{"id":2793,"date":"2018-06-21T13:26:53","date_gmt":"2018-06-21T13:26:53","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-alkylation-of-acetylide-anions\/"},"modified":"2018-08-06T15:33:12","modified_gmt":"2018-08-06T15:33:12","slug":"9-8-substitution-with-acetylides","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-substitution-with-acetylides\/","title":{"raw":"9.8. Substitution with acetylides","rendered":"9.8. Substitution with acetylides"},"content":{"raw":"<section class=\"mt-content-container\">\r\n<div id=\"exercise\" class=\"textbox learning-objectives\">\r\n<h3 class=\"boxtitle\">Objectives<\/h3>\r\nAfter completing this section, you should be able to\r\n<ol>\r\n \t<li>write an equation to describe the reaction of an acetylide ion with an alkyl halide.<\/li>\r\n \t<li>discuss the importance of the reaction between acetylide ions and alkyl halides as a method of extending a carbon chain.<\/li>\r\n \t<li>identify the alkyne (and hence the acetylide ion) and the alkyl halide needed to synthesize a given alkyne.<\/li>\r\n \t<li>determine whether or not the reaction of an acetylide ion with a given alkyl halide will result in substitution or elimination, and draw the structure of the product formed in either case.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<div>\r\n<div class=\"textbox tryit\">\r\n<h3 class=\"boxtitle\">Key Term<\/h3>\r\nMake certain that you can define, and use in context, the key term below.\r\n<ul>\r\n \t<li>alkylation<\/li>\r\n<\/ul>\r\n<\/div>\r\n<\/div>\r\n<div id=\"note\" class=\"textbox key-takeaways\">\r\n<h3 class=\"boxtitle\">Study Notes<\/h3>\r\nThe alkylation of acetylide ions is important in organic synthesis because it is a reaction in which a new carbon-carbon bond is formed; hence, it can be used when an organic chemist is trying to build a complicated molecule from much simpler starting materials. The alkyl halide used in this reaction must be primary. Thus, if you were asked for a suitable synthesis of 2,2-dimethyl-3-hexyne, you would choose to attack iodoethane with the anion of 3,3- dimethyl-1-butyne\r\n\r\n<img class=\"alignnone wp-image-4883\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/06153119\/AcetylideAlkylation11.png\" alt=\"\" width=\"639\" height=\"111\" \/>\r\n\r\nrather than to attack 2-iodo-2-methylpropane with the anion of 1-butyne.\r\n\r\n<img class=\"alignnone wp-image-4884\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/06153153\/AcetylideAlkylation21.png\" alt=\"\" width=\"550\" height=\"105\" \/>\r\n\r\n<\/div>\r\n<div class=\"mt-section\">\r\n<h3 class=\"editable\">Nucleophilic substitution reactions of acetylides<a title=\"Edit section\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(Smith)\/Chapter_11%3A_Alkynes\/11.11%3A_Reaction_of_Acetylide_Anions?action=edit&amp;sectionId=2\" rel=\"internal\"><span class=\"icon\"><img class=\"sectionedit\" src=\"http:\/\/a.mtstatic.com\/skins\/common\/icons\/icon-trans.gif?_=d2b40cf1:site_4334#fixme#fixme\" alt=\"Edit section\" \/><\/span><\/a><\/h3>\r\nThe hydrogen on a terminal alkyne is somewhat acidic, with a pK<sub>a<\/sub> of approximately 26.\u00a0 This means that, given a strong enough base, a terminal alkyne can be deprotonated, yielding a powerful carbanion nucleophile called an <em>acetylide<\/em> or <em>alkynide<\/em>.\u00a0 Sodium amide (NaNH<sub>2<\/sub>) (in liquid ammonia) or sodium hydride (NaH) are often used as the base.\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/21132721\/image133.png\" alt=\"image134.png\" width=\"652\" height=\"173\" \/>\r\n\r\nThe alkynyl carbanion can then be combined with a suitable electrophile, such as a primary alkyl bromide, in a carbon-carbon bond-forming\u00a0 S<sub>N<\/sub>2 displacement reaction. Secondary and tertiary alkyl bromides will usually not work in these types of reactions due to competing elimination.\r\n\r\nAcetylide (alkynide) anions are strong bases and strong <a title=\"Electrophiles &amp; Nucleophiles\" href=\"\/Organic_Chemistry\/Fundamentals\/Acids_and_Bases%3B_Electrophiles_and_Nucleophiles\" rel=\"internal\">nucleophiles<\/a>. Therefore, they are able to displace halides and other leaving groups in substitution reactions. The product is a substituted alkyne, as in the examples shown.\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/21132646\/clipboard_1395413624963.png\" alt=\"\" width=\"393\" height=\"37\" \/>\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/21132648\/clipboard_1395413388514.png\" alt=\"\" width=\"356\" height=\"46\" \/>\r\n\r\nSecondary, tertiary or even bulky primary substrates will give elimination by the E2 mechanism.\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/21132650\/clipboard_1395413821274.png\" alt=\"\" width=\"434\" height=\"41\" \/>\r\n\r\n<\/div>\r\n<div class=\"mt-section\">\r\n<div class=\"textbox exercises\">\r\n<div class=\"mt-section\">\r\n<h3 class=\"editable\">Problems<\/h3>\r\n1. The pK<sub>a<\/sub>\u200b of ammonia is 35. \u00a0Estimate the equilibrium constant for the deprotonation of pent-1-yne by amide ion, as shown above.\r\n\r\n<\/div>\r\n<div class=\"mt-section\">\r\n<h3 class=\"editable\">Answers<\/h3>\r\n1. \u00a0Assuming the pK<sub>a<\/sub>\u200b of pent-1-yne is about 25, then the difference in pK<sub>a<\/sub>s is 10. \u00a0Since pentyne is more acidic, the formation of the acetylide will be favored at equilibrium, so the equilibrium constant for the reaction is about 10<sup>10<\/sup>\r\n\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_19\">\r\n<div class=\"mt-section\">\r\n\r\nKhan Academy video:\r\n\r\n<img class=\"alignright size-thumbnail wp-image-4668\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/01170739\/static_qr_code_without_logo5-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/>\r\n\r\n[embed]https:\/\/www.youtube.com\/watch?v=_-I3HdmyYfE[\/embed]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/section>","rendered":"<section class=\"mt-content-container\">\n<div id=\"exercise\" class=\"textbox learning-objectives\">\n<h3 class=\"boxtitle\">Objectives<\/h3>\n<p>After completing this section, you should be able to<\/p>\n<ol>\n<li>write an equation to describe the reaction of an acetylide ion with an alkyl halide.<\/li>\n<li>discuss the importance of the reaction between acetylide ions and alkyl halides as a method of extending a carbon chain.<\/li>\n<li>identify the alkyne (and hence the acetylide ion) and the alkyl halide needed to synthesize a given alkyne.<\/li>\n<li>determine whether or not the reaction of an acetylide ion with a given alkyl halide will result in substitution or elimination, and draw the structure of the product formed in either case.<\/li>\n<\/ol>\n<\/div>\n<div>\n<div class=\"textbox tryit\">\n<h3 class=\"boxtitle\">Key Term<\/h3>\n<p>Make certain that you can define, and use in context, the key term below.<\/p>\n<ul>\n<li>alkylation<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<div id=\"note\" class=\"textbox key-takeaways\">\n<h3 class=\"boxtitle\">Study Notes<\/h3>\n<p>The alkylation of acetylide ions is important in organic synthesis because it is a reaction in which a new carbon-carbon bond is formed; hence, it can be used when an organic chemist is trying to build a complicated molecule from much simpler starting materials. The alkyl halide used in this reaction must be primary. Thus, if you were asked for a suitable synthesis of 2,2-dimethyl-3-hexyne, you would choose to attack iodoethane with the anion of 3,3- dimethyl-1-butyne<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-4883\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/06153119\/AcetylideAlkylation11.png\" alt=\"\" width=\"639\" height=\"111\" \/><\/p>\n<p>rather than to attack 2-iodo-2-methylpropane with the anion of 1-butyne.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-4884\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/06153153\/AcetylideAlkylation21.png\" alt=\"\" width=\"550\" height=\"105\" \/><\/p>\n<\/div>\n<div class=\"mt-section\">\n<h3 class=\"editable\">Nucleophilic substitution reactions of acetylides<a title=\"Edit section\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(Smith)\/Chapter_11%3A_Alkynes\/11.11%3A_Reaction_of_Acetylide_Anions?action=edit&amp;sectionId=2\" rel=\"internal\"><span class=\"icon\"><img decoding=\"async\" class=\"sectionedit\" src=\"http:\/\/a.mtstatic.com\/skins\/common\/icons\/icon-trans.gif?_=d2b40cf1:site_4334#fixme#fixme\" alt=\"Edit section\" \/><\/span><\/a><\/h3>\n<p>The hydrogen on a terminal alkyne is somewhat acidic, with a pK<sub>a<\/sub> of approximately 26.\u00a0 This means that, given a strong enough base, a terminal alkyne can be deprotonated, yielding a powerful carbanion nucleophile called an <em>acetylide<\/em> or <em>alkynide<\/em>.\u00a0 Sodium amide (NaNH<sub>2<\/sub>) (in liquid ammonia) or sodium hydride (NaH) are often used as the base.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/21132721\/image133.png\" alt=\"image134.png\" width=\"652\" height=\"173\" \/><\/p>\n<p>The alkynyl carbanion can then be combined with a suitable electrophile, such as a primary alkyl bromide, in a carbon-carbon bond-forming\u00a0 S<sub>N<\/sub>2 displacement reaction. Secondary and tertiary alkyl bromides will usually not work in these types of reactions due to competing elimination.<\/p>\n<p>Acetylide (alkynide) anions are strong bases and strong <a title=\"Electrophiles &amp; Nucleophiles\" href=\"\/Organic_Chemistry\/Fundamentals\/Acids_and_Bases%3B_Electrophiles_and_Nucleophiles\" rel=\"internal\">nucleophiles<\/a>. Therefore, they are able to displace halides and other leaving groups in substitution reactions. The product is a substituted alkyne, as in the examples shown.<\/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\/3369\/2018\/06\/21132646\/clipboard_1395413624963.png\" alt=\"\" width=\"393\" height=\"37\" \/><\/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\/3369\/2018\/06\/21132648\/clipboard_1395413388514.png\" alt=\"\" width=\"356\" height=\"46\" \/><\/p>\n<p>Secondary, tertiary or even bulky primary substrates will give elimination by the E2 mechanism.<\/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\/3369\/2018\/06\/21132650\/clipboard_1395413821274.png\" alt=\"\" width=\"434\" height=\"41\" \/><\/p>\n<\/div>\n<div class=\"mt-section\">\n<div class=\"textbox exercises\">\n<div class=\"mt-section\">\n<h3 class=\"editable\">Problems<\/h3>\n<p>1. The pK<sub>a<\/sub>\u200b of ammonia is 35. \u00a0Estimate the equilibrium constant for the deprotonation of pent-1-yne by amide ion, as shown above.<\/p>\n<\/div>\n<div class=\"mt-section\">\n<h3 class=\"editable\">Answers<\/h3>\n<p>1. \u00a0Assuming the pK<sub>a<\/sub>\u200b of pent-1-yne is about 25, then the difference in pK<sub>a<\/sub>s is 10. \u00a0Since pentyne is more acidic, the formation of the acetylide will be favored at equilibrium, so the equilibrium constant for the reaction is about 10<sup>10<\/sup><\/p>\n<\/div>\n<\/div>\n<div id=\"section_19\">\n<div class=\"mt-section\">\n<p>Khan Academy video:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-thumbnail wp-image-4668\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3369\/2018\/06\/01170739\/static_qr_code_without_logo5-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/><\/p>\n<p><iframe loading=\"lazy\" id=\"oembed-1\" title=\"Alkyne acidity and alkylation | Alkenes and Alkynes | Organic chemistry | Khan Academy\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/_-I3HdmyYfE?feature=oembed&#38;rel=0\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\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-2793\">\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>9.8 Alkylation of Acetylide Anions. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)  Prof. Steven Farmer (Sonoma State University)  William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook ofu00a0Organicu00a0Chemistry  Prof. Paul G. Wenthold (Purdue University) u00a0. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/LibreTexts\/Sonoma_State_University\/SSU_Chem_335A\/Material_Since_Exam_3_for_the_Final\/Unit_9%3A_Alkynes%3A_An_Introduction_to_Organic_Synthesis\/9.8_Alkylation_of_Acetylide_Anions\">https:\/\/chem.libretexts.org\/LibreTexts\/Sonoma_State_University\/SSU_Chem_335A\/Material_Since_Exam_3_for_the_Final\/Unit_9%3A_Alkynes%3A_An_Introduction_to_Organic_Synthesis\/9.8_Alkylation_of_Acetylide_Anions<\/a>. <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><li>13.6: Synthetic parallel - carbon nucleophiles in the lab. <strong>Authored by<\/strong>: Tim Soderberg. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/13%3A_Reactions_with_stabilized_carbanion_intermediates_I\/13.6%3A_Synthetic_parallel_-_carbon_nucleophiles_in_the_lab#13.6C:_Terminal_alkynes_as_carbon_nucleophiles\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/13%3A_Reactions_with_stabilized_carbanion_intermediates_I\/13.6%3A_Synthetic_parallel_-_carbon_nucleophiles_in_the_lab#13.6C:_Terminal_alkynes_as_carbon_nucleophiles<\/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":8,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"9.8 Alkylation of Acetylide Anions\",\"author\":\"Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)  Prof. Steven Farmer (Sonoma State University)  William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook ofu00a0Organicu00a0Chemistry  Prof. Paul G. Wenthold (Purdue University) u00a0\",\"organization\":\"\",\"url\":\"https:\/\/chem.libretexts.org\/LibreTexts\/Sonoma_State_University\/SSU_Chem_335A\/Material_Since_Exam_3_for_the_Final\/Unit_9%3A_Alkynes%3A_An_Introduction_to_Organic_Synthesis\/9.8_Alkylation_of_Acetylide_Anions\",\"project\":\"\",\"license\":\"cc-by-nc-sa\",\"license_terms\":\"\"},{\"type\":\"cc\",\"description\":\"13.6: Synthetic parallel - carbon nucleophiles in the lab\",\"author\":\"Tim Soderberg\",\"organization\":\"\",\"url\":\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/13%3A_Reactions_with_stabilized_carbanion_intermediates_I\/13.6%3A_Synthetic_parallel_-_carbon_nucleophiles_in_the_lab#13.6C:_Terminal_alkynes_as_carbon_nucleophiles\",\"project\":\"Chemistry LibreTexts\",\"license\":\"cc-by-nc-sa\",\"license_terms\":\"\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-2793","chapter","type-chapter","status-publish","hentry"],"part":26,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/2793","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/users\/311"}],"version-history":[{"count":15,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/2793\/revisions"}],"predecessor-version":[{"id":4886,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/2793\/revisions\/4886"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/parts\/26"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapters\/2793\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/media?parent=2793"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/pressbooks\/v2\/chapter-type?post=2793"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/contributor?post=2793"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/wp-json\/wp\/v2\/license?post=2793"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}