Oxime Formation Beckmann Rearrangement

Oxime Formation + Beckmann Rearrangement (NH₂OH/H⁺ then H₂SO₄)

Oxime Formation & Beckmann Rearrangement


Aldehydes and ketones react smoothly with hydroxylamine (NH₂OH) under mild acid to give oximes. When that oxime is activated with sulfuric acid, the anti substituent migrates to nitrogen while the N–O bond breaks, delivering the Beckmann rearrangement. Aldoximes become nitriles; ketoximes furnish amides or lactams. This guide packages both stages together so you can prep clean oximes in Stage 1 and immediately evaluate their Beckmann behavior in Stage 2.

Quick Summary


  • Stage 1 (NH₂OH/H⁺): Mild acid (AcOH or catalytic TsOH) protonates the carbonyl, hydroxylamine attacks, proton shuttles activate OH for departure, and dehydration delivers the oxime. Removing water (Dean–Stark, sieves) drives the equilibrium.
  • Stage 2 (H₂SO₄): Protonate the oxime oxygen, anti substituent migrates to nitrogen as N–O breaks, water captures the nitrilium, HSO₄⁻ deprotonates to imidate, H₂SO₄ reprotonates nitrogen, and a final sulfate-assisted deprotonation restores the carbonyl.
  • Products: Aldoxime → nitrile. Ketoxime → amide. Cyclic ketoxime → ring-expanded lactam.
  • Migratory aptitude: aryl ≳ tertiary > secondary > primary > methyl > hydrogen. Only the group anti to the leaving OH migrates.
  • Conditions overview: Stage 1 uses mild acid in EtOH, MeOH, or toluene (with water removal). Stage 2 uses conc. H₂SO₄ at 0–25 °C to activate the oxime, followed by controlled warming to complete rearrangement.

Mechanism (Stage 1) – Hydroxylamine Condensation to Oximes


Stage 1 Step 1: protonate the carbonyl oxygen so the carbon becomes more electrophilic.
**Step 1 – Carbonyl protonation:** Mild acid delivers a proton to the carbonyl oxygen, priming the carbon for nucleophilic attack.
Stage 1 Step 2: hydroxylamine attacks the activated carbonyl to give a carbinolamine.
**Step 2 – Hydroxylamine attack:** NH₂OH adds through its nitrogen lone pair to give the carbinolamine (hemiaminal).
Stage 1 Step 3: proton shuttles convert the leaving OH into OH2+ while neutralising nitrogen.
**Step 3 – Proton transfers:** Catalytic acid/base relays convert the OH into OH₂⁺ and neutralise nitrogen so water can leave.
Stage 1 Step 4: water leaves to generate the C=N bond.
**Step 4 – Dehydration:** Loss of water generates the C=N bond (iminium-like intermediate).
Stage 1 Step 5: deprotonation returns the neutral oxime (E or Z).
**Step 5 – Deprotonation:** A base removes the extra proton, giving the neutral oxime (noting possible E/Z geometry).
Stage 1 Step 6: equilibrium reminder; remove water to drive the condensation.
**Step 6 – Equilibrium reminder:** Oxime formation is reversible. Remove water (Dean–Stark, sieves, azeotropes) to maximise conversion.

Mechanism (Stage 2) – Beckmann Rearrangement under H₂SO₄


Stage 2 Step 1: protonate the oxime oxygen to make a better leaving group.
**Step 1 – Oxime activation:** Sulfuric acid protonates (or sulfonates) the oxime oxygen, aligning the anti group for migration.
Stage 2 Step 2: the anti substituent migrates to nitrogen as N–O cleaves.
**Step 2 – Anti migration:** The anti substituent migrates to nitrogen while the N–O bond breaks, producing the nitrilium ion.
Stage 2 Step 3: water adds to the nitrilium carbon.
**Step 3 – Water capture:** Water attacks the nitrilium to give an imidate cation (or hemimal).
Stage 2 Step 4: HSO4- deprotonates the bound OH2+, delivering the neutral imidate.
**Step 4 – HSO₄⁻ deprotonation:** The conjugate base removes the OH₂⁺ proton, generating a neutral imidate.
Stage 2 Step 5: the acid delivers a proton to nitrogen.
**Step 5 – Nitrogen protonation:** Sulfuric acid can reprotonate nitrogen, ensuring the imidate is set up for the final deprotonation.
Stage 2 Step 6: HSO4- removes the proton from the carbonyl oxygen, restoring the neutral amide.
**Step 6 – Final sulfate deprotonation:** HSO₄⁻ removes the proton from the carbonyl oxygen, regenerating the neutral amide/lactam (or nitrile if an aldoxime).
Stage 2 final panel: lactam product after Beckmann rearrangement.
**Final panel – Product:** The rearrangement delivers the amide or lactam (aldoximes give nitriles). This matches the mechanism solver’s concluding frame.

Worked Examples


Cyclohexanone → ε-Caprolactam

Stage 1 – Oxime formation (NH₂OH)
Cyclohexanone reactant + NH₂OH reagent button (Stage 1) → Cyclohexanone oxime intermediate

Dean–Stark removal of water in toluene or xylene pushes cyclohexanone to its oxime cleanly.

Stage 2 – Beckmann rearrangement (NH₂OH + H₂SO₄)
Cyclohexanone oxime intermediate + NH₂OH + H₂SO₄ reagent button (Stage 2) → ε-Caprolactam product

Controlled addition of conc. H₂SO₄ at 0 °C then a gentle warm-up delivers ε-caprolactam (nylon‑6 monomer).

Acetophenone → Acetanilide

Stage 1 – Oxime formation (NH₂OH)
Acetophenone reactant + NH₂OH reagent button (Stage 1) → Acetophenone oxime intermediate

Use ethanol or methanol with a catalytic acid to form the acetophenone oxime; keep the mixture water-lean.

Stage 2 – Beckmann rearrangement (NH₂OH + H₂SO₄)
Acetophenone oxime intermediate + NH₂OH + H₂SO₄ reagent button (Stage 2) → Acetanilide product

Slowly protonate the oxime at 0 °C, then warm to 50–60 °C to favour phenyl migration and deliver acetanilide after neutralisation.

Scope & Limitations


  • Aldehydes vs ketones: Aldehydes condense fastest and ultimately yield nitriles. Ketones need better water removal but give amides. Cyclic ketones expand by one atom to lactams.
  • Migrating group control: Only the substituent anti to –OH migrates. Equilibrate (acid or base) to set the E/Z geometry if necessary. Migratory aptitude: aryl ≳ tertiary > secondary > primary > methyl > hydrogen.
  • Sensitive functional groups: Stage 1 is mild; Stage 2 uses strong acid, so protect acid-labile substituents. Strongly basic or oxidising groups (peroxides, nitros) may fail.
  • Competitive pathways: Hydroxylamine can over-condense or rearrange if the carbonyl is highly activated. In Stage 2, excessive heat causes secondary sulfonation or dehydration of neighboring alcohols.

Practical Tips


  • Generate hydroxylamine in situ (NH₂OH·HCl + NaOAc) or buy anhydrous NH₂OH for cleaner Stage 1 outcomes. Maintain pH ≈ 4–5: too acidic suppresses nucleophilicity, too basic slows condensation.
  • Remove water continuously for ketones. Dean–Stark (toluene), molecular sieves (MeOH), or azeotropic distillation all work.
  • For Stage 2, chill the oxime/H₂SO₄ mixture to 0 °C during protonation. Then warm gradually (≤60 °C) to control migration and water addition before any higher-temperature workup.
  • Quench carefully: Beckmann rearrangements often release heat. Dilute with ice and neutralise slowly with aqueous base (NaOAc, NaHCO₃) to prevent amide hydrolysis.
  • For lactam syntheses (e.g., ε-caprolactam), isolate the oxime hydrochloride, wash, then perform the rearrangement in oleum or conc. H₂SO₄ with a staged temperature ramp.

Exam-Style Summary


  1. Stage 1: Protonate the carbonyl → NH₂OH attack → proton shuttles → water leaves → neutral oxime (remember E/Z geometry).
  2. Stage 2: Protonate oxime O → anti group migrates (N–O breaks) → water captures nitrilium → HSO₄⁻ deprotonates to imidate → acid reprotonates nitrogen → HSO₄⁻ removes the carbonyl proton → amide/lactam (or nitrile for aldoximes).
  3. Migratory aptitude controls regiochemistry and only the anti group migrates. Cyclic ketoximes expand by one carbon.
  4. Products: Aldoxime → nitrile. Ketoxime → amide. Cyclic ketoxime → lactam. Plan protecting groups for strongly acid-labile substituents.

Related Reading

Interactive Toolbox


  • Mechanism Solver – step through the NH₂OH oxime build and the H₂SO₄ Beckmann rearrangement presets.
  • Reaction Solver – compare oxime/Beckmann vs. hydrazone/Wolff-Kishner vs. semicarbazone routes.
  • IUPAC Namer – confirm oxime, nitrile, and amide nomenclature before final answers.