Regioselectivity of Electrophilic Aromatic Substitution

3 Key excerpts on "Regioselectivity of Electrophilic Aromatic Substitution"

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  Synthesis of Aromatic Compounds

  • Kenneth E. Maly, Kenneth Maly(Authors)
  • 2022(Publication Date)
  • De Gruyter

    (Publisher)

  2  Electrophilic aromatic substitution

  2.1  Introduction

  By virtue of their π-bonds, aromatic compounds undergo reactions with electrophiles, often in the presence of a Lewis acid catalyst. However, unlike alkenes, which undergo electrophilic addition reactions, aromatic compounds generally undergo electrophilic substitution, where initial electrophilic addition is followed by a deprotonation to re-aromatize. In this chapter, we will review the basic principles of electrophilic aromatic substitution, the scope of electrophiles that can be introduced onto an aromatic ring, reactivity and regioselectivity considerations, and applications in the synthesis of substituted aromatic compounds.

  2.2  General mechanistic principles

  A generic electrophilic aromatic substitution (also referred to as an SE Ar mechanism) proceeds via an arenium ion mechanism, where the electrophile is attacked by the π-electrons of the aromatic ring to form a cationic intermediate, which is re-aromatized upon deprotonation to give the substituted aromatic ring (Figure 2.1 ).

  Figure 2.1: Generalized mechanism for electrophilic aromatic substitution.

  It should be noted that the first step is generally the rate-determining step because aromatic stabilization is broken when the electrophile adds to the ring. The intermediate, referred to as an arenium ion or a Wheland intermediate, does not possess aromatic stabilization but is stabilized by resonance. Deprotonation to form the final product occurs rapidly because aromaticity is restored when the final product is formed. As we will see, the reactivity and regiochemistry of electrophilic aromatic substitution can be explained by this mechanism and in particular by the nature of the arenium ion intermediate.

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  Practical Synthetic Organic Chemistry

  Reactions, Principles, and Techniques

  • Stéphane Caron(Author)
  • 2020(Publication Date)
  • Wiley

    (Publisher)

  247 5 Electrophilic Aromatic Substitution Stéphane Caron and Emma McInturff Pfizer Worldwide R&D, Groton, CT, USA CHAPTER MENU Introduction, 247 Nitrogen Electrophiles, 247 Sulfur Electrophiles, 250 Halogenation, 253 Carbon Electrophiles, 257 5.1 Introduction Electrophilic aromatic substitution reactions are the most commonly used methods to derivatize simple aromatic substrates. 1 The parameters that control the outcome of these reactions are generally well understood. Electron-rich arenes will often undergo facile reactions, while electron-poor arenes require more forcing conditions or will not react at all. The factors that control the regiochemical outcome of the reaction on substituted arenes follow the general rule that electron-rich substituents direct primarily to the para-position and to a lesser extent, the ortho-position, while electron withdrawing groups will favor meta substitution. Halogens are also ortho/para directors but reduce the rate of substitution relative to more electron-rich substituents. For aromatic rings with multiple substituents, the most electron-rich functional group usually has the dominant effect. Most of the reactions presented in this chapter pro- ceed at room temperature or above and many require the presence of a protic or Lewis acid in stoichiometric amount. The most commonly utilized Lewis acid is AlCl 3 , but many others are acceptable as well. This chapter is organized based on the nature of the electrophile and then subdivided by the type of products obtained from the substitution. Many reactions with little practical use have been omitted. 5.2 Nitrogen Electrophiles 5.2.1 Nitration Nitration is the most utilized reaction for incorporation of a nitrogen substituent on an aromatic ring. A desirable feature of this reaction is that it directly functionalizes an arene C—H bond, and the reagent used, nitric acid, is inex- pensive.

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  Organic Chemistry

  • David R. Klein(Author)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  Courtesy of Andy Washni k Top (Blue spurt) April30/Getty Images 18 18.1 Introduction to Electrophilic Aromatic Substitution 18.2 Halogenation 18.3 Sulfonation 18.4 Nitration 18.5 Friedel–Crafts Alkylation 18.6 Friedel–Crafts Acylation 18.7 Activating Groups 18.8 Deactivating Groups 18.9 Halogens: The Exception 18.10 Determining the Directing Effects of a Substituent 18.11 Multiple Substituents 18.12 Synthesis Strategies 18.13 Nucleophilic Aromatic Substitution 18.14 Elimination-Addition 18.15 Identifying the Mechanism of an Aromatic Substitution Reaction Aromatic Substitution Reactions DID YOU EVER WONDER . . . what food coloring is? Look at the ingredients of Fruity Pebbles and you will find compounds such as Red #40 and Yellow #6. What are these substances that can be found in so many of the foods that we regularly eat? I n this chapter, we will learn about the most common reactions of aromatic rings, with the main focus on electrophilic aromatic substitution reactions. During the course of our discussion, we will see that many common food colorings are aromatic compounds that are synthesized using this reaction type, and we will also see how extensive research of aromatic compounds in the early twentieth cen- tury made significant contributions to the field of medicine. This chapter will paint Fruity Pebbles in a whole new light. 18.2 Halogenation 829 DO YOU REMEMBER? Before you go on, be sure you understand the following topics. If necessary, review the suggested sections to prepare for this chapter. • Resonance Structures (Sections 2.7–2.11) • Delocalized Lone Pairs (Section 2.12) • Lewis Acids (Section 3.10) • Reading Energy Diagrams (Section 6.6) • Retrosynthetic Analysis (Section 11.5) • Aromaticity and Nomenclature of Aromatic Compounds (Sections 17.1–17.4) Take the DO YOU REMEMBER? QUIZ in the online course to check your understanding. 18.1 Introduction to Electrophilic Aromatic Substitution In Chapter 17, we explored the remarkable stability of benzene.

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