Skip to main content
SpringerLink
Log in

Substitution Reactions on Aromatic Compounds

  • Chapter
Organic Mechanisms

Abstract

Substitution reactions on aromatic compounds are the most important methods for the preparation of aromatic compounds. Synthesizing them from nonaromatic precursors is considerably less important. Via substitution reactions, electrophiles and nucleophiles can be introduced into aromatics. A series of mechanisms is available for this. Those that are discussed in this chapter are listed in Table 5.1.

Substitution Reactions of Aromatic Compounds: Mechanistic Alternatives*

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • M. Sainsbury, “Aromatic Chemistry,” Oxford University Press, Oxford, U. K., 1992.

    Google Scholar 

  • D. T. Davies, “Aromatic Heterocyclic Chemistry,” Oxford University Press, New York, 1992.

    Google Scholar 

5.1

  • S. W. Slayden, J. F. Liebman, “The Energetics of Aromatic Hydrocarbons: An Experimental Thermochemical Perspective,” Chem. Rev. 2001, 101, 1541–1566.

    Article  CAS  Google Scholar 

  • R. J. K. Taylor, “Electrophilic Aromatic Substitution,” Wiley, Chichester, U. K., 1990.

    Google Scholar 

  • H. Mayr, B. Kempf, A. R. Ofial, “π-Nucleophilicity in Carbon-Carbon Bond-Forming Reactions,” Acc. Chem. Rev. 2003, 36, 66–77.

    Article  CAS  Google Scholar 

  • D. Lenoir, “The Electrophilic Substitution of Arenes: Is the π Complex a Key Intermediate and What is its Nature?”, Angew. Chem. Int. Ed. Engl. 2003, 42, 854–857.

    Article  CAS  Google Scholar 

  • F. Effenberger, “1,3,5-Tris(dialkylamino)benzenes: Model Compounds for the Electrophilic Substitution and Oxidation of Aromatic Compounds,” Acc. Chem. Res. 1989, 22, 27–35.

    Article  CAS  Google Scholar 

  • C. B. de Koning, A. L. Rousseau, W. A. L. van Otterlo, “Modern Methods for the Synthesis of Substituted Naphthalenes,” Tetrahedron 2003, 59, 7–36.

    Article  Google Scholar 

  • K. K. Laali, “Stable Ion Studies of Protonation and Oxidation of Polycyclic Arenes,” Chem. Rev. 1996, 96, 1873–1906.

    Article  CAS  Google Scholar 

  • A. R. Katritzky, W. Q. Fan, “Mechanisms and Rates of Electrophilic Substitution Reactions of Heterocycles,” Heterocycles 1992, 34, 2179–2229.

    Article  Google Scholar 

  • L. I. Belen’kii, I. A. Suslov, N. D. Chuvylkin, “Substrate and Positional Selectivity in Electrophilic Substitution Reactions of Pyrrole, Furan, Thiophene, and Selenophene Derivatives,” Chem. Heterocycl. Compd. 2003, 39, 36–48.

    Article  CAS  Google Scholar 

5.2

  • M. R. Grimmett, “Halogenation of Heterocycles: II. Six-and Seven-Membered Rings,” Adv. Heterocycl. Chem. 1993, 58, 271–345.

    Article  CAS  Google Scholar 

  • C. M. Suter and A. W. Weston, “Direct Sulfonation of Aromatic Hydrocarbons and Their Halogen Derivatives,” Org. React. 1946, 3, 141–197.

    Google Scholar 

  • G. A. El-Hiti, “Recent Advances in the Synthesis of Sulfonic Acids,” Sulfur Rep. 2001, 22, 217–250.

    Article  CAS  Google Scholar 

  • L. Eberson, M. P. Hartshorn, F. Radner, “Ingold’s Nitration Mechanism Lives!”, Acta Chem. Scand. 1994, 48, 937–950.

    Article  CAS  Google Scholar 

  • B. P. Cho, “Recent Progress in the Synthesis of Nitropolyarenes. A Review,” Org. Prep. Proced. Int. 1995, 27, 243–272.

    Article  CAS  Google Scholar 

  • J. H. Ridd, “Some Unconventional Pathways in Aromatic Nitration,” Acta Chem. Scand. 1998, 52, 11–22.

    Article  CAS  Google Scholar 

  • H. Zollinger, “Diazo Chemistry I, Aromatic and Heteroaromatic Compounds,” VCH Verlagsgesellschaft, Weinheim, Germany, 1994.

    Google Scholar 

  • C. C. Price, “The Alkylation of Aromatic Compounds by the Friedel-Crafts Method,” Org. React. 1946, 3, 1–82.

    Google Scholar 

  • G. A. Olah, R. Krishnamurti, G. K. S. Prakash, “Friedel-Crafts Alkylations,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 3, 293, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • H. Heaney, “The Bimolecular Aromatic Friedel-Crafts Reaction,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 733, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • H. Heaney, “The Intramolecular Aromatic Friedel-Crafts Reaction,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 753, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • T. Ohwada, “Reactive Carbon Electrophiles in Friedel-Crafts Reactions,” Reviews on Heteroatom Chemistry 1995, 12, 179.

    CAS  Google Scholar 

  • R. C. Fuson and C. H. McKeever, “Chloromethylation of Aromatic Compounds,” Org. React. 1942, 1, 63–90.

    Google Scholar 

  • E. Berliner, “The Friedel and Crafts Reaction with Aliphatic Dibasic Acid Anhydrides,” Org. React. 1949, 5, 229–289.

    CAS  Google Scholar 

  • I. Hashimoto, T. Kawaji, F. D. Badea, T. Sawada, S. Mataka, M. Tashiro, G. Fukata, “Regioselectivity of Friedel-Crafts Acylation of Aromatic-Compounds with Several Cyclic Anhydrides,” Res. Chem. Intermed. 1996, 22, 855–869.

    Article  Google Scholar 

  • A. R. Martin, “Uses of the Fries Rearrangement for the Preparation of Hydroxyaryl Ketones,” Org. Prep. Proced. Int. 1992, 24, 369.

    Article  CAS  Google Scholar 

  • O. Meth-Cohn, S. P. Stanforth, “The Vilsmeier-Haack Reaction,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 777, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • G. Jones, S. P. Stanforth, “The Vilsmeier Reaction of Fully Conjugated Carbocycles and Heterocycles,” Org. React. 1997, 49, 1–330.

    CAS  Google Scholar 

5.3

  • L. Brandsma, “Aryl and Hetaryl Alkali Metal Compounds,” in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952, Carbanions (M. Hanack, Ed.), Vol. E19d, 369, Georg Thieme Verlag, Stuttgart, 1993.

    Google Scholar 

  • H. Gilman, J. W. Morton, Jr., “The Metalation Reaction with Organolithium Compounds,” Org. React. 1954, 8, 258–304.

    Google Scholar 

  • V. Snieckus, “Regioselective Synthetic Processes Based on the Aromatic Directed Metalation Strategy,” Pure Appl. Chem. 1990, 62, 671.

    Article  CAS  Google Scholar 

  • V. Snieckus, “The Directed Ortho Metalation Reaction. Methodology, Applications, Synthetic Links, and a Nonaromatic Ramification,” Pure Appl. Chem. 1990, 62, 2047–2056.

    Article  CAS  Google Scholar 

  • V. Snieckus, “Directed Ortho Metalation. Tertiary Amide and O-Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics,” Chem. Rev. 1990, 90, 879–933.

    Article  CAS  Google Scholar 

  • V. Snieckus, “Combined Directed Ortho Metalation-Cross Coupling Strategies. Design for Natural Product Synthesis,” Pure Appl. Chem. 1994, 66, 2155–2158.

    Article  CAS  Google Scholar 

  • K. Undheim, T. Benneche, “Metalation and Metal-Assisted Bond Formation in π-Electron Deficient Heterocycles,” Acta Chem. Scand. 1993, 47, 102–121.

    Article  CAS  Google Scholar 

  • H. W. Gschwend, H. R. Rodriguez, “Heteroatom-Facilitated Lithiations,” Org. React. 1979, 26, 1–360.

    CAS  Google Scholar 

  • R. D. Clark, A. Jahangir, “Lateral Lithiation Reactions Promoted by Heteroatomic Substituents,” Org. React. 1995, 47, 1–314.

    CAS  Google Scholar 

  • R. G. Jones, H. Gilman, “The Halogen-Metal Interconversion Reaction with Organolithium Compounds,” Org. React. 1951, 6, 339–366.

    Google Scholar 

  • W. E. Parham, C. K. Bradsher, “Aromatic Organolithium Reagents Bearing Electrophilic Groups. Preparation by Halogen-Lithium Exchange,” Acc. Chem. Res. 1982, 15, 300.

    Article  CAS  Google Scholar 

  • N. Sotomayor, E. Lete, “Aryl and Heteroaryllithium Compounds by Metal-Halogen Exchange. Synthesis of Carbocyclic and Heterocyclic Systems,” Curr. Org. Chem. 2003, 7, 275–300.

    Article  CAS  Google Scholar 

  • Najera, J. M. Sansano, M. Yus, “Recent Synthetic Uses of Functionalized Aromatic and Heteroaromatic Organolithium Reagents Prepared by Non-Deprotonating Methods,” Tetrahedron 2003, 59, 9255–9303.

    Article  CAS  Google Scholar 

  • P. Knochel, W. Dohle, N. Gommermann, F. F. Kneisel, F. Kopp, T. Korn, I. Sapountzis, V. A. Vu, “Highly Functionalized Organomagnesium Reagents Prepared through Halogen-Metal Exchange,” Angew. Chem. Int. Ed. Engl. 2003, 42, 4302–4320.

    Article  CAS  Google Scholar 

  • P. Sadimenko, “Organometallic Compounds of Furan, Thiophene, and Their Benzannulated Derivatives,” Adv. Heterocycl. Chem. 2001, 78, 1–64.

    Article  CAS  Google Scholar 

  • A. R. Martin, Y. Yang, “Palladium Catalyzed Cross-Coupling Reactions of Organoboronic Acids with Organic Electrophiles,” Acta Chem. Scand. 1993, 47, 221–230.

    Article  CAS  Google Scholar 

  • A. Suzuki, “New Synthetic Transformations via Organoboron Compounds,” Pure Appl. Chem. 1994, 66, 213–222.

    Article  CAS  Google Scholar 

  • N. Miyaura, A Suzuki, “Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds,” Chem. Rev. 1995, 95, 2457–2483.

    Article  CAS  Google Scholar 

  • N. Miyaura, “Synthesis of Biaryls via the Cross-Coupling Reaction of Arylboronic Acids,” in Advances in Metal-Organic Chemistry (L. S. Liebeskind, Ed.), JAI Press, Greenwich, 1998, 6, 187–243.

    Google Scholar 

5.4

  • R. K. Norris, “Nucleophilic Coupling with Aryl Radicals,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 4, 451, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • A. Roe, “Preparation of Aromatic Fluorine Compounds from Diazonium Fluoroborates: The Schiemann Reaction,” Org. React. 1949, 5, 193–228.

    CAS  Google Scholar 

  • N. Kornblum, “Replacement of the Aromatic Primary Amino Group by Hydrogen,” Org. React. 1944, 2, 262–340.

    Google Scholar 

5.5

  • C. Paradisi, “Arene Substitution via Nucleophilic Addition to Electron Deficient Arenes,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 4, 423, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • I. Gutman (Ed.), “Nucleophilic Aromatic Displacement: The Influence of the Nitro Group,” VCH, New York, 1991.

    Google Scholar 

  • V. M. Vlasov, “Nucleophilic Substitution of the Nitro Group, Fluorine and Chlorine in Aromatic Compounds,” Russ. Chem. Rev. 2003, 72, 681–764.

    Article  CAS  Google Scholar 

  • N. V. Alekseeva, L. N. Yakhontov, “Reactions of Pyridines, Pyrimidines, and 1,3,5-Triazines with Nucleophilic Reagents,” Russ. Chem. Rev. 1990, 59, 514–530.

    Article  Google Scholar 

  • D. B. Kimball, M. M. Haley, “Triazenes: A Versatile Tool in Organic Synthesis,” Angew. Chem. Int. Ed. Engl. 2002, 41, 3338–3351.

    Article  CAS  Google Scholar 

5.6

  • J. Suwinski, K. Swierczek, “Cine- and Tele-Substitution Reactions,” Tetrahedron 2001, 57, 1639–1662.

    Article  CAS  Google Scholar 

Further Reading

  • M. Carmack, M. A. Spielman, “The Willgerodt Reaction,” Org. React. 1946, 3, 83–107.

    Google Scholar 

  • S. Sethna, R. Phadke, “The Pechmann Reaction,” Org. React. 1953, 7, 1–58.

    Google Scholar 

  • H. Wynberg, E. W. Meijer, “The Reimer-Tiemann Reaction,” Org. React. 1982, 28, 1–36.

    CAS  Google Scholar 

  • W. E. Truce, “The Gattermann Synthesis of Aldehydes,” Org. React. 1957, 9, 37–72.

    Google Scholar 

  • N. N. Crounse, “The Gattermann-Koch Reaction,” Org. React. 1949, 5, 290–300.

    CAS  Google Scholar 

  • A. H. Blatt, “The Fries Reaction”, Org. React. 1942, 1, 342–369.

    Google Scholar 

  • P. E. Spoerri, A. S. DuBois, “The Hoesch Synthesis,” Org. React. 1949, 5, 387–412.

    CAS  Google Scholar 

  • W. E. Bachmann, R. A. Hoffman, “The Preparation of Unsymmetrical Biaryls by the Diazo Reaction and the Nitrosoacetylamine Reaction,” Org. React. 1944, 2, 224–261.

    Google Scholar 

  • DeLos F. DeTar, “The Pschorr Synthesis and Related Diazonium Ring Closure Reactions,” Org. React. 1957, 9, 409–462.

    Google Scholar 

  • C. S. Rondestvedt, Jr., “Arylation of Unsaturated Compounds by Diazonium Salts,” Org. React. 1960, 11, 189–260.

    CAS  Google Scholar 

  • C. S. Rondestvedt, Jr., “Arylation of Unsaturated Compounds by Diazonium Salts (The Meerwein Arylation Reaction),” Org. React. 1976, 24, 225–259.

    CAS  Google Scholar 

  • M. Braun, “New Aromatic Substitution Methods,” in Organic Synthesis Highlights (J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn, H.-U. Reißig, Eds.), VCH, Weinheim, New York, 1991, 167–173.

    Google Scholar 

  • J. F. Bunnett, “Some Novel Concepts in Aromatic Reactivity,” Tetrahedron 1993, 49, 4477.

    Article  CAS  Google Scholar 

  • G. A. Artamkina, S. V. Kovalenko, I. P. Beletskaya, O. A. Reutov, “Carbon-Carbon Bond Formation in Electron-Deficient Aromatic Compounds,” Russ. Chem. Rev. (Engl. Transl.) 1990, 59, 750.

    Article  Google Scholar 

  • C. D. Hewitt, M. J. Silvester, “Fluoroaromatic Compounds: Synthesis, Reactions and Commercial Applications,” Aldrichim. Acta 1988, 21, 3–10.

    CAS  Google Scholar 

  • R. A. Abramovitch, D. H. R. Barton, J.-P. Finet, “New Methods of Arylation,” Tetrahedron 1988, 44, 3039.

    Article  CAS  Google Scholar 

  • J. H. Clark, T. W. Bastock, D. Wails (Eds.), “Aromatic Fluorination,” CRC, Boca Raton, 1996.

    Google Scholar 

  • L. Delaude, P. Laszlo, K. Smith, “Heightened Selectivity in Aromatic Nitrations and Chlorinations by the Use of Solid Supports and Catalysts,” Acc. Chem. Res. 1993, 26, 607–613.

    Article  CAS  Google Scholar 

  • J. K. Kochi, “Inner-Sphere Electron Transfer in Organic Chemistry. Relevance to Electrophilic Aromatic Nitration,” Acc. Chem. Res. 1992, 25, 39–47.

    Article  CAS  Google Scholar 

  • L. Eberson, M. P. Hartshorn, F. Radner, “Electrophilic Aromatic Nitration Via Radical Cations: Feasible or Not?,” in Advances in Carbocation Chemistry (J. M. Coxon, Ed.) JAI, Greenwich, CT, 1995.

    Google Scholar 

  • H. Ishibashi, M. Ikeda, “Recent Progress in Electrophilic Aromatic Substitution with a-Thiocarbocations,” Rev. Heteroatom Chem. 1996, 14, 59–82.

    CAS  Google Scholar 

  • H. Heaney, “The Bimolecular Aromatic Mannich Reaction,” in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 2, 953, Pergamon Press, Oxford, 1991.

    Google Scholar 

  • P. E. Fanta, “The Ullmann Synthesis of Biaryls,” Synthesis 1974, 9.

    Google Scholar 

  • J. A. Lindley, “Copper Assisted Nucleophilic Substitution of Aryl Halogen,” Tetrahedron 1984, 40, 1433.

    Article  CAS  Google Scholar 

  • G. P. Ellis, T. M. Romsey-Alexander, “Cyanation of Aromatic Halides,” Chem. Rev. 1987, 87, 779.

    Article  CAS  Google Scholar 

  • I. A. Rybakova, E. N. Prilezhaeva, V. P. Litvinov, “Methods of Replacing Halogen in Aromatic Compounds by RS-Functions,” Russ. Chem. Rev. (Engl. Transl.) 1991, 60, 1331.

    Article  Google Scholar 

  • O. N. Chupakhin, V. N. Charushin, H. C. van der Plas, “Nucleophilic Aromatic Substitution of Hydrogen,” Academic Press, San Diego, CA, 1994.

    Google Scholar 

  • J. M. Saveant, “Mechanisms And Reactivity In Electron-Transfer-Induced Aromatic Nucleophilic Substitution—Recent Advances,” Tetrahedron 1994, 50, 10117.

    Article  CAS  Google Scholar 

  • A. J. Belfield, G. R. Brown, A. J. Foubister, “Recent Synthetic Advances in the Nucleophilic Amination of Benzenes,” Tetrahedron 1999, 55, 11399–11428.

    Article  CAS  Google Scholar 

  • M. Makosza, “Neue Aspekte der nucleophilen Substitution von Arenen,” Chem. unserer Zeit 1996, 30, 134–140.

    Article  CAS  Google Scholar 

  • J. Scott Sawyer, “Recent Advances in Diaryl Ether Synthesis,” Tetrahedron 2000, 56, 5045–5065.

    Article  CAS  Google Scholar 

Download references

Editor information

Editors and Affiliations

  1. Department of Chemistry, University of Missouri-Columbia, 601 S. College Avenue, Columbia, Missouri, 65211

    Michael Harmata (Norman Rabjohn Distinguished Professor of Chemistry) (Norman Rabjohn Distinguished Professor of Chemistry)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

(2010). Substitution Reactions on Aromatic Compounds. In: Harmata, M. (eds) Organic Mechanisms. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-03651-4_5

Download citation

Publish with us

Policies and ethics

Search

Navigation