{"id":47734,"date":"2023-09-04T17:02:31","date_gmt":"2023-09-04T11:17:31","guid":{"rendered":"https:\/\/thechemistrynotes.com\/?p=47734"},"modified":"2023-09-04T17:02:35","modified_gmt":"2023-09-04T11:17:35","slug":"gabriel-phthalimide-synthesis-mechanism","status":"publish","type":"post","link":"https:\/\/thechemistrynotes.com\/gabriel-phthalimide-synthesis-mechanism\/","title":{"rendered":"Gabriel Phthalimide Synthesis: Definition, Mechanism, Applications, Limitations"},"content":{"rendered":"\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"1205\" height=\"631\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Gabriel-phthalimide-synthesis.jpg\" alt=\"Gabriel phthalimide synthesis\" class=\"wp-image-47739\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Gabriel-phthalimide-synthesis.jpg 1205w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Gabriel-phthalimide-synthesis-300x157.jpg 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Gabriel-phthalimide-synthesis-1024x536.jpg 1024w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Gabriel-phthalimide-synthesis-768x402.jpg 768w\" sizes=\"(max-width: 1205px) 100vw, 1205px\" \/><\/figure>\n\n\n\n<p>The Gabriel phthalimide synthesis is a chemical reaction that converts\u00a0primary <a href=\"https:\/\/thechemistrynotes.com\/haloalkanes-alkyl-halides\/\">alkyl halides<\/a> to <a href=\"https:\/\/thechemistrynotes.com\/primary-secondary-and-tertiary-amines\/\">primary amines<\/a>. It is a nucleophilic substitution process that is mostly utilized to\u00a0produce\u00a0primary amines. Siegmund Gabriel, a German scientist, and his friend James Dornbush discovered the Gabriel Synthesis in 1887. It is a straightforward and effective process for producing a wide range of primary\u00a0amines from easily available starting materials. Additionally, the process of the reaction takes place at\u00a0moderate conditions, so,\u00a0no abrasive chemicals or high temperatures are needed. As phthalimide is employed in this reaction along with a base, is known as Gabriel phthalimide synthesis. It is also known as Gabriel synthesis.<\/p>\n\n\n\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_65 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\/gabriel-phthalimide-synthesis-mechanism\/#what-is-gabriels-phthalimide-synthesis\" title=\"What is Gabriel&#8217;s phthalimide synthesis?\">What is Gabriel&#8217;s phthalimide synthesis?<\/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\/gabriel-phthalimide-synthesis-mechanism\/#mechanism-of-gabriel-phthalimide-synthesis\" title=\"Mechanism of &nbsp;Gabriel phthalimide synthesis\">Mechanism of &nbsp;Gabriel phthalimide synthesis<\/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\/gabriel-phthalimide-synthesis-mechanism\/#applications-of-gabriel-phthalimide-synthesis\" title=\"Applications of Gabriel phthalimide synthesis\">Applications of Gabriel phthalimide synthesis<\/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\/gabriel-phthalimide-synthesis-mechanism\/#limitations-of-gabriel-phthalimide-synthesis\" title=\"Limitations of Gabriel phthalimide synthesis\">Limitations of Gabriel phthalimide synthesis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/thechemistrynotes.com\/gabriel-phthalimide-synthesis-mechanism\/#references\" title=\"References\">References<\/a><\/li><\/ul><\/nav><\/div>\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"what-is-gabriels-phthalimide-synthesis\"><\/span><strong>What is Gabriel&#8217;s phthalimide synthesis?<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p>In the presence of strong bases like KOH, and NaOH, alkyl halide reacts with pthalamide to give N-alkyl pthalimide. N-alkyl phthalimide on hydrolysis produces primary amine. This is known as Gabriel phthalimide synthesis.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-23.png\" alt=\"\" class=\"wp-image-47736\" style=\"width:755px;height:172px\" width=\"755\" height=\"172\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-23.png 975w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-23-300x68.png 300w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/image-23-768x175.png 768w\" sizes=\"(max-width: 755px) 100vw, 755px\" \/><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"mechanism-of-gabriel-phthalimide-synthesis\"><\/span><strong>Mechanism of &nbsp;Gabriel phthalimide synthesis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p><strong>Step I: <\/strong>The reaction begins with the conversion of phthalimide to potassium phthalimide via the addition of an alkali base such as KOH or NaOH. Deprotonation of nitrogen occurs when protons are removed from the nitrogen of phthalimide.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis-929x1024.png\" alt=\"Mechanism of  Gabriel phthalimide synthesis\" class=\"wp-image-47737\" style=\"width:573px;height:632px\" width=\"573\" height=\"632\" srcset=\"https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis-929x1024.png 929w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis-272x300.png 272w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis-768x847.png 768w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis-1393x1536.png 1393w, https:\/\/thechemistrynotes.com\/wp-content\/uploads\/2023\/09\/Mechanism-of-Gabriel-phthalimide-synthesis.png 1847w\" sizes=\"(max-width: 573px) 100vw, 573px\" \/><\/figure><\/div>\n\n\n<p><strong>Step II: <\/strong>With potassium phthalimide, the Gabriel phthalimide synthesis continues. Deprotonation causes the nitrogen in potassium phthalimide to acquire a negative charge. This negatively charged nitrogen can now operate as a nucleophile, reacting with alkyl halide via the bimolecular nucleophilic substitution process, also known as the SN<sub>2<\/sub> reaction. Gabriel phthalimide&#8217;s nucleophilic nitrogen attacks\u00a0the electrophilic carbon of alkyl halide. The potassium ion from KOH reacts with the halogen of an alkyl halide to create KX. N-alkyl phthalimide is formed when the alkyl group of alkyl halide attaches to nucleophilic nitrogen.<\/p>\n\n\n\n<p><strong>Step III:<\/strong> In the third stage, which is comparable to the base-catalyzed hydrolysis of esters except that the resulting bond is between nitrogen and the R group rather than oxygen and nitrogen, the R group joins with the nitrogen atom. The hydroxide ion in potassium hydroxide subsequently binds to the carbon atom, causing the N-alkyl phthalimide to dissociate and produce\u00a0a primary amine.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"applications-of-gabriel-phthalimide-synthesis\"><\/span><strong>Applications of Gabriel phthalimide synthesis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul>\n<li>The Gabriel synthesis has the fundamental advantage of preventing overalkylation.<\/li>\n\n\n\n<li>The Gabriel reaction has been expanded to include sulfonamide and imide alkylation followed by deprotection to yield amines.<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"limitations-of-gabriel-phthalimide-synthesis\"><\/span><strong>Limitations of Gabriel phthalimide synthesis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul>\n<li>The Gabriel phthalimide synthesis technique can only produce primary alkyl amines.<\/li>\n\n\n\n<li>A secondary or tertiary amine cannot be produced from it.<\/li>\n\n\n\n<li>As aryl halides do not undergo simple nucleophilic substitution, aryl amines cannot be synthesized using the Gabriel technique.<\/li>\n\n\n\n<li>The use of acidic\/basic hydrolysis leads to a low yield, and the use of hydrazine can make the synthesis conditions relatively severe.<\/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>The Gabriel phthalimide synthesis is a chemical reaction that converts\u00a0primary alkyl halides to primary amines. It is a nucleophilic substitution process that is mostly utilized to\u00a0produce\u00a0primary amines. Siegmund Gabriel, a &#8230; <a title=\"Gabriel Phthalimide Synthesis: Definition, Mechanism, Applications, Limitations\" class=\"read-more\" href=\"https:\/\/thechemistrynotes.com\/gabriel-phthalimide-synthesis-mechanism\/\" aria-label=\"Read more about Gabriel Phthalimide Synthesis: Definition, Mechanism, Applications, Limitations\">Read more<\/a><\/p>\n","protected":false},"author":4,"featured_media":47739,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[2845,242,2847,2846,2844],"_links":{"self":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/47734"}],"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=47734"}],"version-history":[{"count":3,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/47734\/revisions"}],"predecessor-version":[{"id":47740,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/posts\/47734\/revisions\/47740"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/media\/47739"}],"wp:attachment":[{"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/media?parent=47734"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/categories?post=47734"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/thechemistrynotes.com\/wp-json\/wp\/v2\/tags?post=47734"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}