Edexcel International A Level Chemistry: Organic synthesis (YCH11)

This guide teaches Topic 20: Organic Synthesis, outcomes 20.1 to 20.5, as set out in Issue 1 (September 2017) of Pearson Edexcel’s International Advanced Subsidiary/Advanced Level in Chemistry specification, YCH11. It is International A2 (IA2) content in Unit 5 (Transition Metals and Organic Nitrogen Chemistry), and it includes Core Practical 16, the preparation of aspirin. The specification says this section draws on the organic chemistry from the whole course, so expect familiar reactions in new combinations.

Linked pages: condensed revision notes and a practice set; the course hub and its printable checklist; the free diagnostic quizzes. For background on spectra, see mass spectra and infrared spectroscopy and, for C=O reactions, carbonyl compounds.

Coverage of Topic 20

Spec ref	You should be able to
20.1	Deduce empirical, molecular and structural formulae from combustion analysis, percentage composition, functional group tests, IR, mass spectra and NMR (¹³C and proton)
20.2	Lengthen a carbon chain with Grignard reagents (Mg in dry ether), reacting them with CO₂ and with carbonyl compounds
20.3 i	Predict and explain the properties of unfamiliar compounds containing familiar functional groups
20.3 ii	Plan reaction schemes of up to four steps, including unfamiliar reactions you are given
20.3 iii	Select suitable practical procedures
20.3 iv	Choose control measures from hazard data
20.4	Core Practical 16: the preparation of aspirin
20.5 i–ix	Explain reflux, washing, solvent extraction, recrystallisation, drying, distillation, steam distillation, and melting and boiling temperature determination

20.1 Working out a structure from data

Use the evidence in a fixed order.

1. Empirical formula from combustion masses or percentage composition.
2. Molecular formula from Mr (the molecular ion, M⁺, in the mass spectrum).
3. Functional groups from chemical tests and the IR spectrum.
4. Carbon skeleton from NMR: number of environments, peak areas and splitting.

From combustion: all carbon ends up in CO₂ and all hydrogen in H₂O. Mass of oxygen in the sample = sample mass − mass of C − mass of H.

Worked example 1: combustion, then spectra

Complete combustion of 0.264 g of compound P (C, H and O only) gives 0.528 g of CO₂ and 0.216 g of H₂O. M⁺ is at m/z = 88. The IR spectrum has a very broad absorption across roughly 2500–3300 cm⁻¹ and a strong one near 1710 cm⁻¹. The proton NMR spectrum has three peaks: a doublet (area 6), a septet (area 1) and a singlet near δ 11–12 (area 1). Identify P.

n(C) = n(CO₂) = 0.528 ÷ 44.0 = 0.0120 mol → 0.144 g
n(H) = 2 × n(H₂O) = 2 × (0.216 ÷ 18.0) = 0.0240 mol → 0.024 g
mass of O = 0.264 − 0.144 − 0.024 = 0.096 g → 0.096 ÷ 16.0 = 0.0060 mol
C : H : O = 0.0120 : 0.0240 : 0.0060 = 2 : 4 : 1   empirical formula C₂H₄O (Mr 44.0)
88 ÷ 44 = 2, so molecular formula C₄H₈O₂

The broad 2500–3300 cm⁻¹ band is O–H in a carboxylic acid, and 1710 cm⁻¹ is C=O. The singlet near δ 11–12 is the COOH proton. A doublet of area 6 means two equivalent CH₃ groups next to one H; the septet of area 1 is that H, next to six H atoms (n + 1 = 7). P is 2-methylpropanoic acid, (CH₃)₂CHCOOH. Butanoic acid, the straight-chain isomer, would give four proton environments, not three. P’s ¹³C spectrum would show three peaks, since the two CH₃ carbons are equivalent.

Chemical tests confirm groups: effervescence with sodium carbonate solution shows COOH; an orange precipitate with 2,4-DNPH shows C=O in an aldehyde or ketone; Tollens’ or Fehling’s then picks out aldehydes.

20.2 Grignard reagents: adding carbon atoms

A Grignard reagent forms when a halogenoalkane reacts with magnesium turnings in dry ether (ethoxyethane):

CH₃CH₂Br + Mg → CH₃CH₂MgBr        (ethylmagnesium bromide)

In R–MgX the carbon bonded to magnesium carries a δ− charge, so it behaves as a nucleophile. It attacks the δ+ carbon of CO₂ or of a C=O group and forms a new C–C bond. The ether must be dry, because water destroys the reagent (it gives the alkane, RH). The intermediate is then hydrolysed with dilute acid.

Grignard reacts with	Product after dilute acid	Carbons added
CO₂ (e.g. solid CO₂)	carboxylic acid, RCOOH	1 (the COOH carbon)
methanal, HCHO	primary alcohol, RCH₂OH	1
any other aldehyde, R′CHO	secondary alcohol, RCH(OH)R′	carbons of R′CHO
ketone, R′COR″	tertiary alcohol, RC(OH)R′R″	carbons of the ketone

CH₃CH₂MgBr + CO₂ → CH₃CH₂COOMgBr
CH₃CH₂COOMgBr + H₂O → CH₃CH₂COOH + Mg(OH)Br     (in dilute acid)

Worked example 2: choosing the pair

Make 2-methylbutan-2-ol, CH₃CH₂C(OH)(CH₃)₂. The OH carbon carries three alkyl groups, so it is a tertiary alcohol: a Grignard reagent plus a ketone. Split one bond from that carbon. Ethylmagnesium bromide + propanone works: CH₃CH₂MgBr adds to the C=O carbon of (CH₃)₂CO, and hydrolysis gives the alcohol. Methylmagnesium iodide + butanone also works. Check each pair by counting carbons: 2 + 3 = 5.

20.3 Problem solving

i Predicting properties of unfamiliar compounds

List every functional group first, then predict each one’s behaviour separately. For example, HOCH₂CH₂CHO contains a primary alcohol and an aldehyde, so it:

• forms hydrogen bonds (O–H), so it is likely to be soluble in water;
• gives a silver mirror with Tollens’ reagent and an orange precipitate with 2,4-DNPH (aldehyde);
• gives steamy fumes of HCl with PCl₅ (OH group);
• is oxidised fully by excess acidified dichromate(VI) under reflux, at both ends, to HOOCCH₂COOH.

Explain each prediction by naming the group responsible.

ii Planning routes of up to four steps

Write the start and target side by side. Ask three questions: has the carbon count changed? Which functional group must appear or go? Has the group moved? Then work backwards from the target.

Chain-lengthening tools you know: KCN in ethanol (+1 C, via a nitrile), HCN addition to C=O (+1 C), Friedel-Crafts on arenes, and Grignard reagents (+1 C or more).

Worked example 3: a four-step route

Make 3-methylbutan-2-one, CH₃COCH(CH₃)₂, from 2-bromopropane and ethanol.

Work back: the ketone comes from oxidising the secondary alcohol 3-methylbutan-2-ol. That alcohol comes from a Grignard reagent and an aldehyde: (CH₃)₂CHMgBr + CH₃CHO.

Step	Reaction	Reagents and conditions
1	ethanol → ethanal	K₂Cr₂O₇ with dilute H₂SO₄; warm and distil off the aldehyde as it forms
2	2-bromopropane → (CH₃)₂CHMgBr	Mg turnings, dry ether
3	Grignard + ethanal → 3-methylbutan-2-ol	in dry ether, then dilute acid
4	alcohol → 3-methylbutan-2-one	K₂Cr₂O₇ with dilute H₂SO₄, heat under reflux

To confirm the ketone, check three results: 2,4-DNPH gives an orange solid; Fehling’s solution stays blue; iodine in alkali gives pale yellow iodoform, because of the CH₃CO– group.

When a question gives you an unfamiliar reaction, use it exactly as described. Each extra step lowers the overall yield, so prefer the shorter route when two work.

iii and iv Procedures and hazards

Match the procedure to the job: reflux to heat a slow reaction, distillation to collect a volatile product, recrystallisation for a solid. Then match each hazard to a control:

Hazard in the data	Control measure
Highly flammable (ether, ethanol)	No naked flames; heat with a water bath or electric heater
Corrosive (conc. acids, ethanoic anhydride)	Gloves and eye protection; add slowly
Toxic or harmful vapour	Fume cupboard
Irritant solid or dust	Avoid skin contact; gloves
Reacts violently with water (Grignard, acyl chlorides)	Dry apparatus and solvents

A control must answer the stated hazard. “Wear goggles” alone does not deal with a flammable solvent.

20.4 Core Practical 16: preparing aspirin

Aspirin (2-ethanoyloxybenzoic acid) forms when the phenol OH of 2-hydroxybenzoic acid reacts with ethanoic anhydride:

C₇H₆O₃ + (CH₃CO)₂O → C₉H₈O₄ + CH₃COOH
2-hydroxybenzoic acid + ethanoic anhydride → aspirin + ethanoic acid

A typical method: mix the solid acid with excess ethanoic anhydride and a few drops of concentrated phosphoric(V) or sulfuric acid as a catalyst. Warm in a hot water bath. Add cold water to destroy the excess anhydride, cool in ice to crystallise the crude product, and collect it by filtration under reduced pressure. Recrystallise, dry, weigh, and measure the melting temperature. Pure aspirin melts at about 135–136 °C.

Worked example 4: yield

3.45 g of 2-hydroxybenzoic acid (Mr 138.0) is used with 5.0 cm³ of ethanoic anhydride (density 1.08 g cm⁻³, Mr 102.0). 3.06 g of dry, recrystallised aspirin (Mr 180.0) is obtained.

n(acid) = 3.45 ÷ 138.0 = 0.0250 mol
n(anhydride) = (5.0 × 1.08) ÷ 102.0 = 0.0529 mol  → anhydride in excess
theoretical mass of aspirin = 0.0250 × 180.0 = 4.50 g
percentage yield = 3.06 ÷ 4.50 × 100 = 68.0%

Losses come from product left dissolved in the recrystallisation solvent, transfers and incomplete reaction.

20.5 Techniques for preparation and purification

• i Refluxing: heat with a vertical condenser so vapour condenses and runs back. Volatile reactants are not lost and the mixture can be heated for a long time. Add anti-bumping granules.
• ii Washing: shake the crude organic liquid with water to remove water-soluble impurities, or with sodium carbonate solution to remove acids. Release the CO₂ pressure in the separating funnel often.
• iii Solvent extraction: shake the mixture with an immiscible solvent in which the product dissolves better, let the layers separate and run them off. Several small portions extract more than one large portion.
• iv Recrystallisation: dissolve the impure solid in the minimum volume of hot solvent, filter hot to remove insoluble impurities, cool so the product crystallises, then collect the crystals by suction filtration, rinse them with ice-cold solvent and leave them to dry. Soluble impurities stay in solution.
• v Drying: add an anhydrous salt such as magnesium sulfate or calcium chloride to the organic liquid until the liquid is clear and the solid no longer clumps, then decant or filter.
• vi Distillation: heat the liquid with the thermometer bulb level with the side arm. Collect the fraction that distils close to the product’s boiling temperature.
• vii Steam distillation: pass steam through the mixture, or boil it with water. A volatile, water-immiscible compound distils with the water below 100 °C, so a compound that would decompose at its own boiling temperature is collected safely.
• viii Melting temperature: pack a little dry solid into a capillary tube sealed at one end and raise the temperature gently as you approach the expected value. A pure solid melts sharply at the data value; impurities lower it and spread it over a range.
• ix Boiling temperature: distil the liquid and read the steady thermometer temperature. Compare it with the data value.

Common errors

• Forgetting to add the O mass by difference in combustion problems.
• Treating the Grignard step as aqueous: the reaction needs dry ether, with acid only at the end.
• Counting the carbonyl compound’s carbons wrongly when naming a Grignard product.
• Planning a route that oxidises an alcohol to an acid when the target is an aldehyde: distil, do not reflux.
• Giving a control measure that does not match the hazard.
• Stating a yield above 100% without saying the product is still wet or impure.

Next steps

Read the revision notes, then try the practice questions. Tick off 20.1 to 20.5 on the checklist and take a free diagnostic.

Official syllabus

Source: Pearson Edexcel International Advanced Subsidiary/Advanced Level in Chemistry, specification XCH11/YCH11, Issue 1, September 2017 (Pearson Education Limited). This page covers Topic 20: Organic Synthesis, outcomes 20.1 to 20.5, including Core Practical 16, in Unit 5.