usage of a chiral adsorbent causes enantiomers to interact and travel through the column at different rates, allowing for their individual collection.

E and Z Designations for Alkenes

• The E/Z notation is used instead of cis/trans notation for molecules with different groups attached to the C=C double bond.
• cis and trans designation is inadequate to differentiate between two diastereomers.

Assigning E or Z to a C=C Double Bond

• Prioritize the groups attached to the C=C double bond based on atomic number.
• Z (zussamen, together) is present if the top priority groups are on the same side of the C=C double bond.
• E (entgegen, opposite) is present if the top priority groups are on the opposite side of the C=C double bond.