Amines and Ketones/Aldehydes

Amine nucleophiles (alkylation)

2º amine reacts via SN2 (CH₃Br) to form 3º amine, but then re-reacts to form ammonium salt (4º amine). LEADS TO OVER-ALKYLATION

Azide nucleophiles

Alkyl halide + NaN₃, THEN H₂/Pd or 1) LiAlH₄ 2) H₂O = 1º amine

Gabriel Amine Synthesis

Phthalimide + KOH, EtOH, THEN alkyl halide and DMF. Hydrolyze with NH₂NH₂ (or NaOH or H₃O⁺) = 1º amine. MANY BYPRODUCTS

Reductive amination (other than H₂ for selectivity reasons)

Aldehyde/ketone + 1º amine —> imine + Na(OAc)₃BH [H+] —> more reactive iminium = 2º amine. Repeat for 3º amine

H₂N-R’

Aldehyde/ketone to imine, loses H₂O

Na(OAc)₃BH and [H⁺]

H⁺ converts imine to iminium. Na(OAc)₃ converts iminium to 2º amine and is less reactive than NaBH₄.

Amine acylation

Amine + acid chloride + pyridine = amide

EAS reactions with arylamines

NH₂ is strong EDG, leads to overbromination. React NH₂ with acid chloride and pyridine to form amide, THEN Br₂ then NaOH or H₃O⁺

Cyanohydrin

Ketone/aldehyde + HCN. Can be further reducted to B-amino alcohol (1. LiAlH₄ 2. H₂O) or carboxylic acid (H₃O⁺ and heat)

Imine

Ketone/aldehyde + 1º amine - H₂O = imine

Enamine

Ketone/aldehyde + 2º amine - H₂O = enamine

Wolff-Kishner Reaction

Ketone + H₂NNH₂ + KOH - H₂O = reduced ketone (alkane)

Acetal

Ketone/aldehyde + alcohol + H⁺ cat. = acetal (2 RO groups). Cyclic acetal uses tethered alcohol

Wittig Reaction

Ketone/aldehyde + ylide (PPh₃ and CH₃Br then BuLi + THF) = alkene + O=PPh₃