Stereochemistry Lecture Review

Stereochemistry

• Refers to the 3-dimensional properties and reactions of molecules.
• Has its own language and terms that must be understood for effective communication.

Definitions

• Stereoisomers: Compounds with identical connectivity but different spatial arrangements.
• Enantiomers: Type of stereoisomers that are non-superimposable mirror images; differ only in optical rotation direction (+ or -).
• Diastereomers: Stereoisomers that are not mirror images; possess distinct physical properties.

More Definitions

• Asymmetric Center: An sp³ hybridized carbon atom with four different groups attached.
• Optical Activity: The capability to rotate plane-polarized light.
• Chiral Compound: A compound exhibiting optical activity; its mirror image cannot be superimposed.
• Polarimeter: A device used to measure the optical rotation of chiral compounds.

Chirality

• Chirality: Often referred to as "handedness"; an object is chiral if its mirror image differs from itself.

Achiral Compounds

• Achiral: Molecules whose mirror images can be superimposed.
• Plane of Symmetry: A molecule with this trait is considered achiral.

Stereoisomers Insights

• Enantiomers: Requires chiral molecules; every chiral molecule has an enantiomer.

Chiral Carbon Atom

• Carbon atom connected to four distinct groups is termed chiral; its mirror image differs (forms an enantiomer).

Stereocenters

• An asymmetric carbon serves as a common example of a chirality center.
• Stereocenters: Any atom where the interchange of two groups gives rise to a stereoisomer.

Examples of Chirality Centers

• Asymmetric carbon atoms represent chirality centers and hence stereocenters.

Achiral Examples

• When mirror images of a compound can be superimposed perfectly, it indicates the compound is achiral.

Planes of Symmetry

• A molecule possessing a plane of symmetry is classified as achiral.

Cis and Trans Cyclic Compounds

• Cis compounds: Typically have planes of symmetry leading them to be achiral.
• Trans compounds: Lack planes of symmetry, resulting in non-superimposable images and potential enantiomers.

(R) and (S) Configuration

• IUPAC names both enantiomers of alanine as 2-aminopropanoic acid.
• Biological activity can depend on the enantiomeric form, illustrated in alanine's metabolism.
• Distinguishing enantiomers involves utilizing stereochemical modifiers (R) and (S).

Cahn–Igold–Prelog Priority System

• Assigns priorities to the four groups attached to an asymmetric carbon atom based on atomic number.
• High priority is given to atoms with larger atomic numbers, sequence being: I > Br > Cl > S > F > O > N > C more than 13 > C more than 12 > H.

Assigning Priorities

• In instances of equal atomic numbers, move to subsequent atoms for a tie-breaker.
• Multiple Bonds: Considered as if bonded to separate atoms for prioritization.

Determining Configuration

• Rotate the molecule so the lowest priority group is in the back.
• Draw an arrow from highest to lowest priority (4), clockwise = (R) and counterclockwise = (S).

Properties of Enantiomers

• Identical boiling/melting points, density, and refractive indices; differ in how they interact with chiral environments such as enzymes.

Polarized Light

• Plane-polarized light contains waves vibrating in a single plane.

Optical Activity

• Enantiomers rotate plane-polarized light in opposite directions but with the same degree of rotation.

Polarimeter Settings

• Clockwise rotation = + (dextrorotatory), counterclockwise = - (levorotatory).

Specific Rotation Formula

• Specific rotation
  [\alpha]D = \frac{\alpha{observed}}{c \cdot l}
  where:
• \alpha_{observed} = measured in polarimeter,
• c = concentration (g/mL),
• l = path length (dm).

Example of Specific Rotation Calculation

• If 6 g of 2-butanol diluted to 40 mL in a 200 mm polarimeter indicates 4.05^ ext{°} counterclockwise:
• Concentration: 0.15 \text{ g/mL} and path length: 2 \text{ dm} for specific rotation as:
  [\alpha]_D = -\frac{4.05}{0.15 \cdot 2} = -13.5^ ext{°}

Biological Discrimination Example

• (R)-(-)-epinephrine fits enzyme active sites, while (S)-(+)-epinephrine does not.

Racemic Mixtures

• Contain equal quantities of d- and l-enantiomers, denoted by (d,l) or (±).
• Optically inactive; may possess different b.p. and m.p.

Optical Purity Calculation

• Optical purity (o.p.) is defined as:
  o.p. = \frac{observed \ rotation}{rotation \ of \ pure \ enantiomer} \times 100.

Example of % Composition in a Mixture

• Specific rotation for (S)-2-iodobutane is +15.90^ ext{°}; if mixture = -3.18^ ext{°}, then:
• o.p. = \frac{3.18}{15.90} \times 100 = 20\%
• l = 60\%, d = 40\%$$ // (S) being levorotatory.

Fischer Projections

• Linear representation of 3D molecule with chiral centers at intersections of lines.
• Horizontal lines project outward, vertical lines lie backwards.

Fischer Rules

• Carbon chain on vertical axis; top is highest oxidized carbon; rotation of 180° permissible, 90° rotation not.

Meso Compounds

• Meso: Have internal plane of symmetry making them achiral, even with chirality centers present.

Properties of Diastereomers

• Diastereomers present different physical properties, making separation feasible.
• In contrast, enantiomers only differ in interactions with chiral molecules and how polarized light's rotated, complicating separation.

Chemical Resolution of Enantiomers

• To separate enantiomers, react racemic mixtures with a pure chiral compound to generate diastereomers, which can then be separated effectively.