Q3(a). Tollens condensation; aldol, Jones oxidation and Fischer indole

Introduction. Both parts start with aldol chemistry. In (i) formaldehyde, which has no α-H, acts only as the electrophile, and finally as the hydride donor of a crossed Cannizzaro step. In (ii) an intramolecular aldol closes a six-membered ring, and the 1,3-dione formed is converted into an indole by the Fischer indole synthesis.

(i) Acetaldehyde with excess formaldehyde: pentaerythritol

1. OH⁻ removes an α-H of acetaldehyde to form the enolate ⁻CH₂CHO.
2. The enolate attacks HCHO (the more reactive, unhindered carbonyl): crossed aldol gives HOCH₂CH₂CHO. The two remaining α-H atoms react the same way, giving (HOCH₂)₃C-CHO (pentaerythrose), which has no α-H left.
3. Crossed Cannizzaro: OH⁻ adds to HCHO; the anion H₂C(OH)O⁻ transfers a hydride to the CHO of pentaerythrose. Formaldehyde, the better hydride donor, is oxidised to formate.

CH₃CHO + 4 HCHO + NaOH → C(CH₂OH)₄ + HCOO⁻ Na⁺ Major products: pentaerythritol, C(CH₂OH)₄ and sodium formate.

(ii) X and Y

Scheme: 5-Oxohexanal closes to a six-membered ring; Jones oxidation gives cyclohexane-1,3-dione.

X. In 5-oxohexanal the methyl ketone forms the enolate at its CH₃ group; this enolate attacks the aldehyde carbon five atoms away and closes a six-membered ring (the unstrained size, favoured over a four-membered ring from the other α-carbon). The aldol is 3-hydroxycyclohexanone; Jones reagent oxidises the secondary alcohol to a ketone: X = cyclohexane-1,3-dione, C₆H₈O₂, as the formula requires (the dehydrated enone would be C₆H₈O).

Y (Fischer indole synthesis).

1. Phenylhydrazine condenses with one C=O of X to give the phenylhydrazone.
2. Acid catalyses tautomerisation to the ene-hydrazine (C=C towards the ring CH₂, which lies between the two carbonyls and enolises easily).
3. A [3,3]-sigmatropic rearrangement breaks the weak N–N bond and forms a new C–C bond to the ortho carbon of the benzene ring (RDS).
4. The ring re-aromatises; the aniline NH₂ attacks the imine carbon to form a cyclic aminal.
5. Loss of NH₃ gives the aromatic indole.

Scheme: Y = 1,2,3,9-tetrahydro-4H-carbazol-4-one

Conclusion. (i) Pentaerythritol and sodium formate (three aldol additions, then a crossed Cannizzaro reduction). (ii) X = cyclohexane-1,3-dione; Y = 1,2,3,9-tetrahydro-4H-carbazol-4-one, formed by a Fischer indole synthesis through a [3,3]-sigmatropic step.

Application. Pentaerythritol is made this way on a large scale for alkyd resins and the explosive PETN; tetrahydrocarbazol-4-one is the starting material for the anti-emetic drug ondansetron.