Electrophilic Substitution of Benzene

11 Key excerpts on "Electrophilic Substitution of Benzene"

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  eBook - ePub

  Principles of Organic Synthesis

  • Richard O.C. Norman(Author)
  • 2017(Publication Date)
  • Routledge

    (Publisher)

  Electrophilic aromatic substitution 11 11.1  The mechanism of substitution

  The substitution of benzene by an electrophilic reagent (E+ ) occurs in two stages: the reagent adds to one carbon atom of the nucleus, giving a carbocation in which the positive charge is delocalized over three carbon atoms, and a proton is then eliminated from this adduct:

  The electrophile may be a charged species, such as the nitronium ion,

  NO 2 +

  , which participates in nitration (section 11.4 ), and the t-butyl cation, (CH3 )3 C+ , which participates in Friedel-Crafts t-butylation (section 11.3 ), or it may be a neutral species which can absorb the pair of electrons provided by the aromatic nucleus. The latter class includes reagents such as sulfur trioxide (in sulfonation, section 11.5 ) which absorb the electron-pair without bond breakage,

  and those such as the halogens in which uptake of the electron-pair leads to bond breakage and the formation of a stable anion, The following are the chief characteristics of these reactions.

  (1)  The intermediate carbocation adducts are too unstable to be isolated as salts except in special circumstances. For example, benzotrifluoride reacts with nitryl fluoride (NO2 F) and boron trifluoride at low temperatures to give a crystalline product thought to be the salt,

  This product is stable only to −50°C, above which it decomposes into m-nitrobenzotrifluoride, hydrogen fluoride, and boron trifluoride. The relative stability of this adduct is associated with the stability of the fluoroborate anion.

  (2)  In most instances, the first step in the process is rate-determining, e.g. in the nitration and bromination of benzene. There are some reactions in which the second step (loss of the proton) is rate-determining; sulfonation is the best known example.

  (3)  The reactions are, with few exceptions, irreversible and the products formed are kinetically controlled (p. 68 ). Two important exceptions are sulfonation (section 11.5 ) and Friedel-Crafts alkylation (section 11.3 a); the reversibility of these reactions can lead to the formation of the thermodynamically controlled products in appropriate conditions. Use may be made of this fact in synthesis (p. 364 ), but in some situations it proves to be disadvantageous (p. 390

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  Organic Chemistry

  • David R. Klein(Author)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  • Electrophilic aromatic substitution involves two steps: • Formation of the sigma complex, or arenium ion. This step is endergonic. • Deprotonation, which restores aromaticity. • Aluminum tribromide (AlBr 3 ) is another common Lewis acid that can serve as a suitable alternative to FeBr 3 . • Chlorination of benzene is accomplished with a suitable Lewis acid, such as aluminum trichloride. SECTION 18.3 • Sulfur trioxide (SO 3 ) is a very powerful electrophile that is present in fuming sulfuric acid. Benzene reacts with SO 3 in a reversible process called sulfonation. SECTION 18.4 • A mixture of sulfuric acid and nitric acid produces a small amount of nitronium ion (NO 2 + ). Benzene reacts with the nitronium ion in a process called nitration. • A nitro group can be reduced to an amino group, providing a two-step method for installing an amino group. SECTION 18.5 • Friedel–Crafts alkylation enables the installation of an alkyl group on an aromatic ring. • In the presence of a Lewis acid, an alkyl halide is converted into a carbocation, which can be attacked by benzene in an electrophilic aromatic substitution. • A Friedel–Crafts alkylation is only efficient in cases where car- bocation rearrangements cannot occur. • When choosing an alkyl halide, the carbon atom connected to the halogen must be sp 3 hybridized. • Polyalkylations are common and can generally be avoided by controlling the reaction conditions. SECTION 18.6 • Friedel–Crafts acylation enables the installation of an acyl group on an aromatic ring. • When treated with a Lewis acid, an acyl chloride will generate an acylium ion, which is resonance stabilized and not susceptible to carbocation rearrangements. • When a Friedel–Crafts acylation is followed by a Clemmensen reduction, the net result is the installation of an alkyl group. This two-step process is a useful synthetic method for install- ing alkyl groups that cannot be installed efficiently with a direct alkylation process.

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  Foundations of Chemistry

  An Introductory Course for Science Students

  • Philippa B. Cranwell, Elizabeth M. Page(Authors)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  15 The chemistry of aromatic compounds At the end of this chapter, students should be able to: • Understand the structure of benzene and other aromatic compounds • Be able to describe and explain electrophilic aromatic substitution, S E Ar • Determine if a ring substituent is activating or deactivating • Compare and contrast the reactivity of benzene, phenol, and aniline with electrophiles 15.1 Benzene 15.1.1 The structure of benzene Benzene , C 6 H 6 , is a molecule that can be described as aromatic . This is because when benzene and benzene-containing compounds were first isolated, they were noted to smell pleasant, so their name was derived from the Greek ‘ aroma ’ , meaning spice, which was then used in Latin to mean ‘ sweet smell ’ . Benzene is a simple aromatic compound that is often studied in undergraduate courses. It is a colourless liquid with a slightly sweet odour and is fully aromatic. Benzene can be represented in a number of ways depending upon what information needs to be depicted (Figure 15.1). Each carbon atom in the benzene molecule is trigonal planar in geometry, with a bond angle of 120 between the other two carbon atoms and the hydro-gen. In terms of the bonding, there are three σ bonds and one π bond per carbon atom. The π bond is formed by an electron in the p orbital of one carbon atom overlapping with an electron in a p orbital on an adjacent carbon atom. This overlap causes a cyclic system of bonding p orbitals (or π bonds) to be formed, where the electrons are free to move around the ring. The movement of electrons in this manner is called delocalisation , and benzene can be said to have a delocalised electron system above and below the ring . Benzene has a delocalised electron system above and below the ring. For a refresher on the shapes of molecules, please see Chapter 2. Foundations of Chemistry: An Introductory Course for Science Students , First Edition. Philippa B. Cranwell and Elizabeth M. Page. © 2021 John Wiley & Sons Ltd.

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  Organic Chemistry

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

    (Publisher)

  • Electrophilic aromatic substitution involves two steps: • Formation of the sigma complex, or arenium ion. This step is endergonic. • Deprotonation, which restores aromaticity. • Aluminum tribromide (AlBr 3 ) is another common Lewis acid that can serve as a suitable alternative to FeBr 3 . • Chlorination of benzene is accomplished with a suitable Lewis acid, such as aluminum trichloride. SECTION 18.3 • Sulfur trioxide (SO 3 ) is a very powerful electrophile that is present in fuming sulfuric acid. Benzene reacts with SO 3 in a reversible process called sulfonation. SECTION 18.4 • A mixture of sulfuric acid and nitric acid produces a small amount of nitronium ion (NO 2 + ). Benzene reacts with the nitronium ion in a process called nitration. • A nitro group can be reduced to an amino group, providing a two-step method for installing an amino group. SECTION 18.5 • Friedel–Crafts alkylation enables the installation of an alkyl group on an aromatic ring. • In the presence of a Lewis acid, an alkyl halide is converted into a carbocation, which can be attacked by benzene in an electrophilic aromatic substitution. • A Friedel–Crafts alkylation is only efficient in cases where car- bocation rearrangements cannot occur. • When choosing an alkyl halide, the carbon atom connected to the halogen must be sp 3 hybridized. • Polyalkylations are common and can generally be avoided by controlling the reaction conditions. SECTION 18.6 • Friedel–Crafts acylation enables the installation of an acyl group on an aromatic ring. • When treated with a Lewis acid, an acyl chloride will generate an acylium ion, which is resonance stabilized and not susceptible to carbocation rearrangements. • When a Friedel–Crafts acylation is followed by a Clem- mensen reduction, the net result is the installation of an alkyl group. This two-step process is a useful synthetic method for installing alkyl groups that cannot be installed efficiently with a direct alkylation process.

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  Organic Chemistry

  A Mechanistic Approach

  • Penny Chaloner(Author)
  • 2014(Publication Date)
  • CRC Press

    (Publisher)

  E + E H + E H + Plus other resonance forms in which there is no intact benzene ring Plus other resonance forms in which there is no intact benzene ring E + E H + FIGURE 12.44 Mechanism.and.regiochemistry.of.electrophilic.substitution.of.naphthalene. Br 2 + Br – 12.16 12.11 –HBr, Δ Br Br H Br H Br H FIGURE 12.45 Bromination.of.anthracene. 528 12.4 Reactions of Polycyclic Aromatic Compounds PROBLEM 12.11 Predict the product(s) of the electrophilic substitution of 12.17 and 12.18: HO NO 2 HOOC OH 12.17 12.18 Solutions HO NO 2 NO 2 NO 2 E + HO HO E E The ring bearing the −OH group is more electron rich and hence more reactive with electro- philes. OH is ortho, para-directing and activating, but the para-position is blocked by the ring. Given that the 1-position of naphthalene is favored over the 2-position, the second product will probably predominate under conditions of kinetic control. E + HOOC HOOC OH OH E E OH HOOC O O Xylene, heat O O O O FIGURE 12.46 Diels–Alder.reaction.of.anthracene.and.maleic.anhydride. Chapter 12 – Electrophilic Aromatic Substitution 529 This problem is similar to the previous one. OH is electron donating and activating and COOH is electron withdrawing and deactivating, so the ring bearing the OH group is more elec- tron rich, and hence electrophilic reaction occurs in this ring. OH is ortho, para-directing, and the naphthalene substitutes preferentially at the 1-position, so the first product will predominate under conditions of kinetic control. In both problems, substitution at the less hindered posi- tion would predominate under conditions of thermodynamic control, because of the unfavorable peri-interaction in the kinetic products. 12.5 HETEROCYCLIC AROMATIC COMPOUNDS We refer to compounds as heterocycles when there is an atom other than carbon as part of the ring.

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  Organic Chemistry as a Second Language

  Second Semester Topics

  • David R. Klein(Author)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  To put it simply, Lewis acids are just compounds that can accept electrons. Another common Lewis acid is FeBr 3 : 62 CHAPTER 4 ELECTROPHILIC AROMATIC SUBSTITUTION Br Fe Br Br Br Fe Br Br LB Lewis Base Lewis Acid Now let’s consider what happens when Br 2 is treated with a Lewis acid, such as AlBr 3 . The Lewis acid can accept electrons from Br 2 : Br Al Br Br Br Al Br Br Br Br Br Br The resulting complex can then serve as a source of Br + , like this: Br Al Br Br Br Br Br Al Br Br Br Br It is probably not accurate to think of this as a free Br + that can exist in solution by itself. Rather, the complex can transfer Br + to an attacking nucleophile: Br Al Br Br Br Br Nuc This complex serves as a delivery agent of Br + Br Al Br Br Br Br Nuc + The important point is that this complex can function as a delivery agent of Br + , and that is what we needed in order to force a reaction between benzene and bromine. So, now let’s try our reaction again. When we treat benzene with bromine in the presence of a Lewis acid, such as AlBr 3 , a reaction is indeed observed. BUT it is not the reaction that we expected. Look closely at the product: Br 2 AlBr 3 Br This is NOT an addition reaction. Rather, it is a substitution reaction. One of the aromatic protons was replaced with bromine. Since the ring is being treated with an electrophile (Br + ), we call this reaction an electrophilic aromatic substitution. To see how this reaction occurs, let’s take a close look at the accepted mechanism. It is absolutely critical that you fully understand this mechanism, because we will soon see that ALL electrophilic aromatic substitution reactions follow a similar mechanism. The first step shows the ring acting as a nucleophile to attack the complex, thereby transferring Br + to the aromatic ring: H Br Br Al Br Br Br Br Br Al Br Br Br + 4.1 HALOGENATION AND THE ROLE OF LEWIS ACIDS 63 This step generates an intermediate that is not aromatic.

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  Experimental Organic Chemistry

  A Miniscale & Microscale Approach

  • John Gilbert, Stephen Martin(Authors)
  • 2015(Publication Date)
  • Cengage Learning EMEA

    (Publisher)

  They will also allow you to make a semi-qualitative assessment of relative reactivities. The discussion that follows will first focus on the issue of relative rates of substitution and then on that of orientation in the reaction. Ar HOAc An arene H + Br 2 Ar An aryl bromide ( colorless ) Br + HBr Bromine ( red-brown ) (15.20) (15.21) Copyright 2016 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Chapter 15 ■ Electrophilic Aromatic Substitution 529 Studies of electrophilic substitutions on arenes are reported in which the exper-imental conditions allow a direct comparison of the relative reaction rates. For example, the relative reactivities of benzene and toluene toward halogenation, acet-ylation, sulfonation, nitration, and methylation have been determined. In all cases, electrophilic aromatic substitution was more rapid with toluene. For example, bro-mination of toluene is some 600 times faster than that of benzene. Such studies have led to the classification of substituents as ring activators or deactivators , depending on whether the substituted arene reacts faster or slower than benzene itself. Thus, the methyl group of toluene is a ring activator. The effect substituents have on the relative rate of a specific type of S E 2 reaction may exceed several orders of magnitude, and the range of reactivity when compar-ing substituents may be enormous. For example, phenol reacts 10 12 times faster and nitrobenzene reacts 10 5 times slower than benzene in electrophilic bromination.

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  Organic Reaction Mechanisms 2018

  An Annual Survey Covering the Literature Dated January to December 2018

  • Mark G. Moloney(Author)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  Electrophilic Aromatic Substitution 213 N N N Me Me Au Cl N Me Me O O ( 61 ) Scheme 27 benzene using bioethanol instead of fossil-derived ethylene has been studied using solid-state NMR spectroscopy, UV–Vis diffuse reflectance spectroscopy and mass spectrometry. Surface-adsorbed zeolite–aromatic π -complexes, and Wheland-type σ -complexes were detected. 118 Iodobenzene diacetates undergo ortho -proparylation in an iodonio [3,3] rearrangement of the intermediate allenyl iodonium ion generated on reaction with propargyl silanes or stannanes. The authors describe the process as a hypervalent iodine guided electrophilic substitution (HIGES) rather than a sigmatropic rearrangement, due to the asynchronous nature of the process as shown by DFT calculations. An activation barrier Δ G ‡ was calculated to be 59 kJ mol –1 significantly lower than for classical aromatic Claisen rearrangements. A dependency on the electronic nature of para substituents was also shown with Δ G ‡ for the 4-methoxy substituted compound being 45 kJ mol –1 . 119 Hypervalent iodine-guided electrophilic substitution has also been proposed as an alterna-tive mechanism to the reductive iodonio-Claisen rearrangement (RICR) to account for the para selectivity when benzyl silanes or trifluoroborates were used instead of allylic silanes in the reaction with PhI(OAc) 2 . The acetoxy group in the activated iodonium ion ( 62 ) directs delivery of the benzyl fragment to the para position (Scheme 28). The ortho isomer was not observed. 120 (AcO) 2 I Ph M Tf 2 O or BF 3 .Et 2 O M = SiMe 3 or BF 3 K I O O M Ph I Ph ( 62 ) + Scheme 28 Mechanistic studies on alkylations mediated by sulfur based reagents have appeared. Benzo-furanones and oxindoles have been difluoromethylated using a difluoromethyl sulfonium ylide. Deuterium labelling studies indicated a mechanism involving difluorocarbene, 121 while a tran-sition metal-free strategy for aryl C( sp 2 ) − C( sp 3 ) cross-coupling between arylboronic acids and

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  Organic Reaction Mechanisms 2015

  An annual survey covering the literature dated January to December 2015

  • A. C. Knipe(Author)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 Introduction The recent trend of the increasing use of transition-metal catalysts to effect substi- tutions continues. These catalysts are particularly important for reactions involving carbon–carbon bond formation, and these processes, both electrophilic and nucle- ophilic, are summarized in a single section. Transition-metal-catalysed reactions involving bond formation to oxygen, sulfur, nitrogen, and the halogens are covered in separate sections on nucleophilic and aromatic substitutions. General A computational study has shown that the Bell–Evans–Polanyi principle, which shows that differences in activation energies between related reactions are proportional to their reaction enthalpies, effectively predicts regioselectivity in electrophilic aromatic substitutions. 1 A study using mass spectrometry and DFT (density function theory) calculations has indicated a difference in the behaviour, in the gas phase, of chloroben- zene and fluorobenzene with lanthanide cations. Chlorine transfer involves initial Organic Reaction Mechanisms 2015, First Edition. Edited by A. C. Knipe. © 2019 John Wiley & Sons Ltd. Published 2019 by John Wiley & Sons Ltd. 251 252 Organic Reaction Mechanisms 2015 coordination of the lanthanide ion to the aromatic ring, whereas fluorine transfer occurs directly to the metal. 2 Methods of synthesis of aryl fluorides have been summarized in a review that covers the use of nucleophilic and electrophilic reagents as well as metal-catalysed pathways. 3 Diaryliodonium salts (1) carrying the pentafluorosulfanyl substituent have been pre- pared; their reaction with carbon, oxygen, nitrogen, and sulfur nucleophiles gives a wide range of SF 5 -substituted arenes. 4 The use of the nonionic surfactant TPGS-750- M has been shown to allow the S N Ar substitution of halogens by oxygen, nitrogen, and sulfur nucleophiles in water.

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  Reactions of Aromatic Compounds

  • R.G. Compton, C.H. Bamford, C.F.H. Tipper†, R.G. Compton, C.H. Bamford, C.F.H. Tipper†(Authors)
  • 1972(Publication Date)
  • Elsevier Science

    (Publisher)

  Finally, it is interesting to note that the similarity between benzenesulphonyl- ation and benzoylation also shows up in the log& : log& ratios for toluene which are O.56lE4 and 0.54188, respectively, indicating a similar size of electrophile in each case. 5. Electrophilic halogenation 5.1 POSITIVE HALOGENATION The addition of mineral acids to hypohalous acids produces a large increase in the rate at which these latter acids halogenate and reaction under these con- ditions is usually referred to as “positive halogenation” which has been subjected to intensive kinetic studies. Whilst there is ample evidence supporting the existence References pp. 388-406 84 KINETICS OF ELECTROPHILIC AROMATIC SUBSTITUTION of positive chlorinating and brominating species, the arguments regarding positive iodination are somewhat controversial since the kinetic data can also be inter- preted in favour of molecular iodine as electrophile. 5.1.1 Positive bromination Positive bromination was first observed by Shilov and Kaniaev' who found that the bromination of sodium anisole-m-sulphonate by bromine-free hypo- bromous acid was accelerated by the addition of nitric or sulphuric acids, and was governed by the kinetic equation Rate = k3[ArH][HOBrl[H' 1 (89) The choice of conditions is fairly critical in studying positive bromination for it has been shown'g0 that the rate of hypobromous acid decomposition is given by k,[HOBrI3 [OH-], hence dilute solutions of hypobromous acid and the presence of strong mineral acid are the most satisfactory if the kinetics are not to become too complicated. With these conditions, Wilson and Soper' investigated the bromination of benzene and 2-nitroanisole by hypobromous acid and found that the reaction rate was very slow but increased rapidly with increasing [H'] and they therefore proposed that the brominating species was H20Br'.

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  Organic Chemistry

  • T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  Rationalize this difference in behavior. 1 2 3 4 5 6 7 8 15.63 Furan undergoes electrophilic aromatic substitution. Use resonance structures for possible arenium ion intermediates to predict whether furan is likely to undergo bromination more rapidly at C2 or at C3. Br 2 , FeBr 3 3 2 Furan O 15.64 A CD bond is harder to break than a CH bond, and, consequently, reactions in which CD bonds are broken proceed more slowly than reactions in which CH bonds are broken. What mecha- nistic information comes from the observation that perdeuterated benzene, C 6 D 6 , is nitrated at the same rate as normal benzene, C 6 H 6 ? 15.65 Acetanilide was subjected to the following sequence of reactions: (1) concd H 2 SO 4 ; (2) HNO 3 , heat; (3) H 2 O, H 2 SO 4 , heat, then HO − . The 13 C NMR spectrum of the final product gives six signals. Write the structure of the final product. 726 CHAPTER 15 Reactions of Aromatic Compounds 15.66 The compound phenylbenzene (C 6 H 5  C 6 H 5 ) is called biphenyl, and the ring carbons are num- bered in the following manner: 3 2′ 4′ 3′ 6′ 5′ 5 6 4 2 Use models to answer the following questions about substituted biphenyls. (a) When certain large groups occupy three or four of the ortho positions (e.g., 2, 6, 2′, and 6′), the substituted biphenyl may exist in enan- tiomeric forms. An example of a biphenyl that exists in enantiomeric forms is the compound in which the following substituents are present: 2-NO 2 , 6-CO 2 H, 2′-NO 2 , 6′-CO 2 H. What factors account for this? (b) Would you expect a biphenyl with 2-Br, 6-CO 2 H, 2′-CO 2 H, 6′-H to exist in enantiomeric forms? (c) The biphenyl with 2-NO 2 , 6-NO 2 , 2′-CO 2 H, 6′-Br cannot be resolved into enantiomeric forms. Explain. 15.67 Explain how it is possible for 2,2′-dihydroxy-1,1′-binaphthyl to exist in enantiomeric forms. OH OH 15.68 The lignins are macromolecules that are major components of the many types of wood, where they bind cellulose fibers together in these natural composites.

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