Amines

Amines思维导图，包括：Chemistry、Heterocyclic ammines、Amine synthesis、Ammine's reaction四部分内容。

Amines

• Chemistry
  • Nucleophilicity/Basidity
    • The lewis unshared pair do exist。。
      • Alkyl ammine is most basic
        • entire deprotonates in physiologic PH 7.3
      • pi synstem will delocalize the long pair
        • decrease in
          • Nucleophilicity
          • Basidity
            • but pyridine carbon is more basic than pyrole
            • more N on 1 heterocycle further reduce basidity
      • electron withdrawing groups on aromatic ring further weaken the basidity
        • -F, -Cl, -Br, -I
        • -NO2, -CN, -CHO, -CN, -CO2R, -COR, -CO2H
      • electron donating groups further increase the basidity
        • -CH3, -OCH3, -OH, -NH2
      • the amide is less basic than amine due to the longpair is attracted and delocalized by oxygen
  • stereochemistry
    • pyramidal inversion
      • barrier only 25kj/mol
• Heterocyclic ammines
  • Compounds contain one or more nirtogen atoms
    • Chemistry
      • saturated heterocycles have similar chemistry as their open chained analogs
      • Unsaturated aromatic heterocycles
        • pyrrole
          • 5 membered ring
          • long pair is part of pi system
            • not basic at all
          • C2 derivating electrophilic substitution
        • imidazole
        • pyridine
          • 6 membered ring
          • long pair not part of pi system
            • basic but less than normal alkyl amine
          • C3 derivating electrophilic substitution
            • but not reactive
              • long pair interfer
              • N inductive effect
            • no friedel-crafts reactions
            • no nitration
        • pyrimidine
        • fused ring heterocycles
          • quinoline
          • isoquinoline
          • indole
          • purine
        • very stable
          • undergo
            • aromatic elctrophilic substitution
              • Halogenation, nitration, sulfonation, and friedel-crafts acylation
              • derivative effect look at the stability of intermediate cation
• Amine synthesis
  • Aryl ammine
    • nitrition of an aromatic ring followed by reduction.
      • H2, Pt or Fe, H3O+
  • Alkyl ammine
    • SN2 reaction of ammonia or an amine with an alkyl halide
    • Reductive methods
      • LiAH4 reduction of amides and nitriles
      • Reductive amination
        • aldehyde or ketone is treated with amine in the presence of a reducing agent NaBH4
• Ammine's reaction
  • Alkylation
    • SN2 reaction with alkyl halides
      • ammonia+ RX---primary ammine+ RX----secondary ammine+ RX----tertiray ammine+ RX-----Quaternary ammonium salt
        • The problem is: you can't stop
          • use NaN3 can make it only 1 step, because the azide product is not nucleuphilic, but requires further reduction
  • nucleophylic acyl substitution with acid chlorides produce amides
    • usually use pyridine as solvent
  • Reductive amination
    • nucleophylic addition with ketone/aldehyde produce Imine/enamines
      • followed bt reduction by NaBH4 or H2/Ni
        • NADH in biological system
      • can accurately produce primary, secondary, tertiary amines
        • use ammonia, primary amine, secondary amine.
  • E2 hofmann elimination
    • produce less highly substituted alkenes
      • due to steric hinder of the leaving group
    • they are first quaternized by treatment with idomethane and then heated with silver oxide
      • excess CH3I converting NH2 into a possitive charge trialkylamine leaving group
        • 3 SN2 reactions
        • only way to make ammine a better leaving group
        • bulky, steric hindered
      • Then E2 happend by a base(typically Ag2O) deprotonate the less hindered carbon
    • common style in biological system
      • but only convert ammine into ammonium
  • Electrophilic Aromatic substitution
    • amino group is strong activating and ortho- and para- directing
    • but can't stop at single substitution state, and can't have Friedel crafts reaction
      • but amide can
        • so usually Electrophilic aromatic substitusion with amido substituted
          • mono bromo product because its less basic and less activating