16: Chemistry of Benzene - Electrophilic Aromatic Substitution
- Page ID
- 448708
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)When you have completed Chapter 16, you should be able to
- fulfill all of the detailed objectives listed under each individual section.
- solve road-map problems that require an understanding of the chemistry discussed in this chapter and those that preceded it.
- design multistep syntheses using the reactions discussed in this and the preceding chapters. In particular you should be prepared to show how an aromatic compound containing two or more substituents could be synthesized, taking care to introduce the substituents into the ring in the correct order.
- define, and use in context, the key terms introduced.
In the preceding chapter, you studied the concept of aromaticity and spent considerable time on the theoretical aspects of the chemistry of aromatic compounds. In this chapter, you will begin to study the chemical reactions of aromatic compounds, focusing in particular on electrophilic aromatic substitution, and to a lesser extent on nucleophilic aromatic substitution. We will discuss, in detail, the mechanism of electrophilic substitution, paying particular attention to the factors that determine both the rate and position of substitution in those aromatic compounds which already have one or more substituents present in the aromatic ring. When we discuss nucleophilic aromatic substitution, you will see that it can be achieved by two different mechanisms, one of which involves the formation of an unusual looking intermediate, benzyne.
You will also see how alkyl and acyl groups can be introduced on to an aromatic ring; how, once introduced, alkyl groups can be converted to carboxyl groups; and how bromine can be introduced to the alkyl side chain of alkylbenzene. The latter reaction is particularly useful because the benzylic bromide so produced undergoes the reactions of a typical alkyl bromide, thus providing us with a synthetic route to a large variety of compounds.
- 16.0: Why This Chapter?
- The most common reaction of aromatic compounds is electrophilic aromatic substitution, in which an electrophile (E+) reacts with an aromatic ring and substitutes for one of the hydrogens. The reaction is characteristic of all aromatic rings, not just benzene and substituted benzenes. In fact, the ability of a compound to undergo electrophilic substitution is a good test of aromaticity.
- 16.1: Electrophilic Aromatic Substitution Reactions - Bromination
- Before seeing how electrophilic aromatic substitutions occur, let’s briefly recall what we said in the chapter on Alkenes: Structure and Reactivity about electrophilic alkene additions. When a reagent such as HCl adds to an alkene, the electrophilic hydrogen ion approaches the π electrons of the double bond and forms a bond to one carbon, leaving a positive charge at the other carbon. This carbocation intermediate then reacts with the nucleophilic Cl– ion to yield the addition product.
- 16.2: Other Aromatic Substitutions
- There are many other kinds of electrophilic aromatic substitutions besides bromination, and all occur by the same general mechanism. Let’s look at some of these other reactions briefly.
- 16.3: Alkylation and Acylation of Aromatic Rings - The Friedel-Crafts Reaction
- The Friedel-Crafts reactions, including alkylation and acylation, are key methods for modifying aromatic rings. Alkylation introduces alkyl groups using alkyl halides and a Lewis acid catalyst, while acylation introduces acyl groups through acyl chlorides or anhydrides. These reactions enhance the functional diversity of aromatic compounds, although they can lead to polyalkylation and rearrangements. The choice of reagent and conditions significantly affects the reaction's outcome.
- 16.4: Substituent Effects in Electrophilic Substitutions
- Substituent effects in electrophilic aromatic substitution influence the reactivity and orientation of the reaction. Electron-donating groups (EDGs) enhance reactivity and direct substitution to ortho and para positions, while electron-withdrawing groups (EWGs) decrease reactivity and favor meta substitution. The nature of the substituent significantly affects the electrophilic aromatic substitution mechanism, making it essential to understand these effects for predicting product outcomes.
- 16.5: Trisubstituted Benzenes- Additivity of Effects
- The section discusses the additivity of substituent effects in trisubstituted benzenes, emphasizing that the combined effects of individual substituents influence both reactivity and orientation in electrophilic aromatic substitution reactions. The overall influence on substitution patterns is determined by the nature and position of the substituents, illustrating how their combined effects can enhance or diminish the electrophilic reactivity of the benzene ring. For further details, you can rea
- 16.6: Nucleophilic Aromatic Substitution
- Nucleophilic aromatic substitution (NAS) involves a nucleophile replacing a leaving group on an aromatic ring, necessitating an electron-withdrawing group near the leaving group to stabilize the intermediate formed. This mechanism contrasts with electrophilic aromatic substitution, highlighting distinct reactivity patterns in aromatic compounds. The process is critical for understanding substitution reactions in organic chemistry.
- 16.7: Benzyne
- Benzyne is a highly reactive intermediate formed during nucleophilic aromatic substitution, characterized by a six-membered aromatic ring containing a triple bond. This compound arises when a strong base eliminates a leaving group from a substituted aromatic compound. Benzyne's reactivity allows it to participate in various chemical reactions, such as adding nucleophiles to the ring. Its unique structure challenges traditional views of aromatic stability and reactivity.
- 16.8: Oxidation of Aromatic Compounds
- Aromatic compounds undergo oxidation reactions that typically involve the conversion of alkyl side chains into carboxylic acids or phenols into quinones. Oxidizing agents such as permanganate or chromic acid can facilitate these transformations. The process highlights the stability of the aromatic ring, which remains intact during oxidation, and can lead to valuable functional group modifications.
- 16.9: Reduction of Aromatic Compounds
- Reduction of aromatic compounds typically involves converting aromatic rings to cyclohexane derivatives. Common reducing agents include hydrogen with a catalyst, lithium aluminum hydride, and catalytic hydrogenation. This process results in the saturation of the aromatic ring, impacting the compound's reactivity and properties. Such transformations are crucial in synthetic organic chemistry for modifying the structure and functionality of aromatic compounds.
- 16.10: Synthesis of Polysubstituted Benzenes
- The ability to plan a successful multi step synthesis of complex molecules is one of the goals of organic chemists. It requires a working knowledge of the uses and limitations of many organic reactions - not only which reactions to use, but when. A few examples follow:
- 16.11: Chemistry Matters—Combinatorial Chemistry
- Combinatorial chemistry involves creating diverse libraries of compounds through systematic combinations of chemical building blocks. This approach accelerates drug discovery and materials development by enabling rapid synthesis and evaluation of numerous compounds simultaneously. Techniques like solid-phase synthesis and high-throughput screening are commonly employed to identify promising candidates efficiently.
- 16.13: Summary
- The summary highlights the key concepts of electrophilic aromatic substitution (EAS), including the nature of electrophiles, the role of aromaticity, and the influence of substituents on reactivity and orientation. It discusses various substitution reactions, such as alkylation and acylation, along with the formation of intermediates. Additionally, the importance of regioselectivity and the distinction between electrophilic and nucleophilic substitutions in aromatic compounds are emphasized.
- 16.14: Summary of Reactions
- The summary of reactions in electrophilic aromatic substitution outlines the key transformations involving benzene and its derivatives. It details the processes of alkylation, acylation, and the effects of various substituents on reaction rates and regioselectivity. The summary emphasizes the role of intermediates, like sigma complexes, and the contrasting mechanisms of nucleophilic aromatic substitution. The overall significance of these reactions in organic synthesis is highlighted.