{"id":429,"date":"2018-11-26T16:03:15","date_gmt":"2018-11-26T16:03:15","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&p=429"},"modified":"2022-01-28T07:16:32","modified_gmt":"2022-01-28T07:16:32","slug":"14-3-the-general-mechanism-chemistry-libretexts","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/14-3-the-general-mechanism-chemistry-libretexts\/","title":{"raw":"14.2. Examples of electrophilic aromatic substitution","rendered":"14.2. Examples of electrophilic aromatic substitution"},"content":{"raw":"
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A detailed look at electrophilic aromatic substitution reactions (EAS)<\/h2>\r\nAs outlined in the previous section<\/a>, the basic mechanism for EAS involves electrophilic addition to form a non-aromatic Wheland intermediate, which then loses H+ through electrophile elimination.\u00a0 The Wheland intermediate is stabilized by resonance, but it is still much less stable than the starting material; this loss of aromaticity means that the first step (electrophilic addition) is always the rate determining step in EAS.\u00a0 The second step (electrophile addition) regenerates the aromatic system and it is a faster step.\r\n\r\nMany electrophiles (such as Br2<\/sub>) are not sufficiently electrophilic to react on their own, so many EAS reactions rely on a catalyst in order to activate the electrophile.\u00a0 These catalysts are always either Bronsted-Lowry acids<\/a> or Lewis acids<\/a>.\r\n\r\nThe following examples of EAS, beginning with bromination, serve to illustrate how the reaction works in practice.\r\n

Bromination and chlorination<\/h2>\r\nA chlorine or bromine may be introduced using the element (Cl2<\/sub>, Br2<\/sub>) in the presence of the related iron(III) halide (FeCl3<\/sub> or FeBr3<\/sub>) as the Lewis acid catalyst.\u00a0 However, since iron(III) halides are easily deactivated by water from the air, it is common to use iron metal powder, since this reacts easily with Cl2<\/sub> or Br2<\/sub> to form FeCl3<\/sub> or FeBr3<\/sub> respectively.\u00a0 The mechanism (shown for bromination) is a typical EAS, comprising (1) electrophile activation (by coordination), then (2) electrophilic addition to form the Wheland intermediate, and finally (3) electrophile elimination to lose H+<\/sup>.\r\n\r\nStep 1: Formation of the electrophile by reaction of Br2<\/sub> with FeBr3<\/sub>.\r\n<\/em><\/strong>\r\n\r\n\"\"\r\n\r\nStep 2: Electrophilic addition of activated bromine<\/strong>\r\n\r\n\"Benzene\r\n\r\n<\/div>\r\nStep 3: Electrophile elimination from the Wheland Intermediate to form the aryl bromide product<\/strong>\r\n\r\n\"Loss\r\n
\r\n\r\nThe free energy reaction coordinate diagram for this reaction is shown below.\u00a0 It has been simplified to use pre-formed Br+, so in effect it starts at step 2 in the above mechanism. Note that the rate determining step is where the high-energy Wheland Intermediate is formed by electrophilic attack of the Br+ on the aromatic ring.\u00a0 This intermediate is much less stable than the aromatic reactant and aromatic product, because it is not aromatic and it is charged - though it is somewhat stabilized by delocalization of the + charge through resonance.\r\n

Free energy reaction coordinate diagram for bromination of benzene to produce bromobenzene<\/h3>\r\n\"Free\r\n\r\nAlso, an animated diagram<\/a> of this mechanism may be viewed.\r\n\r\n\"\"\r\n\r\nThis mechanism for electrophilic aromatic substitution should be considered in context with other mechanisms involving carbocation intermediates. These include SN<\/sub>1<\/a> and E1 reactions<\/a> of alkyl halides, and Br\u00f8nsted acid addition reactions of alkenes<\/a>.\r\n\r\nTo summarize, when carbocation intermediates are formed one can expect them to react further by one or more of the following modes:<\/strong>\r\n\r\n1. <\/strong> The cation may bond to a nucleophile to give a substitution or addition product (coordination).\r\n2. <\/strong> The cation may transfer a proton to a base, giving a double bond product (electrophile elimination).\r\n3. <\/strong> The cation may rearrange<\/a> to a more stable carbocation, and then react by mode #1 or #2.\r\n\r\nSN<\/sub>1 and E1 reactions are respective examples of the first two modes of reaction. The second step of alkene addition reactions proceeds by the first mode, and any of these three reactions may exhibit molecular rearrangement if an initial unstable carbocation is formed. The carbocation intermediate in electrophilic aromatic substitution (the Wheland intermediate) is stabilized by charge delocalization (resonance) so it is not subject to rearrangement. In principle it could react by either mode 1 or 2, but the energetic advantage of reforming an aromatic ring leads to exclusive reaction by mode 2 (i.e.,<\/em> proton loss).\r\n\r\n<\/div>\r\n
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Synthesis of benzene derivatives via electrophilic aromatic substitution<\/h2>\r\n
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This section is on the general mechanism of how an electrophilic atom becomes a part of a benzene ring through the substitution of a hydrogen. Common reactions that proceed by electrophilic aromatic substitution include the nitration and sulfonation of benzene, hydration of benzene, Friedel-Crafts acylation and Friedel-Crafts alkylation.\u00a0 The catalysts and co-reagents serve to generate the strong electrophilic species needed to effect the initial step of the substitution. The specific electrophile (E or E+<\/sup>) believed to function in each type of reaction is listed in the right hand column.\r\n
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Specific Reactions<\/em><\/caption>
Reaction<\/strong><\/th>\r\nReagent<\/strong><\/th>\r\nCatalyst<\/strong><\/th>\r\nProduct<\/strong><\/th>\r\nE+<\/sup>\u00a0or E<\/strong><\/th>\r\n<\/tr>\r\n<\/thead>\r\n
Halogenation<\/a><\/strong><\/td>\r\n\u00a0X2<\/sub>\u00a0(X=Cl, Br)\r\n\r\nX2<\/sub> (X = I)<\/td>\r\nFeX3<\/sub>\r\n\r\nHNO3<\/sub><\/td>\r\nArCl, ArBr\r\n\r\nArI<\/td>\r\nX+<\/sup>\r\n\r\n<\/span>H<\/span><\/span><\/span><\/span>2<\/span><\/span><\/span><\/sub><\/span>O<\/span>\u2212<\/span><\/span><\/span>I<\/span>+<\/span><\/span><\/span><\/sup><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/td>\r\n<\/tr>\r\n
Nitration<\/a><\/strong><\/td>\r\nHNO3<\/sub><\/td>\r\nH2<\/sub>SO4<\/sub><\/td>\r\nArNO2<\/sub><\/td>\r\n+NO2<\/sub><\/td>\r\n<\/tr>\r\n
Sulfonation<\/a><\/strong><\/td>\r\nH2<\/sub>SO4<\/sub>\u00a0or H2<\/sub>S2<\/sub>O7<\/sub><\/td>\r\nNone<\/td>\r\nArSO3<\/sub>H<\/td>\r\nSO3<\/sub><\/td>\r\n<\/tr>\r\n
Friedel-Crafts alkylation<\/a><\/strong><\/td>\r\nRX, ArCH2<\/sub>X<\/td>\r\nAlCl3<\/sub><\/td>\r\nAr-R, Ar-CH2<\/sub>Ar<\/td>\r\nR+<\/sup><\/td>\r\n<\/tr>\r\n
ROH<\/td>\r\nHF, H2<\/sub>SO4<\/sub>, or BF3<\/sub><\/td>\r\nAr-R<\/td>\r\nR+<\/sup><\/td>\r\n<\/tr>\r\n
RCH=CH2<\/sub><\/td>\r\nH3<\/sub>PO4<\/sub>\u00a0or HF<\/td>\r\nAr-CHRCH3<\/sub><\/td>\r\nR+<\/sup><\/td>\r\n<\/tr>\r\n
Friedel-Crafts acylation<\/a><\/strong><\/td>\r\nRCOCl<\/td>\r\nAlCl3<\/sub><\/td>\r\nAr-COR<\/td>\r\nRC+<\/sup>=O<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\n
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Electrophilic aromatic substitution reactions - Halogenation<\/h2>\r\n<\/header>
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Study Note<\/p>\r\nThe general mechanism is the key to understanding electrophilic aromatic substitution. You will see similar equations written for nitration, sulfonation, acylation, etc., but the general mechanism is always the same - the major difference being the identity of the electrophile in each case.\u00a0 All involve an electrophilic addition step which is quickly followed by an electrophile elimination step.\r\n\r\n<\/div>\r\n<\/div>\r\nHalogenation is an example of electrophillic aromatic substitution. In electrophilic aromatic substitutions, a benzene is attacked by an electrophile which results in substition of hydrogens. However, halogens are not electrophillic enough to break the aromaticity of benzenes, which require a catalyst (such as FeCl3<\/sub>) to activate.\u00a0 See above for a detailed examination of the mechanism for bromination of benzene.\r\n

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Exercises<\/h3>\r\n
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\r\n\r\n1. <\/strong>What reagents would you need to get the given product?\r\n\r\n\"What\r\n\r\n \r\n\r\n<\/div>\r\n<\/div>\r\n
\r\n\r\n2. <\/strong>What is the major product given the reagents below?\r\n\r\n \r\n\r\n\"Benzene\r\n\r\n \r\n\r\n3. <\/strong>Draw the formation of Cl+ <\/sup>from AlCl3<\/sub>\u00a0<\/sub>and Cl2<\/sub>.\u00a0 (AlCl3<\/sub> acts like FeCl3<\/sub>)\r\n\r\n4<\/strong>. Draw the mechanism of the reaction between Cl+<\/sup> and benzene.\r\n\r\n \r\n
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Solutions<\/h3>\r\n[reveal-answer q=\"789315\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"789315\"]\r\n\r\n1. Cl2<\/sub>\u00a0<\/sub>and AlCl3<\/sub> or Cl2<\/sub> and FeCl3<\/sub>\r\n\r\n2. No Reaction\r\n\r\n\"Structure\r\n\r\n \r\n\r\n3.\r\n\r\n\"alcl3.jpg\"\r\n\r\n4.\r\n\r\n\"answer[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n
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https:\/\/youtu.be\/K2tIixiXGOM\r\n

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Nitration and Sulfonation<\/h2>\r\n<\/header>
Nitration and sulfonation of benzene<\/a> are two examples of electrophilic aromatic substitution<\/a>. The nitronium ion (NO2<\/sub>+<\/sup>) and sulfur trioxide (SO3<\/sub>) are the electrophiles and individually react with benzene to give nitrobenzene and benzenesulfonic acid respectively.\r\n
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Nitration of Benzene<\/h3>\r\nThe source of the nitronium ion is through the protonation of nitric acid by sulfuric acid, which causes the loss of a water molecule and formation of a nitronium ion.\r\n\r\n\"NitrationofBenzene.jpg\"\r\n
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Sulfuric acid activation of nitric acid<\/h3>\r\nThe first step in the nitration of benzene is to activate HNO3<\/sub> with sulfuric acid to produce a stronger electrophile, the nitronium ion.\r\n\r\n\"activationofnitricacid.jpg\"\r\n\r\nBecause the nitronium ion is a good electrophile, it is attacked by benzene to produce nitrobenzene.\r\n\r\n<\/div>\r\n
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Mechanism<\/h3>\r\n\"Mechanismofaromaticnitration.png\"\r\n\r\n(Resonance forms of the intermediate can be seen in the generalized electrophilic aromatic substitution<\/a>)\r\n\r\n<\/div>\r\n<\/div>\r\n
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Sulfonation of benzene<\/h3>\r\nSulfonation is a reversible reaction that produces benzenesulfonic acid by adding sulfur trioxide and fuming sulfuric acid. The reaction is reversed by adding hot aqueous acid to benzenesulfonic acid to produce benzene.\r\n\r\n\"sulfonationofbenzene.jpg\"\r\n
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Mechanism<\/h4>\r\nTo produce benzenesulfonic acid from benzene, fuming sulfuric acid and sulfur trioxide are added. Fuming sulfuric acid, also refered to as oleum<\/em>, is a concentrated solution of dissolved sulfur trioxide in sulfuric acid. The sulfur in sulfur trioxide is electrophilic because the oxygens pull electrons away from it because oxygen is very electronegative. The benzene attacks the sulfur (and subsequent proton transfers occur) to produce benzenesulfonic acid.\r\n\r\n\"mechanismofaromaticsulfonation.png\"\r\n\r\n<\/div>\r\n
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Reverse sulfonation<\/h4>\r\nSulfonation of benzene is a reversible reaction. Sulfur trioxide readily reacts with water to produce sulfuric acid and heat. Therefore, by adding heat to benzenesulfonic acid in diluted aqueous sulfuric acid the reaction is reversed.\r\n\r\n\"Reversesulfonation.jpg\"\r\n\r\n<\/div>\r\n<\/div>\r\n
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Further applications of sulfonation<\/h3>\r\nBecause sulfonation is a reversible reaction, it can also be used in further substitution reactions in the form of a directing blocking group because it can be easily removed. The sulfonic group blocks the carbon from being attacked by other substituents and after the reaction is completed it can be removed by reverse sulfonation. Benzenesulfonic acids are also used in the synthesis of detergents, dyes, and sulfa drugs.\u00a0Benzenesulfonyl chloride is a precursor to sulfonamides, which are used in chemotherapy.\r\n\r\n<\/div>\r\n
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Outside Links<\/h3>\r\nAromatic Sulfonation<\/strong>\r\n