Chapter 23: Amines—properties, preparation, and reactions.

Reductive Amination

Reduction Methods

Reduction Methods

Reductive Amination

• Used to turn aldehyde into amine.

• Amine attacks aldehyde C=O, then imine/iminium forms.

• NaBH3CN reduces iminium by adding H to carbon.

Neutral Amine (1° or 2°) + Aldehyde/Ketone + NaBH3​CN + Mild Acid

reduces the iminium ion intermediate without reducing the starting carbonyl

Gabriel synthesis

• KOH deprotonates phthalimide N to make N nucleophile.

• N attacks primary R-X by SN2.

• Hydrolysis releases the amine.

• Product = primary amine only, avoids over-alkylation.

Gabriel synthesis

• converts an alkyl halide into a primary amine without the risk of over-alkylation.

gabriel synthesis

Direct SN2

• NH3 attacks the carbon attached to X by SN2.

• C-X bond breaks, X leaves.

• Product = primary amine, R-NH2.

• Use excess NH3 to reduce over-alkylation.

Direct SN2

• NH3 attacks R-X by SN2, but the amine product can keep attacking more R-X.

• Each alkylation adds another R group to nitrogen.

• Can form 2°, 3°, and finally quaternary ammonium salt.

• Problem: hard to stop at only primary amine.

Reduction Methods

• Used to turn nitro group into amine.

• Reduction adds H’s to N and removes O’s.

• Common for making amines from nitro compounds.

• Memory: NO2 → NH2

Reduction Methods

• Used to turn nitrile into primary amine.

• Hydride adds to nitrile carbon; C triple N pi electrons go to N.

• Workup protonates N and removes Al complex.

• Memory: CN carbon becomes CH2, N becomes NH2.

Reduction Methods

• Used to turn amide into amine.

• Product: C=O is removed.

• Hydride attacks amide carbonyl carbon; oxygen eventually leaves as Al-O complex.

• Workup gives the amine.

• Memory: amide C=O disappears, N stays.

What does DCC do?

• DCC is a coupling/dehydrating reagent.

• It activates a carboxylic acid so an alcohol or amine can attack.

• Used to make esters or amides from carboxylic acids.

• Mechanism: carboxylic acid O attacks DCC, making a better leaving group.

• Then alcohol/amine attacks the carbonyl, and DCC becomes DCU byproduct.

H2​SO4 reagent

• protonates the carboxylic acid carbonyl O

• makes the carbonyl carbon more electrophilic

• lets the alcohol attack

• It can turn OH into OH2+ so water can leave, or activate a carbonyl so a nucleophile can attack

• catalyst; not added into the final product