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<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd"> <html xmlns="http://www.w3.org/1999/xhtml"> <head profile="http://gmpg.org/xfn/1"> <title>Computational Organic Chemistry » Keto-enol tautomerization</title> <meta name="google-site-verification" content="g1Myv4tUVAmqRbwZeBi7IPuSZpP64RWjVJ6itIoouCo"> <meta http-equiv="Content-Type" content="text/html; charset=UTF-8"> <style type="text/css" media="screen">@import url( /blog/wp-content/themes/comporg/style.css);</style> <link rel="stylesheet" id="wp-block-library-css" href="/blog/wp-includes/css/dist/block-library/style.min.css?ver=5.6.1" type="text/css" media="all"> <script type="text/javascript">  </script> </head> <body> <div id="header"> <div id="header_img"></div> </div> <div id="link_section"> <div style="float:left"> <a href="/blog/about">About this Blog</a> | <a href="/">Book Homepage</a> | <a href="http://www.wiley.com/WileyCDA/WileyTitle/productCd-0471713422.html">Purchase the Book</a> </div> </div> <div id="after_links"></div> <div id="content"> <div id="main"> <h2 class="post-title">Archive for the 'Keto-enol tautomerization' Category</h2> <div class="box"> <h2><a href="/blog/archives/3613" rel="bookmark" title="Permanent Link: Keto-enol Benchmark Study">Keto-enol Benchmark Study</a></h2> <div class="post-content"> <p>The keto-enol tautomerization is a fundamental concept in organic chemistry, taught in the introductory college course. As such, it provides an excellent test reaction to benchmark the performance computational methods. Acevedo and colleagues have reported just such a benchmark study.<a href="#ketoEnolref1"><sup>1</sup></a></p> <p>First, the compare a wide variety of methods, ranging from semi-empirical, to DFT, and to composite procedures, with experimental gas-phase free energy of tautomerization. They use seven such examples, two of which are shown in Scheme 1. The best results from each computation category are AM1, with a mean absolute error (MAE) of 1.73 kcal mol<sup>-1</sup>, M06/6-31+G(d,p), with a MAE of 0.71 kcal mol<sup>-1</sup>, and G4, with a MAE of 0.95 kcal mol<sup>-1</sup>. All of the modern functionals do a fairly good job, with MAEs less than 1.3 kcal mol<sup>-1</sup>.</p> <p align="center"><img src="/blog/wp-content/KetoeEnolImg.png"><br><b>Scheme 1</b></p> <p>As might be expected, the errors were appreciably larger for predicting the free energy of tautomerization, with a good spread of errors depending on the method for handling solvent (PCM, CPCM, SMD) and the choice of cavity radius. The best results were with the G4/PCM/UA0 procedure, though M06/6-31+G(d,p)/PCM and either UA0 or UFF performed quite well, at considerably less computational expense.</p> <h3>References</h3> <p><a name="ketoEnolref1"></a></p> <p>(1) McCann, B. W.; McFarland, S.; Acevedo, O. "Benchmarking Continuum Solvent Models for Keto–Enol Tautomerizations," <i>J. Phys. Chem. A</i> <b>2015</b>, <i>119</i>, 8724-8733, DOI: <a href="http://dx.doi.org/10.1021/acs.jpca.5b04116">10.1021/acs.jpca.5b04116</a>.</p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/keto-enol-tautomerization" rel="category tag">Keto-enol tautomerization</a> &<a href="/blog/archives/category/qm-method" rel="category tag">QM Method</a></span> <span class="user">Steven Bachrach</span> <span class="date">12 Oct 2015</span> <span class="comments"><a href="/blog/archives/3613#respond">No Comments</a></span> </p> </div> <div class="box"> <h2><a href="/blog/archives/1259" rel="bookmark" title="Permanent Link: Catalyzing the keto-enol tautomerization">Catalyzing the keto-enol tautomerization</a></h2> <div class="post-content"> <p>Proton and hydrogen transfers can be catalyzed by many things. Da Silva shows that carboxylic acids can catalyze the hydrogen shift that converts an enol into a carbonyl species.<a href="#formEnol1"><sup>1</sup></a> The specific example is the ethenol to acetaldehyde tautomerization. This reaction has a barrier of 56.6 kcal mol<sup>-1</sup> (computed using the composite method G3SX).</p> <p align="center"><img src="/blog/wp-content/formEnol.gif"></p> <p>With formic acid as the catalyst, the reactant is the hydrogen-bonded complex of ethanol with formic acid and the product is the complex of acetaldehyde with formic acid. The transition state is shown in Figure 1. The barrier is only 5.6 kcal mol<sup>-1</sup>, a significant reduction. da Silva discusses how carboxylic acids might be catalyzing the enol-keto tautomerization in the troposphere and also in combustion reactions.</p> <table align="center" border="0" cellspacing="0" cellpadding="0"> <tr align="center"> <td> <p></p> <div class="jmol" id="formEnolTS"> <a onclick="return false"><br> <img src="/blog/wp-content/formEnolTS.jpg" onclick="insertJmol('formEnolTS',250,250,'formEnolTS.xyz')"><br> </a> </div> </td> </tr> </table> <p align="center">Figure 1. B3LYP/6-31G(2df,p) optimized TS of the formic acid catalyzed enol-keto tautomerization of acetaldehyde.</p> <h3>References</h3> <p><a name="formEnol1"></a></p> <p>(1) da Silva, G., "Carboxylic Acid Catalyzed Keto-Enol Tautomerizations in the Gas Phase," <i>Angew. Chem. Int. Ed.</i>, <b>2010</b>, <i>49</i>, 7523-7525, DOI: <a href="http://dx.doi.org/10.1002/anie.201003530">10.1002/anie.201003530</a></p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/keto-enol-tautomerization" rel="category tag">Keto-enol tautomerization</a></span> <span class="user">Steven Bachrach</span> <span class="date">08 Dec 2010</span> <span class="comments"><a href="/blog/archives/1259#comments">6 Comments</a></span> </p> </div> <div class="box"> <h2><a href="/blog/archives/728" rel="bookmark" title="Permanent Link: Keto-enol tautomerization balancing aromaticity and antiaromaticity">Keto-enol tautomerization balancing aromaticity and antiaromaticity</a></h2> <div class="post-content"> <p>The keto-enol tautomerization is an interesting system for probing relative energies of subtle effects, playing off different bond type (and their associated strengths) with conjugation and hydrogen bonding and strain. Lawrence and Hutchings have now extended this to include the interplay of aromaticity and antiaromaticity in the keto-enol tautomerization of benzodifurantrione <b>1</b>.<a href="#BDT1"><sup>1</sup></a> The keto form <b>1k</b> looks to be the favotable tautomer, containing an aromatic phenyl ring. The enol tautomer <b>1e</b> requires the loss of that aromatic ring. Nonetheless, the enol structure is the only tautomer present in the crystal phase, and the enol tautomer is the dominant structure (if not the exclusive structure) in all solvents tested, including acetic acid, acetone, acetonitrile, chloroform, DMF, DMSO, propanol and toluene. The only solvents where the keto form is dominant are toluene and <i>o</i>-dichlorobenzene.</p> <p align="center"><img src="/blog/wp-content/BDTfig1.gif"></p> <p>So, how does one rationalize this equilibrium? The B3LYP/6-311G(2d,p) structure of the two tautomers are shown in Figure 1. Note that there are two isomers of the enol form, differing on the orientation of the hydroxyl hydrogen. The <i>syn</i> isomer is the lowest energy form, in both the gas phase and in solution (PCM modeling acetonitrile, chlorobenzene and THF). So the enol form is the lowest energy structure when there are no special interactions involving hydrogen bonding or dipolar interactions with the solvent – there is an inherent energy preference for <b>1e</b>.</p> <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr> <td align="center" colspan="2"> <p></p> <div class="jmol" id="BDT1k"> <a onclick="return false"><br> <img src="/blog/wp-content/BDT-1k.jpg" onclick="insertJmol('BDT1k',200,200,'BDT-1k.xyz')"><br> </a> </div> <p><b>1k</b></p> </td> </tr> <tr> <td align="center"> <p></p> <div class="jmol" id="BDT1ea"> <a onclick="return false"><br> <img src="/blog/wp-content/BDT-1e-anti.jpg" onclick="insertJmol('BDT1ea',200,200,'BDT-1e-anti.xyz')"><br> </a> </div> <p><b>1e-anti</b></p> </td> <td align="center"> <p></p> <div class="jmol" id="BDT1es"> <a onclick="return false"><br> <img src="/blog/wp-content/BDT-1e-syn.jpg" onclick="insertJmol('BDT1es',200,200,'BDT-1e-syn.xyz')"><br> </a> </div> <p><b>1e-syn</b></p> </td> </tr> </table> <p align="center"><b>Figure 1</b>. B3LYP/6-311G(2d,p) structures of the tautomers of <b>1</b>.<a href="#BDT1"><sup>1</sup></a></p> <p>To address that, they computed the NICS(0) values for each ring in the two tautomers. The pendant phenyl group is aromatic in both structures, as expected. The lactone ring has NICS values near 0 in both structures. The interior phenyl ring is aromatic (NICS = -7.5) in <b>1k</b> but is non-aromatic in <b>1e</b>, with NICS=-0.4. So the aromaticity of this ring is lost upon enolization, and thus would favor <b>1k</b>. However, the terminal ring in the keto tautomer has NICS = +7.2, suggesting that it is <i>antiaromatic</i>, and upon enolization, the ring becomes slightly aromatic, with NICS = -2.1. Thus, the keto form is plagued by an antiaromatic ring, which is then lost in the enol form. The result is the interplay between losing an aromatic ring and its stabilization when the enol is formed balanced by also losing an antiaromatic ring with its destabilization. The authors do not offer any quantization (rightfully so!) of the stabilization/destabilization associated with these rings. But very subtle effects are clearly at play.</p> <h3>References</h3> <p><a name="BDT1"></a></p> <p>(1) Lawrence, A. J.; Hutchings, M. G.; Kennedy, A. R.; McDouall, J. J. W., "Benzodifurantrione: A Stable Phenylogous Enol," <i>J. Org. Chem.</i>, <b>2010</b>, <i>75</i>, 690–701, DOI: <a href="http://dx.doi.org/10.1021/jo9022155">10.1021/jo9022155</a></p> <h3>InChIs</h3> <p><b>1k</b>: InChI=1/C16H8O5/c17-14-10-7-11-9(6-12(10)21-16(14)19)13(15(18)20-11)8-4-2-1-3-5-8/h1-7,13H<br>InChIKey=GNWKSKHSRUSFBC-UHFFFAOYAC</p> <p><b>1e</b>: InChI=1/C16H8O5/c17-14-10-7-11-9(6-12(10)21-16(14)19)13(15(18)20-11)8-4-2-1-3-5-8/h1-7,17H<br>InChIKey=MZLQKOSFMRKQIO-UHFFFAOYAB</p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> &<a href="/blog/archives/category/keto-enol-tautomerization" rel="category tag">Keto-enol tautomerization</a></span> <span class="user">Steven Bachrach</span> <span class="date">08 Mar 2010</span> <span class="comments"><a href="/blog/archives/728#comments">1 Comment</a></span> </p> </div> <p align="center"></p> </div> <div id="sidebar"> <ul> <li class="box"> <h2> Categories </h2> <ul> <li class="cat-item cat-item-25"> <a 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href="/blog/archives/category/stereochemistry">Stereochemistry</a> (2) </li> <li class="cat-item cat-item-68"> <a href="/blog/archives/category/stereoinduction">stereoinduction</a> (4) </li> <li class="cat-item cat-item-71"> <a href="/blog/archives/category/tunneling">Tunneling</a> (26) </li> <li class="cat-item cat-item-1"> <a href="/blog/archives/category/uncategorized">Uncategorized</a> (57) </li> <li class="cat-item cat-item-82"> <a href="/blog/archives/category/vibrational-frequencies">vibrational frequencies</a> (3) </li> </ul> </li> <li class="box"> <h2> Monthly </h2> <ul> <li><a href="/blog/archives/date/2019/06">June 2019</a></li> <li><a href="/blog/archives/date/2019/04">April 2019</a></li> <li><a href="/blog/archives/date/2019/03">March 2019</a></li> <li><a href="/blog/archives/date/2019/02">February 2019</a></li> <li><a href="/blog/archives/date/2019/01">January 2019</a></li> <li><a href="/blog/archives/date/2018/12">December 2018</a></li> <li><a href="/blog/archives/date/2018/11">November 2018</a></li> <li><a href="/blog/archives/date/2018/10">October 2018</a></li> <li><a href="/blog/archives/date/2018/09">September 2018</a></li> <li><a href="/blog/archives/date/2018/08">August 2018</a></li> <li><a href="/blog/archives/date/2018/07">July 2018</a></li> <li><a href="/blog/archives/date/2018/06">June 2018</a></li> <li><a href="/blog/archives/date/2018/05">May 2018</a></li> <li><a href="/blog/archives/date/2018/04">April 2018</a></li> <li><a href="/blog/archives/date/2018/03">March 2018</a></li> <li><a href="/blog/archives/date/2018/02">February 2018</a></li> <li><a href="/blog/archives/date/2018/01">January 2018</a></li> <li><a href="/blog/archives/date/2017/12">December 2017</a></li> <li><a href="/blog/archives/date/2017/11">November 2017</a></li> <li><a href="/blog/archives/date/2017/10">October 2017</a></li> <li><a href="/blog/archives/date/2017/09">September 2017</a></li> <li><a href="/blog/archives/date/2017/08">August 2017</a></li> <li><a href="/blog/archives/date/2017/07">July 2017</a></li> <li><a href="/blog/archives/date/2017/06">June 2017</a></li> <li><a href="/blog/archives/date/2017/05">May 2017</a></li> <li><a href="/blog/archives/date/2017/04">April 2017</a></li> <li><a href="/blog/archives/date/2017/03">March 2017</a></li> <li><a href="/blog/archives/date/2017/02">February 2017</a></li> <li><a href="/blog/archives/date/2017/01">January 2017</a></li> <li><a href="/blog/archives/date/2016/12">December 2016</a></li> <li><a href="/blog/archives/date/2016/11">November 2016</a></li> <li><a href="/blog/archives/date/2016/10">October 2016</a></li> <li><a href="/blog/archives/date/2016/09">September 2016</a></li> <li><a href="/blog/archives/date/2016/08">August 2016</a></li> <li><a href="/blog/archives/date/2016/07">July 2016</a></li> <li><a href="/blog/archives/date/2016/06">June 2016</a></li> <li><a href="/blog/archives/date/2016/05">May 2016</a></li> <li><a href="/blog/archives/date/2016/04">April 2016</a></li> <li><a href="/blog/archives/date/2016/03">March 2016</a></li> <li><a href="/blog/archives/date/2016/02">February 2016</a></li> <li><a href="/blog/archives/date/2016/01">January 2016</a></li> <li><a href="/blog/archives/date/2015/12">December 2015</a></li> <li><a href="/blog/archives/date/2015/11">November 2015</a></li> <li><a href="/blog/archives/date/2015/10">October 2015</a></li> <li><a href="/blog/archives/date/2015/09">September 2015</a></li> <li><a href="/blog/archives/date/2015/08">August 2015</a></li> <li><a href="/blog/archives/date/2015/07">July 2015</a></li> <li><a href="/blog/archives/date/2015/06">June 2015</a></li> <li><a href="/blog/archives/date/2015/05">May 2015</a></li> <li><a href="/blog/archives/date/2015/04">April 2015</a></li> <li><a href="/blog/archives/date/2015/03">March 2015</a></li> <li><a href="/blog/archives/date/2015/02">February 2015</a></li> <li><a href="/blog/archives/date/2015/01">January 2015</a></li> <li><a href="/blog/archives/date/2014/12">December 2014</a></li> <li><a href="/blog/archives/date/2014/11">November 2014</a></li> <li><a href="/blog/archives/date/2014/10">October 2014</a></li> <li><a href="/blog/archives/date/2014/09">September 2014</a></li> <li><a href="/blog/archives/date/2014/08">August 2014</a></li> <li><a href="/blog/archives/date/2014/07">July 2014</a></li> <li><a href="/blog/archives/date/2014/06">June 2014</a></li> <li><a href="/blog/archives/date/2014/05">May 2014</a></li> <li><a href="/blog/archives/date/2014/04">April 2014</a></li> <li><a href="/blog/archives/date/2014/03">March 2014</a></li> <li><a href="/blog/archives/date/2014/02">February 2014</a></li> <li><a href="/blog/archives/date/2014/01">January 2014</a></li> <li><a href="/blog/archives/date/2013/12">December 2013</a></li> <li><a href="/blog/archives/date/2013/11">November 2013</a></li> <li><a href="/blog/archives/date/2013/10">October 2013</a></li> <li><a href="/blog/archives/date/2013/09">September 2013</a></li> <li><a href="/blog/archives/date/2013/08">August 2013</a></li> <li><a href="/blog/archives/date/2013/07">July 2013</a></li> <li><a href="/blog/archives/date/2013/06">June 2013</a></li> <li><a href="/blog/archives/date/2013/05">May 2013</a></li> <li><a href="/blog/archives/date/2013/04">April 2013</a></li> <li><a href="/blog/archives/date/2013/03">March 2013</a></li> <li><a href="/blog/archives/date/2013/02">February 2013</a></li> <li><a href="/blog/archives/date/2013/01">January 2013</a></li> <li><a href="/blog/archives/date/2012/12">December 2012</a></li> <li><a href="/blog/archives/date/2012/11">November 2012</a></li> <li><a href="/blog/archives/date/2012/10">October 2012</a></li> <li><a href="/blog/archives/date/2012/09">September 2012</a></li> <li><a href="/blog/archives/date/2012/08">August 2012</a></li> <li><a href="/blog/archives/date/2012/07">July 2012</a></li> <li><a href="/blog/archives/date/2012/06">June 2012</a></li> <li><a href="/blog/archives/date/2012/05">May 2012</a></li> <li><a href="/blog/archives/date/2012/04">April 2012</a></li> <li><a href="/blog/archives/date/2012/03">March 2012</a></li> <li><a href="/blog/archives/date/2012/02">February 2012</a></li> <li><a href="/blog/archives/date/2012/01">January 2012</a></li> <li><a href="/blog/archives/date/2011/12">December 2011</a></li> <li><a href="/blog/archives/date/2011/11">November 2011</a></li> <li><a href="/blog/archives/date/2011/10">October 2011</a></li> <li><a href="/blog/archives/date/2011/09">September 2011</a></li> <li><a href="/blog/archives/date/2011/08">August 2011</a></li> <li><a href="/blog/archives/date/2011/07">July 2011</a></li> <li><a href="/blog/archives/date/2011/06">June 2011</a></li> <li><a href="/blog/archives/date/2011/05">May 2011</a></li> <li><a href="/blog/archives/date/2011/04">April 2011</a></li> <li><a href="/blog/archives/date/2011/03">March 2011</a></li> <li><a href="/blog/archives/date/2011/02">February 2011</a></li> <li><a href="/blog/archives/date/2011/01">January 2011</a></li> <li><a href="/blog/archives/date/2010/12">December 2010</a></li> <li><a href="/blog/archives/date/2010/11">November 2010</a></li> <li><a href="/blog/archives/date/2010/10">October 2010</a></li> <li><a href="/blog/archives/date/2010/09">September 2010</a></li> <li><a href="/blog/archives/date/2010/08">August 2010</a></li> <li><a href="/blog/archives/date/2010/07">July 2010</a></li> <li><a href="/blog/archives/date/2010/06">June 2010</a></li> <li><a href="/blog/archives/date/2010/05">May 2010</a></li> <li><a href="/blog/archives/date/2010/04">April 2010</a></li> <li><a href="/blog/archives/date/2010/03">March 2010</a></li> <li><a href="/blog/archives/date/2010/02">February 2010</a></li> <li><a href="/blog/archives/date/2010/01">January 2010</a></li> <li><a href="/blog/archives/date/2009/12">December 2009</a></li> <li><a href="/blog/archives/date/2009/11">November 2009</a></li> <li><a href="/blog/archives/date/2009/10">October 2009</a></li> <li><a href="/blog/archives/date/2009/09">September 2009</a></li> <li><a href="/blog/archives/date/2009/08">August 2009</a></li> <li><a href="/blog/archives/date/2009/07">July 2009</a></li> <li><a href="/blog/archives/date/2009/06">June 2009</a></li> <li><a href="/blog/archives/date/2009/05">May 2009</a></li> <li><a href="/blog/archives/date/2009/04">April 2009</a></li> <li><a href="/blog/archives/date/2009/03">March 2009</a></li> <li><a href="/blog/archives/date/2009/02">February 2009</a></li> <li><a href="/blog/archives/date/2009/01">January 2009</a></li> <li><a href="/blog/archives/date/2008/12">December 2008</a></li> <li><a href="/blog/archives/date/2008/11">November 2008</a></li> <li><a href="/blog/archives/date/2008/10">October 2008</a></li> <li><a href="/blog/archives/date/2008/09">September 2008</a></li> <li><a href="/blog/archives/date/2008/08">August 2008</a></li> <li><a href="/blog/archives/date/2008/07">July 2008</a></li> <li><a href="/blog/archives/date/2008/06">June 2008</a></li> <li><a href="/blog/archives/date/2008/05">May 2008</a></li> <li><a href="/blog/archives/date/2008/04">April 2008</a></li> <li><a href="/blog/archives/date/2008/03">March 2008</a></li> <li><a href="/blog/archives/date/2008/02">February 2008</a></li> <li><a href="/blog/archives/date/2008/01">January 2008</a></li> <li><a href="/blog/archives/date/2007/12">December 2007</a></li> <li><a href="/blog/archives/date/2007/11">November 2007</a></li> <li><a href="/blog/archives/date/2007/10">October 2007</a></li> <li><a href="/blog/archives/date/2007/09">September 2007</a></li> <li><a href="/blog/archives/date/2007/08">August 2007</a></li> <li><a href="/blog/archives/date/2007/07">July 2007</a></li> </ul> </li> </ul> <a rel="license" href="https://creativecommons.org/licenses/by-nd/3.0/"> <img alt="Creative Commons License" style="border-width:0" 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