(a) The compound A, acetal of acetaldehyde, on reaction with B, under given reaction conditions, yields C and the final product…

(a) Claisen and Johnson–Claisen rearrangements

(i) Structures of C and D, with mechanism

A is acetaldehyde dimethyl acetal, CH₃CH(OMe)₂, and B is a secondary allylic alcohol, R–CH(OH)–CH=CH₂. Heating the two with a weak acid (propionic acid) is the standard way to make an allyl vinyl ether in situ, and the ether then undergoes a Claisen rearrangement.

1. Trans-acetalisation. Propionic acid protonates one OMe of A, and MeOH leaves to give the oxocarbenium ion CH₃–CH=O⁺Me. The OH of B adds to this ion, and loss of H⁺ gives the mixed acetal CH₃CH(OMe)–O–CH(R)CH=CH₂.
2. Elimination of MeOH. Protonation of the remaining OMe and loss of MeOH give a second oxocarbenium ion. Loss of an α-proton from its CH₃ then produces the enol ether. C = allyl vinyl ether, CH₂=CH–O–CH(R)–CH=CH₂.
3. [3,3]-Sigmatropic (Claisen) rearrangement on heating. In a concerted, chair-like six-membered transition state, the allylic C–O σ-bond breaks while a new C–C bond forms between the terminal CH₂ of the vinyl group and the terminal CH₂ of the allyl group. The π bonds move to C=O and to a new internal C=C. Forming a strong C=O bond makes the step irreversible. D = γ,δ-unsaturated aldehyde, OHC–CH₂–CH₂–CH=CH–R, formed mainly as the (E)-alkene because R sits equatorial in the chair transition state.

C=COC(R)C=C  >>  O=CCC/C=C/R

(Example with R = CH₃: C = 3-(vinyloxy)but-1-ene and D = (E)-hex-4-enal, both C₆H₁₀O. The rearrangement is an isomerisation.)

(ii) With the ortho-ester E (trimethyl orthoacetate): the Johnson–Claisen rearrangement

E, CH₃C(OMe)₃, exchanges one OMe with the allylic alcohol under the same acid catalysis. It then loses MeOH to give a ketene acetal, CH₂=C(OMe)–O–CH(R)CH=CH₂, which carries one more OMe than C. The same [3,3] shift then produces an ester instead of an aldehyde.

• Product: the γ,δ-unsaturated methyl ester MeO₂C–CH₂–CH₂–CH=CH–R (for R = CH₃, methyl (E)-hex-4-enoate), together with 2 MeOH.

(b)(i) Photochemical route to vitamin D and sunlight

Ergosterol (A) has a cyclohexa-1,3-diene unit (Δ⁵,⁷) in ring B, closed by the C9–C10 σ-bond. Precalciferol (B) has no ring B: the C9–C10 bond is broken, and the molecule is a (6Z)-hexatriene running C10=C5–C6=C7–C8=C9.

Mechanism

1. The Δ⁵,⁷-diene absorbs UV-B light (about 290–315 nm). It is promoted to its excited state, where the HOMO is ψ₄ of the triene being formed.
2. A 6π electrocyclic ring opening follows. For 4n + 2 electrons the photochemically allowed mode is conrotatory, and this mode opens ring B with correct stereochemistry to give precalciferol.
3. Precalciferol then isomerises thermally at body temperature by a [1,7]-sigmatropic hydrogen shift, antarafacial and thermally allowed. An H moves from the C-19 methyl to C-9, which gives the 10(19)-exocyclic methylene triene of vitamin D₂ (ergocalciferol). In human skin the same sequence converts 7-dehydrocholesterol into vitamin D₃. Hydroxylation in the liver (C-25) and kidney (C-1) then gives the active hormone.

Why the deficiency is endemic where sunlight is scarce. The ring-opening step has no thermal alternative. The thermally allowed disrotatory opening of the fused, rigid ring is not accessible at body temperature, so without UV-B photons the provitamin is not converted. At high latitudes, in long winters, under persistent cloud, smog or full clothing, UV-B reaching the skin is too weak to drive the step. Few foods contain much vitamin D, so poor Ca²⁺ absorption leads to rickets in children and osteomalacia in adults. The deficiency is endemic where UV-B is scarce because the key step in making the vitamin is photochemical.

(b)(ii) p-Bromonitrobenzene to m-bromobenzoic acid

The conversion takes one step, the von Richter reaction: p-bromonitrobenzene is heated with KCN in aqueous ethanol.

p-BrC₆H₄NO₂ + CN⁻ → m-BrC₆H₄COO⁻ + N₂, and acidification gives m-bromobenzoic acid.

Mechanism (cine substitution)

1. CN⁻ adds to the ring carbon ortho to NO₂, which is meta to Br, to give a Meisenheimer-type σ-adduct.
2. A nitro oxygen attacks the neighbouring nitrile carbon, and the cyclic adduct opens to an o-nitroso benzamide.
3. The amide N and the nitroso N condense to form an N=N bond in a cyclic intermediate.
4. Attack by hydroxide expels N₂, the carboxylate forms, and a proton ends up on the carbon that carried NO₂.

The COOH therefore ends up ortho to the old NO₂ position, which is meta to Br.

(c)(i) Product of CHCl₂CF₃ with EtO⁻ and its energy profile

Product: CF₂=CCl₂ (1,1-dichloro-2,2-difluoroethene), formed by E1cB elimination of HF.

• The C–H proton is unusually acidic. The carbanion ⁻CCl₂–CF₃ is stabilised by the strong –I effect of CF₃ and by the two polarisable chlorines on the carbanion carbon.
• The only leaving groups β to that carbanion are fluorines, and C–F cleavage is difficult. Deprotonation is therefore fast and reversible, and loss of F⁻ is rate-limiting: an E1cB(reversible) mechanism.
• Kinetic evidence. When the reaction is run with EtO⁻ in EtOD, the recovered substrate has exchanged its H for D faster than it forms alkene. The carbanion must therefore form and return to substrate many times before F⁻ is lost. For the same reason the elimination shows little primary H/D isotope effect.

The energy profile shows a low TS1 for fast, reversible proton removal and a carbanion in a genuine potential well. TS2, where C–F breaks, is the highest point, so it controls the rate.

(c)(ii) SN2 reactivity order of A–D

Order of increasing S_N2 reactivity: A ≈ B < D < C, where A = 1-bromobicyclo[2.2.1]heptane, B = 1-bromobicyclo[2.2.2]octane, C = tert-butyl bromide and D = 9-bromo-9-phenyl-9,10-dihydroanthracene.

• A and B (bridgehead bromides): no S_N2 at all. Backside attack would have to come from inside the cage, where the C–Br σ* lobe points. The rigid framework also cannot flatten into a trigonal-bipyramidal transition state or allow Walden inversion. The more compact norbornyl cage (A) is the more rigid of the two.
• D: extremely slow. The reacting carbon is tertiary and carries three aryl groups: the phenyl and the two fused rings. They screen the back face more heavily than the three methyls of C.
• C: the "fastest" of the four. It is also tertiary, but its small methyl groups still allow some backside approach, so a very slow S_N2 is possible.

All four are tertiary halides, and in practice none reacts usefully by S_N2. In polar solvents C and D react by S_N1 instead, D very rapidly because its cation is stabilised by resonance over three rings. A and B resist even S_N1, because a bridgehead cation cannot become planar (Bredt-type strain). If the examiner intends ionisation (S_N1) reactivity, the order is A < B < C < D: the norbornyl cation is the most strained, the bicyclo[2.2.2]octyl cation somewhat less so, the tert-butyl cation is freely planar, and the cation from D is both tertiary and benzylic.