(a) (i) Predict the reaction mechanism and the major product formed when methyl cyanide is heated with dilute hydrochloric acid…

3. (a) (i) Methyl cyanide + dilute HCl, heat

• Major product: acetic acid (ethanoic acid), with ammonium chloride. CH₃CN + 2 H₂O + HCl → CH₃COOH + NH₄Cl. The reaction goes through acetamide.

Mechanism, stage 1 (nitrile → amide):

• H⁺ protonates the nitrile nitrogen (CH₃–C≡N⁺–H). This makes the sp carbon strongly electrophilic.
• Water, a weak nucleophile, adds to that carbon. Loss of H⁺ gives the imidic acid CH₃–C(OH)=NH.
• The imidic acid tautomerises to the more stable amide, CH₃CONH₂ (acetamide).

Mechanism, stage 2 (amide → acid):

• The carbonyl oxygen of the amide is protonated.
• Water adds, giving the tetrahedral intermediate CH₃C(OH)₂NH₃⁺.
• NH₃ is expelled and is immediately captured as NH₄⁺. This makes the step irreversible and drives the reaction to completion.
• Mild conditions: with short times or controlled acid, the reaction can be stopped at acetamide. Prolonged heating gives the acid.

(a) (ii) Br₂ + 2-butenes: stereospecific anti addition

• Step 1: the π bond polarises Br₂ and a cyclic bromonium ion forms. The alkene geometry is frozen in this three-membered ring: there is no open carbocation and no C–C rotation.
• Step 2: Br⁻ opens the ring by backside (SN2-like) attack from the face opposite the bridging Br. The two Br atoms therefore end up anti.
• cis-2-Butene: the bromonium ion has a mirror plane. Br⁻ attacks C-2 or C-3 with equal probability, giving (2R,3R)- and (2S,3S)-2,3-dibromobutane in a 1 : 1 ratio. This is an optically inactive racemic mixture.
• trans-2-Butene: anti attack at either carbon, on either face, gives the same (2R,3S) isomer. It has an internal mirror plane (Br on the same side in the Fischer projection), so it is meso.
• Why this proves anti addition: syn addition, or a free carbocation, would give the opposite outcome or a mixture. The clean stereospecificity is therefore evidence for the bridged bromonium ion.

(b) (i) Enone formation: 6π electrocyclisation, then hydrolysis

• The substrate is a conjugated hexatriene: CH₂=C(OMe)–C=C–CH=CH–CO₂Me. The central C=C is the cyclohexene ring bond, which holds the triene in the required cis (s-cis, s-cis) arrangement.
• At 215 °C, thermal 6π electrocyclic ring closure forms a new σ bond between the triene termini (the CH₂ and the CH bearing CO₂Me). The product is a cyclohexadiene fused to the cyclohexane ring, and the OMe group is now on an enol-ether C=C.

Why it is disrotatory (Woodward–Hoffmann rules):

• The system has 6 π electrons, which is 4n+2.
• The thermal HOMO of a hexatriene is ψ₃, whose terminal lobes have the same sign on the same face.
• Bonding overlap therefore requires the termini to rotate in opposite senses (disrotatory), which is symmetry-allowed.
• Here one terminus is CH₂, so the only new stereocentre is the CH–CO₂Me carbon, and the product is racemic.

Step 2, HCl(aq)/EtOH:

• The methyl enol ether is protonated at carbon and hydrolysed to a ketone, with loss of MeOH. This first gives a β,γ-unsaturated ketone.
• Acid-catalysed enolisation moves the C=C into conjugation with C=O at the ring fusion. The product is the thermodynamically preferred α,β-unsaturated ketone (octalone), methyl 4-oxo-1,2,3,4,5,6,7,8-octahydronaphthalene-2-carboxylate.
• Overall sequence: electrocyclisation → enol-ether hydrolysis → conjugation. It is not a Claisen rearrangement, because there is no allyl vinyl ether.

(b) (ii) Classification of the rearrangement at 33 °C

Class: [3,3]-sigmatropic shift (a Cope rearrangement of the divinylcyclopropane type).

• The reacting 1,5-diene is CH₂=CH–C6–C1–C2=C3.
• The σ bond that migrates is the strained cyclopropane bond C1–C6, which sits in position 1,1′ of the two allyl fragments.
• A new σ bond forms between atoms 3 and 3′ (vinyl CH₂ and ring C3), converting endo-6-vinylbicyclo[3.1.0]hex-2-ene into bicyclo[3.2.1]octa-2,6-diene.

Symmetry: allowed.

• Six electrons (two π bonds and one σ bond) reorganise in a cyclic array: 4n+2.
• With both allyl components suprafacial ([π2s + σ2s + π2s]), the transition state is aromatic (Hückel), so the reaction is thermally allowed.

Why it is so fast:

• The rigid bicycle holds the endo vinyl group over the ring, so it must react through a boat-like transition state.
• Breaking a cyclopropane bond releases about 115 kJ mol⁻¹ of ring strain, so the reaction proceeds even at 33 °C.

(b) (iii) Diels–Alder: 2-methoxy-5-methyl-1,4-benzoquinone + butadiene (100 °C)

• Roles: butadiene is the diene. The quinone is the dienophile, because each of its C=C bonds is activated by two C=O groups.
• Site selectivity: the OMe-substituted C=C is a vinylogous ester. Oxygen lone-pair donation makes it electron-rich and a poor dienophile. The methyl-substituted C=C is only weakly deactivated, so butadiene adds there.

Product: cis-2-methoxy-4a-methyl-4a,5,8,8a-tetrahydronaphthalene-1,4-dione (racemic).

• The new cyclohexene ring carries an angular methyl group at the ring fusion.
• The enone C=C bearing OMe survives, between the two C=O groups.
• Stereochemistry: the addition is suprafacial on the dienophile, so the angular CH₃ and the ring-fusion H end up cis (cis ring fusion). The endo/exo question does not arise, because butadiene is unsubstituted.
• Context: this is the first step of Woodward's total synthesis of steroids (cholesterol and cortisone, 1951–52). There, base later epimerised the cis adduct to the trans-fused isomer.

(c) (i) RCOCl → RN=C=O via a nitrene (Curtius rearrangement)

• Step 1: azide ion substitutes chloride at the acyl carbon (addition–elimination) in an inert solvent, giving the acyl azide R–C(=O)–N=N⁺=N⁻.
• Step 2: on heating, N₂ (an excellent, entropically favoured leaving group) is lost. This leaves the acyl nitrene R–C(=O)–N̈:, a neutral, monovalent nitrogen with only six valence electrons, which is electron-deficient like a carbene.
• Step 3: the electron-deficient N accepts R, which migrates from carbon to nitrogen with its bonding pair (a 1,2-shift). This gives the isocyanate R–N=C=O. In water the isocyanate would go on to the amine plus CO₂, and in alcohol to a carbamate.

Evidence for the nitrene / intramolecular pathway:

• A chiral R group migrates with complete retention of configuration.
• Crossover experiments give no mixed products, so the migration is intramolecular.
• Photolysis of acyl azides gives products of nitrene trapping (C–H insertion into the solvent, aziridines with alkenes).
• The nitrene route is the classical textbook description. Kinetic and computational studies suggest the thermal reaction is largely concerted, with loss of N₂ and migration occurring together, so a free nitrene is established mainly under photolysis.

Orbital pictures of the nitrene:

• N makes one σ bond to R and holds a lone pair in an sp-type orbital pointing away from R. It has two non-bonding p orbitals (pₓ and p_y), perpendicular to the R–N axis, which share the remaining 2 electrons.
• Triplet: one electron in each p orbital, with parallel spins. By Hund's rule this is the ground state of NH and most alkyl and aryl nitrenes. It behaves as a diradical: it abstracts H atoms and adds to alkenes non-stereospecifically.
• Singlet: both electrons paired in one p orbital, with the other p orbital empty. It is electrophilic and carbene-like, adds to alkenes stereospecifically and inserts into C–H bonds. Acyl nitrenes gain extra singlet stabilisation from the neighbouring C=O.

(c) (ii) Account for the following

(1) Indole substitutes at C-3.

• Attack of E⁺ at C-3 gives a σ-complex whose positive charge sits on C-2, directly next to N. The N lone pair therefore stabilises it as an iminium ion (every atom has an octet), and the benzene ring stays fully aromatic.
• Attack at C-2 puts the charge on C-3. That cation is stabilised only as a benzylic cation; N can share the charge only through a quinoid form that destroys the benzene sextet.
• The C-3 intermediate, and so the transition state leading to it, is much lower in energy. Indole therefore behaves like an enamine at C-3: bromination, Vilsmeier formylation and the Mannich reaction (giving gramine) all occur at C-3.

(2) Chlorobenzene resists nucleophilic substitution.

• Resonance: the Cl lone pair conjugates with the ring, giving the C–Cl bond partial double-bond character. The bond is shorter (about 170 pm, against 178 pm in CH₃Cl) and stronger.
• sp² carbon: the sp²-hybridised carbon (more s character) holds the bonding electrons more tightly, making Cl⁻ harder to expel.
• No SN2: backside attack is impossible because the ring blocks the σ* orbital, and inversion at a ring carbon is geometrically forbidden.
• No SN1: the phenyl cation would be very unstable, with its empty sp² orbital not conjugated with the π system.
• Repulsion: the electron-rich π cloud repels incoming nucleophiles.
• When substitution does occur: only under forcing conditions (Dow process: NaOH, about 623 K, high pressure), through benzyne (NaNH₂), or by SNAr when –NO₂ groups sit ortho/para to Cl. For example, 2,4-dinitrochlorobenzene reacts readily through a Meisenheimer complex.