{"id":1474,"date":"2011-04-12T07:13:02","date_gmt":"2011-04-12T12:13:02","guid":{"rendered":"https:\/\/www.masterorganicchemistry.com\/?p=1474"},"modified":"2026-05-02T09:11:02","modified_gmt":"2026-05-02T14:11:02","slug":"what-makes-a-good-leaving-group","status":"publish","type":"post","link":"https:\/\/www.masterorganicchemistry.com\/2011\/04\/12\/what-makes-a-good-leaving-group\/","title":{"rendered":"What Makes A Good Leaving Group?"},"content":{"rendered":"<p><strong>Good Leaving Groups Are Weak Bases<\/strong><\/p>\n<ul>\n<li>A\u00a0<strong>leaving group<\/strong> <span style=\"color: #993366;\"><em>(a.k.a. &#8220;nucleofuge&#8221;)<\/em><\/span> is the new Lewis base that is generated in various substitution and elimination reactions when a new bond is formed to carbon.<\/li>\n<li>Just as acid-base reactions favor reactions where a stronger acid plus a stronger base results in a weaker acid and a weaker base, substitution and elimination reactions tend to favor reactions where the <strong>leaving group is a weaker base than the nucleophile<\/strong> <span style=\"color: #993366;\"><em>(or base, in the case of elimination reactions)<\/em><\/span><\/li>\n<li>Using pK<sub>a<\/sub> values it is possible to make good predictions as to whether various substitution or elimination reactions are favorable. Good leaving groups tend to be <strong>weak bases<\/strong>, i.e. the conjugate bases of strong acids (I<sup>&#8211;<\/sup>, Br<sup>&#8211;<\/sup>, Cl<sup>&#8211;<\/sup>, TsO<sup>&#8211;<\/sup>, H<sub>2<\/sub>O)<\/li>\n<li>Poor leaving groups (which tend to be strong bases) can be made into better leaving groups through addition of a strong acid (or a Lewis acid). <span style=\"color: #993366;\"><em>For example, alcohols can be converted into alkyl chlorides through addition of HCl.\u00a0<\/em><\/span><\/li>\n<li>Although the relative basicity of the nucleophile\/leaving group is a good guide, a prominent exception is fluoride (F-) which is a weak base but tends not to act as a leaving group due to the extremely strong C-F bond (about 130 kcal\/mol).<\/li>\n<li>When the basicity of the nucleophile and leaving group are comparable (i.e. within about 5-10 pK<sub>a<\/sub> units), an equilibrium may be established.<\/li>\n<\/ul>\n<p><img fetchpriority=\"high\" decoding=\"async\" class=\"alignnone wp-image-31511\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/0-Summary-What-Makes-A-Good-Leaving-Group-Good-Leaving-Groups-Are-Weak-Bases.gif\" alt=\"Summary-What Makes A Good Leaving Group - Good Leaving Groups Are Weak Bases\" width=\"630\" height=\"601\" \/><\/a><\/p>\n<p><strong>Table of Contents<\/strong><\/p>\n<ol>\n<li><a href=\"#one\">What Is A Leaving Group?<\/a><\/li>\n<li><a href=\"#two\">The Principle of Acid-Base Mediocrity, Revisited<\/a><\/li>\n<li><a href=\"#three\">Using a pKa Table To Evaluate Leaving Group Ability<\/a><\/li>\n<li><a href=\"#four\">The Conjugate Acid Is A Better Leaving Group<\/a><\/li>\n<li><a href=\"#five\">The Conjugate Base Is A <em>Worse<\/em> Leaving Group<\/a><\/li>\n<li><a href=\"#six\">Exceptions &#8211; Fluorine<\/a><\/li>\n<li><a href=\"#seven\">The Best Leaving Group of All (N2)<\/a><\/li>\n<li><a href=\"#eight\">Summary<\/a><\/li>\n<li><a href=\"#notes\">Notes<\/a><\/li>\n<li><a href=\"#quiz\">Quiz Yourself!<\/a><\/li>\n<li><a href=\"#references\">(Advanced) References and Further Reading<\/a><\/li>\n<\/ol>\n<hr \/>\n<h2><a id=\"one\"><\/a>1. A Leaving Group Is Just A Nucleophile Going In Reverse<\/h2>\n<p>Many reactions that involve <strong>nucleophiles<\/strong> and\u00a0<strong>bases<\/strong> result in the formation of a\u00a0<strong>leaving group\u00a0<\/strong>(also called a &#8220;<a href=\"https:\/\/goldbook.iupac.org\/terms\/view\/N04246\">nucleofuge<\/a>&#8220;).<\/p>\n<p>So what is a leaving group, anyway?<\/p>\n<p>Well, a <strong>leaving group<\/strong> is just a <strong>nucleophile<\/strong> acting in <strong>reverse<\/strong>.<\/p>\n<p>That is, whereas a <strong>nucleophile<\/strong> is the Lewis base that <strong>forms<\/strong> a new bond with a carbon, the<strong> leaving group<\/strong> is the Lewis base that results after <strong>breaking<\/strong> a bond with the carbon.<\/p>\n<p>Here is an example of a reaction that produces a leaving group.\u00a0 This is a nucleophilic substitution reaction &#8211; specifically a nucleophilic substitution reaction at an alkyl carbon with with a bimolecular rate-determining step (SN2).<\/p>\n<p><img decoding=\"async\" class=\"alignnone wp-image-31467\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/1-Example-of-a-nucleophilic-substitution-reaction-with-four-components-substrate-nucleophile-product-and-leaving-group.gif\" alt=\"Example of a nucleophilic substitution reaction with four components - substrate nucleophile product and leaving group\" width=\"640\" height=\"207\" \/><\/a><\/p>\n<p>Note that this reaction has <strong>four<\/strong> components.<\/p>\n<ul>\n<li>A <strong>substrate <\/strong>(an alkyl halide in this case, which will be acting as an electrophile)<\/li>\n<li>A\u00a0<strong>nucleophile<\/strong> (the CH<sub>3<\/sub>CH<sub>2<\/sub>O(-) ion)<\/li>\n<li>The\u00a0<strong>product<\/strong> (the ether)<\/li>\n<li>The <strong>leaving group<\/strong> (the chloride ion, Cl(-)\u00a0 )<\/li>\n<\/ul>\n<p>A C-O bond is formed, and a C-Cl bond is broken.<\/p>\n<p>To see a few more examples of reactions that result in leaving groups we will cover below, <a href=\"\" class=\"custom-tooltip\" data-image=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-1-Various-Examples-of-reactions-with-leaving-groups-including-nucleophilic-substitution-and-elimination.gif\" data-link=\"\" data-title=\"\" data-text=\"\"> hover here for a pop-up image <\/a> or click on this <a href=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-1-Various-Examples-of-reactions-with-leaving-groups-including-nucleophilic-substitution-and-elimination.gif\">link<\/a>.<\/p>\n<p>There is nothing stopping us from taking the reaction drawn above and flipping it around to give a reaction that goes in the opposite reaction. So let&#8217;s draw that out:<\/p>\n<p><img decoding=\"async\" class=\"alignnone wp-image-31468\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/2-Reversing-the-direction-on-a-nucleophiic-substitution-reaction-still-gives-same-four-components-substrate-nucleophile-product-and-leaving-group.gif\" alt=\"Reversing the direction on a nucleophiic substitution reaction still gives same four components - substrate nucleophile product and leaving group\" width=\"640\" height=\"226\" \/><\/a><\/p>\n<p>Note how in this drawing, the Cl(-) is the <strong>nucleophile<\/strong> and the RO(-) is the<strong> leaving group<\/strong>.<\/p>\n<p>Note that I&#8217;m <strong>not<\/strong> saying that these two reactions are equally <strong>likely<\/strong>.\u00a0 Just because we can\u00a0<strong>draw<\/strong> these two reactions does <strong>not<\/strong> mean that they are <strong>equally<\/strong> favored in a reaction vessel.<\/p>\n<p>However, it\u00a0<em>is<\/em> true that, <em>as drawn<\/em>, both of these reactions are nucleophilic substitution reactions, because we are forming and breaking a bond on the same carbon.<\/p>\n<p>That being said: which reaction do you think is more favored?<\/p>\n<p>In other words, if we ran the experiments, which reaction would you <strong>predict<\/strong> to proceed to completion?<\/p>\n<div class=\"wq-quiz-wrapper\" data-id=\"34761\"><style type=\"text\/css\" id=\"wq-flip-custom-css\">.wq-quiz-wrapper[data-id=\"34761\"] {\n--wq-question-width: 100%;\n--wq-question-color: #009cff;\n--wq-question-height: auto;\n--wq-font-color: #444;\n}\n\n\t\t\t.wq-quiz-wrapper[data-id=\"34761\"] {\n\t\t\t\t--wq-question-width: 600px;\n\t\t\t}\n\n\t\t\t@media screen and (max-width: 600px) {\n\t\t\t\t.wq-quiz-wrapper[data-id=\"34761\"] .wq_singleQuestionWrapper { width:100% !important; height:auto !important; }\n\t\t\t}\n\t\t<\/style><!-- wp quiz -->\n<div id=\"wp-quiz-34761\" class=\"wq_quizCtr single flip_quiz wq-quiz wq-quiz-34761 wq-quiz-flip wq-layout-single wq-skin-traditional wq-should-show-correct-answer\" data-quiz-id=\"34761\">\n<div class=\"wq-questions wq_questionsCtr\">\n\t<div class=\"wq-question wq_singleQuestionWrapper wq-question-9zq2n\" data-id=\"9zq2n\">\n\n\t\n\t<div class=\"item_top\">\n\t\t<div class=\"title_container\">\n\t\t\t<div class=\"wq_questionTextCtr\">\n\t\t\t\t<h4 class=\"wq-question-title\"><\/h4>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\t<div class=\"card \">\n\t\t<div class=\"front\" >\n\t\n\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-images\/2377-Front.gif\" \/>\n\t\t\n\t\t\n\t\n\t\n\t\t\t<span class=\"top-desc\">Click to Flip<\/span>\n\t<\/div>\n\t\t<div class=\"back\" >\n\t\n\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-images\/2377-Reverse.gif\" \/>\n\t\t\n\t\t\n\t\n\t<\/div>\n\t<\/div>\n\n\t\n<\/div>\n<\/div>\n<\/div>\n<!-- \/\/ wp quiz-->\n<\/div><!-- End .wq-quiz-wrapper -->\n<p>Congratulations if you said, the top one.<\/p>\n<p><strong>Why?<\/strong><\/p>\n<h2><a id=\"two\"><\/a>2. Are Substitution and Elimination Reactions Just Fancy Extensions of Acid Base Reactions?<\/h2>\n<p>Let&#8217;s change one little thing about that reaction above, and see if this looks a bit more familiar.<\/p>\n<p>In the acid-base reaction between H-Cl and NaOCH<sub>2<\/sub>CH<sub>3<\/sub> to give CH<sub>3<\/sub>CH<sub>2<\/sub>OH and NaCl, which direction would be more favored?<\/p>\n<p>You might recall the <strong>Principle of Acid-Base Mediocrity<\/strong>: Stronger acid plus stronger base gives weaker acid and weaker base. (<em>See post: <a href=\"https:\/\/www.masterorganicchemistry.com\/2010\/09\/29\/how-to-use-a-pka-table\/\">How To Use a pK<sub>a<\/sub> Table<\/a><\/em>).<\/p>\n<p>So the favored direction of this acid-base reaction is formation of the <strong>weaker<\/strong> <strong>base<\/strong> (Cl -)<\/p>\n<p>Just as acid-base reactions tend to be favored when we go from a stronger base to a weaker base, substitution and elimination reactions <strong>also<\/strong> tend to be favored when the leaving group is a weaker base than the nucleophile (or base).<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31469\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/4-stronger-acid-and-stronger-base-gives-weaker-acid-and-weaker-base-also-substitution-reactions-favor-formation-of-the-weaker-base.gif\" alt=\"stronger acid and stronger base gives weaker acid and weaker base - also substitution reactions favor formation of the weaker base\" width=\"640\" height=\"384\" \/><\/a><\/p>\n<p>In fact, the four components of an acid base reaction map pretty well onto the four components of the nucleophilic substitution reactions, above.<\/p>\n<ul>\n<li>Acid\u00a0 \u2192 substrate<\/li>\n<li>Base \u2192 nucleophile<\/li>\n<li>Conjugate acid \u2192 product<\/li>\n<li>Conjugate base \u2192 leaving group<\/li>\n<\/ul>\n<p>The substitution above also favors formation of the weaker base (Cl-) from the stronger base (CH<sub>3<\/sub>CH<sub>2<\/sub>O-)<\/p>\n<p>For that matter, so does this elimination reaction<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31470\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/5-in-elimination-reactions-e2-the-favored-direction-is-one-where-the-stronger-base-gives-rise-to-a-weaker-base-leaving-group.gif\" alt=\"-in elimination reactions e2 the favored direction is one where the stronger base gives rise to a weaker base leaving group\" width=\"640\" height=\"212\" \/><\/a><\/p>\n<p>If the leaving group and base are flipped, the reaction is much less favored. To see this &#8220;flipped&#8221; reaction, <a href=\"\" class=\"custom-tooltip\" data-image=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-2-Example-of-a-failed-elimination-reaction-E2-where-the-base-is-a-weaker-base-than-the-leaving-group.gif\" data-link=\"\" data-title=\"\" data-text=\"\"> hover here for a pop-up image <\/a> or click on this <a href=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-2-Example-of-a-failed-elimination-reaction-E2-where-the-base-is-a-weaker-base-than-the-leaving-group.gif\">link<\/a>.<br \/>\nThis is also the case with the loss of leaving group in this SN1 reaction:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31471\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/6-in-sn1-reactions-the-more-favored-sn1-reaction-will-be-one-where-there-is-a-weaker-base-as-a-leaving-group.gif\" alt=\"in sn1 reactions the more favored sn1 reaction will be one where there is a weaker base as a leaving group\" width=\"639\" height=\"277\" \/><\/a><\/p>\n<p>There are many more examples, like these nucleophilic acyl substitution reactions that you will see in Org 2. To see an example,\u00a0 <a href=\"\" class=\"custom-tooltip\" data-image=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-3-Example-of-a-favorable-nucleophilic-acyl-substitution-reaction-where-the-leaving-group-is-a-weaker-base-.gif\" data-link=\"\" data-title=\"\" data-text=\"\"> hover here for a pop-up image <\/a> or click on this <a href=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/Supp-3-Example-of-a-favorable-nucleophilic-acyl-substitution-reaction-where-the-leaving-group-is-a-weaker-base-.gif\">link<\/a>.<br \/>\nGenerally speaking, the\u00a0<strong>weaker the base,\u00a0<\/strong>the <strong>better the leaving group<\/strong>.<\/p>\n<p>We can reverse this and also say that\u00a0<strong>the stronger the base, the worse the leaving group<\/strong>.<\/p>\n<h2><a id=\"three\"><\/a>3. Using a pK<sub>a<\/sub> Table To Determine Leaving Group Ability<\/h2>\n<p>If base strength determines leaving group ability, then a <strong>pK<sub>a<\/sub> table<\/strong> should be a pretty good guide to determining leaving group ability.<\/p>\n<p>In a previous post (<span style=\"color: #993366;\"><em>See: <\/em><\/span><a href=\"https:\/\/www.masterorganicchemistry.com\/2010\/09\/29\/how-to-use-a-pka-table\/\"><span style=\"color: #993366;\"><em>How To Use a pK<sub>a<\/sub> Table<\/em><\/span><\/a>) we went through this in considerable detail.<\/p>\n<p>Recall that the <strong>stronger<\/strong> the <strong>acid<\/strong>, the <strong>weaker<\/strong> the <strong>conjugate base<\/strong>.That means that the top portion of a pK<sub>a<\/sub> table should be an excellent guide to the best leaving groups. The conjugate bases of strong acids, such as I(-), Br(-), Cl(-), HOSO<sub>3<\/sub>(-), TsO(-), H<sub>2<\/sub>O, and others are <strong>weak bases<\/strong> and <strong>great<\/strong> leaving groups.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31472\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/7-example-of-a-pka-table-for-determinination-of-good-leaving-groups-the-conjugate-bases-of-strong-acids-are-good-leaving-groups-such-as-chloride-bromide-iodide-and-tosylate.gif\" alt=\"example of a pka table for determinination of good leaving groups - the conjugate bases of strong acids are good leaving groups such as chloride bromide iodide and tosylate\" width=\"640\" height=\"516\" \/><\/a><\/p>\n<p>Here is another example of a favorable reaction, where the nucleophile is more basic than the leaving group:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31473\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/8-example-of-a-favorable-substitution-reaction-is-one-where-nucleophile-is-a-stronger-base-than-the-leaving-group-for-example-thiolate-and-bromide.gif\" alt=\"example of a favorable substitution reaction is one where nucleophile is a stronger base than the leaving group for example thiolate and bromide\" width=\"639\" height=\"332\" \/><\/a><\/p>\n<p><span style=\"color: #993366;\"><em>Note that pK<sub>a<\/sub>H is shorthand for &#8220;the pK<sub>a<\/sub> of the conjugate acid&#8221;.\u00a0<\/em><\/span><\/p>\n<p>On the other hand, the bottom part of a pK<sub>a<\/sub> table should be a guide to the <strong>worst<\/strong> leaving groups &#8211; the conjugate bases of weak acids, such as H(-) and H<sub>3<\/sub>C(-) are extremely strong bases.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31477\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/9-example-of-an-unfavorable-substitution-reaction-is-one-where-a-weaker-nucleophile-results-in-a-leaving-group-which-is-a-stronger-base.gif\" alt=\"example of an unfavorable substitution reaction is one where a weaker nucleophile results in a leaving group which is a stronger base\" width=\"639\" height=\"316\" \/><\/a><\/p>\n<p>This is why we never see alkyl groups or hydride ions as leaving groups.<\/p>\n<p>I should stress that comparing the basicity of the nucleophile and leaving group is a good place to start, but is <strong>not the only variable<\/strong>. <span style=\"color: #993366;\"><em>The relative strength of the bonds being broken and formed is also a factor, which comes up most prominently with fluorine (see <a href=\"#six\">Exceptions<\/a>, below).\u00a0<\/em><\/span><\/p>\n<p>When the nucleophile and leaving group are of <strong>comparable<\/strong> basicity (i.e. within about 5-10 pK<sub>a<\/sub> units), substitution reactions are potentially <strong>reversible<\/strong>, and the equilibrium can be driven to one side or the other depending on what conditions we choose. [<a href=\"#noteone\"><span style=\"color: #993366;\">Note 1<\/span><\/a>]<\/p>\n<p>Also, it&#8217;s important to remember that acidity and basicity (i.e. pK<sub>a<\/sub>) are measured by the position of an <strong>equilibrium<\/strong> (think &#8220;differences in energy&#8221;) whereas nucleophilicity is measured by\u00a0<strong>reaction rates\u00a0<\/strong>since many reactions of nucleophiles are irreversible. So although the correlation is very good, it isn&#8217;t perfect.<\/p>\n<p>Also, be on the lookout for acid-base reactions. A good rule of thumb is that acid-base reactions are fast, relative to substitution and elimination reactions (<span style=\"color: #993366;\"><em>see post: <a style=\"color: #993366;\" href=\"https:\/\/www.masterorganicchemistry.com\/2012\/05\/21\/acid-base-reactions-are-fast\">Acid-Base Reactions are Fast<\/a><\/em><\/span>)<\/p>\n<h2><a id=\"four\"><\/a>4. The Conjugate Acid Is A Better Leaving Group<\/h2>\n<p>Hydroxide ions are <strong>poor<\/strong> leaving groups because they are strong bases.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31481\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/10-the-hydroxide-ion-is-a-poor-leaving-group-in-substitution-reactions-because-it-is-a-strong-base-1.gif\" alt=\"the hydroxide ion is a poor leaving group in substitution reactions because it is a strong base\" width=\"639\" height=\"163\" \/><\/a><\/p>\n<p>We might ask ourselves: is there some way to <strong>modify<\/strong> the OH so that when the C-O bond breaks, the leaving group is a <strong>weaker<\/strong> base? Then it would be more favorable.<\/p>\n<p>Yes, there is a simple and effective way to make OH a better leaving group.<\/p>\n<p>If we just add strong <strong>acid<\/strong>, then we make the conjugate acid of R-OH, which is R-OH<sub>2<\/sub>(+).<\/p>\n<p>Now, if Cl(-) attacks, our leaving group will be the weak base H<sub>2<\/sub>O. This is a factor of 10<sup>14<\/sup> less basic than HO(-).<\/p>\n<p>So in the presence of acid, this reaction becomes <em>much<\/em> more favorable. The <strong>conjugate acid<\/strong> is a\u00a0<strong>better<\/strong> leaving group! <span style=\"color: #993366;\">(<em>This is one of the major applications of <strong>acid<\/strong>\u00a0<strong>catalysis<\/strong> in organic chemistry.)<\/em><\/span><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31475\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/11-the-conjugate-acid-is-a-better-leaving-group-because-it-is-a-weaker-base-protonation-of-alcohols-results-in-formation-of-H2O-which-is-a-much-better-leaving-group.gif\" alt=\"the conjugate acid is a better leaving group because it is a weaker base - protonation of alcohols results in formation of H2O which is a much better leaving group\" width=\"641\" height=\"340\" \/><\/a><\/p>\n<p>In the chapter on alcohols, we&#8217;ll see that many substitution and elimination reactions of alcohols\u00a0<strong>require<\/strong> acid in order for the OH group to leave.<\/p>\n<p><strong>Lewis acids<\/strong> can be used for this purpose as well. [<a href=\"#notetwo\"><span style=\"color: #993366;\">Note 2<\/span><\/a>] We will see many examples of this in the chapter on electrophilic aromatic substitution (<em><span style=\"color: #993366;\">e.g. in the Friedel-Crafts reaction where Lewis acids like AlCl<sub>3<\/sub> are used to make Cl into better leaving groups (See post: <a style=\"color: #993366;\" href=\"https:\/\/www.masterorganicchemistry.com\/2018\/05\/17\/friedel-crafts-alkylation-acylation\/\">The Friedel Crafts Alkylation and Acylation Reactions<\/a><\/span>).<\/em><\/p>\n<p>Other ways to modify -OH to make it into a better leaving group includes transforming them into sulfonates, which are much weaker bases than HO(-).\u00a0 \u00a0[<em>See post: <a href=\"https:\/\/www.masterorganicchemistry.com\/2015\/03\/10\/tosylates-and-mesylates\/\">Tosylates and Mesylates<\/a><\/em>] [<a href=\"#notethree\"><span style=\"color: #993366;\">Note 3<\/span><\/a>]<\/p>\n<h2><a id=\"five\"><\/a>5. The Conjugate Base Is A Worse Leaving Group<\/h2>\n<p>It&#8217;s true that the conjugate acid is a better leaving group. It&#8217;s also worth noting that the <strong>conjugate<\/strong>\u00a0<strong>base<\/strong> is a <strong>worse<\/strong> leaving group.<\/p>\n<p>Also, acid-base reactions are <strong>faster<\/strong>, generally speaking, than substitution and elimination reactions.<\/p>\n<p>If a strong base is added to a species with an acidic proton, the acid-base reaction will occur first. This will give the conjugate base, which will possess a much worse leaving group than the neutral species.<\/p>\n<p>Here&#8217;s an example. You might think the leaving group here is HO(-) . It&#8217;s not. The leaving group would have to be O(2-)<\/p>\n<div class=\"wq-quiz-wrapper\" data-id=\"34762\"><style type=\"text\/css\" id=\"wq-flip-custom-css\">.wq-quiz-wrapper[data-id=\"34762\"] {\n--wq-question-width: 100%;\n--wq-question-color: #009cff;\n--wq-question-height: auto;\n--wq-font-color: #444;\n}\n\n\t\t\t.wq-quiz-wrapper[data-id=\"34762\"] {\n\t\t\t\t--wq-question-width: 600px;\n\t\t\t}\n\n\t\t\t@media screen and (max-width: 600px) {\n\t\t\t\t.wq-quiz-wrapper[data-id=\"34762\"] .wq_singleQuestionWrapper { width:100% !important; height:auto !important; }\n\t\t\t}\n\t\t<\/style><!-- wp quiz -->\n<div id=\"wp-quiz-34762\" class=\"wq_quizCtr single flip_quiz wq-quiz wq-quiz-34762 wq-quiz-flip wq-layout-single wq-skin-traditional wq-should-show-correct-answer\" data-quiz-id=\"34762\">\n<div class=\"wq-questions wq_questionsCtr\">\n\t<div class=\"wq-question wq_singleQuestionWrapper wq-question-vh46q\" data-id=\"vh46q\">\n\n\t\n\t<div class=\"item_top\">\n\t\t<div class=\"title_container\">\n\t\t\t<div class=\"wq_questionTextCtr\">\n\t\t\t\t<h4 class=\"wq-question-title\"><\/h4>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\t<div class=\"card \">\n\t\t<div class=\"front\" >\n\t\n\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-images\/2378-Front.gif\" \/>\n\t\t\n\t\t\n\t\n\t\n\t\t\t<span class=\"top-desc\">Click to Flip<\/span>\n\t<\/div>\n\t\t<div class=\"back\" >\n\t\n\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-images\/2378-Reverse.gif\" \/>\n\t\t\n\t\t\n\t\n\t<\/div>\n\t<\/div>\n\n\t\n<\/div>\n<\/div>\n<\/div>\n<!-- \/\/ wp quiz-->\n<\/div><!-- End .wq-quiz-wrapper -->\n<p>That&#8217;s a much worse leaving group.<\/p>\n<p>Along the same lines, don&#8217;t forget that carboxylic acids&#8230;. are acids!<\/p>\n<h2><a id=\"six\"><\/a>6. Exceptions<\/h2>\n<p>Is that all there is to it? Just apply the Principle of Acid-Base Mediocrity and we&#8217;re done with it?<\/p>\n<p>Not quite. It wouldn&#8217;t be organic chemistry if we didn&#8217;t mention some exceptions.<\/p>\n<p>One prominent exception is <strong>fluorine<\/strong>. Fluoride ion (F-) is a weak base (the pK<sub>a<\/sub> of HF is 3.8) , but generally a poor leaving group in substitution reactions. [<a href=\"#notefour\"><span style=\"color: #993366;\">Note 4<\/span><\/a>]<\/p>\n<p>One key reason is the strength of the C-F bond (about 130 kcal\/mol).<\/p>\n<p>Up to this point, we&#8217;ve only really considered the stability of the leaving group relative to the nucleophile. But the stability of the\u00a0<strong>product\u00a0<\/strong>is important as well.<\/p>\n<p>Since the C-F bond is so strong, the reverse reaction (breaking the C-F bond, giving F(-) as a leaving group) would have an extremely high activation energy, making it very unfavorable.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31476\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2022\/10\/13-fluoride-ion-is-a-poor-leaving-group-since-the-C-F-bond-is-extremely-strong-at-about-100-kcal-per-mole.gif\" alt=\"fluoride ion is a poor leaving group since the C-F bond is extremely strong at about 100 kcal per mole\" width=\"640\" height=\"489\" \/><\/a><\/p>\n<p>So the key variable is not just the relative stability of the nucleophile versus the base, but also the strength of the bond that is forming and breaking.<\/p>\n<p><span style=\"color: #993366;\"><em>Another example of a reaction where fluorine is a leaving group is nucleophilic aromatic substitution, but the breaking of C-F is not the rate-determining step in this case (See Post: <a href=\"https:\/\/www.masterorganicchemistry.com\/2018\/08\/20\/nucleophilic-aromatic-substitution-nas\/\">Nucleophilic Aromatic Substitution<\/a>)<\/em><\/span><\/p>\n<h2><a id=\"seven\"><\/a>7. The Best Leaving Group Of All<\/h2>\n<p>Probably the best leaving group of all is dinitrogen (N<sub>2<\/sub>). Not only is nitrogen exceptionally stable &#8211; after all, it&#8217;s 79% of our atmosphere and is essentially inert &#8211; it is a gas, which means that any organic reaction where N<sub>2<\/sub> is displaced will result in it bubbling out of solution, rendering the reaction essentially irreversible<span style=\"color: #993366;\"><em> (sometimes explosively so!).\u00a0<\/em><\/span><\/p>\n<p>Amines (R-NH<sub>2<\/sub>) can be converted into diazonium salts R-N\u2261N(+) with nitrous acid (HONO) through a process called &#8220;diazotization&#8221;.<\/p>\n<p>However dinitrogen is such a good leaving group that sp<sup>3<\/sup>-hybridized carbon atoms bonded to N<sub>2<\/sub> are exceptionally unstable and tend not to stick around long enough to participate in reactions with nucleophiles; once formed, the N<sub>2<\/sub> just leaves, resulting in carbocations (and not uncommonly, shattered glassware) in its wake.<\/p>\n<p>Diazonium salts of sp<sup>2<\/sup>-hybridized carbons are considerably more stable and used in organic reactions; for more information, see this post (<em>See post: <a href=\"https:\/\/www.masterorganicchemistry.com\/2018\/12\/03\/reactions-of-diazonium-salts-sandmeyer-and-related-reactions\/\">Reactions of Diazonium Salts<\/a><\/em>)<\/p>\n<h2><a id=\"eight\"><\/a>8. Summary<\/h2>\n<p>Let&#8217;s review.<\/p>\n<ul>\n<li>Leaving groups are nucleophiles acting in reverse &#8211; i.e. they are Lewis bases formed from the breakage of a bond to carbon.<\/li>\n<li>Just as acid-base reactions are favored in the direction which results in a weaker base being formed from a stronger base, reactions involving leaving groups also tend to be favored in the direction which gives the weaker base.<\/li>\n<li>The conjugate bases of strong acids (e.g. I-, Br-, Cl-, TsO-, H<sub>2<\/sub>O) are good leaving groups.<\/li>\n<li>The conjugate base of weak acids (H-, H<sub>3<\/sub>C(-), alkyl anions) are poor leaving groups.<\/li>\n<li>The <strong>conjugate acid<\/strong> is a <strong>better<\/strong> leaving group. One common example is with alcohols, which can undergo substitution and elimination reactions after the HO is protonated.<\/li>\n<li>The <strong>conjugate base<\/strong> is a <strong>worse<\/strong> leaving group. A good rule of thumb is to do<strong> acid-base reactions first<\/strong>.<\/li>\n<li>Fluoride ion (F-) is a weak base, but a poor leaving group due to the strength of the C-F bond.<\/li>\n<\/ul>\n<p><strong>If you&#8217;re not sure where a reaction is going to happen on a molecule, look for a good leaving group<\/strong>. That&#8217;s usually where the action is!<\/p>\n<hr \/>\n<h2><strong><a id=\"notes\"><\/a>Notes<\/strong><\/h2>\n<div class=\"related-articles\"><p><strong>Related Articles<\/strong><\/p><ul><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2010\/09\/29\/how-to-use-a-pka-table\/\" class=\"\"><span>How to Use a pKa Table<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2012\/06\/18\/what-makes-a-good-nucleophile\/\" class=\"\"><span>What Makes A Good Nucleophile?<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2012\/07\/04\/the-sn2-mechanism\/\" class=\"\"><span>The SN2 Mechanism<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2012\/09\/27\/the-e2-mechanism\/\" class=\"\"><span>The E2 Mechanism<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2011\/05\/06\/nucleophilic-acyl-substitution\/\" class=\"\"><span>Nucleophilic Acyl Substitution (With Negatively Charged Nucleophiles)<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2018\/08\/20\/nucleophilic-aromatic-substitution-nas\/\" class=\"\"><span>Nucleophilic Aromatic Substitution (NAS)<\/span><\/a><\/li><li><a href=\"https:\/\/www.masterorganicchemistry.com\/2011\/12\/03\/reagent-friday-thionyl-chloride-socl2\/\" class=\"\"><span>Thionyl Chloride (SOCl2)<\/span><\/a><\/li><\/ul><\/div>\n<p><strong><a id=\"noteone\"><\/a>Note 1.\u00a0<\/strong>When the basicity of the nucleophile and the leaving group are comparable (i.e. within about 5-10 pK<sub>a<\/sub> units) then the reaction has the potential to be <strong>reversible<\/strong>.<em> (<span style=\"color: #993366;\">For more information on this 5-10 pK<sub>a<\/sub> unit number, see <a style=\"color: #993366;\" href=\"https:\/\/www.masterorganicchemistry.com\/2012\/05\/17\/a-handy-rule-of-thumb-for-acid-base-reactions\/\">A Handy Rule of Thumb For Acid-Base Reactions<\/a>)<\/span><\/em><\/p>\n<p>In this case it is an equilibrium and the position of the equilibrium can be influenced by Le Chatelier&#8217;s principle. For example it is possible to make a reaction proceed from a weaker base to a stronger base by using a large excess of the nucleophile, or by removing the stronger base.<\/p>\n<p>One interesting example is based on different <strong>solubilities<\/strong>. The Finkelstein reaction is a way of making alkyl iodides from alkyl chlorides. There is not a tremendous difference between the leaving group ability of chloride ion or iodide ion. However, there is a significant difference between the <strong>solubility<\/strong> of NaCl (or NaBr) and NaI in <strong>acetone<\/strong>. NaI is soluble in acetone; NaCl is not. Therefore as NaCl is formed, it precipitates out of solution, driving the reaction to the right. Another example of Le Chatelier&#8217;s principle in action!<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-14452\" title=\" \" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2019\/12\/F1-example-of-the-finkelstein-reaction-of-alkyl-chlorides-with-sodium-iodide-leading-to-nacl-crashing-out-in-acetone-solution-driven-by-equilibrium.gif\" alt=\"F1-example-of-the-finkelstein-reaction-of-alkyl-chlorides-with-sodium-iodide-leading-to-nacl-crashing-out-in-acetone-solution-driven-by-equilibrium\" width=\"600\" height=\"266\" \/><\/p>\n<p><strong><a id=\"notetwo\"><\/a>Note 2<\/strong> &#8211; Lewis acids may also be used. With alkyl halides, sometimes silver salts such as AgNO<sub>3<\/sub> or AgBF<sub>4<\/sub> are used to assist with the loss of a Cl or Br group (<span style=\"color: #993366;\"><em>the counter-ion NO<sub>3<\/sub>(-) or BF<sub>4<\/sub>(-)is just a spectator here<\/em><\/span>).\u00a0 The Ag(+) coordinates with the Cl or Br, resulting in a much better leaving group (the silver halide salt).<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31512\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/F2-lewis-acids-make-halogens-better-leaving-groups-eg-silver-salts-with-alkyl-chlorides-or-bromides.gif\" alt=\"lewis acids make halogens better leaving groups eg silver salts with alkyl chlorides or bromides\" width=\"630\" height=\"373\" \/><\/a><\/p>\n<p>Other examples of Lewis acids serving to increase leaving-group ability are found in several reactions of aromatic compounds, such as the Friedel-Crafts acylation reaction, where a Lewis acid (e.g. AlCl<sub>3<\/sub>)\u00a0 assists in loss of Cl from an acid halide:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31513\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/F3-using-alcl3-as-a-lewis-acid-to-make-chloride-a-better-leaving-group.gif\" alt=\"using alcl3 as a lewis acid to make chloride a better leaving group\" width=\"639\" height=\"275\" \/><\/a><\/p>\n<p><strong><a id=\"notethree\"><\/a>Note 3<\/strong>&#8211; Alcohols can be converted into alkyl sulfonates through the use of reagents such as\u00a0<em>p<\/em>-toluenesulfonyl chloride (TsCl) or methanesulfonyl chloride (MsCl). Sulfonates are excellent leaving groups since the negative charge on oxygen can be delocalized through resonance. An even better leaving group than (-)OMs or (-)OTs\u00a0 is the trifluoromethylsulfonyl group (-)OSO<sub>2<\/sub>CF<sub>3<\/sub>\u00a0 &#8220;triflate&#8221; group, where the hydrogen atoms on OMs have been replaced with electron-withdrawing fluorines.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31514\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/F4-converting-alcohols-into-alkyl-sulfonates-which-are-excellent-leaving-groups-in-substitution-reactions.gif\" alt=\"converting alcohols into alkyl sulfonates which are excellent leaving groups in substitution reactions\" width=\"640\" height=\"394\" \/><\/a><\/p>\n<p><strong><a id=\"notefour\"><\/a>Note 4<\/strong> &#8211; Fluorine is a poor leaving group in nucleophilic substitution reactions, but can, in certain cases, be a leaving group in various elimination reactions. One example is the <a href=\"https:\/\/www.masterorganicchemistry.com\/2020\/02\/11\/e1cb-elimination-unimolecular-conjugate-base\/\">E1cb mechanism<\/a>, where the first step is formation of a conjugate base, followed by (rate-determining) elimination of a leaving group.<\/p>\n<p>Another example of fluorine as a leaving group is in the nucleophilic aromatic substitution reaction, where the electron-withdrawing\u00a0 F actually helps to make the carbon more electrophilic. Sanger&#8217;s reagent, which was used to determine the sequence of peptides in insulin, is a useful example of a reagent for promoting nucleophilic aromatic substitution that has fluoride leaving groups.<\/p>\n<p><strong><a id=\"notefive\"><\/a>Note 5<\/strong> &#8211;\u00a0It&#8217;s possible for a species to be <strong>both<\/strong> a good nucleophile and a good leaving group. Nucleophilicity is defined through the <strong>rate<\/strong> of reaction of a nucleophile with a given substrate. The carbon-iodine bond is fairly weak, however (about 50 kcal\/mol), and readily undergoes cleavage.<\/p>\n<p><strong><a id=\"notesix\"><\/a>Note 6 &#8211;\u00a0<\/strong>A more full pK<sub>a<\/sub> table.<\/p>\n<figure id=\"attachment_45783\" aria-describedby=\"caption-attachment-45783\" style=\"width: 640px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-45783\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/F6-pka-table-is-excellent-guide-to-leaving-group-ability-what-makes-a-good-leaving-group.gif\" alt=\"\" width=\"640\" height=\"1054\" \/><\/a><figcaption id=\"caption-attachment-45783\" class=\"wp-caption-text\">pka-table-is-excellent-guide-to-leaving-group-ability-what-makes-a-good-leaving-group<\/figcaption><\/figure>\n<p><strong><a id=\"noteseven\"><\/a>Note 7. <\/strong>My personal\u00a0vote for &#8220;best leaving group of all time&#8221; is found in this reaction.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-31515\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/2011\/04\/F5-the-best-leaving-group-of-all-is-helium.gif\" alt=\"the best leaving group of all is helium\" width=\"641\" height=\"178\" \/><\/a><\/p>\n<p>The researchers wanted to study the properties of the alkynyl cation, which is exceptionally unstable and short-lived. However, by putting a radioactive tritium atom on the terminal carbon, a small amount of beta-decay resulted in a helium atom, which promptly left, resulting in an alkynyl cation (which reacted with the solvent, benzene). Of course they didn&#8217;t wait around for 12 years to get to 50% completion :-) [<a href=\"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/ja00212a052\">Ref<\/a> &#8211;<em> J. Am. Chem. Soc. 1988, 110, 1298<\/em> ]<\/p>\n<hr \/>\n<h2><strong><a id=\"quiz\"><\/a>Quiz Yourself!<\/strong><\/h2>\n\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/2379-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <\/p>\n\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/3115-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <br \/>\n<\/p>\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/3116-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <br \/>\n<\/p>\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/3117-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <br \/>\n<\/p>\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/3118-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <br \/>\n<\/p>\n<p class=\"p1\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-26714\" src=\"https:\/\/www.masterorganicchemistry.com\/wp-content\/uploads\/quiz-previews\/3119-Front-Image-Only.png\" alt=\"\" width=\"640\" height=\"616\" \/><\/p>\n<p><a href=\"https:\/\/www.masterorganicchemistry.com\/moc-membership\/\"><strong>Become a\u00a0 MOC member<\/strong><\/a> to see the clickable quiz with answers on the back. <\/p>\n<hr \/>\n<h2><strong><a id=\"references\"><\/a>(Advanced) References and Further Reading<\/strong><\/h2>\n<ol>\n<li><strong>Generation and trapping of an alkynyl cation<\/strong><br \/>\nGiancarlo. Angelini, Michael. Hanack, Jan. Vermehren, and Maurizio. Speranza<br \/>\n<em>Journal of the American Chemical Society<\/em> <strong>1988<\/strong> 110 (4), 1298-1299<br \/>\n<strong>DOI<\/strong>: <a href=\"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/ja00212a052\">10.1021\/ja00212a052<\/a><\/li>\n<li><strong>The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in SN2 Reactions<\/strong><br \/>\nF. G. Bordwell and W. T. Brannen<br \/>\n<em>Journal of the American Chemical Society<\/em> <strong>1964<\/strong> 86 (21), 4645-4650<br \/>\n<strong>DOI<\/strong>: <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/ja01075a025\">10.1021\/ja01075a025<\/a><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Good Leaving Groups Are Weak Bases A\u00a0leaving group (a.k.a. &#8220;nucleofuge&#8221;) is the new Lewis base that is generated in various substitution and elimination reactions when <\/p>\n","protected":false},"author":1,"featured_media":31511,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1410],"tags":[164,176,586,298,353,201,226,243,503,502,271],"post_folder":[],"class_list":["post-1474","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-organic-reaction-primer","tag-acids","tag-bases","tag-conjugate-base","tag-curved-arrows","tag-electron-flow","tag-elimination","tag-leaving-groups","tag-nucleophiles","tag-nucleophilic-substitution","tag-sn1","tag-sn2"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>What makes a good leaving group? 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