CINXE.COM

<!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</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"> <div class="box"> <h2><a href="/blog/archives/4346" rel="bookmark" title="Permanent Link: dJ-DP4 and iJ-DP4: including coupling constants">dJ-DP4 and iJ-DP4: including coupling constants</a></h2> <div class="bottom"> <a href="/blog/archives/category/nmr" rel="category tag">NMR</a> Steven Bachrach 26 Jun 2019 Comments Off on dJ-DP4 and iJ-DP4: including coupling constants <hr> </div> <div class="post-content"> I have written quite a number of <a href="/blog/archives/category/nmr">posts</a> on using quantum mechanics computations to predict NMR spectra that can aid in identifying chemical structure. Perhaps the most robust technique is Goodman’s DP4 method (<a href="/blog/archives/1159">post</a>), which has seen some recent revisions (<a href="/blog/archives/3883">updated DP4</a>, <a href="/blog/archives/3799">DP4+</a>). I have also posted on the use of computed coupling constants (<a href="/blog/?s=coupling">posts</a>). Grimblat, Gavín, Daranas and Sarotti have now combined these two approaches, using computed 1H and 13C chemical shifts and 3JHH coupling constants with the DP4 framework to predict chemical structure.<a href="#JDP4">1</a> They describe two different approaches to incorporate coupling constants: <ul> <li>dJ-DP4 (direct method) incorporates the coupling constants into a new probability function, using the coupling constants in an analogous way as chemical shifts. This requires explicit computation of all chemical shifts and 3JHH coupling constants for all low-energy conformations.</li> <li>iJ-DP4 (indirect method) uses the experimental coupling constants to set conformational constraints thereby reducing the number of total conformations that need be sampled. Thus, large values of the coupling constant (3JHH > 8 Hz) selects conformations with coplanar hydrogens, while small values (3JHH < 4 Hz) selects conformations with perpendicular hydrogens. Other values are ignored. Typically, only one or two coupling constants are used to select the viable conformations.</li> </ul> The authors test these two variants on 69 molecules. The original DP4 method predicted the correct stereoisomer for 75% of the examples, while dJ-DP4 correct identifies 96% of the cases. As a test of the indirect method, they examined marilzabicycloallenes A and B (1 and 2). DP4 predicts the correct stereoisomer with only 3.1% (1) or <0.1% (2) probability. dJ-DP4 predicts the correct isomer for 1 with 99.9% probability and 97.6% probability for 2. The advantage of iJ-DP4 is that using one coupling constant reduces the number of conformations that must be computed by 84%, yet maintains a probability of getting the correct assignment at 99.2% or better. Using two coupling constants to constrain conformations means that only 7% of all of the conformations need to be samples, and the predictive power is maintained. <table align="center" cellpadding="4"> <tr valign="bottom" align="center"> <td> <img src="/blog/wp-content/JDP4img1.png"> 1 </td> <td> <img src="/blog/wp-content/JDP4img2.png"> 2 </td> </tr> </table> Both of these new methods clearly deserve further application. <h3>References</h3> 1. Grimblat, N.; Gavín, J. A.; Hernández Daranas, A.; Sarotti, A. M., “Combining the Power of J Coupling and DP4 Analysis on Stereochemical Assignments: The J-DP4 Methods.” Org. Letters 2019, 21, 4003-4007, DOI: <a href="https://doi.org/10.1021/acs.orglett.9b01193">10.1021/acs.orglett.9b01193</a>. <h3>InChIs</h3> 1: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9+,10-,11+,12+,13+,14+,15-/m0/s1 InChIKey=APNVVMOUATXTFG-NTSAAJDMSA-N 2: InChI=1S/C15H21Br2ClO4/c1-8-15(20)14-6-10(17)12(19)7-11(18)13(22-14)5-9(21-8)3-2-4-16/h3-4,8-15,19-20H,5-7H2,1H3/t2-,8-,9-,10-,11+,12+,13+,14+,15-/m0/s1 InChIKey=APNVVMOUATXTFG-SSBNIETDSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4337" rel="bookmark" title="Permanent Link: Using vibrational frequencies to identify stereoisomers">Using vibrational frequencies to identify stereoisomers</a></h2> <div class="bottom"> <a href="/blog/archives/category/qm-method/dft" rel="category tag">DFT</a> &<a href="/blog/archives/category/vibrational-frequencies" rel="category tag">vibrational frequencies</a> Steven Bachrach 10 Jun 2019 <a href="/blog/archives/4337#respond">No Comments</a> <hr> </div> <div class="post-content"> Can vibrational spectroscopy be used to identify stereoisomers? Medel, Stelbrink, and Suhm have examined the vibrational spectra of (+)- and (-)-α-pinene, (±)-1, in the presence of four different chiral terpenes 2-5.<a href="#chiralVib1">1</a> They recorded gas phase spectra by thermal expansion of a chiral α-pinene with each chiral terpene. <img src="/blog/wp-content/chiralVibImg.png"> For the complex of 4 with (+)-1 or (-)-1 and 5 with (+)-1 or (-)-1, the OH vibrational frequency is identical for the two different stereoisomers. However, the OH vibrational frequencies differ by 2 cm-1 with 3, and the complex of 3/(+)-1 displays two different OH stretches that differ by 11 cm-1. And in the case of the complex of α-pinene with 2, the OH vibrational frequencies of the two different stereoisomers differ by 11 cm-1! The B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1 complexes are shown in Figure 2, and some subtle differences in sterics and dispersion give rise to the different vibrational frequencies. <table align="center" cellpadding="5"> <tr align="center" valign="bottom"> <td> <img src="/blog/wp-content/chiralVibMP.png"> 2/(+)-1 </td> <td> <img src="/blog/wp-content/chiralVibMM.png"> 2/(-)-1 </td> </tr> </table> Figure 2. B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1 Of interest to readers of this blog will be the DFT study of these complexes. The authors used three different well-known methods – B3LYP-D3(BJ)/def2-TZVP, M06-2x/def2-TZVP, and ωB97X-D/def2-TZVP – to compute structures and (most importantly) predict the vibrational frequencies. Interestingly, M06-2x/def2-TZVP and ωB97X-D/ def2-TZVP both failed to predict the vibrational frequency difference between the complexes with the two stereoisomers of α-pinene. However, B3LYP-D3(BJ)/def2-TZVP performed extremely well, with a mean average error (MAE) of only 1.9 cm-1 for the four different terpenes. Using this functional and the larger may-cc-pvtz basis set reduced the MAE to 1.5 cm-1 with the largest error of only 2.5 cm-1. As the authors note, these complexes provide some fertile ground for further experimental and computational study and benchmarking. <h3>Reference</h3> 1. Medel, R.; Stelbrink, C.; Suhm, M. A., “Vibrational Signatures of Chirality Recognition Between α-Pinene and Alcohols for Theory Benchmarking.” Angew. Chem. Int. Ed. 2019, 58, 8177-8181, DOI: <a href="http://dx.doi.org/10.1002/anie.201901687">10.1002/anie.201901687</a>. <h3>InChIs</h3> (-)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m0/s1 InChIKey=GRWFGVWFFZKLTI-IUCAKERBSA-N (+)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m1/s1 InChIKey=GRWFGVWFFZKLTI-RKDXNWHRSA-N 2, (-)borneol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m0/s1 InChiKey=DTGKSKDOIYIVQL-QXFUBDJGSA-N 3, (+)-fenchol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7-8,11H,4-6H2,1-3H3/t7-,8-,10+/m0/s1 InChIKey=IAIHUHQCLTYTSF-OYNCUSHFSA-N 4, (-1)-isopinocampheol: InChI=1S/C10H18O/c1-6-8-4-7(5-9(6)11)10(8,2)3/h6-9,11H,4-5H2,1-3H3/t6-,7+,8-,9-/m1/s1 InChIKey=REPVLJRCJUVQFA-BZNPZCIMSA-N 5, (1S)-1-phenylethanol: InChI=1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3/t7-/m0/s1 InChIKey=WAPNOHKVXSQRPX-ZETCQYMHSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4329" rel="bookmark" title="Permanent Link: Trispericyclic transition state">Trispericyclic transition state</a></h2> <div class="bottom"> <a href="/blog/archives/category/dynamics" rel="category tag">Dynamics</a> Steven Bachrach 09 Apr 2019 <a href="/blog/archives/4329#comments">2 Comments</a> <hr> </div> <div class="post-content"> A major topic of this blog has been the growing body of studies that demonstrate that dynamic effects can control reaction products (see these <a href="/blog/archives/category/dynamics">posts</a>). Often these examples crop up with valley ridge inflection points. Another cause can be bispericyclic transition states, first discovered by Caramella et al for the dimerization of cyclopentadiene.<a href="#trisperi1">1</a> The Houk group now reports on the first trispericyclic transition state.<a href="#trisperi2">2</a> Using ωB97X-D/6-31G(d), they examined the reaction of the tropone derivative 1 with dimethylfulvene 2. Three possible products can arrive from different pericyclic reactions: 3, the [4+6] product; 4, the [6+4] product; and 5, the [8+2] product. The thermodynamic product is predicted to be 5, but it is only 1.2 kcal mol-1 lower in energy than 4 and 6.2 kcal mol-1 lower than 3. <img src="/blog/wp-content/trisperiImg.png"> They identified one transition state originating from the reactants TS1. Hypothesizing that it would be trispericyclic, they performed a molecular dynamics study with trajectories starting from TS1. They ran a total of 142 trajectories, and 87% led to 3, 3% led to 4, and 3% led to 5. This demonstrates the unusual nature of TS1 and the dynamic effects on this reaction surface. <table align="center" border="0" cellspacing="0" cellpadding="5"> <tr align="center"> <td colspan="2"> <img src="/blog/wp-content/trisperiTS1.png"> TS1 </td> </tr> <tr align="center" valign="bottom"> <td> <img src="/blog/wp-content/trisperiTS1.png"> TS2 </td> <td> <img border="0" src="/blog/wp-content/trisperiTS1.png"> TS3 </td> </tr> </table> Figure 1. ωB97X-D/6-31G(d) optimized geometries of TS1-TS3. Additionally, there are two different Cope rearrangements (through TS2 and TS3) that convert 3 into 4 and 5. Some trajectories can pass from TS1 and then directly through either TS2 or TS3 and these give rise to products 4 and 5. In other words, some trajectories will pass from a trispericyclic transition state and then through a bispericyclic transition state before ending in product. <h3>References</h3> 1. 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> 2. Xue, X.-S.; Jamieson, C. S.; Garcia-Borràs, M.; Dong, X.; Yang, Z.; Houk, K. N., “Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity.” J. Am. Chem. Soc. 2019, 141, 1217-1221, DOI: <a href="https://doi.org/10.1021/jacs.8b12674">10.1021/jacs.8b12674</a>. <h3>InChIs</h3> 1: InChI=1S/C10H6N2/c11-7-10(8-12)9-5-3-1-2-4-6-9/h1-6H InChIKey=KAWLLELUFONBGI-UHFFFAOYSA-N 2: InChI=1S/C8H10/c1-7(2)8-5-3-4-6-8/h3-6H,1-2H3 InChIKey=WXACXMWYHXOSIX-UHFFFAOYSA-N 3: InChI=1S/C18H16N2/c1-11(2)17-15-7-8-16(17)14-6-4-3-5-13(15)18(14)12(9-19)10-20/h3-8,13-16H,1-2H3 InChIKey=DRPXVBLNTKGMTB-UHFFFAOYSA-N 4: InChI=1S/C18H16N2/c1-18(2)13-6-8-14(12(10-19)11-20)15(9-7-13)16-4-3-5-17(16)18/h3-9,13,15-16H,1-2H3 InChIKey=FSIPGNLAWKVXDD-UHFFFAOYSA-N 5: InChI=1S/C18H16N2/c1-12(2)13-8-9-16-17(13)14-6-4-3-5-7-15(14)18(16,10-19)11-20/h3-9,14,16-17H,1-2H3/t14?,16-,17-/m1/s1 InChIKey=SYLWEGLODFLARZ-VNCLPFQGSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4312" rel="bookmark" title="Permanent Link: Planar ring in a nano-Saturn">Planar ring in a nano-Saturn</a></h2> <div class="bottom"> <a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> &<a href="/blog/archives/category/host-guest" rel="category tag">host-guest</a> Steven Bachrach 26 Mar 2019 <a href="/blog/archives/4312#comments">2 Comments</a> <hr> </div> <div class="post-content"> For the past twelve years, I have avoided posting on any of my own papers, but I will stoop to some shameless promotion to mention my latest paper,<a href="#SaturnBach1">1</a> since it touches on some themes I have discussed in the past. Back in 2011, Iwamoto, et al. prepared the complex of C60 1 surrounded by [10]cycloparaphenylene 2 to make the Saturn-like system 3.<a href="#SaturnBach2">2</a> Just last year, Yamamoto, et al prepared the Nano-Saturn 5a as the complex of 1 with the macrocycle 4a.<a href="#SaturnBach3">3</a> The principle idea driving their synthesis was to utilize a ring that is flatter than 2. The structures of 3 and 5b (made with the parent macrocycle 4b) are shown in side view in Figure 1, and clearly seen is the achievement of the flatter ring. <img src="/blog/wp-content/BachrachImg1.png" alt=""> <table align="center"> <tbody> <tr align="center"> <td> <img src="/blog/wp-content/10cppC60_side.png"> 3 </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/saturnC_side.png"> 5b </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/saturnN1_side.png"> 7 </td> </tr> </tbody> </table> Figure 1. Computed structures of 3, 5, and 7. However, the encompassing ring is not flat, with dihedral angles between the anthrenyl groups of 35°. This twisting is due to the steric interactions of the ortho-ortho’ hydrogens. A few years ago, my undergraduate student David Stück and I suggested that selective substitution of a nitrogen for one of the C-H groups would remove the steric interaction,<a href="#SaturnBach4">4</a> leading to a planar poly-aryl system, such as making twisted biphenyl into the planar 2-(2-pyridyl)-pyridine (Scheme 1) Scheme 1. <img src="/blog/wp-content/BachrachImg2.png" alt=""> Following this idea leads to four symmetrical nitrogen-substituted analogues of 4b; and I’ll mention just one of them here, 6. <img src="/blog/wp-content/BachrachImg3.png" alt=""> As expected, 6 is perfectly flat. The ring remains flat even when complexed with 1 (as per B3LYP-D3(BJ)/6-31G(d) computations), see the structure of 7 in Figure 1. I also examined the complex of the flat macrocycle 6 (and its isomers) with a [5,5]-nanotube, 7. The tube bends over to create better dispersion interaction with the ring, which also become somewhat non-planar to accommodate the tube. Though not mentioned in the paper, I like to refer to 7 as Beyoncene, in tribute to <a href="https://www.youtube.com/watch?v=4m1EFMoRFvY">All the Single Ladies</a>. <img src="/blog/wp-content/saturnTubeNtype1.png" alt=""> Figure 2. Computed structure of 7. My sister is a graphic designer and she made this terrific image for this work: <img src="/blog/wp-content/saturnCover.jpg" alt=""> <h3>References</h3> 1. Bachrach, S. M., “Planar rings in nano-Saturns and related complexes.” Chem. Commun. 2019, 55, 3650-3653, DOI: <a href="http://dx.doi.org/10.1039/C9CC01234F">10.1039/C9CC01234F</a>. 2. Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S., “Size-Selective Encapsulation of C60 by [10]Cycloparaphenylene: Formation of the Shortest Fullerene-Peapod.” Angew. Chem. Int. Ed. 2011, 50, 8342-8344, DOI: <a href="http://dx.doi.org/10.1002/anie.201102302">10.1002/anie.201102302</a> 3. Yamamoto, Y.; Tsurumaki, E.; Wakamatsu, K.; Toyota, S., “Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60.” Angew. Chem. Int. Ed. 2018 , 57, 8199-8202, DOI: <a href="http://dx.doi.org/10.1002/anie.201804430">10.1002/anie.201804430</a>. 4. Bachrach, S. M.; Stück, D., “DFT Study of Cycloparaphenylenes and Heteroatom-Substituted Nanohoops.” J. Org. Chem. 2010, 75, 6595-6604, DOI: <a href="http://dx.doi.org/10.1021/jo101371m">10.1021/jo101371m</a> <h3>InChIs</h3> 4b: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H InChIKey=ZYXXLAYETADMDM-UHFFFAOYSA-N 6: InChI=1S/C72H36N12/c1-2-38-14-44-20-45-25-67(73-31-50(45)13-37(1)44)57-9-4-39-15-51-32-74-68(26-46(51)21-61(39)80-57)58-10-5-40-16-52-33-75-69(27-47(52)22-62(40)81-58)59-11-6-41-17-53-34-76-70(28-48(53)23-63(41)82-59)60-12-7-42-18-54-35-77-71(29-49(54)24-64(42)83-60)72-78-36-55-19-43-3-8-56(38)79-65(43)30-66(55)84-72/h1-36H InChIKey=NSSCKPFBHGOOIJ-UHFFFAOYSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4308" rel="bookmark" title="Permanent Link: More DFT benchmarking">More DFT benchmarking</a></h2> <div class="bottom"> <a href="/blog/archives/category/qm-method/dft" rel="category tag">DFT</a> Steven Bachrach 18 Mar 2019 <a href="/blog/archives/4308#respond">No Comments</a> <hr> </div> <div class="post-content"> Selecting the appropriate density functional for one’s molecular system at hand is often a very confounding problem, especially for non-expert or first-time users of computational chemistry. The DFT zoo is vast and confusing, and perhaps what makes the situation worse is that there is no lack of benchmarking studies. For example, I have made more than 30 posts on benchmark studies, and I made no attempt to be comprehensive over the past dozen years! One such benchmark study that I missed was presented by Mardirossian and Head-Gordon in 2017.<a href="#newDFTbench1">1</a> They evaluated 200 density functional using the MGCDB84 database, a combination of data from a number of different groups. They make a series of recommendations for local GGA, local meta-GGA, hybrid GGA, and hybrid meta-GGA functionals. And when pressed to choose just one functional overall, they opt for ωB97M-V, a range-separated hybrid meta-GGA with VV10 nonlocal correlation. Georigk and Mehta<a href="#newDFTbench2">2</a> just recently offer a review of the density functional zoo. Leaning heavily on benchmark studies using the GMTKN55<a href="#newDFTbench3">3</a> database, they report a number of observations. Of no surprise to readers of this blog, their main conclusion is that accounting for London dispersion is essential, usually through some type of correction like those proposed by Grimme. These authors also note the general disparity between the most accurate, best performing functional per the benchmark studies and the results of the <a href="http://www.marcelswart.eu/dft-poll/">DFT poll</a> conducted for many years by Swart, Bickelhaupt and Duran. It is somewhat remarkable that PBE or PBE0 have topped the poll for many years, despite the fact that many newer functionals perform better. As always, when choosing a functional caveat emptor. <h3>References</h3> 1.  Mardirossian, N.; Head-Gordon, M., “Thirty years of density functional theory in computational chemistry: an overview and extensive assessment of 200 density functionals.” Mol. Phys. 2017, 115, 2315-2372, DOI: <a href="https://doi.org/10.1080/00268976.2017.1333644">10.1080/00268976.2017.1333644</a>. 2. Goerigk, L.; Mehta, N., “A Trip to the Density Functional Theory Zoo: Warnings and Recommendations for the User.” Aust. J. Chem. 2019, ASAP, DOI: <a href="https://doi.org/10.1071/CH19023">10.1071/CH19023</a>. 3. Goerigk, L.; Hansen, A.; Bauer, C.; Ehrlich, S.; Najibi, A.; Grimme, S., “A look at the density functional theory zoo with the advanced GMTKN55 database for general main group thermochemistry, kinetics and noncovalent interactions.” Phys. Chem. Chem. Phys. 2017, 19, 32184-32215, DOI: <a href="http://dx.doi.org/10.1039/C7CP04913G">10.1039/C7CP04913G</a>.  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4302" rel="bookmark" title="Permanent Link: dodecaphenyltetracene">dodecaphenyltetracene</a></h2> <div class="bottom"> <a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> Steven Bachrach 25 Feb 2019 <a href="/blog/archives/4302#respond">No Comments</a> <hr> </div> <div class="post-content"> The Pascal group has synthesized dodecaphenyltetracene 1.<a href="#ph12tetR1">1</a> <img src="/blog/wp-content/phTetraceneImg.png"> While this paper has little computational work, it is of interest to readers of this blog since I have discussed many aspect of aromaticity. This new tetracene is notable for its large twisting along the tetracene axis: about 97° in the x-ray structure. I have optimized the structure of 1 at B3LYP-D3(BJ)/6-311G(d) and its structure is shown in Figure 1. It is twisted by about 94°. The computed and x-ray structures are quite similar, as seen in Figure 2. Here the x-ray structure is shown with red balls, the computed structure with gray balls, and hydrogens have been removed for clarity. <img src="/blog/wp-content/phTetraceneB3LYP.png"> Figure 1. B3LYP-D3(BJ)/6-311G(d) optimized structure of 1. <img src="/blog/wp-content/phTetraceneNoH.png"> Figure 2. Comparison of the x-ray (red) and computed (gray) structures of 1. (Hydrogens omitted for clarity.) The authors note that this molecule is chiral, having near D2 symmetry. (The optimized structure has D2 symmetry.) They performed AM1 computations to estimate a very low barrier for racemization of only 17.3 kcal mol-1, leading to a half-life of less than one second at RT. A notable aspect of the molecule is that aromaticity can adapt to significant twisting yet retain aromatic character. For example, the molecule is stable even surviving boiling off of chloroform (61 °C) to form crystals and the majority of the C-C bonds in the tetracene portion have distances typical of aromatic systems (~1.4 Å). <h3>References</h3> 1) Xiao, Y.; Mague, J. T.; Schmehl, R. H.; Haque, F. M.; Pascal Jr., R. A., “Dodecaphenyltetracene.” Angew. Chem. Int. Ed. 2019, 58, 2831-2833, DOI: <a href="http://dx.doi.org/10.1002/anie.201812418">10.1002/anie.201812418</a>. <h3>InChIs</h3> 1: InChI=1S/C90H60/c1-13-37-61(38-14-1)73-74(62-39-15-2-16-40-62)78(66-47-23-6-24-48-66)86-82(70-55-31-10-32-56-70)90-84(72-59-35-12-36-60-72)88-80(68-51-27-8-28-52-68)76(64-43-19-4-20-44-64)75(63-41-17-3-18-42-63)79(67-49-25-7-26-50-67)87(88)83(71-57-33-11-34-58-71)89(90)81(69-53-29-9-30-54-69)85(86)77(73)65-45-21-5-22-46-65/h1-60H InChIKey=NJQABVWYMCSFNE-UHFFFAOYSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4294" rel="bookmark" title="Permanent Link: Very long C-C bond">Very long C-C bond</a></h2> <div class="bottom"> <a href="/blog/archives/category/uncategorized" rel="category tag">Uncategorized</a> Steven Bachrach 23 Jan 2019 <a href="/blog/archives/4294#comments">1 Comment</a> <hr> </div> <div class="post-content"> Chemists are constantly checking the limits of theories, and the limits of bonding is one that has been subject to many tests of late. I have posted on two recent papers (<a href="/blog/archives/4201">here</a>, <a href="/blog/archives/4214">here</a>) that probe just how long a C-C bond can be, and now Li, Miller, and co-workers report a structure that pushes that limit even further out.<a href="#longCarborane1">1</a> They prepared and obtained the x-ray structure of five derivatives of o-carborane, namely compounds 1, 2a, 3a, 3b and 4. In all of these, the C-C bond in the carborane is stretched well beyond that of a typical C-C bond (see Table 1). The longest case is in 3b where the C-C bond length is a whopping 1.931 Å (see Figure 1), which obliterates the previous record holder at 1.798 Å.<a href="#longCarborane2">2</a> B3PW91-D3/cc-pVTZ computations corroborate these structures and the long C-C bond. Scheme 1: Carboranes with long C-C bonds (highlighted in blue) <div class="wp-block-image"><figure class="aligncenter"><img src="/blog/wp-content/carboraneLongImg.png" alt=""></figure></div> Table 1. C-C bond distance (Å) <table align="center" border="0" cellpadding="5"><tbody> <tr> <td> cmpd </td> <td> r(C-C) expt </td> <td> r(C-C) DFT </td> </tr> <tr> <td> 1 </td> <td> 1.829 </td> <td> 1.839 </td> </tr> <tr> <td> 2a </td> <td> 1.720 </td> <td> 1.710 </td> </tr> <tr> <td> 3a </td> <td> 1.893 </td> <td> 1.917 </td> </tr> <tr> <td> 3b </td> <td> 1.931 </td> <td> 1.936 </td> </tr> <tr> <td> 4 </td> <td> 1.627 </td> <td> 1.607 </td> </tr> </tbody></table> <div class="wp-block-image"><figure class="aligncenter"><img src="/blog/wp-content/carboraneLong.png" alt=""></figure></div> Figure 1. B3PW91-D3/cc-pVTZ optimized structure of 3b. Topological electron density analysis locates a bond path between the two carbons in all five structures. The Wiberg bond index is small, with a value of only 0.34 in 3b. Natural bond orbital (NBO) analysis identifies a negative hyperconjugation interaction between the nitrogen lone pair and the σ*C-C orbital. This rationalizes both the very long C-C bond and the very short C-N bonds, and the trends associated with the variation between 1° amine, 2° amine and imine. <h3>References</h3> 1. Li, J.; Pang, R.; Li, Z.; Lai, G.; Xiao, X.-Q.; Müller, T., “Exceptionally Long C−C Single Bonds in Diamino-o-carborane as Induced by Negative Hyperconjugation.” Angew. Chem. Int. Ed. 2019, 58, 1397-1401, DOI: <a href="http://dx.doi.org/10.1002/anie.201812555">10.1002/anie.201812555</a>. 2. Ishigaki, Y.; Shimajiri, T.; Takeda, T.; Katoono, R.; Suzuki, T., “Longest C–C Single Bond among Neutral Hydrocarbons with a Bond Length beyond 1.8 Å.” Chem 2018, 4, 795-806, DOI: <a href="https://doi.org/10.1016/j.chempr.2018.01.011">10.1016/j.chempr.2018.01.011</a>. <h3>InChIs</h3> 3b: InChI=1S/C22H28B10N2/c1-13-7-15(3)19(16(4)8-13)11-33-21-22(34-12-20-17(5)9-14(2)10-18(20)6)25(21)23-27(21)24-30(23,25)28(22,25)29(22)26(21,22,27)31(24,27,29)32(24,28,29)30/h7-10,33-34H,11-12H2,1-6H3 InChIKey=UEZUONSMPNIZRQ-UHFFFAOYSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4271" rel="bookmark" title="Permanent Link: Electrocycic reactions of cethrene derivatives">Electrocycic reactions of cethrene derivatives</a></h2> <div class="bottom"> <a href="/blog/archives/category/qm-method/dft" rel="category tag">DFT</a> &<a href="/blog/archives/category/reactions/electrocyclization" rel="category tag">electrocyclization</a> Steven Bachrach 05 Dec 2018 <a href="/blog/archives/4271#respond">No Comments</a> <hr> </div> <div class="post-content"> Pericyclic reactions remain a fruitful area of research despite the seminal publication of the Woodward-Hoffmann rules decades ago. Here are two related papers of pericyclic reactions that violate the Woodward-Hoffmann rules. First, Solomek, Ravat, Mou, Kertesz, and Jurícek reported on the thermal and photochemical electrocyclization reaction of diphenylcetherene 1a.<a href="#cethreneR1">1</a> Though they were not able to directly detect the intermediate 2, through careful examination of the photochemical reaction, they were able to infer that the thermal cyclization goes via the formally forbidden conrotatory pathway (see Scheme 1). Scheme 2. <img src="/blog/wp-content/cethreneImg1.png"> Kinetic studies estimate the activation barrier is 14.1 kcal mol-1. They performed DFT computations of the parent 1b using a variety of functionals with both restricted and unrestricted wavefunctions. The allowed pathway to 2syn is predicted to be greater than 27 kcal mol-1, while the formally forbidden pathway to 2anti is estimated to have a lower barrier of about 23 kcal mol-1. The two transition states for these different pathways are shown in Figure 1, and the sterics that force a helical structure to 1 help make the forbidden pathway more favorable. <table align="center" border="0" cellspacing="0" cellpadding="3"> <tr align="center" valign="bottom"> <td> <img src="/blog/wp-content/cethreneTSsyn.png"> TS(1b→2b-syn) </td> <td> <img src="/blog/wp-content/cethreneTSanti.png"> TS(1b→2b-anti) </td> </tr> </table> Figure 1. (U)B3LYP/6-31G optimized geometries of the transition states taking 1 into 2. Nonetheless, all of the DFT computations significantly overestimate the activation barrier. The authors make the case that a low-lying singlet excited state results in an early conical intersection that reduces the symmetry from C2 to C1. In this lower symmetry pathway, all of the states can mix, leading to a lower barrier. However, since DFT is intrinsically a single Slater configuration, the mixing of the other states is not accounted for, leading to the overestimated barrier height. In a follow up study, this group examined the thermal and photo cyclization of 13,14-dimethylcethrene 4.<href>2 The added methyl groups make the centhrene backbone more helical, and this precludes the formal allowed disrotatory process. The methyl groups also prohibit the oxidation that occurs with 1, driven by aromatization, allowing for the isolation of the direct product of the cyclization 5. This anti stereochemistry is confirmed by NMR and x-ray crystallography. The interconversion between 4 and 5 can be controlled by heat and light, making the system an interesting photoswitch.</href> <img src="/blog/wp-content/cethreneImg2.png"> Also of interest is the singlet-triplet gap of 1 and 4. The DFT computed ΔEST is about 10 kcal mol-1 for 4, larger than the computed value of 6 kcal mol-1 for 1b. The EPR of 1b does show a signal while that of 4 has no signal. To assess the role of the methyl group, they computed the singlet triplet gaps for 1b and 4 at two different geometries: where the distance between the carbons bearing the methyl groups is that in 1b (3.03 Å) and in 4 (3.37 Å). The lengthening of this distance by the methyl substituents is due to increased helical twist in 4 than in 1b. For 1b, the gap increases with twisting, from 7.1 to 8.3 kcal mol-1, while for 4 the gap increases by 1.8 kcal mol-1 with the increased twisting. This change is less than the effect of methyl substitution, which increases the gap by 2.2 kcal mol-1 at the shorter distance and 2.8 kcal mol-1 at the longer distance. Thus, the electronic (orbital) effect of methyl substitution affects the singlet-triplet gap more than the geometric twisting. <h3>References</h3> <a name="cethreneR1"></a> 1) Šolomek, T.; Ravat, P.; Mou, Z.; Kertesz, M.; Juríček, M., "Cethrene: The Chameleon of Woodward–Hoffmann Rules." J. Org. Chem. 2018, 83, 4769-4774, DOI: <a href="https://doi.org/10.1021/acs.joc.8b00656">10.1021/acs.joc.8b00656</a>. <a name="cethreneR2"></a> 2) Ravat, P.; Šolomek, T.; Häussinger, D.; Blacque, O.; Juríček, M., "Dimethylcethrene: A Chiroptical Diradicaloid Photoswitch." J. Am. Chem. Soc. 2018, 140, 10839-10847, DOI: <a href="https://doi.org/10.1021/jacs.8b05465">10.1021/jacs.8b05465</a>. <h3>InChIs</h3> 1b: InChI=1S/C28H16/c1-5-17-7-3-11-23-25(17)19(9-1)15-21-13-14-22-16-20-10-2-6-18-8-4-12-24(26(18)20)28(22)27(21)23/h1-16H InChIKey=GBMHAGKZRAVBDO-UHFFFAOYSA-N 4: InChI=1S/C30H20/c1-17-9-11-19-5-3-7-21-15-23-13-14-24-16-22-8-4-6-20-12-10-18(2)26(28(20)22)30(24)29(23)25(17)27(19)21/h3-16H,1-2H3 InChIKey=MXTVFWTUCPRNIW-UHFFFAOYSA-N 5: nChI=1S/C30H20/c1-29-13-11-17-5-3-7-19-15-21-9-10-22-16-20-8-4-6-18-12-14-30(29,2)28(24(18)20)26(22)25(21)27(29)23(17)19/h3-16H,1-2H3/t29-,30-/m0/s1 InChIKey=SUMMGEBJORQMAI-KYJUHHDHSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4226" rel="bookmark" title="Permanent Link: C18 carbomers">C18 carbomers</a></h2> <div class="bottom"> <a href="/blog/archives/category/aromaticity" rel="category tag">Aromaticity</a> Steven Bachrach 12 Nov 2018 <a href="/blog/archives/4226#respond">No Comments</a> <hr> </div> <div class="post-content"> Interesting 18 π-electron systems involving cyclooctadecanonenetriyne rings have been synthesized and examined by computations.<a href="#carbomer">1</a> The mono-, di- and tri-C18 ring compounds 1, 2, and 3 were prepared and the x-ray structure of 2 was obtained. The B3PW91/6-31G(d,p) optimized geometries of 1-3 and of the tetra ring 4 are shown in Figure 1. <table align="center" border="o" cellspacing="0" cellpadding="5"> <tr align="center"> <td> <img src="/blog/wp-content/carbomerImg1.png"> </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/carbomerImg2.png"> </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/carbomer1.png"> 1 </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/carbomer2.png"> 2 </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/carbomer3.png"> 3 </td> </tr> <tr align="center"> <td> <img src="/blog/wp-content/carbomer4.png"> 4 </td> </tr> </table> Figure 1. B3PW91/6-31G(d,p) optimized geometries of 1-4. Since the rings are composed of 18 π-electrons in the π-system perpendicular to the nearly planar ring, the natural question is to wonder if the ring is aromatic. The authors computed NICS(0) and NICS(1) values at the center of the C18 rings. For all four compounds, both the NICS(0) and NICS(1) values are negative, ranging from -12.4 to -14.9 ppm, indicating that the rings are aromatic. <h3>References</h3> <a name="carbomer"></a> 1) Chongwei, Z.; Albert, P.; Carine, D.; Brice, K.; Alix, S.; Valérie, M.; Remi, C., "Carbo‐biphenyls and Carbo‐terphenyls: Oligo(phenylene ethynylene) Ring Carbo‐mers." Angew. Chem. Int. Ed. 2018, 57, 5640-5644, DOI: <a href="http://dx.doi.org/10.1002/anie.201713411">10.1002/anie.201713411</a>. <h3>InChIs</h3> 1: InChI=1S/C58H54/c1-3-5-7-9-11-17-27-49-37-41-55(51-29-19-13-20-30-51)45-47-57(53-33-23-15-24-34-53)43-39-50(28-18-12-10-8-6-4-2)40-44-58(54-35-25-16-26-36-54)48-46-56(42-38-49)52-31-21-14-22-32-52/h13-16,19-26,29-36H,3-12,17-18,27-28H2,1-2H3 InChIKey=KWXYBTWOEJBCQD-UHFFFAOYSA-N 2: InChI=1S/C102H74/c1-3-5-7-9-11-21-39-83-59-67-95(87-41-23-13-24-42-87)75-79-99(91-49-31-17-32-50-91)71-63-85(64-72-100(92-51-33-18-34-52-92)80-76-96(68-60-83)88-43-25-14-26-44-88)57-58-86-65-73-101(93-53-35-19-36-54-93)81-77-97(89-45-27-15-28-46-89)69-61-84(40-22-12-10-8-6-4-2)62-70-98(90-47-29-16-30-48-90)78-82-102(74-66-86)94-55-37-20-38-56-94/h13-20,23-38,41-56H,3-12,21-22,39-40H2,1-2H3 InChIKey=HHRPTZGYBIHFOL-UHFFFAOYSA-N 3: InChI=1S/C146H94/c1-3-5-7-9-11-25-51-117-81-93-135(123-53-27-13-28-54-123)105-109-139(127-61-35-17-36-62-127)97-85-119(86-98-140(128-63-37-18-38-64-128)110-106-136(94-82-117)124-55-29-14-30-56-124)77-79-121-89-101-143(131-69-43-21-44-70-131)113-115-145(133-73-47-23-48-74-133)103-91-122(92-104-146(134-75-49-24-50-76-134)116-114-144(102-90-121)132-71-45-22-46-72-132)80-78-120-87-99-141(129-65-39-19-40-66-129)111-107-137(125-57-31-15-32-58-125)95-83-118(52-26-12-10-8-6-4-2)84-96-138(126-59-33-16-34-60-126)108-112-142(100-88-120)130-67-41-20-42-68-130/h13-24,27-50,53-76H,3-12,25-26,51-52H2,1-2H3 InChIKey=WCBXPLIBHKYESX-UHFFFAOYSA-N 4: InChI=1S/C190H114/c1-3-5-7-9-11-29-63-151-103-119-175(159-65-31-13-32-66-159)135-139-179(163-73-39-17-40-74-163)123-107-153(108-124-180(164-75-41-18-42-76-164)140-136-176(120-104-151)160-67-33-14-34-68-160)97-99-155-111-127-183(167-81-47-21-48-82-167)143-147-187(171-89-55-25-56-90-171)131-115-157(116-132-188(172-91-57-26-58-92-172)148-144-184(128-112-155)168-83-49-22-50-84-168)101-102-158-117-133-189(173-93-59-27-60-94-173)149-145-185(169-85-51-23-52-86-169)129-113-156(114-130-186(170-87-53-24-54-88-170)146-150-190(134-118-158)174-95-61-28-62-96-174)100-98-154-109-125-181(165-77-43-19-44-78-165)141-137-177(161-69-35-15-36-70-161)121-105-152(64-30-12-10-8-6-4-2)106-122-178(162-71-37-16-38-72-162)138-142-182(126-110-154)166-79-45-20-46-80-166/h13-28,31-62,65-96H,3-12,29-30,63-64H2,1-2H3 InChIKey=LLVPDVPZEIYJGN-UHFFFAOYSA-N  </div> </div> <div class="bottom2"></div> <div class="box"> <h2><a href="/blog/archives/4265" rel="bookmark" title="Permanent Link: Dynamics in the C-H insertion reaction of vinyl cations">Dynamics in the C-H insertion reaction of vinyl cations</a></h2> <div class="bottom"> <a href="/blog/archives/category/dynamics" rel="category tag">Dynamics</a> &<a href="/blog/archives/category/authors/houk" rel="category tag">Houk</a> Steven Bachrach 09 Oct 2018 <a href="/blog/archives/4265#respond">No Comments</a> <hr> </div> <div class="post-content"> A recent paper by Papov, Shao, Bagdasarian, Benton, Zou, Yang, Houk, and Nelson uncovers a vinyl cation insertion reaction that once again involves dynamic effects.<a href="#VinylCatR1">1</a> They find that vinyl triflates and cyclic vinyl triflates will react with [Ph3C]+[HCB11Cl11]– and triethylsilane to generate vinyl cations that can then be trapped through a C-H insertion reaction. For example, cyclohexenyl triflate 1 reacts in a cyclohexane solvent to give the insertion product 2. <img src="/blog/wp-content/vinylCatI1.png"> The reactions of isomers 3 and 4 give different ratios of the two products 5 and 6. In both cases, the cyclohexyl is trapped predominantly at the site of the triflate substituent. This means that the mechanism cannot involve a cyclohexene intermediate, since then the two ratios should be identical. <img src="/blog/wp-content/vinylCatI2.png"> They performed molecular dynamic trajectory analysis at the M062X/6-311+G(d,p) level, starting with the two transition states leading from 3 (TS3) and 4 (TS4), the only transition states located for the insertion reaction. The structures of these TSs are shown in Figure 1. <table align="center" border="0" cellspacing="0" cellpadding="5"> <tr align="center" valign="bottom"> <td> <img src="/blog/wp-content/vinylCatTS1.png"> TS3 </td> <td> <img src="/blog/wp-content/vinylCatTS2.png"> TS4 </td> </tr> </table> Figure 1. M062X/6-311+G(d,p) optimized geometries of TS3 and TS4. The trajectories end up in two product basins associated with 5 and 6 starting with either TS3 or TS4. Thus, these transition states are ambimodal, and typical of reactions where dynamic effects dominate. For the reaction of 3, the majority of the trajectories starting at TS3 end up as 5, consistent with the experiments. Similarly, for the trajectories that start at TS4, the majority end up as 6, consistent with experiments. Once again, we see that relatively simple organic reactions do not follow simple reaction mechanisms, that a single transition state leads to two different products and the product distributions are dependent on reaction dynamics. This may not be too surprising for the vinyl cation insertions given the many examples provide by the Tantillo group of cation rearrangements that are controlled by reaction dynamics (see for examples, this <a href="/blog/archives/4251">post</a> and this <a href="/blog/archives/393">post</a>). <h3>References</h3> <a name="VinylCatR1"></a> 1. Popov, S.; Shao, B.; Bagdasarian, A. L.; Benton, T. R.; Zou, L.; Yang, Z.; Houk, K. N.; Nelson, H. M., "Teaching an old carbocation new tricks: Intermolecular C–H insertion reactions of vinyl cations." Science 2018, 361, 381-387, DOI: <a href="http://dx.doi.org/10.1126/science.aat5440">10.1126/science.aat5440</a>. <h3>InChIs</h3> 1: InChI=1S/C7H10F3O3S/c8-7(9,10)14(11,12,13)6-4-2-1-3-5-6/h4H,1-3,5H2,(H,11,12,13) InChIKey=CMPVYBNXADJVOM-UHFFFAOYSA-N 2: InChIInChIKey=WVIIMZNLDWSIRH-UHFFFAOYSA-N 3: InChI=1S/C9H14F3O3S/c1-8(2)5-3-7(4-6-8)16(13,14,15)9(10,11)12/h3H,4-6H2,1-2H3,(H,13,14,15) InChIKey=XDWBLRRAHKBZJR-UHFFFAOYSA-N 4: InChI=1S/C9H14F3O3S/c1-8(2)5-3-4-7(6-8)16(13,14,15)9(10,11)12/h4H,3,5-6H2,1-2H3,(H,13,14,15) InChIKey=YHVCPSRICQJFDT-UHFFFAOYSA-N 5: InChI=1S/C14H26/c1-14(2)10-8-13(9-11-14)12-6-4-3-5-7-12/h12-13H,3-11H2,1-2H3 InChIKey=BZQBWUOXOYWYJC-UHFFFAOYSA-N 6: InChI=1S/C14H26/c1-14(2)10-6-9-13(11-14)12-7-4-3-5-8-12/h12-13H,3-11H2,1-2H3 InChIKey=AENMAOBTECURBO-UHFFFAOYSA-N  </div> </div> <div class="bottom2"></div> <a href="/blog/page/2">Next Page »</a> </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 href="/blog/archives/category/authors/cramer">Cramer</a> (11) </li> <li class="cat-item cat-item-83"> <a href="/blog/archives/category/authors/grimme">Grimme</a> (17) </li> <li class="cat-item cat-item-9"> <a href="/blog/archives/category/authors/houk">Houk</a> (40) </li> <li class="cat-item cat-item-29"> <a href="/blog/archives/category/authors/jorgensen">Jorgensen</a> (3) </li> <li class="cat-item cat-item-16"> <a href="/blog/archives/category/authors/kass">Kass</a> (9) </li> <li class="cat-item cat-item-30"> <a href="/blog/archives/category/authors/schaefer">Schaefer</a> (13) </li> <li class="cat-item cat-item-17"> <a href="/blog/archives/category/authors/schleyer">Schleyer</a> (24) </li> <li class="cat-item cat-item-73"> <a href="/blog/archives/category/authors/schreiner">Schreiner</a> (29) </li> <li class="cat-item cat-item-6"> <a href="/blog/archives/category/authors/singleton">Singleton</a> (11) </li> <li class="cat-item cat-item-18"> <a href="/blog/archives/category/authors/truhlar">Truhlar</a> (8) </li> </ul> </li> <li class="cat-item cat-item-15"> <a href="/blog/archives/category/bond-dissociation-energy">Bond Dissociation Energy</a> (6) </li> <li class="cat-item cat-item-81"> <a href="/blog/archives/category/bsse">BSSE</a> (1) </li> <li class="cat-item cat-item-88"> <a href="/blog/archives/category/cyclophane">cyclophane</a> (0) </li> <li class="cat-item cat-item-4"> <a href="/blog/archives/category/dynamics">Dynamics</a> (35) </li> <li class="cat-item cat-item-57"> <a href="/blog/archives/category/e-publishing">E-publishing</a> (7) </li> <li class="cat-item cat-item-65"> <a href="/blog/archives/category/enzyme">Enzyme</a> (4) </li> <li class="cat-item cat-item-95"> <a href="/blog/archives/category/fep">FEP</a> (1) </li> <li class="cat-item cat-item-86"> <a href="/blog/archives/category/host-guest">host-guest</a> (6) </li> <li class="cat-item cat-item-84"> <a href="/blog/archives/category/hydrogen-bond">Hydrogen bond</a> (5) </li> <li class="cat-item cat-item-91"> <a href="/blog/archives/category/ion-pairs">Ion Pairs</a> (1) </li> <li class="cat-item cat-item-74"> <a href="/blog/archives/category/isotope-effects">Isotope Effects</a> (5) </li> <li class="cat-item cat-item-67"> <a href="/blog/archives/category/keto-enol-tautomerization">Keto-enol tautomerization</a> (3) </li> <li class="cat-item cat-item-54"> <a href="/blog/archives/category/molecules">Molecules</a> (100) <ul class="children"> <li class="cat-item cat-item-48"> <a href="/blog/archives/category/molecules/adamantane">adamantane</a> (3) </li> <li class="cat-item cat-item-26"> <a href="/blog/archives/category/molecules/amino-acids">amino acids</a> (13) </li> <li class="cat-item cat-item-19"> <a href="/blog/archives/category/molecules/annulenes">annulenes</a> (8) </li> <li class="cat-item cat-item-27"> <a href="/blog/archives/category/molecules/benzynes">benzynes</a> (4) </li> <li class="cat-item cat-item-46"> <a href="/blog/archives/category/molecules/biphenyl">biphenyl</a> (1) </li> <li class="cat-item cat-item-70"> <a href="/blog/archives/category/molecules/calixarenes">calixarenes</a> (1) </li> <li class="cat-item cat-item-33"> <a href="/blog/archives/category/molecules/carbenes">carbenes</a> (13) </li> <li class="cat-item cat-item-72"> <a href="/blog/archives/category/molecules/cyclobutadiene">cyclobutadiene</a> (4) </li> <li class="cat-item cat-item-62"> <a href="/blog/archives/category/molecules/dendralenes">dendralenes</a> (1) </li> <li class="cat-item cat-item-66"> <a href="/blog/archives/category/molecules/dewar-benzene">Dewar benzene</a> (1) </li> <li class="cat-item cat-item-39"> <a href="/blog/archives/category/molecules/diradicals">diradicals</a> (8) </li> <li class="cat-item cat-item-59"> <a href="/blog/archives/category/molecules/ephedrine">ephedrine</a> (1) </li> <li class="cat-item cat-item-37"> <a href="/blog/archives/category/molecules/ethyl-cation">ethyl cation</a> (2) </li> <li class="cat-item cat-item-90"> <a href="/blog/archives/category/molecules/fullerene">fullerene</a> (6) </li> <li class="cat-item cat-item-51"> <a href="/blog/archives/category/molecules/fulvalenes">fulvalenes</a> (1) </li> <li class="cat-item cat-item-21"> <a href="/blog/archives/category/molecules/hexacyclinol">hexacyclinol</a> (2) </li> <li class="cat-item cat-item-78"> <a href="/blog/archives/category/molecules/nanohoops">nanohoops</a> (4) </li> <li class="cat-item cat-item-41"> <a href="/blog/archives/category/molecules/non-classical">non-classical</a> (4) </li> <li class="cat-item cat-item-34"> <a href="/blog/archives/category/molecules/norbornyl-cation">norbornyl cation</a> (2) </li> <li class="cat-item cat-item-49"> <a href="/blog/archives/category/molecules/nucleic-acids">nucleic acids</a> (4) </li> <li class="cat-item cat-item-36"> <a href="/blog/archives/category/molecules/oximes">oximes</a> (1) </li> <li class="cat-item cat-item-75"> <a 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">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> <li id="linkcat-58" class="linkcat"> <h2>Chemistry Links</h2> <ul> <li><a href="http://chem-bla-ics.blogspot.com/">Chem-bla-ics</a></li> <li><a href="http://cb.openmolecules.net/">Chemical Blogspace</a></li> <li><a href="http://www.chemspider.com/blog/">ChemSpider Blog</a></li> <li><a href="http://www.ch.ic.ac.uk/rzepa/blog/">Henry Rzepa Blog</a></li> <li><a href="http://wwmm.ch.cam.ac.uk/blogs/murrayrust/">Peter Murray-Rust Blog</a></li> <li><a href="http://cb.openmolecules.net/posts.php?category=Blue%20Obelisk">Planet Blue Obelisk</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>