Mechanism of the Claisen Condensation

<h2><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFdBbJHxNA6dpU1TQLpTMmmLmgBiDNSKbxqQ1M3-t0jEOlzAEpmNqe278I9VCYeQYajLGN4RWDIZOb1MLIghv41nq1ACkt4swGjj3cxLDCQ90DhVsX6QLnsHIzaDN8iFbEhxf0TemnyXA/s1600/claisen.gif" imageanchor="1" style="font-size: medium; font-weight: normal; margin-left: 1em; margin-right: 1em; text-align: center;"><img alt="Mechanism of the Claisen Condensation" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiFdBbJHxNA6dpU1TQLpTMmmLmgBiDNSKbxqQ1M3-t0jEOlzAEpmNqe278I9VCYeQYajLGN4RWDIZOb1MLIghv41nq1ACkt4swGjj3cxLDCQ90DhVsX6QLnsHIzaDN8iFbEhxf0TemnyXA/s1600/claisen.gif" title="Mechanism of the Claisen Condensation" /></a></h2><h2><i style="font-family: Arial, Helvetica, 'sans serif';"><span style="font-size: large;">Mechanism of the Claisen Condensation</span></i></h2><h3><b><i>Reaction type : Nucleophilic Acyl Substitution<a name="more"></a></i></b></h3><div><h4>Summary</h4><ul><li>The Claisen condensation is the ester analogue of the Aldol condensation.</li><li>Reagents : most commonly the base would be the alkoxide, <b>R'O^-</b></li><li>The reaction involves an ester enolate reacting with another molecule of the ester.</li><li>Remember enolates are good nucleophiles and the ester carbonyl <b>C</b> are electrophilic.</li><li>The products of these reactions are <b><i><span style="font-family: Symbol;">b-</span>ketoesters</i></b> which are important, useful synthetic intermediates.</li><li>Note that the product is the original ester with an <b>acyl<span style="color: #3333ff;"> </span></b>group added <i>i.e.</i> an <b>acylation</b> reaction has occurred.</li><li>A simple example of a <b><i>Claisen condensation </i></b>is the reaction of ethyl ethanoate which is shown below in two representations:</li></ul></div><div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRvroNWaiQqc0BfEoj5ZrHmV1qlVqm9h4IisnLrQsue59e9_6ME7BJdS5Zqdl9Fmj-j2gycZknUjwJ26yJxP1UwwgyXjcQm58X8fOcHo_Tvi6Z87SORWYbWM_dkAwdOnPdOmWg37waCIU/s1600/claisenmech.gif" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img alt="Mechanism of the Claisen Condensation" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRvroNWaiQqc0BfEoj5ZrHmV1qlVqm9h4IisnLrQsue59e9_6ME7BJdS5Zqdl9Fmj-j2gycZknUjwJ26yJxP1UwwgyXjcQm58X8fOcHo_Tvi6Z87SORWYbWM_dkAwdOnPdOmWg37waCIU/s1600/claisenmech.gif" title="Mechanism of the Claisen Condensation" /></a></div><div><b style="background-color: white; font-family: Arial;"><br /></b></div><div><b style="background-color: white; font-family: Arial;"><br /></b></div><div><b style="background-color: white; font-family: Arial;">Step 1:</b><span style="background-color: white; font-family: Arial;"> </span><br /><span style="background-color: white; font-family: Arial;">First, an acid-base reaction. The alkoxide functions as a base and removes the acidic </span><span style="background-color: white; font-family: Symbol;">a</span><span style="background-color: white; font-family: Arial;">-hydrogen giving the reactive ester enolate</span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><b style="background-color: white; font-family: Arial;">Step 2:</b><span style="background-color: white; font-family: Arial;"> </span><br /><span style="background-color: white; font-family: Arial;">The nucleophilic ester enolate attacks the carbonyl </span><b style="background-color: white; font-family: Arial;">C</b><span style="background-color: white; font-family: Arial;"> of another ester in a </span><a href="http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch20/ch20-2-1.html" rel="nofollow" style="background-color: white; font-family: Arial;" target="_blank">nucleophilic substitution process</a><span style="background-color: white; font-family: Arial;"> giving the tetrahedral intermediate.</span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="background-color: white; font-family: Arial;"><b>Step 3:</b><br />The intermediate collapses, reforming the <b>C=O</b>, resulting in loss of the leaving group, the alkoxide, leading to the </span><span style="background-color: white; font-family: Symbol;">b</span><span style="background-color: white; font-family: Arial;">-ketoester product.</span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="background-color: white; font-family: Arial;"><br /></span></div><div><span style="font-family: Arial;"><span style="background-color: white;">(nguồn: </span>http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch21/ch21-3-1.html</span><br /><span style="font-family: Arial;">http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch21enolatereactions.html)</span><br /><span style="font-family: Arial;"><br /></span><span style="font-family: Arial;"><br /></span><br /><h4><span style="font-family: Arial; font-size: large;"><i>More than:</i></span></h4></div><div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif;">The general form of a <a href="http://forum-chemistry.blogspot.com/2014/08/claisen-condensationngung-tu-claisen.html" target="_blank">Claisen condensation</a> is as follows:</span></div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif; font-size: x-small;"><br /><img alt="Mechanism of the Claisen Condensation" height="67" src="http://www.chemhelper.com/images/pictures/claisen1.gif" title="Mechanism of the Claisen Condensation" width="344" /></span></div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif;">The first step involves adding a strong base to an ester to generate an enolate at the <span style="font-family: Symbol;">a</span> carbon (note that the enolate has an additional resonance structure).</span></div><div style="background-color: white;"><img alt="Mechanism of the Claisen Condensation" height="276" src="http://www.chemhelper.com/images/pictures/claisen2.gif" title="Mechanism of the Claisen Condensation" width="468" /></div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif;">The enolate can then add to another ester molecule by attacking the carbonyl to make the tetrahedral intermediate. The carbonyl reforms with loss of the alcoxy group to make the <span style="font-family: Symbol;">b</span>-keto ester.</span></div><div style="background-color: white;"><br /></div><div style="background-color: white;"><h4><span style="font-family: Arial, Helvetica, sans-serif;"><b><i>Example of a Claisen condensation:</i></b></span></h4></div><div style="background-color: white;"><img alt="Mechanism of the Claisen Condensation" height="292" src="http://www.chemhelper.com/images/pictures/dieckmann.gif" title="Mechanism of the Claisen Condensation" width="386" /></div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif;">This is an example of an intramolecular Claisen reaction, called a Dieckmann condensation.</span></div><div style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif; font-size: x-small;"><br /></span></div><h3 style="background-color: white;"><span style="font-family: Arial, Helvetica, sans-serif; font-size: x-large;"><i>Learn More:</i></span></h3><div><h3><span style="font-family: Arial, Helvetica, sans-serif; font-size: large;"><i><a href="http://forum-chemistry.blogspot.com/2014/08/mechanism-of-claisen-condensation.html" target="_blank">Claisen condensation mechanism</a></i></span></h3></div><div><h4 style="background-color: white; border: 0px; color: #333333; font-family: Arial, Helvetica, sans-serif; line-height: 18px; margin-bottom: 8px !important; margin-top: 0.25em; padding: 0px; visibility: visible;">1) Enolate formation</h4></div><div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhqCA1Bqlfd4N-eqJVlDQvjlGecMn93w17pMLYxYrvwvUWRhyQakRR6Cfpey0BZABkRvkz5O5eP2SBeDXOG69b4sQ2DompA02Up6Z-A9TjjwyGlLZcYPhcp3qoT5l_HQR4FcILqHz8zUcE/s1600/Claisen+condensation+mechanism.jpg" imageanchor="1" style="clear: left; display: inline !important; margin-bottom: 1em; margin-right: 1em; text-align: center;"><img alt="Mechanism of the Claisen Condensation" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhqCA1Bqlfd4N-eqJVlDQvjlGecMn93w17pMLYxYrvwvUWRhyQakRR6Cfpey0BZABkRvkz5O5eP2SBeDXOG69b4sQ2DompA02Up6Z-A9TjjwyGlLZcYPhcp3qoT5l_HQR4FcILqHz8zUcE/s1600/Claisen+condensation+mechanism.jpg" title="Mechanism of the Claisen Condensation" /></a></div><div><h4 style="background-color: white; border: 0px; color: #333333; font-family: Arial, Helvetica, sans-serif; line-height: 18px; margin-bottom: 8px !important; margin-top: 0.25em; padding: 0px; visibility: visible;">2) Nucleophilic attack</h4></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikMXxJrVLN_xk94Mmf5Xfel7CGlJUcXtXr1MysQnSshFtw-cdbxVjunMc40PQL6fTUozJ6fJx8G4XXjIbTW5th1IOgN1urn-JAT3izR42LffRpCzmuScmZVpR4hwbabI164Ov5p5VHi-w/s1600/Claisen+condensation+mechanism2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img alt="Mechanism of the Claisen Condensation" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikMXxJrVLN_xk94Mmf5Xfel7CGlJUcXtXr1MysQnSshFtw-cdbxVjunMc40PQL6fTUozJ6fJx8G4XXjIbTW5th1IOgN1urn-JAT3izR42LffRpCzmuScmZVpR4hwbabI164Ov5p5VHi-w/s1600/Claisen+condensation+mechanism2.jpg" title="Mechanism of the Claisen Condensation" /></a></div><h4 style="background-color: white; border: 0px; color: #333333; font-family: Arial, Helvetica, sans-serif; line-height: 18px; margin-bottom: 8px !important; margin-top: 0.25em; padding: 0px; visibility: visible;">3) Removal of leaving group<span style="background-color: transparent;"> </span></h4><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZaNkEnkIu_qAZ02xY6apqPvH0TaqO6JORtkfRy0T-RCu06XCA1HTzz44CBoIUBw0K2lqLxWT0dm9ommqUOnFc6Yt-VRV07FUVn5nfpbRZW-PPAOXbJw-1mP_t6HZoDSK9s3lLtxceuHo/s1600/Claisen+condensation+mechanism3.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img alt="Mechanism of the Claisen Condensation" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZaNkEnkIu_qAZ02xY6apqPvH0TaqO6JORtkfRy0T-RCu06XCA1HTzz44CBoIUBw0K2lqLxWT0dm9ommqUOnFc6Yt-VRV07FUVn5nfpbRZW-PPAOXbJw-1mP_t6HZoDSK9s3lLtxceuHo/s1600/Claisen+condensation+mechanism3.jpg" title="Mechanism of the Claisen Condensation" /></a></div><br /></div>

Mechanism of the Claisen Condensation

Mechanism of the Claisen Condensation Reaction type : Nucleophilic Acyl Substitution Summary The Claisen condensation is the ester analogue ...

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