{"id":48331,"date":"2023-09-17T22:06:03","date_gmt":"2023-09-17T16:21:03","guid":{"rendered":"https:\/\/thechemistrynotes.com\/?p=48331"},"modified":"2023-09-17T22:06:06","modified_gmt":"2023-09-17T16:21:06","slug":"knoevenagel-condensation-mechanism","status":"publish","type":"post","link":"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/","title":{"rendered":"Knoevenagel Condensation: Definition, Mechanism, Applications"},"content":{"rendered":"\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"536\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Knoevenagel-condensation-1024x536.jpg\" alt=\"\" class=\"wp-image-48335\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Knoevenagel-condensation-1024x536.jpg 1024w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Knoevenagel-condensation-300x157.jpg 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Knoevenagel-condensation-768x402.jpg 768w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Knoevenagel-condensation.jpg 1205w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p>Knoevenagel condensation is the nucleophilic addition of an active hydrogen compound to a carbonyl group, followed by a dehydration process that eliminates a molecule of water. The result is frequently an alpha, beta conjugated compound.<\/p>\n\n\n\n<p>The Knoevenagel process is a variant of the <a href=\"https:\/\/thechemistrynotes.com\/aldol-condensation-definition-reaction-mechanism-and-applications\/\">Aldol condensation<\/a> reaction. For the synthesis of electrophilic olefins from active methylene and carbonyl molecules, the Knoevenagel reaction is widely recognized.<\/p>\n\n\n\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_64 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title \" >Table of Contents<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #0a0a0a;color:#0a0a0a\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #0a0a0a;color:#0a0a0a\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/#what-is-knoevenagel-condensation\" title=\"What is Knoevenagel condensation?\">What is Knoevenagel condensation?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/#mechanism-of-knoevenagel-condensation\" title=\"Mechanism of Knoevenagel condensation\">Mechanism of Knoevenagel condensation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/#applications-of-knoevenagel-condensation\" title=\"Applications of Knoevenagel condensation\">Applications of Knoevenagel condensation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/#references\" title=\"References\">References<\/a><\/li><\/ul><\/nav><\/div>\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"what-is-knoevenagel-condensation\"><\/span><strong>What is Knoevenagel condensation?<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>The Knoevenagel condensation is an organic reaction that uses an amine base as a catalyst to convert an aldehyde or ketone and activated methylene to a substituted olefin. The reaction begins with the base deprotonating activated methylene to produce a resonance-stabilized\u00a0enolate. In addition, the amine catalyst combines with the aldehyde or ketone to generate an iminium ion intermediate, which is subsequently attacked by the enolate. The base deprotonates the intermediate compound to produce another enolate, while the intermediate&#8217;s amine is protonated. The amine base is later released, the catalyst is regenerated, and the final olefin product is produced.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-45.png\" alt=\"\" class=\"wp-image-48332\" style=\"width:544px;height:97px\" width=\"544\" height=\"97\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-45.png 975w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-45-300x54.png 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-45-768x137.png 768w\" sizes=\"(max-width: 544px) 100vw, 544px\" \/><\/figure><\/div>\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"mechanism-of-knoevenagel-condensation\"><\/span><strong>Mechanism of Knoevenagel condensation<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>Step 1: The activated methylene is deprotonated by the base (piperidine), yielding a carbanion that is resonance stabilized via the enolate ion.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-46.png\" alt=\"\" class=\"wp-image-48333\" style=\"width:477px;height:185px\" width=\"477\" height=\"185\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-46.png 962w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-46-300x116.png 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-46-768x298.png 768w\" sizes=\"(max-width: 477px) 100vw, 477px\" \/><\/figure><\/div>\n\n\n<p>Step 2: The enolate ion undergoes\u00a0a nucleophilic attack on the carbanion belonging to the carbonyl of the ketone.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-47.png\" alt=\"\" class=\"wp-image-48334\" style=\"width:441px;height:280px\" width=\"441\" height=\"280\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-47.png 935w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-47-300x190.png 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-47-768x487.png 768w\" sizes=\"(max-width: 441px) 100vw, 441px\" \/><\/figure><\/div>\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"applications-of-knoevenagel-condensation\"><\/span><strong>Applications of Knoevenagel condensation<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul>\n<li>The Knoevenagel condensation is an important step in the commercial manufacturing of lumefantrine, an antimalarial medication.<\/li>\n\n\n\n<li>The Knoevenagel reaction is utilized in the synthesis of conjugated enones, which are important intermediates in a variety of processes.<\/li>\n\n\n\n<li>A Knoevenagel reaction step is present in the Hantzsch pyridine synthesis, the Gewald reaction, and the Feist\u2014Benaryfuran synthesis. The reaction was also responsible for the discovery of CS gas.<\/li>\n\n\n\n<li>Arylidene cyanoacetates and arylidene malononitriles were synthesized by the Knoevenagel condensation of various aldehydes with ethyl cyanoacetate and malononitrile, respectively, at room temperature or under pressure using imidazole as a catalyst.<\/li>\n\n\n\n<li>Coumarin, indole, quinoline, stilbenes, and other fascinating chemicals have been synthesized using this process.<\/li>\n\n\n\n<li>Knoevenagel&#8217;s utilization of primary and secondary amines and their salts as catalysts established a new platform for amine catalyst research.<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"references\"><\/span><strong>References<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul>\n<li>Morrison R. T. &amp; Boyd R. N. (1983).&nbsp;<em>Organic chemistry<\/em>&nbsp;(4th ed.). Allyn and Bacon.<\/li>\n\n\n\n<li>Smith M. &amp; March J. (2001).&nbsp;<em>March\u2019s Advanced Organic Chemistry: Reactions Mechanisms and Structure<\/em>&nbsp;(5th ed.). Wiley.<\/li>\n\n\n\n<li>Ghosh, S.K.,&nbsp;<em>Advanced General Organic Chemistry<\/em>, Second Edition, New Central Book Agency Pvt. Ltd., Kolkatta, 2007.<\/li>\n\n\n\n<li>Bahl, B.S., A., Advanced Organic Chemistry, S. Chand and Company Ltd, New Delhi, 1992. production of polyesters, polyurethanes, and alkaline resins.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Knoevenagel condensation is the nucleophilic addition of an active hydrogen compound to a carbonyl group, followed by a dehydration process that eliminates a molecule of water. The result is frequently &#8230; <a title=\"Knoevenagel Condensation: Definition, Mechanism, Applications\" class=\"read-more\" href=\"https:\/\/thechemistrynotes.com\/knoevenagel-condensation-mechanism\/\" aria-label=\"Read more about Knoevenagel Condensation: Definition, Mechanism, Applications\">Read more<\/a><\/p>\n","protected":false},"author":4,"featured_media":48335,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[2886,2884,2885],"_links":{"self":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/48331"}],"collection":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/comments?post=48331"}],"version-history":[{"count":2,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/48331\/revisions"}],"predecessor-version":[{"id":48337,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/48331\/revisions\/48337"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/media\/48335"}],"wp:attachment":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/media?parent=48331"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/categories?post=48331"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/tags?post=48331"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}