{"id":634,"date":"2018-11-29T22:34:40","date_gmt":"2018-11-29T22:34:40","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&#038;p=634"},"modified":"2020-06-11T06:23:59","modified_gmt":"2020-06-11T06:23:59","slug":"17-1-nucleophilic-aromatic-substitution","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/17-1-nucleophilic-aromatic-substitution\/","title":{"raw":"17.1 Nucleophilic aromatic substitution","rendered":"17.1 Nucleophilic aromatic substitution"},"content":{"raw":"<header class=\"elm-header\">\r\n<div class=\"elm-header-custom\">\r\n<div class=\"mt-container-secondary\"><\/div>\r\n<\/div>\r\n<\/header><article id=\"elm-main-content\" class=\"elm-content-container\"><section class=\"mt-content-container\">\r\n<div id=\"skills\">\r\n<div class=\"textbox learning-objectives\">\r\n<h3>Learning Objectives<\/h3>\r\n<div id=\"skills\">\r\n\r\nAfter completing this section, you should be able to\r\n<ol>\r\n \t<li>identify the conditions necessary for an aryl halide to undergo nucleophilic aromatic substitution, and give an example of such a reaction.<\/li>\r\n \t<li>write the detailed mechanism for a nucleophilic aromatic substitution reaction.<\/li>\r\n \t<li>compare the mechanism of a nucleophilic aromatic substitution reaction and the S<sub>N<\/sub>1 and S<sub>N<\/sub>2 mechanisms discussed earlier.<\/li>\r\n \t<li>identify the product formed when a given nucleophile reacts with a given aryl halide in a nucleophilic aromatic substitution reaction.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Key Terms<\/h3>\r\n<div>\r\n\r\nMake certain that you can define, and use in context, the key terms below.\r\n<ul>\r\n \t<li>Meisenheimer complex<\/li>\r\n \t<li>nucleophilic aromatic substitution<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"note\">\r\n<div class=\"textbox shaded\">\r\n<div id=\"note\">\r\n<h3 class=\"boxtitle\">Study Notes<\/h3>\r\nA <em>nucleophilic aromatic substitution reaction<\/em> is a reaction in which one of the substituents in an aromatic ring is replaced by a nucleophile.\r\n\r\nA <em>Meisenheimer complex<\/em> is a negatively charged intermediate formed by the attack of a nucleophile upon one of the aromatic-ring carbons during the course of a nucleophilic aromatic substitution reaction. A typical Meisenheimer complex is shown in the reaction scheme below. Notice how this particular complex can be formed from two different starting materials by using a different nucleophile in each case.\r\n\r\n<img class=\"aligncenter\" style=\"width: auto\" src=\"http:\/\/chem.libretexts.org\/@api\/deki\/files\/87355\/16-7.png?origin=mt-web\" alt=\"reaction scheme showing Meisenheimer complex\" \/>\r\n\r\n<strong>Figure 16.2:<\/strong> The formation of a typical Meisenheimer complex.\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_1\" class=\"mt-section\">\r\n<h3 class=\"editable\">A Nucleophilic Aromatic Displacement Reactions of Aryl Halides<\/h3>\r\nThe carbon-halogen bonds of aryl halides are like those of alkenyl halides in being much stronger than those of alkyl halides (see Table 4-6). The simple aryl halides generally are resistant to attack by nucleophiles in either S<sub>N<\/sub>1 or S<sub>N<\/sub>2 reactions (Table 14-6). However, this low reactivity can be changed dramatically by changes in the reaction conditions and the structure of the aryl halide. In fact, nucleophilic displacement becomes quite rapid\r\n<ol start=\"1\">\r\n \t<li>when the aryl halide is activated by substitution with strongly electron-attracting groups such as NO<sub>2<\/sub>, and<\/li>\r\n \t<li>when very strongly basic nucleophilic reagents are used.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n<h3 class=\"editable\">Addition-Elimination Mechanism of Nucleophilic Substitution of Aryl Halides<\/h3>\r\nAlthough simple aryl halides are inert to the usual nucleophilic reagents, considerable activation is produced by strongly electron-attracting substituents in either the ortho or para positions, or both. For example, the displacement of chloride ion from 1-chloro-2,4-dinitrobenzene by dimethylamine occurs readily in ethanol solution at room temperature. Under the same conditions chlorobenzene completely fails to react; thus the activating influence of the two nitro groups amounts to a factor of at least 108:\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163510\/BPOCchapter14-6-6b-3.png\" alt=\"\" width=\"400px\" height=\"114px\" \/><img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163512\/BPOCchapter14-6-6b-4.png\" alt=\"\" width=\"205\" height=\"130\" \/>\r\n\r\nA related reaction is that of 2,4-dinitrofluorobenzene with the amino groups of peptides and proteins, and this reaction provides a means for analysis of the N-terminal amino acids in polypeptide chains.\r\n\r\nIn general, the reactions of activated aryl halides closely resemble the S<sub>N<\/sub>2-displacement reactions of aliphatic halides. The same nucleophilic reagents are effective (e.g., CH<sub>3<\/sub>O\u00af, HO\u00af, and RNH<sub>2<\/sub>); the reactions are second order overall (first order in halide and first order in nucleophile); and for a given halide the more nucleophilic the attacking reagent, the faster the reaction. However, there must be more than a subtle difference in mechanism because an aryl halide is unable, to pass through the same type of transition state as an alkyl halide in S<sub>N<\/sub>2 displacements.\r\n\r\nThe generally accepted mechanism of nucleophilic aromatic substitution of aryl halides carrying activating groups involves two steps. The first step involves attack of the nucleophile Nuc\u00af on the carbon bearing the halogen substituent to form an intermediate (shown in the box). This intermediate is stabilized by resonance; in particular, the negative charge can be delocalized into the <em>ortho\/para<\/em> electron-withdrawing group (in this example, an <em>ortho<\/em> nitro group). The aromatic system is destroyed on forming the anion, and the carbon at the reaction site changes from planar (sp<sup>2<\/sup> bonds) to tetrahedral (sp<sup>3<\/sup> bonds).\r\n\r\nIn the second step, loss of an anion, X\u00af or Nuc\u00af, regenerates an aromatic system, and, if X\u00af is lost, the overall reaction is nucleophilic displacement of X by Nuc.\u00a0 The most convenient resonance form has been used for the anion, to keep the mechanism simple.\r\n\r\n<img class=\"alignnone wp-image-3137\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/11061428\/Nucleophilic-Aromatic-Substitution-Mechanism.png\" alt=\"Mechanisms for nucleophilic aromatic substitution, with Nuc- adding, then X- being eliminated\" width=\"743\" height=\"342\" \/>\r\n\r\nIn the case of a neutral nucleophilic reagent, HY, the reaction sequence would be the same except for the necessary adjustments in the charge of the intermediate, with a final acid-base step.\r\n\r\n&nbsp;\r\n\r\nWhy is this reaction pathway generally unfavorable for simple aryl halides? If no electron-withdrawing group is present, the carbons in the ring alone cannot stabilize the minus charge enough for the reaction to occur.\u00a0 When strongly electron-attracting groups are located on the ring at the ortho-para positions, the intermediate anion is stabilized by delocalization of electrons from the ring carbons to more favorable locations on the substituent groups.\r\n\r\nAs another example, consider the displacement of bromine by OCH<sub>3<\/sub> in the reaction of 4-bromonitrobenzene and methoxide ion:\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163523\/BPOCchapter14-6-6b-91.png\" alt=\"\" width=\"326\" height=\"152\" \/>\r\n\r\nThe anionic intermediate formed by addition of methoxide ion to the aryl halide can be described by the valence-bond structures 5a-5d. Of these structures 5d is especially important because in it the charge is transferred from the ring carbons to the oxygen of the nitro substituent:\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163526\/BPOCchapter14-6-6b-10.png\" alt=\"\" width=\"400px\" height=\"135px\" \/>\r\n\r\nSubstituents in the meta positions have much less effect on the reactivity of an aryl halide because delocalization of electrons to the substituent is not possible. No formulas can be written analogous to 5c and 5d in which the negative charges are both on atoms next to positive nitrogen, <img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163527\/BPOCchapter14-6-6b-11.png\" alt=\"\" width=\"100px\" height=\"45px\" \/> and <img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163528\/BPOCchapter14-6-6b-12.png\" alt=\"\" width=\"100px\" height=\"41px\" \/>\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163530\/BPOCchapter14-6-6b-13.png\" alt=\"\" width=\"400px\" height=\"98px\" \/>\r\n\r\nIn a few instances, stable compounds resembling the postulated reaction intermediate have been isolated. One classic example is the complex 7 (isolated by J. Meisenheimer), which is the product of the reaction of either the methyl aryl ether 6 with potassium ethoxide, or the ethyl aryl ether 8 and potassium methoxide:\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163532\/BPOCchapter14-6-6b-14.png\" alt=\"\" width=\"500px\" height=\"133px\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_3\" class=\"mt-section\">\r\n<h3 class=\"editable\">Exercises<\/h3>\r\n<div id=\"s61721\" class=\"mt-include\">\r\n<div id=\"section_26\" class=\"mt-section\">\r\n<h4 id=\"Questions-61721\">Questions<\/h4>\r\n<strong>Q16.7.1<\/strong>\r\n\r\nPropose a mechanism for the following reaction:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163535\/16-7-1qu.png\" alt=\"\" width=\"596\" height=\"158\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_27\" class=\"mt-section\">\r\n<h4 id=\"Solutions-61721\">Solutions<\/h4>\r\n<strong>S16.7.1<\/strong>\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163539\/16.7.png\" alt=\"\" width=\"578\" height=\"441\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_4\" class=\"mt-section\">\r\n<h3>Khan academy video<\/h3>\r\nhttps:\/\/youtu.be\/6xy02bQS2Zg\r\n\r\n<img class=\"alignnone wp-image-2873 size-thumbnail\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/07184802\/frame-23-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/>\r\n<h3 class=\"editable\">Contributors<\/h3>\r\n<ul>\r\n \t<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\r\n \t<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\r\n \t<li>William Reusch, Professor Emeritus (<a class=\"external\" title=\"http:\/\/www.msu.edu\/\" href=\"http:\/\/www.msu.edu\/\" target=\"_blank\" rel=\"external nofollow noopener\">Michigan State U.<\/a>), <a class=\"external\" title=\"Template:ContribReusch\" href=\"https:\/\/www2.chemistry.msu.edu\/faculty\/reusch\/VirtTxtJml\/intro1.htm\" target=\"_blank\" rel=\"external nofollow noopener\">Virtual Textbook of\u00a0Organic\u00a0Chemistry<\/a><\/li>\r\n<\/ul>\r\n<ul>\r\n \t<li><span class=\"person_name\">John D. Robert <\/span>and <span class=\"person_name\">Marjorie C.<\/span> <span class=\"person_name\">Caserio <\/span>(1977) <em>Basic Principles of Organic Chemistry, second edition.<\/em> W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, \"You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.\"<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/section><\/article>","rendered":"<header class=\"elm-header\">\n<div class=\"elm-header-custom\">\n<div class=\"mt-container-secondary\"><\/div>\n<\/div>\n<\/header>\n<article id=\"elm-main-content\" class=\"elm-content-container\">\n<section class=\"mt-content-container\">\n<div id=\"skills\">\n<div class=\"textbox learning-objectives\">\n<h3>Learning Objectives<\/h3>\n<div id=\"skills\">\n<p>After completing this section, you should be able to<\/p>\n<ol>\n<li>identify the conditions necessary for an aryl halide to undergo nucleophilic aromatic substitution, and give an example of such a reaction.<\/li>\n<li>write the detailed mechanism for a nucleophilic aromatic substitution reaction.<\/li>\n<li>compare the mechanism of a nucleophilic aromatic substitution reaction and the S<sub>N<\/sub>1 and S<sub>N<\/sub>2 mechanisms discussed earlier.<\/li>\n<li>identify the product formed when a given nucleophile reacts with a given aryl halide in a nucleophilic aromatic substitution reaction.<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Key Terms<\/h3>\n<div>\n<p>Make certain that you can define, and use in context, the key terms below.<\/p>\n<ul>\n<li>Meisenheimer complex<\/li>\n<li>nucleophilic aromatic substitution<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"note\">\n<div class=\"textbox shaded\">\n<div id=\"note\">\n<h3 class=\"boxtitle\">Study Notes<\/h3>\n<p>A <em>nucleophilic aromatic substitution reaction<\/em> is a reaction in which one of the substituents in an aromatic ring is replaced by a nucleophile.<\/p>\n<p>A <em>Meisenheimer complex<\/em> is a negatively charged intermediate formed by the attack of a nucleophile upon one of the aromatic-ring carbons during the course of a nucleophilic aromatic substitution reaction. A typical Meisenheimer complex is shown in the reaction scheme below. Notice how this particular complex can be formed from two different starting materials by using a different nucleophile in each case.<\/p>\n<p><img decoding=\"async\" class=\"aligncenter\" style=\"width: auto\" src=\"http:\/\/chem.libretexts.org\/@api\/deki\/files\/87355\/16-7.png?origin=mt-web\" alt=\"reaction scheme showing Meisenheimer complex\" \/><\/p>\n<p><strong>Figure 16.2:<\/strong> The formation of a typical Meisenheimer complex.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_1\" class=\"mt-section\">\n<h3 class=\"editable\">A Nucleophilic Aromatic Displacement Reactions of Aryl Halides<\/h3>\n<p>The carbon-halogen bonds of aryl halides are like those of alkenyl halides in being much stronger than those of alkyl halides (see Table 4-6). The simple aryl halides generally are resistant to attack by nucleophiles in either S<sub>N<\/sub>1 or S<sub>N<\/sub>2 reactions (Table 14-6). However, this low reactivity can be changed dramatically by changes in the reaction conditions and the structure of the aryl halide. In fact, nucleophilic displacement becomes quite rapid<\/p>\n<ol start=\"1\">\n<li>when the aryl halide is activated by substitution with strongly electron-attracting groups such as NO<sub>2<\/sub>, and<\/li>\n<li>when very strongly basic nucleophilic reagents are used.<\/li>\n<\/ol>\n<\/div>\n<div id=\"section_2\" class=\"mt-section\">\n<h3 class=\"editable\">Addition-Elimination Mechanism of Nucleophilic Substitution of Aryl Halides<\/h3>\n<p>Although simple aryl halides are inert to the usual nucleophilic reagents, considerable activation is produced by strongly electron-attracting substituents in either the ortho or para positions, or both. For example, the displacement of chloride ion from 1-chloro-2,4-dinitrobenzene by dimethylamine occurs readily in ethanol solution at room temperature. Under the same conditions chlorobenzene completely fails to react; thus the activating influence of the two nitro groups amounts to a factor of at least 108:<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163510\/BPOCchapter14-6-6b-3.png\" alt=\"\" width=\"400px\" height=\"114px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163512\/BPOCchapter14-6-6b-4.png\" alt=\"\" width=\"205\" height=\"130\" \/><\/p>\n<p>A related reaction is that of 2,4-dinitrofluorobenzene with the amino groups of peptides and proteins, and this reaction provides a means for analysis of the N-terminal amino acids in polypeptide chains.<\/p>\n<p>In general, the reactions of activated aryl halides closely resemble the S<sub>N<\/sub>2-displacement reactions of aliphatic halides. The same nucleophilic reagents are effective (e.g., CH<sub>3<\/sub>O\u00af, HO\u00af, and RNH<sub>2<\/sub>); the reactions are second order overall (first order in halide and first order in nucleophile); and for a given halide the more nucleophilic the attacking reagent, the faster the reaction. However, there must be more than a subtle difference in mechanism because an aryl halide is unable, to pass through the same type of transition state as an alkyl halide in S<sub>N<\/sub>2 displacements.<\/p>\n<p>The generally accepted mechanism of nucleophilic aromatic substitution of aryl halides carrying activating groups involves two steps. The first step involves attack of the nucleophile Nuc\u00af on the carbon bearing the halogen substituent to form an intermediate (shown in the box). This intermediate is stabilized by resonance; in particular, the negative charge can be delocalized into the <em>ortho\/para<\/em> electron-withdrawing group (in this example, an <em>ortho<\/em> nitro group). The aromatic system is destroyed on forming the anion, and the carbon at the reaction site changes from planar (sp<sup>2<\/sup> bonds) to tetrahedral (sp<sup>3<\/sup> bonds).<\/p>\n<p>In the second step, loss of an anion, X\u00af or Nuc\u00af, regenerates an aromatic system, and, if X\u00af is lost, the overall reaction is nucleophilic displacement of X by Nuc.\u00a0 The most convenient resonance form has been used for the anion, to keep the mechanism simple.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-3137\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/11061428\/Nucleophilic-Aromatic-Substitution-Mechanism.png\" alt=\"Mechanisms for nucleophilic aromatic substitution, with Nuc- adding, then X- being eliminated\" width=\"743\" height=\"342\" \/><\/p>\n<p>In the case of a neutral nucleophilic reagent, HY, the reaction sequence would be the same except for the necessary adjustments in the charge of the intermediate, with a final acid-base step.<\/p>\n<p>&nbsp;<\/p>\n<p>Why is this reaction pathway generally unfavorable for simple aryl halides? If no electron-withdrawing group is present, the carbons in the ring alone cannot stabilize the minus charge enough for the reaction to occur.\u00a0 When strongly electron-attracting groups are located on the ring at the ortho-para positions, the intermediate anion is stabilized by delocalization of electrons from the ring carbons to more favorable locations on the substituent groups.<\/p>\n<p>As another example, consider the displacement of bromine by OCH<sub>3<\/sub> in the reaction of 4-bromonitrobenzene and methoxide ion:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163523\/BPOCchapter14-6-6b-91.png\" alt=\"\" width=\"326\" height=\"152\" \/><\/p>\n<p>The anionic intermediate formed by addition of methoxide ion to the aryl halide can be described by the valence-bond structures 5a-5d. Of these structures 5d is especially important because in it the charge is transferred from the ring carbons to the oxygen of the nitro substituent:<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163526\/BPOCchapter14-6-6b-10.png\" alt=\"\" width=\"400px\" height=\"135px\" \/><\/p>\n<p>Substituents in the meta positions have much less effect on the reactivity of an aryl halide because delocalization of electrons to the substituent is not possible. No formulas can be written analogous to 5c and 5d in which the negative charges are both on atoms next to positive nitrogen, <img decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163527\/BPOCchapter14-6-6b-11.png\" alt=\"\" width=\"100px\" height=\"45px\" \/> and <img decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163528\/BPOCchapter14-6-6b-12.png\" alt=\"\" width=\"100px\" height=\"41px\" \/><\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163530\/BPOCchapter14-6-6b-13.png\" alt=\"\" width=\"400px\" height=\"98px\" \/><\/p>\n<p>In a few instances, stable compounds resembling the postulated reaction intermediate have been isolated. One classic example is the complex 7 (isolated by J. Meisenheimer), which is the product of the reaction of either the methyl aryl ether 6 with potassium ethoxide, or the ethyl aryl ether 8 and potassium methoxide:<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163532\/BPOCchapter14-6-6b-14.png\" alt=\"\" width=\"500px\" height=\"133px\" \/><\/p>\n<\/div>\n<div id=\"section_3\" class=\"mt-section\">\n<h3 class=\"editable\">Exercises<\/h3>\n<div id=\"s61721\" class=\"mt-include\">\n<div id=\"section_26\" class=\"mt-section\">\n<h4 id=\"Questions-61721\">Questions<\/h4>\n<p><strong>Q16.7.1<\/strong><\/p>\n<p>Propose a mechanism for the following reaction:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163535\/16-7-1qu.png\" alt=\"\" width=\"596\" height=\"158\" \/><\/p>\n<\/div>\n<div id=\"section_27\" class=\"mt-section\">\n<h4 id=\"Solutions-61721\">Solutions<\/h4>\n<p><strong>S16.7.1<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/26163539\/16.7.png\" alt=\"\" width=\"578\" height=\"441\" \/><\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_4\" class=\"mt-section\">\n<h3>Khan academy video<\/h3>\n<p><iframe loading=\"lazy\" id=\"oembed-1\" title=\"Nucleophilic aromatic substitution I | Aromatic Compounds | Organic chemistry | Khan Academy\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/6xy02bQS2Zg?feature=oembed&#38;rel=0\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-2873 size-thumbnail\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/07184802\/frame-23-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/><\/p>\n<h3 class=\"editable\">Contributors<\/h3>\n<ul>\n<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\n<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\n<li>William Reusch, Professor Emeritus (<a class=\"external\" title=\"http:\/\/www.msu.edu\/\" href=\"http:\/\/www.msu.edu\/\" target=\"_blank\" rel=\"external nofollow noopener\">Michigan State U.<\/a>), <a class=\"external\" title=\"Template:ContribReusch\" href=\"https:\/\/www2.chemistry.msu.edu\/faculty\/reusch\/VirtTxtJml\/intro1.htm\" target=\"_blank\" rel=\"external nofollow noopener\">Virtual Textbook of\u00a0Organic\u00a0Chemistry<\/a><\/li>\n<\/ul>\n<ul>\n<li><span class=\"person_name\">John D. Robert <\/span>and <span class=\"person_name\">Marjorie C.<\/span> <span class=\"person_name\">Caserio <\/span>(1977) <em>Basic Principles of Organic Chemistry, second edition.<\/em> W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, &#8220;You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format.&#8221;<\/li>\n<\/ul>\n<\/div>\n<\/section>\n<\/article>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-634\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>16.7: Nucleophilic Aromatic Substitution. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl FCIC; Prof. Steven Farmer; William Reusch, professor Emeritus; John D. Robert and Marjorie C. Caserio. <strong>Provided by<\/strong>: Athabasca University; Sonoma State University, Michigan State U. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_16%3A_Chemistry_of_Benzene_-_Electrophilic_Aromatic_Substitution\/16.07_Nucleophilic_Aromatic_Substitution\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_16%3A_Chemistry_of_Benzene_-_Electrophilic_Aromatic_Substitution\/16.07_Nucleophilic_Aromatic_Substitution<\/a>. <strong>Project<\/strong>: Chemistry LibreTexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":311,"menu_order":1,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"16.7: Nucleophilic Aromatic Substitution\",\"author\":\"Dr. Dietmar Kennepohl FCIC; Prof. Steven Farmer; William Reusch, professor Emeritus; John D. Robert and Marjorie C. 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