Organic Chemistry

Structure, stereochemistry and the reactions that follow from them

About this course

The chemistry of carbon compounds — notation, conformation and stereochemistry, acidity, the core reaction classes from substitution to carbonyl chemistry, aromaticity and orbital symmetry, ending with structure determination and synthesis.

What you will be able to do

  • Draw and interpret skeletal structures, conformations and strain
  • Assign configuration to chiral centres and distinguish enantiomers from diastereomers
  • Use pKa values to predict the direction of acid-base reactions
  • Predict the products and mechanisms of substitution, elimination, addition and carbonyl reactions
  • Identify an unknown from its data and plan a multi-step synthesis

What this course covers

  • pKa as energy: the master conversion
  • pKa as equilibrium position, not rate
  • Four structural effects on acidity
  • pKa table as a mechanism diagnostic
  • The leveling effect and base selection
  • Aldol first step: two-route worked example
  • Carbonyl polarization and electrophilic carbon
  • Bond strength vs. reactivity distinction
  • Hydration equilibrium: electronic and steric control
  • Two-face geometry and stereochemical outcomes
  • Conjugate addition vs. 1,2-addition (charge vs. orbital control)
  • Addition vs. substitution at the tetrahedral intermediate
  • Catenation and chain survival: the key ratio
  • Hybridization and molecular geometry
  • Combinatorial explosion of structural isomers
  • Inertness of the C–H scaffold and the functional group concept
  • Course framework: reactivity as a difference
  • Conformational energy scan of ethane (rotation barrier)
  • Chirality: definition and the meso case
  • Cahn-Ingold-Prelog (R/S) priority rules
  • R/S labels carry no physical information
  • What is the same and what differs between enantiomers
  • Historical discovery of chirality: Biot and Pasteur
  • Optical rotation and enantiomeric excess
  • Anomeric effect: failure of conformational analysis to predict glucose equilibrium
  • Degrees of Unsaturation as a Molecular Constraint
  • Infrared Spectroscopy as Functional-Group Filter
  • Mass Spectrum Isotope Patterns and Carbon Count
  • Counting NMR Signals by Symmetry
  • Structure Determination as a Constraint Funnel
  • Recommended Order of Spectral Analysis
  • 2^N as an upper bound on stereoisomer count
  • Stereoisomer classification: enantiomers vs. diastereomers
  • Meso compounds and Fischer projections
  • Physical property differences of diastereomers
  • Resolution: converting an enantiomer pair into diastereomers
  • Tartaric acid as capstone: Pasteur's luck and the racemate anomaly
  • Acid derivatives family and reactivity ladder
  • Addition–elimination mechanism of acyl substitution
  • Directionality of the ladder: downhill-only rule
  • Acid and base catalysis in acyl substitution
  • Testing the amide resonance explanation computationally
  • Biological consequences of the amide's ladder position
  • Skeletal notation: what is omitted and why
  • Notation encodes chemistry, not just convenience
  • Degrees of unsaturation
  • Systematic naming as an algorithm
  • Canonical form and decidable molecular identity
  • Independent verification of the heptane isomer count
  • Worked naming example: 3,4,6-trimethyloctane
  • Retrosynthetic disconnection and legality rule
  • Functional group interconversion as a repositioning move
  • Acid derivative ladder as a route-level constraint
  • Degrees of unsaturation as a route audit tool
  • Yield multiplication and convergent synthesis
  • Protecting groups as a quantifiable yield cost
  • Course-wide recurring methods: the accounting
  • Two Mechanisms of Nucleophilic Substitution
  • Rate Law as Mechanistic Evidence
  • Leaving Group Ability and the pKa Table
  • Factors Governing Mechanism Selection
  • Stereochemical Consequences: Inversion and Ion Pairs
  • Concurrent Mechanisms and the Rate Law with Two Terms
  • Alkene stability measured by heats of hydrogenation
  • Antiperiplanar requirement of E2 elimination
  • Menthyl vs. neomenthyl chloride: geometry controls product
  • Hofmann product: base size, not base strength
  • E1 vs. E2 rate laws and the four-exit competition
  • Four independent dials controlling elimination vs. substitution
  • Central principle: preference vs. access
  • Measuring benzene's extra stability
  • Resonance energy and benzene's notation
  • Hückel's rule: conditions and electron count
  • Aromaticity and anomalous C–H acidity
  • Why benzene substitutes rather than adds
  • Diagnostic framework and method caution
  • Butane's torsional rotation and conformational preference
  • Ring strain measured from heats of combustion
  • Two-effect model: angle strain and torsional strain
  • The cyclohexane chair: geometry and ring-flip dynamics
  • A values: the cost of axial substitution
  • Worked example: 1,4-dimethylcyclohexane and additivity of A values
  • Three-Point Attachment Rule
  • Enantiomeric Excess as a Boltzmann Ratio
  • Thalidomide: Racemization Invalidates the Standard Moral
  • Asymmetric Catalysis and Its Economics
  • Unifying Spine: Ordinary Sterics Read as a Ratio
  • Three Levers for Achieving Target ee
  • Pericyclic reactions: no intermediate, concerted mechanism
  • Stereospecificity as proof of no intermediate
  • The Woodward–Hoffmann thermal/photochemical selection rule
  • Light inverts the rule: electrocyclic stereochemistry
  • Aromaticity and the selection rule as the same function
  • Stereospecificity vs. stereoselectivity: the endo rule contrast
  • Markovnikov's Rule Restated as Mechanism
  • Designed Experiment as a Method for Testing Rules
  • Quantitative Carbocation Stability via Hydride Affinity
  • Carbocation Rearrangements (Hydride and Alkyl Shifts)
  • Bromonium Ion and Anti Addition Stereochemistry
  • Radical Addition and the Anti-Markovnikov Outcome

Syllabus

  1. Structure and Notation

    1. L1 · Why Carbon
    2. L2 · The Notation Is the Theory
    3. L3 · Conformation and Strain

  2. Stereochemistry

    1. L4 · Chirality
    2. L5 · Diastereomers
    3. L6 · Why Stereochemistry Matters

  3. Acidity and the Core Reactions

    1. L7 · pKa Is the Whole Table
    2. L8 · Substitution
    3. L9 · Elimination
    4. L10 · Addition to Alkenes

  4. Carbonyls, Aromaticity and Orbital Symmetry

    1. L11 · The Carbonyl
    2. L12 · Acid Derivatives
    3. L13 · Aromaticity
    4. L14 · Orbital Symmetry

  5. Structure Determination and Synthesis

    1. L15 · Solving an Unknown
    2. L16 · Synthesis and Send-off