Part 6: Structure deduction, Grignard reagents and synthetic routes

Combine composition, reactions and spectra, then plan routes of up to four steps with complete structures, carbon counts and conditions.

A combustion result measures carbon and hydrogen indirectly

For complete combustion of a compound containing only C, H and O, every carbon atom becomes one CO₂ and every pair of H atoms becomes one H₂O. Calculate n(C) = n(CO₂) and n(H) = 2n(H₂O). Find the masses of C and H; oxygen in the original sample is obtained by difference, not from the total oxygen in the combustion products.

Original worked data: 0.440 g compound gives 0.880 g CO₂ and 0.360 g H₂O. Using C = 12, H = 1, O = 16, n(C) = 0.880/44 = 0.0200 mol and n(H) = 2(0.360/18) = 0.0400 mol. Their masses are 0.240 g and 0.0400 g. Original O mass = 0.440 − 0.240 − 0.0400 = 0.160 g, hence n(O) = 0.0100 mol.

The atom ratio 0.0200:0.0400:0.0100 simplifies to 2:4:1, giving empirical formula C₂H₄O, formula mass 44. If mass spectrometry gives Mᵣ = 88, the multiplier is 88/44 = 2, so the molecular formula is C₄H₈O₂. For percentage composition use a convenient 100 g sample and divide each mass by its atomic mass; never divide percentages directly to obtain an atom ratio.

Only calculate oxygen by difference if the sample’s elements are known. Incomplete combustion, impure samples or unmeasured nitrogen would invalidate that assumption. Preserve unrounded mole ratios until a plausible small whole-number ratio is established.

Combine independent constraints before selecting a structure

For the original C₄H₈O₂ example, a strong IR absorption near 1740 cm⁻¹ and no broad acid/alcohol O–H band support an ester among the proposed candidates. IR alone cannot uniquely prove the ester structure or rule out every alternative combination of groups. Hydrolysis producing ethanol and ethanoic acid fixes the ester as CH₃COOCH₂CH₃.

Illustrative high-resolution proton NMR then gives a three-H singlet near δ 2.0, a two-H quartet near δ 4.1 and a three-H triplet near δ 1.2. The singlet is CH₃CO, and the quartet/triplet pair is OCH₂CH₃. Four carbon environments are expected in the ¹³C spectrum. Each observation independently fits ethyl ethanoate.

Use a table or numbered chain of evidence: formula constrains atoms; chemical tests and IR suggest functional groups; mass fragments suggest pieces; carbon NMR counts environments; proton NMR links H groups. Finally check the candidate against every observation, including absent signals. Detailed NMR and accurate-mass methods are developed in Topic 19. Missing an observation should remain an explicit uncertainty, not be silently ignored.

Magnesium reverses the reactive character of carbon

A halogenoalkane reacts with magnesium in dry ether to form a Grignard reagent, RMgX. Carbon in the C–Mg bond has substantial δ− character and can act as a nucleophile towards carbonyl carbon or CO₂. Writing R⁻ is a useful reactivity model, not a claim that a free isolated carbanion is the only species present.

Dry apparatus and anhydrous ether are essential. Water and other protic compounds destroy the reagent by protonating the carbon group: RMgX + H₂O → RH + Mg(OH)X. This consumes the reagent before the intended C–C bond forms. Ether also coordinates to magnesium and provides the reaction medium.

Generate and react the reagent first; add dilute acid or water for controlled work-up only after the C–C-forming reaction. Substrates containing free OH, COOH or NH groups can consume a Grignard reagent by acid–base chemistry. Account for those groups in unfamiliar routes rather than applying the addition pattern blindly.

Join the nucleophilic carbon to the electrophilic carbon

With methanal, RMgX forms an alkoxide that gives a primary alcohol RCH₂OH after work-up. Other aldehydes give secondary alcohols RCH(OH)R′; ketones give tertiary alcohols RR′C(OH)R″. The carbonyl carbon becomes the alcohol carbon, and the Grignard carbon group is attached directly to it.

Carbon dioxide gives a magnesium carboxylate before work-up, then RCOOH after acidification. Its carbon adds one carbon to the Grignard skeleton. Do not draw the free acid as stable in a mixture still containing unused Grignard reagent.

Worked ethylmagnesium-bromide comparison: methanal gives propan-1-ol; ethanal gives butan-2-ol; propanone gives 2-methylbutan-2-ol; CO₂ gives propanoic acid. Count 2 + 1, 2 + 2, 2 + 3 and 2 + 1 carbons respectively. The change in alcohol class follows how many carbon groups were initially attached to the carbonyl carbon.

Work backwards from the bond that must be made

First compare starting and target carbon counts and locate the target functional group. Ask which known reaction creates that group, then whether the required precursor can be made from the starting material. Label every arrow with reagents and conditions and draw every intermediate, not just a chain of reaction names.

One-carbon extension options include halogenoalkane → nitrile → acid/amine, carbonyl → hydroxynitrile, and Grignard + CO₂. Grignard + carbonyl can join larger fragments. Oxidation, reduction and substitution commonly change functional groups while preserving the existing carbon skeleton.

Original three-step route: 1-bromopropane → butanenitrile using cyanide in ethanol with heat → butylamine using LiAlH₄ in dry ether then work-up → N-butylethanamide using ethanoyl chloride with excess amine/base as appropriate. The nitrile step adds one carbon; the final acylation adds an ethanoyl group to N.

Original four-step route: benzene → nitrobenzene with concentrated HNO₃/H₂SO₄ and controlled warming → phenylammonium salt by Sn/concentrated HCl and heat → phenylamine by NaOH → N-phenylethanamide with ethanoyl chloride. If a scheme counts reduction plus alkaline work-up as one preparative arrow, state both operations on that arrow rather than omitting the work-up.

A shorter route is useful only if it is selective and workable

For sequential steps, fractional yields multiply. Three independent steps of 85.0%, 90.0% and 80.0% give 0.850 × 0.900 × 0.800 = 0.612, or 61.2% overall, relative to the stoichiometric starting limit. Adding percentages would give a physically meaningless result.

Assess selectivity, separation, hazards, atom economy and energy use alongside yield. A halogenoalkane/ammonia route is short but may over-alkylate; a nitrile route can improve product class control but adds a step and involves toxic cyanide. An acid-chloride route is reactive but sensitive to moisture and generates corrosive coproducts.

In unfamiliar synthesis, use supplied reaction information and propose a chemically compatible sequence. Protecting groups may be mentioned as an extension when two functional groups interfere, but detailed protection chemistry is not a routine recall demand here.

Quick checks

Original Finesse questions. Reveal the indicative worked solutions after attempting each question; these are not official Edexcel mark allocations.

Sources