Organic Synthesis

Full Notes

Deducing Formulae from Experimental Data

You need to be able to determine empirical formulae, molecular formulae and structural formulae of compounds using given data from a range of techniques - for example mass spectrometry (see mass spectrometry), IR spectroscopy (see IR spectroscopy) and NMR spectroscopy (see NMR) as well as observations from chemical tests (for example 2,4-DNPH for carbonyls, bromine water for alkenes, etc).

Planning reaction schemes

Matt’s Exam Tip

Synthesis questions can look overwhelming! Focus on one thing at a time and remember that no matter how complicated the molecules may look, the functional group conversions will only be ones you have seen and learnt about before. Focus on the functional groups in the molecules that are changing, rather than focusing on the whole molecule overall.

Example Synthesising Ethylamine (C₂H₅NH₂) from Ethene (C₂H₄)

A typical exam question may get you to fill in missing steps for a synthesis. Such as making ethylamine from ethene.

A possible route may be.

1. Hydration of Ethene to Ethanol
   Reagents: Steam, H₃PO₄ catalyst
   C₂H₄ + H₂O → C₂H₅OH
2. Conversion of Ethanol to Bromoethane
   Reagents: HBr
   C₂H₅OH + HBr → C₂H₅Br + H₂O
3. Nucleophilic Substitution with Ammonia
   Reagents: Excess NH₃
   C₂H₅Br + NH₃ → C₂H₅NH₂ + HBr

Using Grignard Reagents to Increase Chain Length

Grignard reagents are organomagnesium compounds of the form RMgX, where R is an alkyl group and X is a halogen (typically Br or Cl).

They can be used to increase the length of the carbon chain in a molecule.

Preparation:

React a haloalkane with magnesium in dry ether:

CH₃CH₂Br + Mg → CH₃CH₂MgBr

These are extremely reactive and must be kept dry (otherwise they would react with water).

Uses:

React with CO₂, followed by hydrolysis, to form a carboxylic acid:

• CH₃CH₂MgBr + CO₂ → CH₃CH₂COOMgBr
• Then hydrolyse → CH₃CH₂COOH

React with aldehydes or ketones to form alcohols :

• CH₃CH₂MgBr + CH₃CHO → CH₃CH(OH)CH₂CH₃
• (forms a secondary alcohol)

Selecting and Justifying Practical Organic Techniques

When designing a synthetic procedure, you need to:

• Choose appropriate reagents and conditions.
• Select appropriate control measures (e.g., use of fume hoods, gloves, eye protection) to minimise risks such as flammability, toxicity, or corrosivity.

Purification and Analysis Techniques

All practical techniques required are outlined required practicals (see required practicals).

Refluxing

• Used when heating a reaction mixture to prevent loss of volatile substances.
• Vertical condenser allows vapour to condense and return to the flask.

Purification by Washing

• Removes soluble impurities. Often involves washing with water, dilute acid, or alkali depending on the impurity type.

Solvent Extraction

• Separates the product from an aqueous reaction mixture into an organic solvent in a separating funnel.

Recrystallisation

• Removes soluble and insoluble impurities from the solid.
• Dissolve the impure solid in a hot solvent.
• Filter hot, allow to cool slowly → pure crystals form.
• Filter under reduced pressure (use a Buchner Funnel), rinse crystals with cold water and dry.

Drying

• Use anhydrous salts (e.g., MgSO₄ or CaCl₂) to remove residual water from organic solvents.

Distillation / Steam Distillation

• Simple distillation separates liquids by boiling point.
• Steam distillation is used to purify or isolate organic compounds that may decompose and break apart at their boiling points.

How it works:

• Steam is passed through a mixture containing the desired compound.
• The compound and water co-distil (boil together) at a lower temperature than the boiling point of either liquid on its own.
• This allows the compound to evaporate without decomposing, then be condensed and collected.

Melting and Boiling Point Determination

• Confirms purity:
• Sharp melting point indicates a pure substance.
• Compare observed values with data to identify the compound.

Summary

• Use analytical data to deduce empirical and molecular formula and structure.
• Grignard reagents extend chains and make alcohols or acids.
• Plan multi-step routes by focusing on functional group changes.
• Apply correct lab techniques for heating, purification and analysis.
• Use control measures to reduce risk with hazardous or flammable reagents.