Stereochemistry in Organic Chemistry

Published by CHEMASH • Updated for clarity • September 6, 2025.

Overview

Stereochemistry studies how the 3-dimensional arrangement of atoms affects chemical and physical properties. It’s essential for understanding reaction mechanisms, biological activity of drugs, and material behaviour.

Example: Enantiomers of drugs (e.g., ibuprofen) can have different biological effects.

Types of Isomerism

1. Structural (Constitutional) Isomerism – different connectivity of atoms.
2. Stereoisomerism – same connectivity but different 3D arrangement.

Stereoisomerism Classification

• Conformational Isomerism – rotation around single bonds (Newman).
• Configurational Isomerism – cannot interconvert by rotation alone; includes geometrical (cis/trans, E/Z) and optical (chiral) isomerism.

Geometrical Isomerism (cis-trans / E-Z)

Occurs where rotation is restricted (e.g., C=C double bonds, small rings).

• Cis – identical groups on the same side.
• Trans – identical groups on opposite sides.

E–Z System (Cahn–Ingold–Prelog)

Used when substituents are different; assign priority by atomic number and compare positions.

Example: 2-butene — cis (Z): CH₃ groups same side; trans (E): opposite sides.

Optical Isomerism & Chirality

Enantiomers are non-superimposable mirror images. A molecule is chiral if it has no internal plane of symmetry.

• Chiral center: typically a carbon attached to four different groups.
• Enantiomers: identical physical properties except rotation of plane-polarized light and interactions with other chiral substances.
• Diastereomers: stereoisomers that are not mirror images.

Optical Activity

Measured with a polarimeter: dextrorotatory (+) rotates clockwise; levorotatory (−) rotates anticlockwise.

Example: Lactic acid (CH₃–CH(OH)–COOH) has one chiral center → two enantiomers.

Meso Compounds

A meso compound has multiple stereocentres but an internal symmetry plane that makes it achiral.

Example: Tartaric acid (one stereochemical form is meso and optically inactive).

Representation of Stereochemistry

• Fischer projections — convenient for sugars and amino acids.
• Newman projections — visualize conformations around single bonds.
• Sawhorse projections — diagonal 3D perspective.
• Wedge–dash notation — solid wedge out of page, hashed wedge into page.

Importance of Stereochemistry

• Drug design and pharmacology
• Enzyme specificity
• Flavors and fragrances
• Polymer properties and materials science

Interesting fact: The thalidomide tragedy (1960s) highlighted the importance of stereochemistry — one enantiomer caused birth defects.

MCQs

1. Which of the following defines a chiral carbon?
   • a) Carbon with three identical groups
   • b) Carbon with four different groups
   • c) Carbon with a double bond
   • d) Carbon in a ring
   Answer: b) Carbon with four different groups.
   Explanation: A chiral center (stereocenter) usually has four different substituents, creating non-superimposable mirror images.
2. Which isomerism is due to restricted rotation about a bond?
   • a) Optical isomerism
   • b) Structural isomerism
   • c) Geometrical (cis–trans) isomerism
   • d) Conformational isomerism
   Answer: c) Geometrical (cis–trans) isomerism.
   Explanation: Restricted rotation, such as around a double bond, gives rise to cis/trans or E/Z isomers.
3. Which projection is best for showing staggered and eclipsed conformations?
   • a) Fischer
   • b) Newman
   • c) Wedge–dash
   • d) Sawhorse
   Answer: b) Newman.
   Explanation: Newman projections show view down a bond and can represent staggered/eclipsed conformations clearly.
4. Which system assigns priority when naming E/Z isomers?
   • a) R/S rules
   • b) Cahn–Ingold–Prelog priority rules
   • c) Fisher projection rules
   • d) Markovnikov’s rule
   Answer: b) Cahn–Ingold–Prelog priority rules.
   Explanation: CIP rules assign priorities to substituents to determine E or Z configuration.

Quiz (10 questions with answers)

1. What is a chiral carbon? A carbon atom with four different groups attached.
2. Which type of isomerism arises due to restricted rotation? Geometrical (cis–trans) isomerism.
3. What is the difference between enantiomers and diastereomers? Enantiomers are mirror images; diastereomers are not mirror images and have different physical properties.
4. Which system is used to assign priority in E/Z isomerism? Cahn–Ingold–Prelog rules.
5. What is a meso compound? A molecule with multiple stereocentres but an internal plane of symmetry making it achiral.
6. Name two projection methods used in stereochemistry. Fischer and Newman projections.
7. What property is used to distinguish enantiomers in the lab? Optical rotation of plane-polarized light measured with a polarimeter.
8. What type of isomers are cis- and trans-butene? Geometrical isomers (E/Z isomers).
9. What causes optical activity in a molecule? Presence of chirality (asymmetric centers) or overall chiral arrangement.
10. Which projection shows the conformation of single bonds? Newman projection.

Frequently Asked Questions

Q: How do I determine if a molecule is chiral?

A: Look for stereocentres (atoms with four different substituents) and absence of an internal plane of symmetry. Try to draw its mirror image — if non-superimposable, it’s chiral. Q: Can a molecule with two chiral centres be achiral? A: Yes — if the molecule has an internal plane of symmetry (a meso compound), it can be achiral despite stereocentres. Q: What’s the practical importance of stereochemistry in drugs? A: Enantiomers can interact differently with biological targets; one enantiomer could be therapeutic while the other is inactive or harmful. Drug development often isolates the active enantiomer

References & Links

• External: Stereochemistry — Wikipedia