Stereochemistry Notes

Stereochemistry

• Branch of chemistry studying the spatial arrangement of atoms in molecules.
• Isomers: Same molecular formula, different atom arrangement.

Isomers

• Constitutional Isomers
  • Functional
  • Positional
  • Skeletal
• Stereoisomers
  • Geometric
    • Cis & Trans System
    • E & Z System
  • Optical
    • Enantiomers

Constitutional Isomers

• Functional Isomerism
  • Isomers with different functional groups.
  • Example: C3H6O can be propanal (aldehyde) or propanone (ketone).
• Positional Isomerism
  • Same molecular formula, different functional group position.
  • Example: C3H7Br, bromine on end or middle carbon.
• Skeletal Isomerism
  • Branching in carbon chains.
  • Example: Butane (C4H10), straight or branched chain.

Geometric Isomerism

• Carbon-carbon double bond (C=C) has one sigma and one pi bond.
• Pi bond prevents free rotation.
• Cis Isomer: Same groups on the same side of C=C.
• Trans Isomer: Same groups on opposite sides of C=C.
• E/Z System: Used when cis/trans is not applicable (4 different substituents).
  • Determine priority at each end of alkene.
  • E Isomer: higher priority groups on opposite sides (entgegen = opposite)
  • Z Isomer: higher priority groups on same side (zusammen = together)
• Priority Rules
  • Look at the first atom attached to the alkene carbon
  • Higher atomic number = higher priority
  • If same atomic number, higher atomic mass = higher priority (e.g., D > H, {}^{13}C > {}^{12}C)

Optical Isomers

• Ability to rotate plane of polarized light.
• All optical isomers have a chiral center.
• Chiral Center: Carbon atom with 4 different groups attached.
  • A chiral molecule has no plane of symmetry

Wedge and Dash Notation

• Represents 3D structure.
• Find chiral center.
• Construct 3D structure.

Enantiomers

• Mirror images, non-superimposable.
• Same physical/chemical properties, different physiological functions.

R & S System

• Chiral centers labeled R or S.
• Rank substituents by priority (highest atomic number).
• If a to b to c is clockwise: R (rectus).
• If a to b to c is counter-clockwise: S (sinister).
• Enantiomers have different rotation.

Chiral Drugs

• Only one enantiomer may be active.
• Examples:
  • Ibuprofen: S isomer reduces inflammation.
  • Methyl dopa: S isomer reduces hypertension.
  • Penicillamine: S isomer treats arthritis, R isomer is toxic.
  • Thalidomide: R enantiomer cured morning sickness, S enantiomer caused birth defects.