Nitrile To Aldehyde Dibalh

Nitrile Reactions: Nitrile to Aldehyde with DIBAL-H

Diisobutylaluminum hydride (DIBAL-H, DIBAH, i-Bu2AlH) converts nitriles (R-CN) into aldehydes when the reaction is run cold (typically -78 C in toluene, hexanes, or THF), the hydride charge is limited to ~1 equiv, and a careful aqueous workup is performed. DIBAL-H acts as both a Lewis acid and hydride donor: Al coordinates the nitrile nitrogen, a single hydride transfers to the nitrile carbon forming an imine-aluminum complex, and aqueous workup hydrolyzes this imine to release the aldehyde plus ammonia (or an ammonium salt). If the mixture warms or excess hydride remains, a second hydride reduces the imine to a primary amine.


Key Emphasis (Teaching Pivots)

  • Temperature + equivalents control selectivity. Nitriles stop at aldehydes with ~1.0-1.2 equiv DIBAL-H at -78 C plus a cold aqueous quench. Warming toward 0 C or using >1.5 equiv drives over-reduction to primary amines.
  • Imine intermediate is key. Al-N coordination activates the nitrile; one hydride generates an imine-Al complex that remains "frozen" at -78 C. Aqueous acid (H3O+) hydrolyzes the imine through an iminium intermediate to the aldehyde.
  • Compare to LiAlH4. LAH reduces nitriles all the way to primary amines (2 hydrides). DIBAL-H at low temperature stops at the imine/aldehyde stage.

Quick Summary

  • Reagents/conditions: DIBAL-H (1.0-1.2 equiv), toluene/hexanes/THF, -78 C; slow addition to the cold nitrile solution; quench at -78 C with MeOH, then dilute aqueous acid (H3O+) or NH4Cl.
  • Outcome: R-CN + H3O+ workup -> R-CHO + NH4+. The nitrile loses nitrogen as ammonia/ammonium.
  • Over-reduction risk: >1.5-2 equiv DIBAL-H, letting the mixture warm before quench, or using excess LiAlH4 converts the imine all the way to the primary amine.
  • Comparison: LiAlH4 reduces nitriles directly to amines (2 H transfers); DIBAL-H at -78 C can be "frozen" at the imine stage, which hydrolyzes to aldehyde.

Mechanism - Imine Formation and Hydrolysis

Step 1: Nitrile nitrogen coordinates to DIBAL-H.
Step 1 - Lewis-acid coordination. The nitrile nitrogen lone pair coordinates to the aluminum center, activating the CN triple bond toward hydride delivery.
Step 2: Hydride transfer from Al-H to the nitrile carbon.
Step 2 - Single hydride delivery. The Al-H bond supplies hydride to the nitrile carbon. One pi bond of the CN shifts to nitrogen, forming an imine-aluminum complex (C=N-Al).
Step 3: Stable imine-aluminum complex at -78 C.
Step 3 - Imine-Al complex (frozen at -78 C). The imine-aluminum intermediate is stable at low temperature. This is where the reaction "stops" until workup.
Step 4: H3O+ protonates imine nitrogen, Al-N bond cleaves.
Step 4 - Aqueous workup: protonation. H3O+ protonates the imine nitrogen while the Al-N bond cleaves, forming an iminium ion (R-CH=NH2+).
Step 5: Water attacks iminium carbon.
Step 5 - Water attacks iminium. Water acts as a nucleophile, attacking the electrophilic iminium carbon. The C=N pi bond breaks, placing electrons on nitrogen.
Step 6: Proton shuttle - H2O deprotonates OH2+, H3O+ protonates NH2.
Step 6 - Proton shuttle. The hemiaminal intermediate undergoes proton transfer: H2O deprotonates the OH2+ to OH, while H3O+ protonates NH2 to NH3+. This sets up elimination.
Step 7: 1,2-Elimination - O lone pair forms C=O, NH3 departs.
Step 7 - 1,2-Elimination. The oxygen lone pair attacks carbon to form C=O (oxonium intermediate) while NH3 departs as a leaving group.
Step 8: Water deprotonates oxonium to give neutral aldehyde.
Step 8 - Deprotonation. Water deprotonates the oxonium ion to give the neutral aldehyde product.
Step 9: Final aldehyde product.
Step 9 - Aldehyde product. The aldehyde (R-CHO) is isolated along with NH4+ (or NH3) as the nitrogen byproduct.

Mechanistic Checklist (Exam Focus)

  • Show Al-N coordination followed by a single Al-H hydride arrow to the nitrile carbon.
  • Name/depict the imine-Al complex intermediate - students should recognize it as the "frozen" species at -78 C.
  • Track the nitrogen fate: the imine hydrolyzes to release NH3/NH4+ during aqueous workup.
  • Include the over-reduction trap: warm temperatures or excess hydride reduce the imine further to the primary amine.
  • Imine hydrolysis follows the standard mechanism: protonate N -> water attacks C -> proton shuttle -> eliminate NH3 -> deprotonate oxonium.

Worked Examples

Example A - Benzonitrile. 1.05 equiv DIBAL-H in toluene at -78 C, followed by dilute H3O+ workup, releases benzaldehyde and ammonium ion.
Example A reactant: benzonitrile
Reactant
Reagent: DIBAL-H then H3O+
Reagent
Example A product: benzaldehyde
Product
Example B - 3-Methylbutanenitrile. The cold protocol furnishes 3-methylbutanal cleanly; warming would push to 3-methylbutylamine.
Example B reactant: 3-methylbutanenitrile
Reactant
Reagent: DIBAL-H then H3O+
Reagent
Example B product: 3-methylbutanal
Product

Scope & Limitations

  • Works best: Aliphatic and aryl nitriles. Benzonitrile and simple alkyl nitriles convert cleanly to aldehydes.
  • Functional groups tolerated (pre-quench): Al-H reagents demand strictly aprotic, oxygen-free setups. Protect alcohols/phenols if they would react with DIBAL-H. Esters can be reduced by DIBAL-H (different product - see ester guides).
  • Temperature: Keep <= -60 C until after the aqueous quench to avoid runaway hydride transfer to the imine.
  • Over-reduction: >1.5 equiv hydride, warming before quench, or using LiAlH4 gives primary amines.

Edge Cases & Exam Traps

  • Warm quench: Letting the mixture warm toward 0 C before quenching allows the second hydride to reduce the imine to the amine.
  • Excess reagent: Stock DIBAL-H solutions are often >1.0 M; miscalculations lead to >1.5 equiv and over-reduction to amines.
  • LiAlH4 confusion: LAH always reduces nitriles to amines (2 hydride additions). DIBAL-H at -78 C is special because it can stop at 1 hydride.
  • Protic solvent before quench: EtOH, MeOH, or water prior to the planned quench destroys Al-H and derails the reaction.

Practical Tips

  • Calibrate the reagent. Verify the actual concentration of the DIBAL-H solution and charge only 1.0-1.2 equiv for aldehyde stops.
  • Add to cold substrate. Cool the nitrile solution to -78 C first, then add DIBAL-H slowly while monitoring.
  • Aqueous acidic workup. Unlike esters (which can use neutral conditions), nitrile reductions require acidic conditions (dilute HCl or H3O+) to hydrolyze the imine intermediate to the aldehyde.
  • Workup: Filter off Al salts (Celite) before concentration to minimize side reactions.
  • Safety: DIBAL-H is pyrophoric; work behind a blast shield, maintain positive N2 flow, and vent carefully during quench.

Exam-Style Summary

Nitrile + DIBAL-H (~1.0 equiv, -78 C) -> imine-Al complex (frozen) -> H3O+ workup -> aldehyde + NH4+. Excess hydride or warming delivers the primary amine. The imine hydrolysis follows standard carbonyl-forming elimination from a hemiaminal.


Interactive Toolbox

  • Mechanism Solver - Enter any nitrile and see the full 9-step mechanism for DIBAL-H reduction to aldehyde.
  • Reaction Solver - Provide a nitrile and the Solver predicts aldehyde vs amine outcomes based on your reagent/temperature inputs.
  • IUPAC Namer - Use it to name the aldehyde and amine products.