Synthetic routes
Specification Reference 6.2.5 (b)–(c)
Quick Notes
- Multi-Stage Synthesis
- You need to be able to propose multi-step synthetic routes.
- Use knowledge of interconversions and reactivity of functional groups.
- Molecules with Multiple Functional Groups
- Identify and distinguish individual functional groups.
- Predict chemical reactivity and physical properties based on functional groups in the molecule.
Full Notes
Molecules with Several Functional Groups
Many organic compounds contain more than one functional group. When predicting reactions:
- Identify functional groups present: Alcohols, carboxylic acids, ketones, esters, alkenes, amines, nitriles, etc.
- Predict reactivity and interactions: Some groups will react differently depending on the rest of molecule and give the molecule unique properties (for example, solubility of alcohols decreases with chain length).
Being able to recognise and understand multiple functional groups is essential in planning synthetic pathways and understanding physical properties (like solubility or acidity).
Multi-Stage Synthetic Routes
A multi-stage synthesis involves several successive reactions to convert a starting material into a desired product.
Designing a route:
- Use a series of known functional group interconversions.
- Consider order: some groups may interfere with others or need to be protected.
- Each stage should be practical and based on familiar reactions (e.g. oxidation, substitution, esterification).
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:
- Hydration of Ethene to Ethanol
Reagents: Steam, H3PO4 catalyst
C2H4 + H2O → C2H5OH - Conversion of Ethanol to Bromoethane
Reagents: HBr
C2H5OH + HBr → C2H5Br + H2O - Nucleophilic Substitution with Ammonia
Reagents: Excess NH3
C2H5Br + NH3 → C2H5NH2 + HBr
OCR Functional Group Interconversion Summary
| From | To | Reagents & Conditions | Reaction Type |
|---|---|---|---|
| Alkane | Haloalkane | Cl2 or Br2, UV light | Free-radical substitution |
| Alkene | Alkane | H2, Ni catalyst, 150 °C | Electrophilic addition (hydrogenation) |
| Alkene | Haloalkane | HCl / HBr (g) | Electrophilic addition |
| Alkene | Dihaloalkane | Br2 (aq) or (in organic solvent) | Electrophilic addition |
| Alkene | Alcohol | Steam, H3PO4 catalyst, 300 °C, 60 atm | Electrophilic addition |
| Alcohol (1°) | Aldehyde | K2Cr2O7/H2SO4 (distillation) | Oxidation |
| Alcohol (1°) | Carboxylic acid | K2Cr2O7/H2SO4 (reflux) | Oxidation |
| Alcohol (2°) | Ketone | K2Cr2O7/H2SO4 (reflux) | Oxidation |
| Alcohol (any) | Alkene | Conc. H3PO4 or H2SO4, heat | Elimination (dehydration) |
| Alcohol (any) | Haloalkane | NaBr + H2SO4 or PX3 | Nucleophilic substitution |
| Haloalkane (1°) | Alcohol | Aqueous NaOH, reflux | Nucleophilic substitution |
| Haloalkane (1°) | Nitrile | KCN in ethanol, reflux | Nucleophilic substitution |
| Haloalkane (1°) | Amine (aliphatic) | Excess NH3 in ethanol, heat under pressure | Nucleophilic substitution |
| Nitrile | Amine | H2/Ni catalyst OR LiAlH4 | Reduction |
| Nitrile | Carboxylic acid | HCl(aq), reflux | Hydrolysis |
| Aldehyde | Carboxylic acid | K2Cr2O7/H2SO4 (reflux) | Oxidation |
| Aldehyde / Ketone | Alcohol | NaBH4 (aq) | Nucleophilic addition (reduction) |
| Aldehyde / Ketone | Hydroxynitrile | HCN (via NaCN + H+) | Nucleophilic addition |
| Carboxylic acid | Ester | Alcohol + H2SO4 catalyst, heat | Esterification |
| Ester | Carboxylic acid + alcohol | Dilute HCl, reflux | Acid hydrolysis |
| Ester | Carboxylate salt + alcohol | Dilute NaOH, reflux | Base hydrolysis |
| Nitrobenzene | Phenylamine | Sn + conc. HCl, reflux then NaOH | Reduction |
| Acyl chloride | Amide (1° or 2°) | NH3 or amine | Nucleophilic addition–elimination |
| Acyl chloride | Ester | Alcohol | Nucleophilic addition–elimination |
| Acyl chloride | Carboxylic acid | H2O | Nucleophilic addition–elimination |
| Benzene | Nitrobenzene | Conc. HNO3 + H2SO4, 50–60 °C | Electrophilic substitution |
| Benzene | Halobenzene | Cl2 or Br2 + AlCl3 or AlBr3 catalyst | Electrophilic substitution |
| Benzene | Alkylbenzene | Haloalkane + AlCl3 | Friedel–Crafts alkylation |
| Benzene | Acylbenzene | Acyl chloride + AlCl3 | Friedel–Crafts acylation |
| Phenol | 2,4,6-tribromophenol | Br2 (aq) | Electrophilic substitution |
| Phenol | Nitrophenol | Dilute HNO3 | Electrophilic substitution |
| Dicarboxylic acid + Diol | Polyester | Heat, catalyst | Condensation polymerisation |
| Dicarboxylic acid + Diamine | Polyamide | Heat, catalyst | Condensation polymerisation |
| Amino acid | Zwitterion | pH ≈ isoelectric point | Acid–base behaviour |
| Amino acid | Peptide / Protein | Condensation between NH2 and COOH | Peptide bond formation |
Summary
- Many organic compounds contain more than one functional group, which affects their reactivity and properties.
- Multi-stage synthesis involves using known interconversions to build a route from starting material to product.
- Order of steps matters and sometimes protecting groups are needed.