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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 » 2008 » December</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 December, 2008</h2> <div class="box"> <h2><a href="/blog/archives/105" rel="bookmark" title="Permanent Link: A planar cyclooctatetraene">A planar cyclooctatetraene</a></h2> <div class="post-content"> The planar substituted cyclooctatetraene 1 has been prepared and characterized.<a href="#NishR1">1</a> The B3LYP/6-31G(d) optimized geometry is shown in Figure 1. <table border="0" cellspacing="0" cellpadding="4" align="center"> <tr> <td valign="middle" align="center"> <img src="/blog/wp-content/nish-1.gif"> 1 </td> <td valign="middle" align="center"> <img src="/blog/wp-content/nish-2.gif"> 2 </td> </tr> </table> <table align="center" border="0" cellspacing="0" cellpadding="0"> <tr> <td align="center"> <div class="jmol" id="nish1C"> <a onclick="return false"> <img src="/blog/wp-content/nish1.gif" onclick="insertJmol('nish1C',200,200,'nish1.xyz')"> </a> </div> 1 </td> </tr> </table> Figure 1. B3LYP/6-31G(d) optimized geometry of 1. The 1H NMR spectrum of 1 shows the bridgehead proton has only a small upfield shift (Δδ = 0.18ppm) relative that of 2. This suggests that both molecules have similar degrees of aromaticity/antiaromaticity, and since both molecules display large bond alternation (ΔR = 0.169 Å in 1 and 0.089 Å in 2) one can argue that both paratropic and diatropic ring currents are attenuated in both molecules. However, the NICS value of 1 is 10.6 ppm, indicative of considerable antiaromatic character, though this NICS value is much reduced from that in planar cyclooctatetraene constrained to the ring geometry of 1 (22.1 ppm). Rabinowitz and Komatsu argue that large HOMO-LUMO gap of 1 is responsible for the reduced antiaromatic character of 1. Though not discussed in their paper, the aromatic stabilization (destabilization) energy of 1 can be computed. I took two approaches, shown in Reactions 1 and 2. The energies of the two reactions are -13.8 kcal mol-1 for Reaction 1 and -3.4 kcal mol-1 for Reaction 2. The large exothermicity of Reaction 1 reflects the strain of packing the four bicyclo moieties near each other, forcing the neighboring bridgehead hydrogens to be directed right at each other. The strain is better compensated in Reaction 2 by using 3 as the reference. Since 3 is of C2 symmetry, some strain relief remains a contributor to the overall reaction energy. Thus it appears that if 1 is antiaromatic, if manifests in little energetic consequence. Reaction 1 <img src="/blog/wp-content/nish-3.gif"> Reaction 2 <img src="/blog/wp-content/nish-4.gif"> <h3>References</h3> (1) Nishinaga, T.; Uto, T.; Inoue, R.; Matsuura, A.; Treitel, N.; Rabinovitz, M.; Komatsu, K., "Antiaromaticity and Reactivity of a Planar Cyclooctatetraene Fully Annelated with Bicyclo[2.1.1]hexane Units," Chem. Eur. J., 2008, 14, 2067-2074, DOI: <a href="http://dx.doi.org/10.1002/chem.200701405">10.1002/chem.200701405</a> <h3>InChIs</h3> 1: InChI=1/C24H24/c1-9-2-10(1)18-17(9)19-11-3-13(4-11)21(19)23-15-7-16(8-15)24(23)22-14-5-12(6-14)20(18)22/h9-16H,1-8H2/b19-17-,20-18-,23-21-,24-22- InChIKey=PUZMOHQGDBIGOO-LEYBOLSUBU 2: InChI=1/C18H18/c1-7-2-8(1)14-13(7)15-9-3-11(4-9)17(15)18-12-5-10(6-12)16(14)18/h7-12H,1-6H2 InChIKey=ULLLVKXTLZQQFF-UHFFFAOYAL 3: InChI=1/C14H16/c1-7-9-3-11(4-9)13(7)14-8(2)10-5-12(14)6-10/h9-12H,1-6H2/b14-13- InChIKey=CSIHJUFBXMYVBH-YPKPFQOOBF  </div> <a href="/blog/archives/category/molecules/annulenes" rel="category tag">annulenes</a> &<a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> Steven Bachrach 18 Dec 2008 <a href="/blog/archives/105#comments">1 Comment</a> </div> <div class="box"> <h2><a href="/blog/archives/104" rel="bookmark" title="Permanent Link: Arginine:water cluster">Arginine:water cluster</a></h2> <div class="post-content"> The gas phase structure of the amino acids is in their canonical or neutral form, while their aqueous solution phase structure is zwitterionic. An interesting question is how many water molecules are needed to make the zwitterionic structure more energetically favorable than the neutral form. For glycine, it appears that seven water molecules are needed to make the zwitterion the favorable tautomer.<a href="#argR1">1,2</a> Arginine, on the other hand, appears to require only one water molecule to make the zwitterion lower in energy than the neutral form.<a href="#argR3"">3</a> The B3LYP/6-311++G** structures of the lowest energy neutral (1N) and zwitterion (1Z) cluster with one water are shown in Figure 1. The zwitterion is 1.68 kcal mol-1 lower in energy. What makes this zwitterion so favorable is that the protonation occurs on the guanidine group, not on the amine group. The guanidine group is more basic than the amine. Further, the water can accept a proton from both nitrogens of the guanidine and donate a proton to the carboxylate group. <table border="0" cellspacing="0" cellpadding="3" align="center"> <tr> <td align="center"> <div class="jmol" id="argC"> <a onclick="return false"> <img src="/blog/wp-content/argC.gif" onclick="insertJmol('argC',200,200,'argC.xyz')"> </a> </div> 1N (1.68) </td> <td align="center"> <div class="jmol" id="argZ"> <a onclick="return false"> <img src="/blog/wp-content/argZ.gif" onclick="insertJmol('argZ',200,200,'argZ.xyz')"> </a> </div> 1Z (0.0) </td> </tr> </table> Figure 1. B3LYP/6-311++G** structures and relative energies (kcal mol-1) of the lowest energy arginine neutral (1N) and zwitterion (1Z) cluster with one water.<a href="#argR3"">3</a> <h3>References</h3> (1) Aikens, C. M.; Gordon, M. S., "Incremental Solvation of Nonionized and Zwitterionic Glycine," J. Am. Chem. Soc., 2006, 128, 12835-12850, DOI: <a href="http://dx.doi.org/10.1021/ja062842p">10.1021/ja062842p</a>. (2) Bachrach, S. M., "Microsolvation of Glycine: A DFT Study," j. Phys. Chem. A, 2008, 112, 3722-3730, DOI: <a href="http://dx.doi.org/10.1021/jp711048c">10.1021/jp711048c</a>. (3) Im, S.; Jang, S.-W.; Lee, S.; Lee, Y.; Kim, B., "Arginine Zwitterion is More Stable than the Canonical Form when Solvated by a Water Molecule," J. Phys. Chem. A, 2008, 112, 9767-9770, DOI: <a href="http://dx.doi.org/10.1021/jp801933y">10.1021/jp801933y</a>. <h3>InChIs</h3> 1: InChI=1/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10)/f/h8,10-11H,9H2 InChIKey=ODKSFYDXXFIFQN-MYOKTFMPCK  </div> <a href="/blog/archives/category/molecules/amino-acids" rel="category tag">amino acids</a> &<a href="/blog/archives/category/solvation" rel="category tag">Solvation</a> Steven Bachrach 15 Dec 2008 <a href="/blog/archives/104#comments">1 Comment</a> </div> <div class="box"> <h2><a href="/blog/archives/103" rel="bookmark" title="Permanent Link: Another review of Computational Organic Chemistry">Another review of Computational Organic Chemistry</a></h2> <div class="post-content"> I am grateful for another very nice review of my book Computational Organic Chemistry, this one appearing in Organic Process Research and Development written by Eddy M. E. Viseux: Org. Process Res. Dev., 2008, 12, 1313, DOI: <a href="http://dx.doi.org/10.1021/op800178c">10.1021/op800178c</a>.  </div> <a href="/blog/archives/category/uncategorized" rel="category tag">Uncategorized</a> Steven Bachrach 12 Dec 2008 <a href="/blog/archives/103#respond">No Comments</a> </div> <div class="box"> <h2><a href="/blog/archives/102" rel="bookmark" title="Permanent Link: Strain and aromaticity in the [n](2,7)pyrenophanes">Strain and aromaticity in the [n](2,7)pyrenophanes</a></h2> <div class="post-content"> Once again into the breach – how much strain can an aromatic species withstand and remain aromatic? Cyranski, Bodwell and Schleyer employ the [n](2,7)pyrenophanes 1 to explore this question.<a href="#pphaneR1">1</a> As the tethering bridge gets shorter, the pyrene framework must pucker, presumably reducing its aromatic character. Systematic shrinking allows one to examine the loss of aromaticity as defined by aromatic stabilization energy (ASE), magnetic susceptibility exaltation (Λ) and NICS, among other measures. They examined the series of pyrenophanes where the tethering chain has 6 to 12 carbon atoms. I have shown the structures of three of these compounds in Figure 1. The bend angle α is defined as the angle made between the outside ring plane and the horizon. Relative ASE is computed using Reaction 1, which cleverly avoids the complication of exactly (a) what is the ASE of pyrene itself and (b) what is the strain energy in these compounds. <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr align="center"> <td align="center"> <div class="jmol" id="pphane6"> <a onclick="return false"> <img src="/blog/wp-content/pphane6.gif" onclick="insertJmol('pphane6',200,200,'pphane6.xyz')"> </a> </div> 1a </td> <td align="center"> <div class="jmol" id="pphane9"> <a onclick="return false"> <img src="/blog/wp-content/pphane9.gif" onclick="insertJmol('pphane9',200,200,'pphane9.xyz')"> </a> </div> 1d </td> </tr> <tr> <td align="center" colspan="2"> <div class="jmol" id="pphane12"> <a onclick="return false"> <img src="/blog/wp-content/pphane12.gif" onclick="insertJmol('pphane12',200,200,'pphane12.xyz')"> </a> </div> 1g </td> </tr> </table> Figure 1. B3LYP/6-311G** optimized geometries of 1a, 1d, and 1g.<a href="#pphaneR1">1</a> Reaction 1 <img src="/blog/wp-content/pphane1.gif"> The results of the computations for this series of pyrenophanes is given in Table 1. The bending angle smoothly increases with decreasing length of the tether. The ASE decreases in the same manner. The ASE correlates quite well with the bending angle, as does the relative magnetic susceptibility exaltation. The NICS(1) values become less negative with decreasing tether length. Table 1. Computed values for the pyrenophanes. <table align="center" border="0" cellspacing="2" cellpadding="3"> <tr> <td colspan="5"> <hr> </td> </tr> <tr> <td> Compound </td> <td> αa </td> <td> ΔASEb </td> <td> Rel. Λc </td> <td> NICS(1)d </td> </tr> <tr> <td colspan="5"> <hr> </td> </tr> <tr> <td> 6(2,7)pyrenophane 1a </td> <td> 39.7 </td> <td> -15.8 </td> <td> 18.8 </td> <td> -7.8, -4.1 </td> </tr> <tr> <td> 7(2,7)pyrenophane 1b </td> <td> 32.7 </td> <td> -12.1 </td> <td> 17.5 </td> <td> -8.7, -4.5 </td> </tr> <tr> <td> 8(2,7)pyrenophane 1c </td> <td> 26.5 </td> <td> -10.6 </td> <td> 14.3 </td> <td> -9.6, -5.2 </td> </tr> <tr> <td> 9(2,7)pyrenophane 1d </td> <td> 21.3 </td> <td> -7.5 </td> <td> 11.3 </td> <td> -10.6, -5.5 </td> </tr> <tr> <td> 10(2,7)pyrenophane 1e </td> <td> 15.9 </td> <td> -6.2 </td> <td> 9.5 </td> <td> -11.3, -6.2 </td> </tr> <tr> <td> 11(2,7)pyrenophane 1f </td> <td> 11.0 </td> <td> -3.4 </td> <td> 7.0 </td> <td> -12.0, -6.4 </td> </tr> <tr> <td> 12(2,7)pyrenophane 1g </td> <td> 7.2 </td> <td> -3.1 </td> <td> 6.3 </td> <td> -12.6, -7.0 </td> </tr> <tr> <td> pyrene </td> <td> 0.0 </td> <td> 0.0 </td> <td> 0.0 </td> <td> -13.9, -7.8 </td> </tr> <tr> <td colspan="5"> <hr> ain degrees.bin kcal mol-1, from Reaction 1. cin cgs.ppm. din ppm, for the outer and inner rings. </td> </tr> </table> All of these trends are consistent with reduced aromaticity with increased out-of-plane distortion of the pyrene framework. What may be surprising is the relatively small loss of aromaticity in this sequence. Even though the bend angle is as large as almost 40°, the loss of ASE is only 16 kcal mol-1, only about a quarter of the ASE of pyrene itself. Apparently, aromatic systems are fairly robust! <h3>References</h3> <a name="pphaneR1"></a> (1) Dobrowolski, M. A.; Cyranski, M. K.; Merner, B. L.; Bodwell, G. J.; Wu, J. I.; Schleyer, P. v. R., "Interplay of π-Electron Delocalization and Strain in [n](2,7)Pyrenophanes," J. Org. Chem., 2008, 73, 8001-8009, DOI: <a href="http://dx.doi.org/10.1021/jo8014159">10.1021/jo8014159</a> <h3>InChIs</h3> 1a: InChI=1/C22H20/c1-2-4-6-16-13-19-9-7-17-11-15(5-3-1)12-18-8-10-20(14-16)22(19)21(17)18/h7-14H,1-6H2 InChIKey=SJCYSWGQWCIONQ-UHFFFAOYAF 1b: InChI=1/C23H22/c1-2-4-6-16-12-18-8-10-20-14-17(7-5-3-1)15-21-11-9-19(13-16)22(18)23(20)21/h8-15H,1-7H2 InChIKey=VHVKAELFYUXZEM-UHFFFAOYAW 1c: InChI=1/C24H24/c1-2-4-6-8-18-15-21-11-9-19-13-17(7-5-3-1)14-20-10-12-22(16-18)24(21)23(19)20/h9-16H,1-8H2 InChIKey=HXPWDTNIUQNKLV-UHFFFAOYAQ 1d: InChI=1/C25H26/c1-2-4-6-8-18-14-20-10-12-22-16-19(9-7-5-3-1)17-23-13-11-21(15-18)24(20)25(22)23/h10-17H,1-9H2 InChIKey=DWYMZJZWMFVOIR-UHFFFAOYAM 1e: InChI=1/C26H28/c1-2-4-6-8-10-20-17-23-13-11-21-15-19(9-7-5-3-1)16-22-12-14-24(18-20)26(23)25(21)22/h11-18H,1-10H2 InChIKey=PZBADGOJPAEUIK-UHFFFAOYAZ 1f: InChI=1/C27H30/c1-2-4-6-8-10-20-16-22-12-14-24-18-21(11-9-7-5-3-1)19-25-15-13-23(17-20)26(22)27(24)25/h12-19H,1-11H2 InChIKey=YVZIXELCLJHDLW-UHFFFAOYAO 1g: InChI=1/C28H32/c1-2-4-6-8-10-12-22-19-25-15-13-23-17-21(11-9-7-5-3-1)18-24-14-16-26(20-22)28(25)27(23)24/h13-20H,1-12H2 InChIKey=QDAMLTATWKFTFB-UHFFFAOYAF Pyrene: InChI=1/C16H10/c1-3-11-7-9-13-5-2-6-14-10-8-12(4-1)15(11)16(13)14/h1-10H InChIKey=BBEAQIROQSPTKN-UHFFFAOYAB 4,9-dimethylenepyrene: InChI=1/C18H12/c1-11-9-13-5-4-8-16-12(2)10-14-6-3-7-15(11)17(14)18(13)16/h3-10H,1-2H2 InChIKey=XAAPFSHIUHWWCM-UHFFFAOYAM  </div> <a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> &<a href="/blog/archives/category/molecules/polycyclic-aromatics" rel="category tag">polycyclic aromatics</a> &<a href="/blog/archives/category/authors/schleyer" rel="category tag">Schleyer</a> Steven Bachrach 11 Dec 2008 <a href="/blog/archives/102#respond">No Comments</a> </div> <div class="box"> <h2><a href="/blog/archives/101" rel="bookmark" title="Permanent Link: Insights into dynamic effects">Insights into dynamic effects</a></h2> <div class="post-content"> Singleton has taken another foray into the murky arena of “dynamic effects”, this time with the aim of trying to provide some guidance towards making qualitative product predictions.<a href="#singletonR1">1</a> He has examined four different Diels-Alder reaction involving two diene species, each of which can act as either the diene or dienophile. I will discuss the results of two of these reactions, namely the reactions of 1 with 2 (Reaction 1) and 1 with 3 (Reaction 2). <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr> <td align="center"> Reaction 1 <img src="/blog/wp-content/singR1.gif"> </td> </tr> <tr> <td align="center"> Reaction 2 <img src="/blog/wp-content/singR2.gif"> </td> </tr> </table> In the experimental studies, Reaction 1 yields only 4, while reaction 2 yields both products in the ratio 6:7 = 1.6:1. Standard transition state theory would suggest that there are two different transition states for each reaction, one corresponding to the 4+2 reaction where 1 is the dienophile and the other TS has 1 as the dienophile. Then one would argue that in Reaction 1, the TS leading to 4 is much lower in energy than that leading to 5, and for Reaction 2, the TS state leading to 6 lies somewhat lower in energy than that leading to 7. Now the interesting aspect of the potential energy surfaces for these two reactions is that there are only two transition states. The first corresponds to the Cope rearrangement between the two products (connecting 4 to 5 on the PES of Reaction 1 and 6 to 7 on the PES of Reaction 2). That leaves only one TS connecting reactants to products! These four TSs are displayed in Figure 1. <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr> <td> Reaction 1 </td> <td> Reaction 2 </td> </tr> <tr> <td align="center"> <div class="jmol" id="sing1"> <a onclick="return false"> <img src="/blog/wp-content/singTS1.gif" onclick="insertJmol('sing1',200,200,'singTS1.xyz')"> </a> </div> TS 12→45 </td> <td align="center"> <div class="jmol" id="sing2"> <a onclick="return false"> <img src="/blog/wp-content/singTS2.gif" onclick="insertJmol('sing2',200,200,'singTS2.xyz')"> </a> </div> TS 13→67 </td> </tr> <tr> <td align="center"> <div class="jmol" id="sing3"> <a onclick="return false"> <img src="/blog/wp-content/singTS3.gif" onclick="insertJmol('sing3',200,200,'singTS3.xyz')"> </a> </div> Cope TS 4→5 </td> <td align="center"> <div class="jmol" id="sing4"> <a onclick="return false"> <img src="/blog/wp-content/singTS4.gif" onclick="insertJmol('sing4',200,200,'singTS4.xyz')"> </a> </div> Cope TS 6→7 </td> </tr> </table> Figure 1. MPW1K/6-31+G** TSs on the PES of Reactions 1 and 2.<a href="#singletonR1">1</a> These transition states are “bispericyclic” (first recognized by Caramella<a href="#singletonR2">2</a>), having the characteristics of both possible Diels-Alder reactions, i.e. for Reaction 1 these are the [4π1+2π2] and [4π2+2π1]. What this implies is that the reactants come together, cross over a single transition states and then pass over a bifurcating surface where the lowest energy path (the IRC or reaction path) continues on to one product only. The second product, however, can be reached by passing over this same transition state and then following some other non-reaction path. This sort of surface is ripe for experiencing non-statistical behavior, or “dynamic effects”. Trajectory studies were then performed to explore the product distributions. Starting from TS 12→45, 39 trajectories were followed: 28 ended with 4 and 10 ended with 5 while one trajectory recrossed the transition state. Isomerization of 5 into 4 is possible, and the predicted low barrier for this explains the sole observation of 4. For Reaction 2, of the 33 trajectories that originated at TS 13→67, 12 led to 6 and 19 led to 7. This distribution is consistent with the experimental product distribution of a slight excess of 7 over 6. Once again we see here a relatively simple reaction whose product distribution is only interpretable using expensive trajectory computations, and the result leave little simplifying concepts to guide us in generalizing to other (related) systems. Singleton does provide two rules-of-thumb that may help prod us towards creating some sort of dynamic model. First, he notes that the geometry of the single transition state that “leads” to the two products can suggest the major product. The TS geometry can be “closer” to one product over the other. For example, in TS 12→45 the two forming C-C bonds that differentiate the two products are 2.95 and 2.99 Å, and the shorter distance corresponds to forming 4. In TS 13→67, the two C-C distances are 2.83 and 3.13 Å, with the shorter distance corresponding to forming 6. The second point has to do with the position of the second TS, the one separating the two products. This TS acts to separate the PES into two basins, one for each product. The farther this TS is from the first TS, the greater the selectivity. As Singleton notes, neither of these points is particularly surprising in hindsight. Nonetheless, since we have so little guidance in understanding reactions that are under dynamic control, any progress here is important. <h3>References</h3> <a name="singletonR1"></a> (1) Thomas, J. B.; Waas, J. R.; Harmata, M.; Singleton, D. A., "Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface," J. Am. Chem. Soc. 2008, 130, 14544-14555, DOI: <a href="http://dx.doi.org/10.1021/ja802577v">10.1021/ja802577v</a>. <a name="singletonR2"></a> (2) Caramella, P.; Quadrelli, P.; Toma, L., "An Unexpected Bispericyclic Transition Structure Leading to 4+2 and 2+4 Cycloadducts in the Endo Dimerization of Cyclopentadiene," J. Am. Chem. Soc. 2002, 124, 1130-1131, DOI: <a href="http://dx.doi.org/10.1021/ja016622h">10.1021/ja016622h</a> <h3>InChIs</h3> 1: InChI=1/C7H6O3/c1-10-7(9)5-2-3-6(8)4-5/h2-4H,1H3 InChIKey=XDEAUYSKQHEYSC-UHFFFAOYAM 2: InChI=1/C8H12/c1-2-8-6-4-3-5-7-8/h2,6H,1,3-5,7H2 InChIKey=SDRZFSPCVYEJTP-UHFFFAOYAI 3: InChI=1/C6H6O/c1-2-6-4-3-5-7-6/h2-5H,1H2 InChIKey=QQBUHYQVKJQAOB-UHFFFAOYAO 4: InChI=1/C15H18O3/c1-18-14(17)15-9-8-13(16)12(15)7-6-10-4-2-3-5-11(10)15/h6,8-9,11-12H,2-5,7H2,1H3/t1,12-,15+/m1/s1 InChIKey=IASNDVSMFFVIFJ-GDHFLIHABF 5: InChI=1/C15H18O3/c1-18-15(17)13-8-11-10(7-12(13)14(11)16)9-5-3-2-4-6-9/h5,8,10-12H,2-4,6-7H2,1H3 InChIKey=XOFSMKQRRVWZHS-UHFFFAOYAW 6: InChI=1/C13H12O4/c1-16-13(15)10-6-8-7(5-9(10)12(8)14)11-3-2-4-17-11/h2-4,6-9H,5H2,1H3 InChIKey=HTSLDILNKGZMHE-UHFFFAOYAH 7: InChI=1/C13H12O4/c1-16-12(15)13-6-4-10(14)8(13)2-3-11-9(13)5-7-17-11/h3-9H,2H2,1H3/t8-,9?,13-/m1/s1 InChIKey=URYPWPBQFGUBGW-KEJGKJRFBM  </div> <a href="/blog/archives/category/dynamics" rel="category tag">Dynamics</a> &<a href="/blog/archives/category/authors/singleton" rel="category tag">Singleton</a> Steven Bachrach 09 Dec 2008 <a href="/blog/archives/101#respond">No Comments</a> </div> <div class="box"> <h2><a href="/blog/archives/100" rel="bookmark" title="Permanent Link: Computing Rotoxanes – a performance study">Computing Rotoxanes – a performance study</a></h2> <div class="post-content"> Host-guest recognition is a major theme of modern chemistry. Computation of these systems remains a real challenge for many reasons, especially the typically large size of the molecules involved and the need for accurately computing weak, non-covalent interactions. This latter point remains a major problem with density functional theory. Goddard has now examined a rotaxane system.<a href="#goddardR1">1</a> Goddard employed a variety of functionals (B3LYP. PBE, and MO6 variants) to 1, a compound prepared by Stoddart.<a href="#goddardR2">2</a> The counterion of the experimentally prepared rotoxane is PF6–; in the computations, Goddrad employed either no counterions or four chloride ions. <img src="/blog/wp-content/goddard1.gif"> The optimized structure of 1 without counterions computed at B3LYP/6-31G** and MO6-L/6-31G** are shown in Figure 1. The major difference in these structures is the orientation of the naphthyl group inside the host. B3LYP predicts that it is skewed, while MO6-L predicts that it lies parallel to the bipyridinium side. The x-ray structure has the parallel structure, similar to that found with MO6-L, though the pendant bis-i-proylphenyl ring is farther down in the x-ray structure than in the computed structure. <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr> <td align="center"> (a) <div class="jmol" id="godB"> <a onclick="return false"> <img src="/blog/wp-content/goddardB.gif" onclick="insertJmol('godB',200,200,'goddardB.xyz')"> </a> </div> </td> <td align="center"> (b) <div class="jmol" id="godM"> <a onclick="return false"> <img src="/blog/wp-content/goddardM.gif" onclick="insertJmol('godM',200,200,'goddardM.xyz')"> </a> </div> </td> </tr> </table> Figure 1. Optimized structure of 14+ (a) B3LYP/6-31G** and (b) MO6-L/6-31G**.<a href="#goddardR1">1</a> None of the methods perform particularly well in computing the binding energy of the host and guest. The experimental value is -4.9 ± 1 kcal mol-1. In the gas phase, the two methods predict that the system is bound, -24.9 (B3LYP, -75.2 kcal mol-1, MO6-L). In acetonitrile, B3LYP predicts that it is unbound, while MO6-L predicts a binding energy of -27.5 kcal mol-1. Inclusion of four chloride ions leads to some improvement in the binding energy in the gas phase but not for the solution phase. The excitation energy is 3.50 eV.Computation of the excitation energy is poor with B3LYP (1.33 eV) but nearly exact with MO6-HF//MO6-L (3.42 eV). Goddard concludes that computation of these sort of interlocked molecules should be performed with the MO6 family of functionals, but clearly more work is needed if accurate energies are required. <h3>References</h3> <a name="goddardR1"></a> (1) Benitez, D.; Tkatchouk, E.; Yoon, I.; Stoddart, J. F.; Goddard, W. A., "Experimentally-Based Recommendations of Density Functionals for Predicting Properties in Mechanically Interlocked Molecules," J. Am. Chem. Soc., 2008, 130, 14928-14929, DOI: <a href="http://dx.doi.org/10.1021/ja805953u">http://dx.doi.org/10.1021/ja805953u</a>. <a name="goddardR2"></a> (2) Nygaard, S.; Leung, K. C. F.; Aprahamian, I.; Ikeda, T.; Saha, S.; Laursen, B. W.; Kim, S.-Y.; Hansen, S. W.; Stein, P. C.; Flood, A. H.; Stoddart, J. F.; Jeppesen, J. O., "Functionally Rigid Bistable [2]Rotaxanes," J. Am. Chem. Soc., 2007, 129, 960-970, DOI: <a href="http://dx.doi.org/10.1021/ja0663529">http://dx.doi.org/10.1021/ja0663529</a> <h3>InChIs</h3> Guest: InChI=1/C28H32O3/c1-6-22-10-7-14-26-25(22)13-9-15-27(26)30-18-16-29-17-19-31-28-23(20(2)3)11-8-12-24(28)21(4)5/h1,7-15,20-21H,16-19H2,2-5H3 InChIKey=HYRADSXCSHFXAZ-UHFFFAOYAJ Host: InChI=1/C36H32N4/c1-2-30-4-3-29(1)25-37-17-9-33(10-18-37)35-13-21-39(22-14-35)27-31-5-7-32(8-6-31)28-40-23-15-36(16-24-40)34-11-19-38(26-30)20-12-34/h1-24H,25-28H2/q+4 InChIKey=URORLZXVTFVIPS-UHFFFAOYAV  </div> <a href="/blog/archives/category/qm-method/dft" rel="category tag">DFT</a> Steven Bachrach 04 Dec 2008 <a href="/blog/archives/100#comments">1 Comment</a> </div> <div class="box"> <h2><a href="/blog/archives/99" rel="bookmark" title="Permanent Link: Errors in DFT: computation of the Diels-Alder reaction">Errors in DFT: computation of the Diels-Alder reaction</a></h2> <div class="post-content"> Concern about the use of DFT for general use in organic chemistry remains high; see my previous posts (<a href="http://hackberry.chem.trinity.edu/blog/?p=52">1</a>, <a href="http://hackberry.chem.trinity.edu/blog/?p=45">2</a>, <a href="http://hackberry.chem.trinity.edu/blog/?p=32">3</a>). Houk has now examined the reaction enthalpies of ten simple Diels-Alder reactions using a variety of functionals in the search for the root cause of the problem(s).<a href="#DFT3">1</a> The ten reactions are listed in Scheme 1, and involve cyclic and acyclic dienes and either ethylene or acetylene as the dienophile. Table 1 lists the minimum and maximum deviation of the DFT enthalpies relative to the CBS-QB3 enthalpies (which are in excellent accord with experiment). Clearly, all of the DFT methods perform poorly, with significant errors in these simple reaction energies. The exception is the MO6-2X functional, whose errors are only slightly larger than that found with the SCS-MP2 method. Use of a larger basis set (6-311+G(2df,2p)) reduced errors only a small amount. <table border="0" cellspacing="0" cellpadding="3" align="center"> <tr> <td colspan="2"> Scheme 1 </td> </tr> <tr> <td valign="top"> <img src="/blog/wp-content/DFT31.gif"> </td> <td valign="top"> <img src="/blog/wp-content/DFT32.gif"> </td> </tr> <tr> <td valign="top"> <img src="/blog/wp-content/DFT33.gif"> </td> <td valign="top"> <img src="/blog/wp-content/DFT34.gif"> </td> </tr> <tr> <td valign="top"> <img src="/blog/wp-content/DFT35.gif"> </td> <td valign="top"> <img src="/blog/wp-content/DFT36.gif"> </td> </tr> <tr> <td valign="top"> <img src="/blog/wp-content/DFT37.gif"> </td> <td valign="top"> <img src="/blog/wp-content/DFT38.gif"> </td> </tr> <tr> <td valign="top"> <img src="/blog/wp-content/DFT39.gif"> </td> <td valign="top"> <img src="/blog/wp-content/DFT310.gif"> </td> </tr> </table> Table 1. Maximum, minimum and mean deviation of reaction enthalpies (kcal mol-1) for the reactions in Scheme 1 using the 6-31+G(d,p) basis set.<a href="#DFT3">1</a> <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr> <td> Method </td> <td> Maximum Deviation </td> <td> Minimum Deviation </td> <td> Mean Deviation </td> </tr> <tr> <td colspan="4"> <hr> </td> </tr> <tr> <td> B3LYP </td> <td> 11.4 </td> <td> 2.4 </td> <td> 7.9 </td> </tr> <tr> <td> mPW1PW91 </td> <td> -8.7 </td> <td> -0.2 </td> <td> -3.6 </td> </tr> <tr> <td> MPWB1K </td> <td> -9.8 </td> <td> -3.6 </td> <td> -6.2 </td> </tr> <tr> <td> M05-2X//B3LYP </td> <td> -6.4 </td> <td> -1.6 </td> <td> -4.1 </td> </tr> <tr style="mso-yfti-irow:5"> <td> M06-2X//B3LYP </td> <td> -4.4 </td> <td> -0.4 </td> <td> -2.5 </td> </tr> <tr> <td> SCS-MP2//B3LYP </td> <td> -3.2 </td> <td> -0.5 </td> <td> -1.9 </td> </tr> <tr> <td colspan="4"> <hr> </td> </tr> </table> In order to discern where the problem originates, they next explore the changes that occur in the Diels-Alder reaction: two π bonds are transformed into one σ and one π bond and the conjugation of the diene is lost, leading to (proto)branching in the product. Reactions 1-3 are used to assess the energy consequence of converting a π bond into a σ bond, creating a protobranch, and the loss of conjugation, respectively. <img src="/blog/wp-content/DFT311.gif"> The energies of these reactions were then evaluated with the various functionals. It is only with the conversion of the π bond into a σ bond that they find a significant discrepancy between the DFT estimates and the CBS-QB3 estimate. DFT methods overestimate the energy for the π → σ exchange, by typically around 5 kcal mol-1, but it can be much worse. Relying on cancellation of errors to save the day for DFT will not work when these types of bond changes are involved. Once again, the user of DFT is severely cautioned! <h3>References</h3> <a name="DFT3"></a> (1) Pieniazek, S. N.; Clemente, F. R.; Houk, K. N., "Sources of Error in DFT Computations of C-C Bond Formation Thermochemistries: π → σ Transformations and Error Cancellation by DFT Methods," Angew. Chem. Int. Ed. 2008, 47, 7746-7749, DOI: <a href="http://dx.doi.org/10.1002/anie.200801843">10.1002/anie.200801843</a>  </div> <a href="/blog/archives/category/qm-method/dft" rel="category tag">DFT</a> &<a href="/blog/archives/category/reactions/diels-alder" rel="category tag">Diels-Alder</a> &<a href="/blog/archives/category/authors/houk" rel="category tag">Houk</a> Steven Bachrach 01 Dec 2008 <a href="/blog/archives/99#comments">3 Comments</a> </div> </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/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">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" aria-current="page">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> 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"> Copyright © 2021 Computational Organic Chemistry. </div> </body> </html>