Ester To Amide Nh3

Ester Reactions: Ester → Amide using Excess NH₃

Ester → Amide (NH₃, excess) | OrgoSolver

Carbonyl Reactions: Formation of Amides from Esters Using Excess Ammonia (NH₃)

Aminolysis of esters with excess ammonia converts R–COOR′ into the primary amide R–CONH₂ through nucleophilic acyl substitution. NH₃ adds to the carbonyl, generating a tetrahedral intermediate; proton transfers convert –OR′ into ROH (a neutral leaving group) and neutralize the nitrogen; collapse expels ROH to give the amide. Because this process is reversible, laboratory procedures employ excess NH₃ (often the solvent) and/or remove ROH to drive the equilibrium forward.


Key Emphasis (Teaching Pivots)

  • Mechanistic spine: Closed-shell nucleophilic acyl substitution — NH₃ addition → tetrahedral intermediate → proton shuttles → collapse to amide + ROH.
  • Equilibrium control: Reaction is reversible; use a large excess of NH₃ (often solvent/pressure) and remove ROH to push conversion. Activated esters help.
  • pKₐ logic: RO⁻ (pKₐ(ROH) ~ 16–18) readily deprotonates RNH₃⁺/NH₄⁺ (pKₐ ~ 9–11), so proton transfers that generate ROH and neutral –NH₂ are favorable.
  • Scope choice: Primary/secondary amines aminolyze esters even faster, but this article focuses on NH₃ → primary amides.

Quick Summary

  • Reagents/conditions: Excess NH₃ (NH₃(l), NH₃ in MeOH/EtOH, or concentrated NH₄OH); heat/pressure as needed; neutral to mildly basic media.
  • Outcome: R–C(=O)OR′ + NH₃ ⇌ R–C(=O)NH₂ + R′OH.
  • Driving forces: Le Châtelier (excess NH₃, removal of ROH) + amide resonance stabilization.
  • Avoid: Strong acid (protonates NH₃ to NH₄⁺) and oxidants that would quench NH₃.

Mechanism — Aminolysis by NH₃ (4 Steps)

Step 1: NH3 adds to the ester carbonyl.
Step 1 — NH₃ adds to the carbonyl (tetrahedral intermediate forms).
Step 2: Lone pair collapses and RO− begins to depart.
Step 2 — The former carbonyl oxygen collapses while the –OR′ group is pushed out (nucleophilic acyl substitution).
Step 3: RO− deprotonates the ammonium nitrogen.
Step 3 — RO⁻ grabs a proton from the ammonium, regenerating NH₂ and giving ROH.
Step 4: Products after aminolysis.
Step 4 — Products: the primary amide (RCONH₂) and the ROH coproduct.

Mechanistic Checklist (Exam Focus)

  • NH₃ adds to the carbonyl — draw the tetrahedral intermediate explicitly.
  • Proton transfers convert –OR′ into ROH and leave the nitrogen as –NH₂.
  • Collapse expels ROH (not RO⁻). Show closed-shell arrows only.
  • Reaction is equilibrium-limited: cite “excess NH₃” or “remove ROH” as the driving force.
  • Product is the primary amide (from NH₃); amide is much less reactive, so over-acylation is not observed.

Worked Examples

Methyl benzoate → benzamide + methanol

NH₃ (excess, MeOH, sealed tube) aminolyzes methyl benzoate to benzamide; methanol is the leaving-group alcohol.

Example A reactant: methyl benzoate Reagent: excess NH3 Example A products: benzamide + methanol

Ethyl acetate → acetamide + ethanol

NH₃ in EtOH/reflux (sealed) converts ethyl acetate to acetamide. Large NH₃ excess is necessary to overcome equilibrium.

Example B reactant: ethyl acetate Reagent: excess NH3 Example B products: acetamide + ethanol

γ-Butyrolactone → 4-hydroxypentanamide

Lactones undergo ring-opening aminolysis, giving hydroxy amides when treated with excess NH₃.

Example C reactant: γ-butyrolactone Reagent: excess NH3 Example C products: 5-hydroxypentanamide

Scope & Limitations

  • General esters: Aliphatic and aryl esters react; aryl esters are slower, but activated ones (p-nitrophenyl, pentafluorophenyl) are fast.
  • Lactones: Open to hydroxy amides (useful for polymer chemistry).
  • Competing processes: In alcoholic solvents, transesterification may compete; maximize NH₃ activity or use NH₃(l).
  • Acidic media: Protonates NH₃ → NH₄⁺ (non-nucleophilic) and halts aminolysis.

pKₐ Notes (Context)

  • pKₐ(NH₄⁺) ≈ 9.2; simple alkylammonium ions pKₐ ≈ 10–11.
  • pKₐ(H₂O) = 15.7; pKₐ(ROH) ≈ 16–18. → RO⁻ is basic enough to deprotonate NH₄⁺/RNH₃⁺, furnishing ROH and neutral –NH₂, which supports the collapse to the amide. These values also show that alkyl amines are at least as basic as NH₃; exclusion of RNH₂/R₂NH here is a scope choice for this article.

Edge Cases & Exam Traps

  • Forgetting equilibrium (no excess NH₃ or ROH removal) — reaction stalls.
  • Drawing RO⁻ as the leaving group (should be ROH after protonation).
  • Confusing with acid chloride aminolysis (esters need harsher conditions / equilibrium tactics).
  • Claiming “over-acylation” — amides are far less reactive than esters, so the reaction stops at the amide.

Practical Tips

  • Use NH₃ in large excess (NH₃(l) or concentrated solutions). Seal tubes/autoclaves when heating volatile NH₃ mixtures.
  • Remove ROH (distillation, extraction) to pull the equilibrium toward the amide.
  • Activated esters or phase-transfer catalysts can lower temperature/time for hindered substrates.
  • Avoid strong acid; even weak acid will protonate NH₃ and quench nucleophilicity.

Exam-Style Summary

Ester + excess NH₃ → NH₃ addition (tetrahedral intermediate) → proton shuttles (–OR′ → ROH; –NH₃⁺ → –NH₂) → collapse to RCONH₂ + ROH. Drive conversion with excess NH₃ or ROH removal. pKₐ(ROH) ≫ pKₐ(NH₄⁺), so RO⁻ readily deprotonates NH₄⁺/RNH₃⁺, supporting amide formation.


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