Q1(d). Baeyer–Villiger oxidation; Bischler–Napieralski synthesis

Introduction. (i) A peracid converts a ketone into an ester (a cyclic ketone into a lactone) by the Baeyer–Villiger oxidation; the more substituted carbon migrates. (ii) A β-arylethylamide closes to a dihydroisoquinoline by the Bischler–Napieralski reaction; Pd/C then dehydrogenates it to the aromatic isoquinoline.

(i) Baeyer–Villiger oxidation

Reading of the question: the 1,6-dione is read with one equivalent of mCPBA, which attacks the C-1 ketone; excess peracid would also convert the C-6 ketone into a lactone.

Scheme: O is inserted between C-1 and the ring-fusion carbon, which migrates with retention.

1. The peracid adds to the C=O to give the tetrahedral Criegee intermediate, C(OH)(O-O-COAr).
2. In the rate-determining step one α-carbon migrates from C to O as ArCO₂⁻ leaves. Migratory aptitude: tertiary > secondary > primary. At C-1 the ring-fusion CH (C-8a, secondary) migrates rather than the CH₂ (C-2, primary), and it moves with retention of configuration.
3. The C-6 ketone has two CH₂ neighbours, gives no regiochemical preference, and is the slower one.

X is the ε-lactone: the original ring A becomes a seven-membered ring containing -O-CO⁻, fused to the cyclohexanone ring (an octahydro-1-benzoxepine-2,7-dione, the second C=O kept).

(ii) Bischler–Napieralski reaction, then dehydrogenation

Scheme: Acylation, cyclodehydration (SEAr on a nitrilium ion) and aromatisation.

1. Acetyl chloride acylates the amine: N-(2-phenylethyl)acetamide.
2. P₂O₅ activates the amide oxygen; loss of water gives an electrophilic nitrilium ion (or imidoyl phosphate), which attacks the ortho position of the ring (intramolecular electrophilic substitution, six-membered ring closure). Loss of H⁺ gives 1-methyl-3,4-dihydroisoquinoline.
3. Pd/C at 100°C removes two H from C-3 and C-4: the ring becomes aromatic.

X = 1-methylisoquinoline.

Conclusion. (i) Baeyer–Villiger oxidation: the ring-fusion carbon migrates to O, giving the seven-membered lactone X. (ii) Bischler–Napieralski reaction followed by Pd/C dehydrogenation: X = 1-methylisoquinoline.

Application. Baeyer–Villiger oxidation makes caprolactone (for polycaprolactone) and steroid lactones; the Bischler–Napieralski route is the standard way into isoquinoline alkaloids such as papaverine.