Q3(e). Morpholine and 4-fluorophenyl methyl sulfone: S_NAr

Introduction. An aryl fluoride carrying a strong electron-withdrawing group para to F undergoes nucleophilic aromatic substitution by addition–elimination (SNAr). The SO₂Me group stabilises the anionic intermediate.

Scheme: Addition of the amine to C–F, then loss of fluoride restores the aromatic ring.

1. The N of morpholine attacks C-1 (bearing F) perpendicular to the ring. The ring loses aromaticity; the negative charge is delocalised to C-2, C-4, C-6 and onto the sulfonyl group at C-4: the Meisenheimer complex. This addition is the rate-determining step.
2. Fluoride leaves and aromaticity returns; K₂CO₃ removes the N-H⁺ proton and neutralises HF. DMSO (polar aprotic) leaves the amine unsolvated and reactive.
3. F is the best leaving group in SNAr (F > Cl > Br > I) because C–F breaking is not rate-limiting and the strong -I effect of F speeds the addition.

Conclusion. Product: 4-[4-(methylsulfonyl)phenyl]morpholine, C₁₁H₁₅NO₃S, by SNAr (addition–elimination through a Meisenheimer complex).

Application. SNAr of activated aryl fluorides with morpholine and piperazine is used industrially to make drugs such as linezolid and the fluoroquinolone antibiotics.