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N-Alkylation of amines and amides

8 real reactions from the literature, on α-halo acids, anilines, ureas and primary alkyl chlorides. Each scheme shows starting materials, conditions and products, with the yield and reference where the source reports them.

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  1. N-alkylation: 4-amino-3-(isopropyl)phenol (an aniline) with 2.2 equiv. MeI; Na2CO3; EtOH gives 4-(dimethylamino)-3-isopropylphenol (the aniline). 48% yield.
    N-alkylationJ. Org. Chem. 1954, 19, 1067

  2. N-alkylation: 6-benzamido-2-bromohexanoic acid (an α-halo acid) with NH4OH gives 2-amino-6-benzamidohexanoic acid (the primary amine).
    N-alkylationOrg. Synth. Coll. Vol. 2, p. 374

  3. N-alkylation: (1,1-dimethylethyl)urea and phthalic anhydride (a cyclic anhydride) with H2NNH2 · HCl; CH3CH2OH, HCl gives tert-butylamine (the primary amine) and 2,3-dihydro-1,4-phthalazinedione (the heteroarene).
    N-alkylationOrg. Synth. Coll. Vol. 3, p. 151

  4. N-alkylation: 2-bromo-3-phenylpropanoic acid (an α-halo acid) with NH3; NH4Br gives dl-phenylalanine (the primary amine).
    N-alkylationOrg. Synth. Coll. Vol. 3, p. 705

  5. N-alkylation: 2-chloro-1,1-diethoxyethane (a primary alkyl chloride) with NH3, CH3OH; 140 °C gives 2,2-diethoxyethylamine (the primary amine).
    N-alkylationOrg. Synth. Coll. Vol. 3, p. 50

  6. N-alkylation: chloroacetic acid (an α-halo acid) with NH4OH; H2O gives glycine (the primary amine).
    N-alkylationOrg. Synth. Coll. Vol. 2, p. 328

  7. N-alkylation: benzyl chloride (a benzylic alkyl chloride) with PhNH2, Δ; aq. NaHCO3 gives benzylaniline.
    N-alkylationOrg. Synth. Coll. Vol. 1, p. 102

  8. N-alkylation: indole with KOH; DMSO gives 1-benzylindole (the heteroarene). 87% yield.
    N-alkylationOrg. Synth. 1974, 54, 58