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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 » 2016 » June</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 June, 2016</h2> <div class="box"> <h2><a href="/blog/archives/3799" rel="bookmark" title="Permanent Link: Predicting chemical structure using DP4+">Predicting chemical structure using DP4+</a></h2> <div class="post-content"> <p>Structure determination has been greatly facilitated by the use of computed NMR spectra to compare with experimental spectra. Perhaps the best method for doing this is the DP4 procedure developed by Smith and Goodman.<a href="#dp4plus1"><sup>1</sup></a> (I have a <a href="/blog/archives/1159">previous post on their paper</a>.) The basic idea is that if you have an experimental NMR spectrum and a number of potential structures, the computed spectra for each possibility are ranked by a statistical treatment based on the Student t-test.</p> <p>Grimblat, Zanardi, and Sarotti question a couple of the assumptions embedded within the DP4 method, and offer a revision that they call DP4+.<a href="#dp4plus2"><sup>2</sup></a> The two assumptions are (1) that the chemical shifts are computed at B3LYP/6-31G**//MMFF and (2) that the chemical shifts are scaled and then utilized in the analysis.</p> <p>To test these assumptions, they examine a set of 72 organic compounds comprising 1219 <sup>13</sup>C shifts and 1123 <sup>1</sup>H shifts. They optimized the structures at B3LYP/6-31G* and computed the chemical shifts of these compounds using the B3LYP and mPW1PW91 functionals with 6 basis sets (6-31G*, 6-31G**, 6-31+G**, 6-311G*, 6-311G**, and 6-311+G**). With all of the combinations, the standard deviation of both the proton and carbon chemical shifts were significantly smaller than with the originally proposed method.</p> <p>With regards to the second assumption, they define a new probability functions that multiplies the error using scaled chemical shifts with the error using unscaled chemical shifts, and this they call DP4+. Again with all of the computational methods, the DP4+ prediction outperforms the DP4 prediction.</p> <p>As a test case, they looked at cryptomoscatone D1 and D2 (<b>1</b>), for which the structures were determined with traditional methods. DP4 predicts that both cryptomoscatone D1 and D2 are structure <b>1d</b>. However, DP4+ correctly predicts that cryptomoscatone D1 is <b>1b</b> and cryptomoscatone D2 is <b>1a</b>.</p> <p align="center"><img src="/blog/wp-content/DP4Pimg1.png"></p> <p>Lin and Tagliatatela-Scafati have reported the use of DP4+ to aid in the structure determination of plakdiepoxide <b>2</b>.<a href="#dp4plus3"><sup>3</sup></a> ROESY NMR could not provide definitive judgement of the stereochemical relationship about the bond between the two epoxide rings. They computed a number of conformers of the model compounds <b>2a</b> and <b>2b</b> at B3LYP/6-31G(d). The computed chemical shifts were then used with the DP4+ procedure to determine that the structure has the stereochemistry of <b>2b</b>.</p> <p align="center"><img src="/blog/wp-content/DP4Pimg2.png"></p> <h3>References</h3> <p><a name="dp4plus1"></a></p> <p>(1) Smith, S. G.; Goodman, J. M. "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," <i>J. Am. Chem. Soc.</i> <b>2010</b>, <i>132</i>, 12946-12959, DOI: <a href="http://dx.doi.org/10.1021/ja105035r">10.1021/ja105035r</a>.</p> <p><a name="dp4plus2"></a></p> <p>(2) Grimblat, N.; Zanardi, M. M.; Sarotti, A. M. "Beyond DP4: an Improved Probability<br> for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts," <i>J. Org. Chem.</i> <b>2015</b>, <i>80</i>, 12526-12534, DOI: <a href="http://dx.doi.org/10.1021/acs.joc.5b02396">10.1021/acs.joc.5b02396</a>.</p> <p><a name="dp4plus3"></a></p> <p>(3) Chianese, G.; Yu, H.-B.; Yang, F.; Sirignano, C.; Luciano, P.; Han, B.-N.; Khan, S.; Lin, H.-W.; Taglialatela-Scafati, O. "PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity," <i>J. Org. Chem.</i> <b>2016</b>, <i>81</i> (12), 5135–5143, DOI: <a href="http://dx.doi.org/10.1021/acs.joc.6b00695">10.1021/acs.joc.6b00695</a>.</p> <h3>InChIs</h3> <p>Cryptomoscatone D1: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15-,16-/m1/s1<br>InChIKey=GOQOIZFMLWZVMB-OUUZNBFFSA-N</p> <p>Cryptomoscatone D2: InChI=1S/C17H20O4/c18-14(10-9-13-5-2-1-3-6-13)11-15(19)12-16-7-4-8-17(20)21-16/h1-6,8-10,14-16,18-19H,7,11-12H2/b10-9+/t14-,15+,16+/m0/s1<br>InChIKey=GOQOIZFMLWZVMB-GLBZDCTLSA-N</p> <p>plakdiepoxide: InChI=1S/C18H32O4/c1-6-9-10-13(4)12-17(7-2)16(22-17)18(8-3)14(21-18)11-15(19)20-5/h13-14,16H,6-12H2,1-5H3/t13?,14-,16-,17+,18-/m0/s1<br>InChIKey=YZQCELNTSCPAPG-KSZMJELXSA-N</p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/nmr" rel="category tag">NMR</a></span> <span class="user">Steven Bachrach</span> <span class="date">20 Jun 2016</span> <span class="comments"><a href="/blog/archives/3799#comments">2 Comments</a></span> </p> </div> <div class="box"> <h2><a href="/blog/archives/3781" rel="bookmark" title="Permanent Link: Mechanism of dimethyldioxirane oxidation">Mechanism of dimethyldioxirane oxidation</a></h2> <div class="post-content"> <p>Dimethyldioxirane can oxidize alkanes to alcohols. The mechanism for the oxidation has been controversial, ranging from concerted, to radical intermediates to an H-abstraction—O-rebound mechanism. Yang, Yu, and Houk now offer a molecular dynamics examination of the reaction of dimethyldioxirane with isobutane.<a href="#dmdo1"><sup>1</sup></a></p> <p>Gas–phase (U)B3LYP/6-311++G(d,p)//(U)B3LYP/6-31G(d) computations give critical points outlined in the reaction below. The structures of the transition states and the intermediate are shown in Figure 1.</p> <p align="center"><img src="/blog/wp-content/DMDOimg.png"></p> <table align="center" border="0" cellspacing="0" cellpadding="4"> <tr align="center" valign="bottom"> <td> <p></p> <div class="jmol" id="DMDOts1"> <a onclick="return false"><br> <img src="/blog/wp-content/DMDOts1.jpg" onclick="insertJmol('DMDOts1',300,300,'DMDOts1.xyz')"></a> </div> <p><b>TS1</b><br>26.6<br>(25.9)</p> </td> <td> <p></p> <div class="jmol" id="DMDOint"> <a onclick="return false"><br> <img src="/blog/wp-content/DMDOint.jpg" onclick="insertJmol('DMDOint',300,300,'DMDOint.xyz')"></a> </div> <p><b>INT</b><br>8.6<br>(9.3)</p> </td> </tr> <tr> </tr> <tr align="center" valign="bottom"> <td> <p></p> <div class="jmol" id="DMDOts2"> <a onclick="return false"><br> <img src="/blog/wp-content/DMDOts2.jpg" onclick="insertJmol('DMDOts2',300,300,'DMDOts2.xyz')"></a> </div> <p><b>TS2</b><br>8.6<br>(-0.8)</p> </td> </tr> </table> <p><b>Figure 1</b>. (U)B3LYP/6-31G(d) optimized geometries of <b>TS1</b>, <b>INT</b>, and <b>TS2</b>. Relative free energies (kcal mol<sup>-1</sup>) in the gas (top) and solution (bottom) phases</p> <p>The PES indicates a rebound mechanism, though in acetone solution phase, there was no transition state located for the second step; it appears to be barrierless. It should be noted that the size of the barrier is very small even in the gas phase. The energy given in Figure 1 is for the gas phase structure computed in solution.</p> <p>Trajectories for both gas and solution phase were computed. For the gas phase, about 90% of the trajectories lead to separated radicals, but in an acetone about 90% of the trajectories lead directly to the alcohol, with only 10% leading to radicals. Even so, the acetone trajectories divide into two types, a dynamically concerted path where the time gap between the formation of the new C-O and O-H bonds is less than 60 fs, and a dynamically stepwise path where the time gap is greater than 60 fs, though for the trajectories that lead to product the gap is typically still less than 150 fs.</p> <h3>References</h3> <p><a name="dmdo1"></a></p> <p>(1) Yang, Z.; Yu, P.; Houk, K. N. "Molecular Dynamics of Dimethyldioxirane C–H Oxidation," <i>J. Am. Chem. Soc.</i> <b>2016</b>, <i>138</i>, 4237-4242, DOI: <a ref="http://dx.doi.org/10.1021/jacs.6b01028">10.1021/jacs.6b01028</a>.</p> <h3>InChIs</h3> <p><b>Dimethyldioxirane</b>: InChI=1S/C3H6O2/c1-3(2)4-5-3/h1-2H3<br>InChIKey=FFHWGQQFANVOHV-UHFFFAOYSA-N</p> <p><b>Isobutane</b>: InChI=1S/C4H10/c1-4(2)3/h4H,1-3H3<br>InChIKey=NNPPMTNAJDCUHE-UHFFFAOYSA-N</p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/authors/houk" rel="category tag">Houk</a></span> <span class="user">Steven Bachrach</span> <span class="date">06 Jun 2016</span> <span class="comments"><a href="/blog/archives/3781#respond">No Comments</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 href="/blog/archives/category/acidity">Acidity</a> (12) </li> <li class="cat-item cat-item-3"> <a href="/blog/archives/category/aromaticity">Aromaticity</a> (91) </li> <li class="cat-item cat-item-53"> <a 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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" aria-current="page">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" src="https://i.creativecommons.org/l/by-nd/3.0/88x31.png"> </a> <br>This work is licensed under a <a rel="license" href="https://creativecommons.org/licenses/by-nd/3.0/">Creative Commons Attribution-No Derivative Works 3.0 Unported License</a>. </div>  <div class="clear"></div> </div>  <div id="footer"> <p>Copyright © 2021 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