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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 » 2015 » February</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 February, 2015</h2> <div class="box"> <h2><a href="/blog/archives/3457" rel="bookmark" title="Permanent Link: Microsolvated structure of β-propiolactone">Microsolvated structure of β-propiolactone</a></h2> <div class="post-content"> <p>The structure of water about a solute remains of critical importance towards understanding aqueous solvation. Microwave spectroscopy and computations are the best tools we have today to gain insight on this problem. This is nicely demonstrated in the Alonso study of the microsolvated structures of β-propiolactone <b>1</b>.<a href="#bpl"><sup>1</sup></a> They employed chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy and MP2(fc)/6-311++G(d,p) computations to examine the structure involving 1-5 water molecules.</p> <p align="center"><img src="/blog/wp-content/BPLimg.png"></p> <p>The computed structures of these microsolvated species are shown in Figure 1. The deviation of the computed and experimental structures (RMS in the atomic positions) is small, though increasing as the size of the cluster increases. The deviation is 0.014 Å for the <b>1</b><sup>. </sup>H<sub>2</sub>O cluster and 0.244 Å for the <b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>5</sub> cluster. They identified two clusters with four water molecules; the lower energy structure, labeled as <b>a</b>, is only 0.2 kJ mol<sup>-1</sup> more stable than structure <b>b</b>.</p> <table align="center" border="0" cellspacing="0" cellpadding="4"> <tr align="center" valign="bottom"> <td> <p></p> <div class="jmol" id="BPL1"> <a onclick="return false"><br> <img src="/blog/wp-content/1hydrateBPL.png" onclick="insertJmol('BPL1',300,300,'1hydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>H<sub>2</sub>O</p> </td> <td> <p></p> <div class="jmol" id="BPL2"> <a onclick="return false"><br> <img src="/blog/wp-content/2hydrateBPL.png" onclick="insertJmol('BPL2',300,300,'2hydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>2</sub></p> </td> </tr> <tr align="center" valign="bottom"> <td colspan="2"> <p></p> <div class="jmol" id="BPL3"> <a onclick="return false"><br> <img src="/blog/wp-content/3hydrateBPL.png" onclick="insertJmol('BPL3',300,300,'3hydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>3</sub></p> </td> </tr> <tr align="center" valign="bottom"> <td> <p></p> <div class="jmol" id="BPL4A"> <a onclick="return false"><br> <img src="/blog/wp-content/4AhydrateBPL.png" onclick="insertJmol('BPL4A',300,300,'4AhydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>4</sub> <b>a</b></p> </td> <td> <p></p> <div class="jmol" id="BPL4B"> <a onclick="return false"><br> <img src="/blog/wp-content/4BhydrateBPL.png" onclick="insertJmol('BPL4B',300,300,'4BhydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>4</sub> <b>b</b></p> </td> </tr> <tr align="center" valign="bottom"> <td colspan="2"> <p></p> <div class="jmol" id="BPL5"> <a onclick="return false"><br> <img src="/blog/wp-content/5hydrateBPL.png" onclick="insertJmol('BPL5',300,300,'5hydrateBPL.xyz')"></a> </div> <p><b>1</b><sup>.</sup>(H<sub>2</sub>O)<sub>5</sub></p> </td> </tr> </table> <p align="center"><b>Figure 1</b>. MP2(fc)/6-311++G(d,p) optimized geometries of the hydrates of <b>1</b>.</p> <p>Water rings are found in the clusters having four or five water molecules, while chains are identified in the smaller clusters. One might imagine water cages appearing with even more water molecules in the microsolvated structures.</p> <h3>References</h3> <p><a name="bpl"></a></p> <p>(1) Pérez, C.; Neill, J. L.; Muckle, M. T.; Zaleski, D. P.; Peña, I.; Lopez, J. C.; Alonso, J. L.; Pate, B. H. <i>Angew. Chem. Int. Ed.</i> <b>2015</b>, <i>54</i>, 979-982, DOI: <a href="http://dx.doi.org/10.1002/anie.201409057">10.1002/anie.201409057</a>.</p> <h3>InChIs</h3> <p><b>1</b>: InChI=1S/C3H4O2/c4-3-1-2-5-3/h1-2H2<br>InChIKey=VEZXCJBBBCKRPI-UHFFFAOYSA-N</p>  </div> <p class="bottom"> <span class="cat"><a href="/blog/archives/category/qm-method/mp" rel="category tag">MP</a> &<a href="/blog/archives/category/solvation" rel="category tag">Solvation</a></span> <span class="user">Steven Bachrach</span> <span class="date">24 Feb 2015</span> <span class="comments"><a href="/blog/archives/3457#comments">1 Comment</a></span> </p> </div> <div class="box"> <h2><a href="/blog/archives/3440" rel="bookmark" title="Permanent Link: Structures of cephalosporolide C, J, and bassianolone">Structures of cephalosporolide C, J, and bassianolone</a></h2> <div class="post-content"> <p>Here is a story that must drive chemical database quality control personnel nuts. Song, et al. noticed that the reported <sup>13</sup>C NMR of the natural products cephalosporolide C <b>1</b>, cephalosporolide J <b>2</b> and bassianolone <b>3</b> are identical.<a href="#cephalospor1"><sup>1</sup></a> Given that it is highly unlikely that two diastereomers would have identical NMR spectra, the likelihood that these three have identical spectra seemed remote at best.</p> <p align="center"><img src="/blog/wp-content/cephalImg.png"></p> <p>Compounds <b>1</b> and <b>2</b> were synthesized and their structures confirmed by x-ray crystallography. Their <sup>13</sup>C NMR spectra show clear distinctions, indicating that the isolated “<b>2</b>” is actually <b>1</b>. Experimental support for the notion that <b>1</b> and <b>3</b> are actually the same was provided by preparing the diacetylide of <b>1</b> and comparing its NMR spectra to that of natural <b>“3”</b>.</p> <p>Quantum computations confirmed that in fact the natural product thought to be <b>3</b> is actually <b>1</b>. The structures of <b>1</b> and <b>3</b> were optimized at B3LYP/6-311+G(2d,p) and <sup>13</sup>C chemical shifts were computed with these geometries at mPW1PW91/6-311+G(2d,p)/CPCM(chloroform). (The computed structures are shown in Figure 1.) The mean absolute deviation (MAD) between the computed and experimental spectra for <b>1</b> is 0.97 ppm, while the MAD for the computed spectrum of <b>3</b> compared with the experimental values is 2.44 ppm, with a maximum error of 5.13ppm, more than twice the maximum error with structure <b>1</b>. The authors attribute the misassignments to a faulty initial spectra of authentic cephalosporolide C <b>1</b>.</p> <table align="center" border="0" cellspacing="0" cellpadding="4"> <tr align="center"> <td> <p></p> <div class="jmol" id="cephal1"> <a onclick="return false"><br> <img src="/blog/wp-content/cephal1.png" onclick="insertJmol('cephal1',300,300,'cephal1.xyz')"></a> </div> <p><b>1</b></p> </td> <td> <p></p> <div class="jmol" id="cephal3"> <a onclick="return false"><br> <img src="/blog/wp-content/cephal3.png" onclick="insertJmol('cephal3',300,300,'cephal3.xyz')"></a> </div> <p><b>3</b></p> </td> </tr> </table> <p align="center"><b>Figure 1</b>. B3LYP/6-311+G(2d,p) optimized geometries of <b>1</b> and <b>3</b>.</p> <h3>References</h3> <p><a name="cephalospor1"></a></p> <p>(1) Song, L.; Lee, K.-H.; Lin, Z.; Tong, R. "Structural Revision of Cephalosporolide J and Bassianolone," <i>J. Org. Chem.</i> <b>2014</b>, <i>79</i>, 1493-1497, DOI: <a href="http://dx.doi.org/10.1021/jo402602h">10.1021/jo402602h</a>.</p> <h3>InChIs</h3> <p><b>1</b>: InChI=1S/C10H16O5/c1-6-2-3-7(11)4-8(12)9(13)5-10(14)15-6/h6,8-9,12-13H,2-5H2,1H3/t6-,8+,9+/m1/s1<br>InChIKey=JTOYXZZLKBAIEJ-YEPSODPASA-N</p> <p><b>2</b>: InChI=1S/C10H16O5/c1-6-2-3-7(11)4-8(12)9(13)5-10(14)15-6/h6,8-9,12-13H,2-5H2,1H3/t6-,8+,9-/m1/s1<br>InChIKey=JTOYXZZLKBAIEJ-BWVDBABLSA-N</p> <p><b>3</b>: InChI=1S/C10H16O5/c1-6(11)2-3-7(12)4-9-8(13)5-10(14)15-9/h6,8-9,11,13H,2-5H2,1H3/t6-,8+,9+/m1/s1<br>InChIKey=ZTRQRDNTNXPRFW-YEPSODPASA-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">16 Feb 2015</span> <span class="comments"><a href="/blog/archives/3440#respond">No Comments</a></span> </p> </div> <div class="box"> <h2><a href="/blog/archives/3438" rel="bookmark" title="Permanent Link: Protocol for computing NMR chemical shifts">Protocol for computing NMR chemical shifts</a></h2> <div class="post-content"> <p>I have posted on the use of <a href="/blog/archives/category/nmr">computed NMR chemical shifts and coupling constants to help aid in structure identification</a>. The second edition of my book <i>Computational Organic Chemistry</i> has a largely all-new chapter on structure identification aided by computed spectra, especially NMR spectra. In my recent opinion piece speculating on challenges in computational organic chemistry,<a href="#nmrProtocal1"><sup>1</sup></a> the first area I highlight is encouraging the larger use of computed spectra as an essential component of structure determination.</p> <p>While more and more non-traditional computational users are employing quantum computations towards these problems, I suspect that many non-users are a bit wary about stepping into an arena they are not expert in, an arena chock-filled with acronyms and methods and potentially little guidance. While some very nice papers<a href="#nmrProtocal2"><sup>2-6</sup></a> and web sites (<a href="http://cheshirenmr.info/">Chemical Shift Repository (Cheshire)</a> and <a href="http://www-jmg.ch.cam.ac.uk/tools/nmr/DP4/">DP4</a>) do outline procedures for using computations in this fashion, they are not truly designed for the non-specialist.</p> <p>Well, fear not any longer. Hoye and coworkers, synthetic chemists who have utilized computational approaches in structure determinations for a number of years, have written a detailed step-by-step protocol for using a standard computational approach towards structure determination.<a href="#nmrProtocal7"><sup>7</sup></a> The article is written with the synthetic chemist in mind, and includes a number of scripts to automate many of the steps.</p> <p>For the specialist, the overall outline of the protocol is fairly routine:</p> <ol> <li>Utilize MacroModel to perform a conformational search for each proposed structure, retaining the geometries within 5 kcal mol<sup>-1</sup> of the global minimum.</li> <li>Optimize these conformations for each structure at M06-2x/6-31+G(d).</li> <li>For each conformation of each structure, compute the <sup>1</sup>H and <sup>13</sup>C chemical shifts, scale them, and determine the Boltzmann weighted chemical shifts</li> <li>Compare these chemical shifts with the experimental values using Mean Absolute Error</li> </ol> <p>The article is straightforward and easily guides the novice user through these steps. Anyone unsure of how to utilize quantum chemical computations in structure determination is well advised to start with this article.</p> <h3>References</h3> <p><a name="nmrProtocal1"></a></p> <p>(1) Bachrach, S. M. "Challenges in computational organic chemistry," <i>WIRES: Comput. Mol. Sci.</i> <b>2014</b>, <i>4</i>, 482-487, DOI: <a href="http://dx.doi.org/10.1002/wcms.1185">10.1002/wcms.1185</a>.</p> <p><a name="nmrProtocal2"></a></p> <p>(2) Lodewyk, M. W.; Siebert, M. R.; Tantillo, D. J. "Computational Prediction of <sup>1</sup>H and <sup>13</sup>C Chemical Shifts: A Useful Tool for Natural Product, Mechanistic, and Synthetic Organic Chemistry," <i>Chem. Rev.</i> <b>2012</b>, <i>112</i>, 1839–1862, DOI: <a href="http://dx.doi.org/10.1021/cr200106v">10.1021/cr200106v</a>.</p> <p>(3) Bally, T.; Rablen, P. R. "Quantum-Chemical Simulation of <sup>1</sup>H NMR Spectra. 2. Comparison of DFT-Based Procedures for Computing Proton-Proton Coupling Constants in Organic Molecules," <i>J. Org. Chem.</i> <b>2011</b>, <i>76</i>, 4818-4830, DOI: <a href="http://dx.doi.org/10.1021/jo200513q">10.1021/jo200513q</a>.></p> <p>(4) Jain, R.; Bally, T.; Rablen, P. R. "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," <i>J. Org. Chem.</i> <b>2009</b>, <i>74</i>, 4017-4023, DOI: <a href="http://dx.doi.org/10.1021/jo900482q">10.1021/jo900482q</a>.</p> <p>(5) Smith, S. G.; Goodman, J. M. "Assigning the Stereochemistry of Pairs of Diastereoisomers Using GIAO NMR Shift Calculation," <i>J. Org. Chem.</i> <b>2009</b>, <i>74</i>, 4597-4607, DOI: <a href="http://dx.doi.org/10.1021/jo900408d">10.1021/jo900408d</a>.</p> <p>(6) 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="nmrProtocal7"></a></p> <p>(7) Willoughby, P. H.; Jansma, M. J.; Hoye, T. R. "A guide to small-molecule structure assignment through computation of (1H and 13C) NMR chemical shifts," <i>Nat. Protocols</i> <b>2014</b>, <i>9</i>, 643-660, DOI: <a href="http://dx.doi.org/10.1038/nprot.2014.042">10.1038/nprot.2014.042</a>.</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">09 Feb 2015</span> <span class="comments"><a href="/blog/archives/3438#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 href="/blog/archives/category/authors">Authors</a> (153) <ul class="children"> <li class="cat-item cat-item-42"> <a href="/blog/archives/category/authors/borden">Borden</a> (12) </li> <li class="cat-item cat-item-12"> <a 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href="/blog/archives/category/molecules/phenyloxenium">phenyloxenium</a> (1) </li> <li class="cat-item cat-item-8"> <a href="/blog/archives/category/molecules/polycyclic-aromatics">polycyclic aromatics</a> (7) </li> <li class="cat-item cat-item-50"> <a href="/blog/archives/category/molecules/propellane">propellane</a> (2) </li> <li class="cat-item cat-item-79"> <a href="/blog/archives/category/molecules/stilbene">stilbene</a> (1) </li> <li class="cat-item cat-item-80"> <a href="/blog/archives/category/molecules/sugars">sugars</a> (5) </li> <li class="cat-item cat-item-85"> <a href="/blog/archives/category/molecules/terpenes">terpenes</a> (2) </li> <li class="cat-item cat-item-89"> <a href="/blog/archives/category/molecules/twistane">twistane</a> (1) </li> </ul> </li> <li class="cat-item cat-item-22"> <a href="/blog/archives/category/nmr">NMR</a> (40) </li> <li class="cat-item cat-item-31"> <a href="/blog/archives/category/optical-rotation">Optical Rotation</a> (16) </li> <li class="cat-item cat-item-28"> <a href="/blog/archives/category/qm-method">QM Method</a> (96) <ul class="children"> <li class="cat-item cat-item-20"> <a href="/blog/archives/category/qm-method/caspt2">CASPT2</a> (1) </li> <li class="cat-item cat-item-7"> <a href="/blog/archives/category/qm-method/dft">DFT</a> (71) </li> <li class="cat-item cat-item-45"> <a href="/blog/archives/category/qm-method/focal-point">focal point</a> (7) </li> <li class="cat-item cat-item-14"> <a href="/blog/archives/category/qm-method/g3">G3</a> (3) </li> <li class="cat-item cat-item-60"> <a href="/blog/archives/category/qm-method/mp">MP</a> (11) </li> </ul> </li> <li class="cat-item cat-item-56"> <a href="/blog/archives/category/reactions">Reactions</a> (83) <ul class="children"> <li class="cat-item cat-item-13"> <a href="/blog/archives/category/reactions/12-addition">1,2-addition</a> (1) </li> <li class="cat-item cat-item-35"> <a href="/blog/archives/category/reactions/aldol">aldol</a> (4) </li> <li class="cat-item cat-item-32"> <a href="/blog/archives/category/reactions/bergman-cyclization">Bergman cyclization</a> (6) </li> <li class="cat-item cat-item-44"> <a href="/blog/archives/category/reactions/claisen-rearrangement">Claisen rearrangement</a> (2) </li> <li class="cat-item cat-item-10"> <a href="/blog/archives/category/reactions/cope-rearrangement">Cope Rearrangement</a> (5) </li> <li class="cat-item cat-item-69"> <a href="/blog/archives/category/reactions/cycloadditions">cycloadditions</a> (12) </li> <li class="cat-item cat-item-23"> <a href="/blog/archives/category/reactions/diels-alder">Diels-Alder</a> (26) </li> <li class="cat-item cat-item-47"> <a href="/blog/archives/category/reactions/electrocyclization">electrocyclization</a> (11) </li> <li class="cat-item cat-item-76"> <a href="/blog/archives/category/reactions/electrophilic-aromatic-substitution">electrophilic aromatic substitution</a> (1) </li> <li class="cat-item cat-item-5"> <a href="/blog/archives/category/reactions/ene-reaction">ene reaction</a> (1) </li> <li class="cat-item cat-item-52"> <a href="/blog/archives/category/reactions/hajos-parrish-reaction">Hajos-Parrish Reaction</a> (1) </li> <li class="cat-item cat-item-61"> <a href="/blog/archives/category/reactions/mannich">Mannich</a> (2) </li> <li class="cat-item cat-item-64"> <a href="/blog/archives/category/reactions/michael-addition">Michael addition</a> (5) </li> <li class="cat-item cat-item-40"> <a href="/blog/archives/category/reactions/ozonolysis">ozonolysis</a> (1) </li> <li class="cat-item cat-item-43"> <a href="/blog/archives/category/reactions/proton-transfer">proton transfer</a> (1) </li> <li class="cat-item cat-item-38"> <a href="/blog/archives/category/reactions/pseudopericyclic">pseudopericyclic</a> (4) </li> <li class="cat-item cat-item-63"> <a href="/blog/archives/category/reactions/strecker">Strecker</a> (1) </li> <li class="cat-item cat-item-24"> <a href="/blog/archives/category/reactions/substitution">Substitution</a> (6) </li> <li class="cat-item cat-item-93"> <a href="/blog/archives/category/reactions/wittig">Wittig</a> (1) </li> </ul> </li> <li class="cat-item cat-item-87"> <a href="/blog/archives/category/second-edition">Second Edition</a> (3) </li> <li class="cat-item cat-item-11"> <a href="/blog/archives/category/solvation">Solvation</a> (17) </li> <li class="cat-item cat-item-77"> <a 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" aria-current="page">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 <strong>Computational Organic Chemistry</strong>. </p> </div> </body> </html>