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Electrophilic aromatic substitution

57 real reactions from the literature: EAS halogenation on alkylbenzenes, biphenyls and phenols; EAS nitration on acyl-deactivated arenes, alkylbenzenes and anilines; and more. Each scheme shows starting materials, conditions and products, with the yield and reference where the source reports them.

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  1. EAS halogenation: 4-nitrotoluene (an alkylbenzene) with Br2; Fe gives 2-bromo-4-nitrotoluene (the aryl bromide). 66% yield.
    EAS halogenationJ. Phys. Chem. A 2017, 121, 5110

  2. EAS nitration: resorcinol (a phenol) with HNO3; AcOH gives 4-nitroresorcinol (the nitroarene). 75% yield.
    EAS nitrationTetrahedron Lett. 2006, 47, 4933

  3. Friedel–Crafts acylation: 1,3-difluorobenzene (a halobenzene) with AlCl3 gives 2-chloro-1-(2,4-difluorophenyl)ethanone (the aryl ketone). 91% yield.
    Friedel–Crafts acylationBioorg. Med. Chem. Lett. 2012, 22, 4887

  4. Friedel–Crafts alkylation: carbazole with (excess); AlCl3 gives 3,6-di-tert-butylcarbazole (the alkylated arene). 72% yield.
    Friedel–Crafts alkylationJ. Phys. Chem. C 2017, 121, 23618

  5. Friedel–Crafts cyclization: 1-methoxy-2-(3-methylbut-2-en-1-yl)benzene (a trisubstituted alkene) with AlCl3; HCl gives 7-methoxy-3,3-dimethyl-1,2-dihydroindene (the fused ring). 60% yield.
    Friedel–Crafts cyclizationBull. Soc. Chim. Belg. 1981, 90, 847

  6. EAS sulfonation: o-toluidine (an aniline) with 1) H2SO4, H2O; 2) Δ gives 4-amino-3-methylbenzenesulfonic acid (the arenesulfonic acid).
    EAS sulfonationOrg. Synth. Coll. Vol. 3, p. 824

  7. Azo coupling: anthranilic acid (an aniline) with 1) HCl / NaNO2; 2) N,N-dimethylaniline gives the azo compound. 64% yield.
    Azo couplingOrg. Synth. 1922, 2, 47

  8. Desulfonation: 4-amino-3-nitrobenzenesulfonic acid (an arenesulfonic acid) with aq. H2SO4; Δ gives 2-nitroaniline (the desulfonated arene).
    DesulfonationOrg. Synth. Coll. Vol. 1, p. 388

  9. Other EAS: hydroquinone diacetate (an ester) with AlCl3; Δ gives 2-acetylhydroquinone (the rearranged product).
    Other EASOrg. Synth. Coll. Vol. 3, p. 280

  10. EAS halogenation: 2-chloro-6-fluorotoluene (an alkylbenzene) with Br2; Fe gives 1-bromo-2-chloro-4-fluoro-3-methylbenzene (the aryl fluoride). 98% yield.
    EAS halogenationJ. Med. Chem. 2009, 52, 7186

  11. EAS nitration: benzene-d6 with HNO3; H2SO4 gives nitrobenzene-d5 (the nitroarene). 96% yield.
    EAS nitrationChem. Eur. J. 2019, 25, 10668

  12. Friedel–Crafts acylation: chroman (an anisole) with AlCl3 gives 1-(3,4-dihydro-2H-1-benzopyran-6-yl)ethan-1-one (the aryl ketone). 85% yield.
    Friedel–Crafts acylationAngew. Chem. Int. Ed. 2019, 58, 15386

  13. EAS nitration: p-cymene (an alkylbenzene) with HNO3; H2SO4, AcOH; -10 to -15 °C gives 1-methyl-2-nitro-4-propan-2-ylbenzene (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 3, p. 653

  14. EAS nitration: N,N-dimethylaniline with HNO3; H2SO4, 5 °C gives N,N-dimethyl-3-nitroaniline (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 3, p. 658

  15. EAS nitration: N-(4-methoxyphenyl)acetamide (an anisole) with Ac2O gives N-(4-methoxy-2-nitrophenyl)acetamide (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 3, p. 661

  16. Friedel–Crafts acylation: phenylacetyl chloride (an alkylbenzene) with AlCl3 gives 2-phenylacetophenone (the aryl ketone).
    Friedel–Crafts acylationOrg. Synth. Coll. Vol. 2, p. 156

  17. Friedel–Crafts alkylation: cyclohexene (a six-membered cycloalkene) with H2SO4 gives cyclohexylbenzene (the alkylated arene).
    Friedel–Crafts alkylationOrg. Synth. Coll. Vol. 2, p. 151

  18. EAS nitration: benzoic acid (an acyl-deactivated arene) with HNO3 (2 equiv.) (fuming), Δ; H2SO4 gives 3,5-dinitrobenzoic acid (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 3, p. 337

  19. EAS nitration: benzaldehyde (an acyl-deactivated arene) with fuming HNO3; H2SO4 gives 3-nitrobenzaldehyde (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 3, p. 644

  20. EAS nitration: acetophenone (an acyl-deactivated arene) with HNO3; H2SO4 gives m-nitroacetophenone (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 2, p. 434

  21. EAS halogenation: 4-nitrotoluene (an alkylbenzene) with Fe, Br2; 80 °C gives 2-bromo-4-nitrotoluene (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 4, p. 114

  22. EAS halogenation: acetophenone (an acyl-deactivated arene) with 1) AlCl3; 2) Br2, AlCl3; 3) H+, H2O gives 3'-bromoacetophenone (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 5, p. 117

  23. Friedel–Crafts cyclization: 4-phenylbutanoyl chloride (an alkylbenzene) with AlCl3; CS2, Δ gives 1-tetralone (the fused ring).
    Friedel–Crafts cyclizationOrg. Synth. Coll. Vol. 2, p. 569

  24. Friedel–Crafts acylation: anthracene with CH3COCl; AlCl3, 0 °C, benzene gives 9-acetylanthracene (the aryl ketone).
    Friedel–Crafts acylationOrg. Synth. Coll. Vol. 4, p. 8

  25. Friedel–Crafts acylation: succinic anhydride (a cyclic anhydride) with AlCl3, Δ gives 3-benzoylpropionic acid (the aryl ketone).
    Friedel–Crafts acylationOrg. Synth. Coll. Vol. 2, p. 81

  26. EAS halogenation: biphenyl with Br2 gives 4,4'-dibromobiphenyl (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 4, p. 256

  27. EAS halogenation: nitrobenzene (a nitroarene) with Br2, Fe; 140 °C gives 1-bromo-3-nitrobenzene (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 1, p. 123

  28. EAS nitration: o-toluidine (an aniline) with 1) Ac2O; 2) HNO3, 10-12 °C; 3) aq. HCl gives 2-methyl-6-nitroaniline (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 4, p. 42

  29. Azo coupling: 4-phenyl-1,2,5-oxadiazol-3-amine (an aniline) and mesitylene (an alkylbenzene) with 1) NOBF4; 2) mesitylene, heat gives the azo compound. 90% yield.
    Azo couplingEur. J. Org. Chem. 2019, 4248

  30. Friedel–Crafts acylation: acenaphthene (a naphthalene) and succinic anhydride (a cyclic anhydride) with AlCl3; nitrobenzene; 0 °C gives 4-(1,2-dihydroacenaphthylen-5-yl)-4-oxobutanoic acid (the aryl ketone).
    Friedel–Crafts acylationOrg. Synth. Coll. Vol. 3, p. 6

  31. EAS halogenation: 2,4-dihydroxybenzoic acid (a phenol) with Br2; AcOH gives 5-bromo-2,4-dihydroxybenzoic acid (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 2, p. 100

  32. Friedel–Crafts alkylation: benzyl chloride (a benzylic alkyl chloride) with Al(Hg), Δ gives diphenylmethane (the alkylated arene).
    Friedel–Crafts alkylationOrg. Synth. Coll. Vol. 2, p. 232

  33. EAS sulfonation: acetanilide with HOSO2Cl; (2 equiv.) gives N-acetylsulfanilyl chloride (the arenesulfonic acid).
    EAS sulfonationOrg. Synth. Coll. Vol. 1, p. 8

  34. Friedel–Crafts acylation: pyrogallol (a phenol) with (CH3CO)2O; ZnCl2, AcOH; 140 - 145 °C gives gallacetophenone (the aryl ketone).
    Friedel–Crafts acylationOrg. Synth. Coll. Vol. 2, p. 304

  35. EAS nitration: methyl benzoate (an acyl-deactivated arene) with HNO3, H2SO4; 5 - 15 °C gives methyl 3-nitrobenzoate (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 1, p. 372

  36. EAS nitration: mesitylene (an alkylbenzene) with HNO3; Ac2O, AcOH gives 2-nitromesitylene (the nitroarene).
    EAS nitrationOrg. Synth. Coll. Vol. 2, p. 449

  37. EAS halogenation: 4-methylacetanilide with Br2 gives N-(2-bromo-4-methylphenyl)acetamide (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 1, p. 111

  38. EAS halogenation: benzene with I2, HNO3 gives iodobenzene (the aryl iodide).
    EAS halogenationOrg. Synth. Coll. Vol. 1, p. 323

  39. EAS halogenation: 2-(N-isopropylamino)-3''-chloropropiophenone (a halobenzene) and 1-phenyl-1-propanone (an aryl ketone) with Early step in synthesis; Cl2 / AlCl3 gives 3'-chloropropiophenone (the aryl chloride).
    EAS halogenationRealOChem worksheet

  40. Friedel–Crafts alkylation: benzene with BF3 gives tert-amylbenzene (the alkylated arene). 96% yield.
    Friedel–Crafts alkylationJ. Am. Chem. Soc. 1959, 81, 1110

  41. EAS halogenation: phenol with Br2; CS2, 5 °C gives 4-bromophenol (the aryl bromide).
    EAS halogenationOrg. Synth. Coll. Vol. 1, p. 128

  42. Friedel–Crafts acylation: thioanisole with AlCl3 gives 1-(4-(methylthio)phenyl)ethan-1-one (the aryl ketone). 79% yield.
    Friedel–Crafts acylationSulfur Lett. 1991, 12, 123

  43. Friedel–Crafts acylation: p-anisoyl chloride (an acid chloride) and benzofuran with AlCl3 gives 3-(4'-methoxybenzoyl)benzofuran (the aryl ketone). 85% yield.
    Friedel–Crafts acylationBioorg. Med. Chem. 2018, 26, 2984

  44. Friedel–Crafts cyclization: an anisole with 1); SOCl2; 2); AlCl3 gives 6-hexoxy-1-benzothiophen-3-one (the fused ring). 62% yield.
    Friedel–Crafts cyclizationTetrahedron Lett. 1994, 35, 7549

  45. Friedel–Crafts cyclization: a benzylic alcohol with H2SO4 gives the fused ring. 85% yield.
    Friedel–Crafts cyclizationJ. Org. Chem. 1973, 38, 1909

  46. Friedel–Crafts alkylation: phenyl(2-thienyl)methanol (a thiophene) with H2SO4 gives 4-[phenyl(thiophen-2-yl)methyl]phenol (the alkylated arene).
    Friedel–Crafts alkylationRealOChem worksheet

  47. Friedel–Crafts cyclization: a benzylic alcohol with H2SO4 gives the fused ring. 70% yield.
    Friedel–Crafts cyclizationJ. Org. Chem. 1973, 38, 1909

  48. Friedel–Crafts cyclization: 4-phenylbutyric acid (an alkylbenzene) with polyphosphoric acid; Δ gives 1-tetralone (the fused ring).
    Friedel–Crafts cyclizationOrg. Synth. Coll. Vol. 3, p. 798

  49. EAS sulfonation: saccharin (an acyl-deactivated arene) and toluene (an alkylbenzene) with HNO3; H2SO4 gives 2-methylbenzenesulfonic acid (the arenesulfonic acid).
    EAS sulfonationRealOChem worksheet

  50. EAS halogenation: veratrole (an anisole) with I2, CF3CO2Ag; CHCl3 gives 4-iodo-1,2-dimethoxybenzene (the aryl iodide).
    EAS halogenationOrg. Synth. Coll. Vol. 4, p. 547

  51. EAS halogenation: 3-fluorobiphenyl with Br2; FeCl3 gives 4-bromo-3'-fluorobiphenyl (the aryl fluoride). >80% yield.
    EAS halogenationNature 2019, 567, 223

  52. EAS nitration: 2,4-dinitrotoluene (an alkylbenzene) with HNO3; H2SO4; 110 °C gives 2,4,6-trinitrotoluene (the nitroarene).
    EAS nitrationRealOChem worksheet

  53. EAS halogenation: tert-butylbenzene (an alkylbenzene) with Br2; Fe gives 1-bromo-4-tert-butylbenzene (the aryl bromide). 75% yield.
    EAS halogenationJ. Am. Chem. Soc. 1944, 66, 914

  54. Friedel–Crafts alkylation: p-cresol (a phenol) with butylated hydroxytoluene gives 2,6-di-tert-butyl-4-methylphenol (the alkylated arene).
    Friedel–Crafts alkylationRealOChem worksheet

  55. EAS halogenation: 1-methylnaphthalene with Br2 / Fe, cat. I2 gives 1-bromo-4-methylnaphthalene (the naphthyl bromide). 94% yield.
    EAS halogenationJ. Org. Chem. 2016, 81, 8544

  56. Friedel–Crafts acylation: 2-[4-(2-methylpropyl)phenyl]propanoic acid (an alkylbenzene) and isobutylbenzene (an alkylbenzene) with AlCl3 gives 4'-isobutylacetophenone (the aryl ketone).
    Friedel–Crafts acylationRealOChem worksheet

  57. EAS halogenation: 2-methylnaphthalene with Br2 / Fe, cat. I2 gives 1-bromo-2-methylnaphthalene (the naphthyl bromide). 83% yield.
    EAS halogenationJ. Org. Chem. 2016, 81, 8544