UPSC Combined Geo-Scientist, Mains · 2026 · Mains Paper III
Q6(c). Gramine from indole and its displacement by cyanide
Question
Identify the major product (X) formed in the following reaction sequence and suggest a suitable mechanism for the conversion of X→ Y: indole + CH₂O, Me₂NH, CH₃CO₂H, H₂O → X; X + NaCN → indole-3-acetonitrile (Y).
Answer in brief
X = gramine (3-(dimethylaminomethyl)indole), by a Mannich reaction at C-3. X→ Y goes by elimination–addition: loss of Me₂NH gives 3-methylene-3H-indole, to which CN⁻ adds.
Key points
- CH₂O + Me₂NH → CH₂=N+Me₂ (iminium); indole attacks through C-3 (the most nucleophilic carbon), then loses H⁺.
- Me₂N⁻ is a poor leaving group for S_N2, but the indole N–H lone pair pushes it out (after protonation or quaternisation) to form the azafulvene (3-methylene-3H-indole). CN⁻ adds at the exocyclic CH₂ (conjugate addition) and N…
The full model answer
Worked out step by step, as it should go in the answer booklet. The solution sheet follows it.
- Formation of X: CH₂O + Me₂NH → CH₂=N+Me₂ (iminium); indole attacks through C-3 (the most nucleophilic carbon), then loses H⁺.
- X→ Y: Me₂N⁻ is a poor leaving group for S_N2, but the indole N–H lone pair pushes it out (after protonation or quaternisation) to form the azafulvene (3-methylene-3H-indole). CN⁻ adds at the exocyclic CH₂ (conjugate addition) and N is reprotonated.
CoversMannich reactionGramine from indole and its displacement by cyanide
All parts of Question 6
- 6(a) Hofmann and Schmidt reactions4 marks
- 6(b) Cannizzaro; LiAlH₄ on a lactam; selective reduction of an ester4 marks
- 6(c) Gramine from indole and its displacement by cyanide4 marks
- 6(d) Benzoin condensation and Darzens reaction4 marks
- 6(e) Two epoxidations of carvone4 marks
- 6(f) Photochemistry of stilbene4 marks
- 6(g) Racemisation of an optically active 1,5-diene4 marks
- 6(h) Identify the amide from its IR bands4 marks
- 6(i) Woodward–Fieser rules for three dienes4 marks
- 6(j) Halogens from the M, M+2 and M+4 peaks4 marks