Organic synthesis and reaction pathwaysEdexcel A-Level Chemistry: Revision notes

Combustion analysis: burn a known mass of compound; CO₂ gives the carbon and H₂O gives the hydrogen; oxygen is found by difference.

Worked example: 0.230 g of a compound of C, H and O gives 0.440 g CO₂ and 0.270 g H₂O.

• n(C) = 0.440 ÷ 44.0 = 0.0100 mol (0.120 g)
• n(H) = 2 × 0.270 ÷ 18.0 = 0.0300 mol (0.030 g)
• mass of O = 0.230 − 0.150 = 0.080 g, n(O) = 0.00500 mol
• ratio C : H : O = 2 : 6 : 1, so the empirical formula is C₂H₆O

The molecular formula is a whole-number multiple of the empirical formula; it is found from the molecular ion peak (m/z 46 gives C₂H₆O). The same approach works from elemental percentage composition (divide each % by Aᵣ).

Characteristic reactions: alkene – bromine water decolourised; carboxylic acid – effervescence with sodium carbonate/hydrogencarbonate; carbonyl – orange precipitate with 2,4-dinitrophenylhydrazine; aldehyde – silver mirror (Tollens') or brick-red precipitate (Fehling's); primary/secondary alcohol or aldehyde – orange to green with acidified dichromate(VI); halogenoalkane – warm with NaOH, acidify with HNO₃, add AgNO₃.

Mass spectrum: the molecular ion peak gives Mᵣ; fragments suggest groups.

Infrared: O–H (alcohol) about 3230–3550 cm⁻¹, O–H (acid) 2500–3300 cm⁻¹ (very broad), C=O 1680–1750 cm⁻¹, N–H 3300–3500 cm⁻¹.

¹H NMR: the number of peaks shows the number of proton environments; the area ratio gives the number of H in each; splitting follows the n + 1 rule.

Work backwards from the target and choose reactions that you know. Useful steps:

• alkene + HBr → bromoalkane; alkane + Br₂ (UV) → bromoalkane
• bromoalkane + NaOH(aq), heat → alcohol; + KCN in ethanol, reflux → nitrile (one carbon longer); + excess NH₃ in ethanol → amine
• nitrile + dilute acid, reflux → carboxylic acid; nitrile + LiAlH₄ in dry ether → amine
• primary alcohol + acidified dichromate(VI) → aldehyde (distil) or carboxylic acid (reflux); secondary alcohol → ketone
• alcohol + concentrated H₃PO₄ or H₂SO₄ → alkene
• benzene + HNO₃/H₂SO₄ → nitrobenzene; nitrobenzene + Sn/HCl → phenylamine

For each step give reagents, conditions and the type of reaction. Count carbon atoms: only cyanide or a Grignard reagent adds carbon atoms to the chain.

A bromoalkane reacts with magnesium turnings in dry ether to form a Grignard reagent:

CH₃CH₂Br + Mg → CH₃CH₂MgBr

The carbon bonded to magnesium is δ–, so the reagent is a strong nucleophile and a strong base. It reacts violently with water, forming an alkane, so everything must be anhydrous.

• With CO₂ (solid), then dilute acid: a carboxylic acid with one more carbon, e.g. CH₃CH₂COOH.
• With methanal, then dilute acid: a primary alcohol.
• With another aldehyde: a secondary alcohol, e.g. CH₃CH₂MgBr + CH₃CHO gives butan-2-ol.
• With a ketone: a tertiary alcohol, e.g. CH₃CH₂MgBr + propanone gives 2-methylbutan-2-ol.

The nucleophilic carbon attacks the δ+ carbonyl carbon; the acid then protonates the intermediate.

• Reflux: heating with a condenser upright so volatile liquids return to the flask and the reaction can run for a long time.
• Distillation: separates liquids with different boiling temperatures; collect the fraction at the boiling temperature of the product.
• Steam distillation: separates a volatile, water-immiscible compound (e.g. phenylamine) from a mixture at below 100 °C, so it does not decompose.
• Solvent extraction: shake with an immiscible solvent in a separating funnel; the organic layer is separated.
• Washing: with sodium hydrogencarbonate solution to remove acidic impurities, then water.
• Drying: an anhydrous salt such as sodium sulfate or magnesium sulfate removes water from a liquid.
• Recrystallisation: dissolve in the minimum hot solvent, cool slowly, filter under reduced pressure, wash, dry.
• Purity: a pure solid has a sharp melting temperature matching data; a pure liquid has a sharp boiling temperature.

A hazard is the potential to cause harm; risk is the chance of harm given how the hazard is used. Use hazard data to select a procedure and to justify control measures.

• Toxic reagents (e.g. cyanide): fume cupboard, gloves, keep away from acid.
• Flammable solvents (e.g. ether): water bath or electric heater, no naked flames, small quantities.
• Corrosive acids: goggles and gloves, add slowly with cooling.
• Water-reactive reagents (Grignard reagents, LiAlH₄): dry apparatus and solvents.

Justify a choice of route by comparing hazards, yield, number of steps and cost.

Core practical 15 (unknowns): identify inorganic ions with tests (carbonate with acid giving CO₂; halides with AgNO₃ then ammonia; sulfate with barium chloride; cations with sodium hydroxide and ammonia) and organic compounds with the tests above (bromine water, 2,4-DNPH, Tollens', acidified dichromate(VI), sodium hydrogencarbonate). Record observations, not conclusions.

Core practical 16 (aspirin): warm salicylic acid with excess ethanoic anhydride and a few drops of concentrated phosphoric(V) acid in a water bath; add cold water to hydrolyse excess anhydride and precipitate crude aspirin; filter under reduced pressure; recrystallise from the minimum hot solvent; dry and take the melting temperature.

% yield = actual mass ÷ theoretical mass × 100. Example: 2.76 g salicylic acid (0.0200 mol) gives 3.60 g aspirin theoretically.