Fluorenyl cation

Aromaticity Steven Bachrach 13 Apr 2015 No Comments

Is the fluorenyl cation 1 antiaromatic or non-aromatic? This is still an open question. But the recent paper by Costa, et al. provides a new path towards potentially answering this question; they have finally synthesized this molecule.1

By photolizing 2 in low-density amorphous ice (LDA ice) and in deuterated ice at 8 K, they have identified a new IR spectrum.

To identify the origin of these spectra, they optimized the geometry of the fluorenyl cation 1 at B3LYP-D3/def2-TZVP (see Figure 1) and computed its IR spectra. These computed IR frequencies were then scaled by 0.97. The agreement between the computed and experimental frequencies is quite reasonable, and the isotopic shifts are also reasonably well reproduced. The agreement is not perfect, as seen in Table 1. Hopefully, further experiments will now be carried out to try to answer the lead question of this post.

Figure 1. B3LYP-D3/def2-TZVP optimized geometry of 1.

Table 1. Experimental and computed IR frequencies (cm-1)
and isotopic shift (in parentheses) of 1.

Calc.

Exp.

1008.8

986

1106.8 (+2.1)

1076.8 (+1.7)

1152.8

1117.2

1198.6

1163.5

1267.0

1235.1

1373.4 (-16.4)

1343.7

1510.8(-8.3)

1469.0 (-7.3)

1530.7 (-3.2)

1490.5 (-1.0)

1616.8(-6.4)

1575.7(-4.4)

1640.9 (0.0)

1601.2 (-4.0)

References

(1) Costa, P.; Trosien, I.; Fernandez-Oliva, M.; Sanchez-Garcia, E.; Sander, W. "The Fluorenyl Cation," Angew. Chem. Int. Ed. 2015, 54, 2656-2660, DOI: 10.1002/anie.201411234.

InChIs

1: InChI=1S/C13H9/c1-3-7-12-10(5-1)9-11-6-2-4-8-13(11)12/h1-9H/q+1
InChIKey=KZCNYQVQQBONEY-UHFFFAOYSA-N

Gas phase structure of uridine

MP &nucleic acids Steven Bachrach 06 Apr 2015 No Comments

To advance our understanding of why ribose takes on the furanose form, rather than the pyranose form, in RNA, Alonso and co-workers have examined the structure of uridine 1 in the gas phase.1


1

Uridine is sensitive to temperature, and so the laser-ablation method long used by the Alonso group is ideal for examining uridine. The microwave spectrum is quite complicated due to the presence of many photofragments. Careful analysis lead to the identification of a number of lines and hyperfine structure that could be definitively assigned to uridine, leading to experimental values of the rotational constants and the diagonal elements of the 14N nuclear quadrupole coupling tensor for each nitrogen. These values are listed in Table 1.

Table 1. Experimental and calculated rotational constants (MHz), quadrupole coupling constants (MHz) and relative energy (kcal mol-1).

 

 

calculated


 

Expt.

anti/C2’-endo-g+

syn/C2’-endo-g+

anti/C3’-endo-g+

anti/C2’-endo-t

syn/C3’-endo-g+

A

885.98961

901.2

935.8

790.0

799.7

925.5

B

335.59622

340.6

308.4

352.6

330.6

300.4

C

270.11210

276.6

266.6

261.4

262.9

264.0

14N1 χxx

1.540

1.50

1.82

1.48

1.46

1.82

14N1 χyy

1.456

1.43

0.73

1.71

1.81

-0.72

14N1 χzz

-2.996

-2.93

-2.56

-3.19

-3.27

-1.11

14N3 χxx

1.719

1.74

2.03

1.78

1.62

1.98

14N3 χyy

1.261

1.11

0.47

1.34

1.51

-0.75

14N3 χzz

-2.979

-2.85

-2.50

-3.12

-3.13

-1.23

Rel E

 

0.0

1.10

1.90

2.00

2.15

In order to assign a 3-D structure to these experimental values, they examined the PES of uridine with molecular mechanics and semi-empirical methods, before reoptimizing the structure of the lowest 5 energy structures at MP2/6-311++G(d,p). Then, comparison of the resulting rotational constants and 14N nuclear quadrupole coupling constants of these computed structures (see Table 1) led to identification of the lowest energy structure (anti/C2’-endo-g+, see Figure 1) in best agreement with the experiment. Once again, the Alonso group has demonstrated the value of the synergy between experiment and computation in structure identification.

Figure 1. MP2/6-311++G(d,p) optimized structure of 1 (anti/C2’-endo-g+).

References

(1) Peña, I.; Cabezas, C.; Alonso, J. L. "The Nucleoside Uridine Isolated in the Gas Phase," Angew. Chem. Int. Ed. 2015, 54, 2991-2994, DOI: 10.1002/anie.201412460.

Inchis:

1: Inchi=1S/C9H12N2O6/c12-3-4-6(14)7(15)8(17-4)11-2-1-5(13)10-9(11)16/h1-2,4,6-8,12,14-15H,3H2,(H,10,13,16)/t4-,6-,7-,8-/m1/s1
InChiKey=DRTQHJPVMGBUCF-XVFCMESISA-N

Molecular rotor and C-Hπ interaction

Aromaticity &Houk &Hydrogen bond Steven Bachrach 23 Mar 2015 No Comments

Molecular rotors remain a fascinating topic – the idea of creating a miniature motor just seems to capture the imagination of scientists. Garcia-Garibay and his group have synthesized the interesting rotor 1, and in collaboration with the Houk group, they have utilized computations to help understand the dynamics of this rotor.1


1

The x-ray structure of this compound, shown in Figure 1, displays two close interactions of a hydrogen on the central phenyl ring with the face of one of the steroidal phenyl rings. Rotation of the central phenyl ring is expected to then “turn off” one or both of these C-Hπ interactions. The authors argue this as a competition between the molecule sampling an enthalpic region, where the molecule has one or two favorable C-Hπ interactions, and the large entropic region where these C-Hπ interactions do not occur, but this space is expected to have a large quantity of energetically similar conformations.

x-ray

1a

1b

Figure 1. X-ray and M06-2x/6-31G(d) optimized structures of 1.

Variable temperature NMR finds the central phenyl hydrogen with a chemical shift of 6.55ppm at 295 K but at 6.32 ppm at 222 K. This suggest as freezing of the conformations at low temperature favoring those conformations possessing the internal C-Hπ interactions. M06-2X/6-31G(d) optimization finds two low-energy conformations with a single C-Hπ interaction. These are shown in Figure 1. No competing conformation was found to have two such interactions. Computations of the chemical shifts of these conformations show the upfield shift of the central phenyl hydrogens. Fitting these chemical shifts to the temperature data gives ΔH = -1.74 kcal mol-1, ΔS = -5.12 esu and ΔG = -0.21 kcal mol-1 for the enthalpic region to entropic region transition.

References

(1) Pérez-Estrada, S.; Rodrı́guez-Molina, B.; Xiao, L.; Santillan, R.; Jiménez-Osés, G.; Houk, K. N.; Garcia-Garibay, M. A. "Thermodynamic Evaluation of Aromatic CH/π Interactions and Rotational Entropy in a Molecular Rotor," J. Am. Chem. Soc. 2015, 137, 2175-2178, DOI: 10.1021/ja512053t.

InChIs

1: InChI=1S/C48H54O4/c1-45-23-19-39-37-15-11-35(51-3)29-33(37)9-13-41(39)43(45)21-27-47(45,49)25-17-31-5-7-32(8-6-31)18-26-48(50)28-22-44-42-14-10-34-30-36(52-4)12-16-38(34)40(42)20-24-46(44,48)2/h5-8,11-12,15-16,29-30,39-44,49-50H,9-10,13-14,19-24,27-28H2,1-4H3
InChIKey=CXZHCTLIHKZRMW-UHFFFAOYSA-N

Structure revision: Vescalagin and Castalagin

NMR Steven Bachrach 09 Mar 2015 No Comments

Vescalagin 1 and castalagin 2 are found in plants and also in wine and whisky. They possess some intriguing stereochemistry and the topic of interest in the paper by Tanaka and coworkers is the stereochemistry of the triphenyl fragment.1 The original proposed structure indicated a (S,S) (1a and 2a) configuration, yet a molecular mechanics study suggest the (S,R) (1b and 2b) configuration would be lower in energy.

1a: R1 = OH, R2 = H
2a: R1 = H, R2 = OH

1b: R1 = OH, R2 = H
2b: R1 = H, R2 = OH

Recognizing the power of DFT computations in resolving this type of structural problem, Tanaka measured the ECD spectrum of the hydrolyzed forms of 1 and 2, namely 3 and 4. The (S,S) and (S,R) isomers of 3 and 4 were subjected to a Monte Carlo search using MM. Low-lying conformers were reoptimized at B3LYP/6-31G(d,p) including PCM, modeling methanol as the solvent. The ECD spectrum was then predicted using all conformations with a population over 1%. The computed spectrum for the (S,R) isomer reproduced the negative Cotton effect at 218 nm observed in the experiment.

3a: R1 = OH, R2 = H
4a: R1 = H, R2 = OH

3b: R1 = OH, R2 = H
3b: R1 = H, R2 = OH

The structures of 1 and 2 of both stereoisomers were next optimized at B3LYP/6-31G(d,p) including PCM. The lowest energy conformation of each is shown in Figure 1. The 1H and 13C chemical shifts were computed at this level, again using all conformations with a population greater than 1%. The correlation coefficient for the fit between the experimental values of the chemical shifts and 1a and 2a are significantly lower for both proton and carbon, while the correlation coefficients compared to 1b and 2b are larger, 0.93 or better. Therefore, the structures of vescalagin is 1b and castalagin is 2b.

1b

2b

Figure 1. B3LYP/6-31G(d,p) optimized geometries of the lowest energy conformers of 1b and 2b.

References

(1) Matsuo, Y.; Wakamatsu, H.; Omar, M.; Tanaka, T. "Reinvestigation of the Stereochemistry of the C-Glycosidic Ellagitannins, Vescalagin and Castalagin," Org. Lett. 2014, 17, 46-49, DOI: 10.1021/ol503212v.

InChIs

1: InChI=1S/C41H26O26/c42-8-1-5-12(24(48)21(8)45)13-6(2-9(43)22(46)25(13)49)39(60)65-34-11(4-63-37(5)58)64-38(59)7-3-10(44)23(47)26(50)14(7)15-18-16(28(52)32(56)27(15)51)17-19-20(30(54)33(57)29(17)53)31(55)35(66-41(19)62)36(34)67-40(18)61/h1-3,11,31,34-36,42-57H,4H2/t11-,31-,34+,35+,36-/m0/s1
InChIKey=UDYKDZHZAKSYCO-KWVBPWBCSA-N

2: InChI=1S/C41H26O26/c42-8-1-5-12(24(48)21(8)45)13-6(2-9(43)22(46)25(13)49)39(60)65-34-11(4-63-37(5)58)64-38(59)7-3-10(44)23(47)26(50)14(7)15-18-16(28(52)32(56)27(15)51)17-19-20(30(54)33(57)29(17)53)31(55)35(66-41(19)62)36(34)67-40(18)61/h1-3,11,31,34-36,42-57H,4H2/t11-,31+,34+,35+,36-/m0/s1
InChIKey=UDYKDZHZAKSYCO-GJTMBUPBSA-N

Microsolvated structure of β-propiolactone

MP &Solvation Steven Bachrach 24 Feb 2015 1 Comment

The structure of water about a solute remains of critical importance towards understanding aqueous solvation. Microwave spectroscopy and computations are the best tools we have today to gain insight on this problem. This is nicely demonstrated in the Alonso study of the microsolvated structures of β-propiolactone 1.1 They employed chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy and MP2(fc)/6-311++G(d,p) computations to examine the structure involving 1-5 water molecules.

The computed structures of these microsolvated species are shown in Figure 1. The deviation of the computed and experimental structures (RMS in the atomic positions) is small, though increasing as the size of the cluster increases. The deviation is 0.014 Å for the 1. H2O cluster and 0.244 Å for the 1.(H2O)5 cluster. They identified two clusters with four water molecules; the lower energy structure, labeled as a, is only 0.2 kJ mol-1 more stable than structure b.

1.H2O

1.(H2O)2

1.(H2O)3

1.(H2O)4 a

1.(H2O)4 b

1.(H2O)5

Figure 1. MP2(fc)/6-311++G(d,p) optimized geometries of the hydrates of 1.

Water rings are found in the clusters having four or five water molecules, while chains are identified in the smaller clusters. One might imagine water cages appearing with even more water molecules in the microsolvated structures.

References

(1) Pérez, C.; Neill, J. L.; Muckle, M. T.; Zaleski, D. P.; Peña, I.; Lopez, J. C.; Alonso, J. L.; Pate, B. H. Angew. Chem. Int. Ed. 2015, 54, 979-982, DOI: 10.1002/anie.201409057.

InChIs

1: InChI=1S/C3H4O2/c4-3-1-2-5-3/h1-2H2
InChIKey=VEZXCJBBBCKRPI-UHFFFAOYSA-N

Structures of cephalosporolide C, J, and bassianolone

NMR Steven Bachrach 16 Feb 2015 No Comments

Here is a story that must drive chemical database quality control personnel nuts. Song, et al. noticed that the reported 13C NMR of the natural products cephalosporolide C 1, cephalosporolide J 2 and bassianolone 3 are identical.1 Given that it is highly unlikely that two diastereomers would have identical NMR spectra, the likelihood that these three have identical spectra seemed remote at best.

Compounds 1 and 2 were synthesized and their structures confirmed by x-ray crystallography. Their 13C NMR spectra show clear distinctions, indicating that the isolated “2” is actually 1. Experimental support for the notion that 1 and 3 are actually the same was provided by preparing the diacetylide of 1 and comparing its NMR spectra to that of natural “3”.

Quantum computations confirmed that in fact the natural product thought to be 3 is actually 1. The structures of 1 and 3 were optimized at B3LYP/6-311+G(2d,p) and 13C chemical shifts were computed with these geometries at mPW1PW91/6-311+G(2d,p)/CPCM(chloroform). (The computed structures are shown in Figure 1.) The mean absolute deviation (MAD) between the computed and experimental spectra for 1 is 0.97 ppm, while the MAD for the computed spectrum of 3 compared with the experimental values is 2.44 ppm, with a maximum error of 5.13ppm, more than twice the maximum error with structure 1. The authors attribute the misassignments to a faulty initial spectra of authentic cephalosporolide C 1.

1

3

Figure 1. B3LYP/6-311+G(2d,p) optimized geometries of 1 and 3.

References

(1) Song, L.; Lee, K.-H.; Lin, Z.; Tong, R. "Structural Revision of Cephalosporolide J and Bassianolone," J. Org. Chem. 2014, 79, 1493-1497, DOI: 10.1021/jo402602h.

InChIs

1: InChI=1S/C10H16O5/c1-6-2-3-7(11)4-8(12)9(13)5-10(14)15-6/h6,8-9,12-13H,2-5H2,1H3/t6-,8+,9+/m1/s1
InChIKey=JTOYXZZLKBAIEJ-YEPSODPASA-N

2: InChI=1S/C10H16O5/c1-6-2-3-7(11)4-8(12)9(13)5-10(14)15-6/h6,8-9,12-13H,2-5H2,1H3/t6-,8+,9-/m1/s1
InChIKey=JTOYXZZLKBAIEJ-BWVDBABLSA-N

3: InChI=1S/C10H16O5/c1-6(11)2-3-7(12)4-9-8(13)5-10(14)15-9/h6,8-9,11,13H,2-5H2,1H3/t6-,8+,9+/m1/s1
InChIKey=ZTRQRDNTNXPRFW-YEPSODPASA-N

Protocol for computing NMR chemical shifts

NMR Steven Bachrach 09 Feb 2015 No Comments

I have posted on the use of computed NMR chemical shifts and coupling constants to help aid in structure identification. The second edition of my book Computational Organic Chemistry has a largely all-new chapter on structure identification aided by computed spectra, especially NMR spectra. In my recent opinion piece speculating on challenges in computational organic chemistry,1 the first area I highlight is encouraging the larger use of computed spectra as an essential component of structure determination.

While more and more non-traditional computational users are employing quantum computations towards these problems, I suspect that many non-users are a bit wary about stepping into an arena they are not expert in, an arena chock-filled with acronyms and methods and potentially little guidance. While some very nice papers2-6 and web sites (Chemical Shift Repository (Cheshire) and DP4) do outline procedures for using computations in this fashion, they are not truly designed for the non-specialist.

Well, fear not any longer. Hoye and coworkers, synthetic chemists who have utilized computational approaches in structure determinations for a number of years, have written a detailed step-by-step protocol for using a standard computational approach towards structure determination.7 The article is written with the synthetic chemist in mind, and includes a number of scripts to automate many of the steps.

For the specialist, the overall outline of the protocol is fairly routine:

  1. Utilize MacroModel to perform a conformational search for each proposed structure, retaining the geometries within 5 kcal mol-1 of the global minimum.
  2. Optimize these conformations for each structure at M06-2x/6-31+G(d).
  3. For each conformation of each structure, compute the 1H and 13C chemical shifts, scale them, and determine the Boltzmann weighted chemical shifts
  4. Compare these chemical shifts with the experimental values using Mean Absolute Error

The article is straightforward and easily guides the novice user through these steps. Anyone unsure of how to utilize quantum chemical computations in structure determination is well advised to start with this article.

References

(1) Bachrach, S. M. "Challenges in computational organic chemistry," WIRES: Comput. Mol. Sci. 2014, 4, 482-487, DOI: 10.1002/wcms.1185.

(2) Lodewyk, M. W.; Siebert, M. R.; Tantillo, D. J. "Computational Prediction of 1H and 13C Chemical Shifts: A Useful Tool for Natural Product, Mechanistic, and Synthetic Organic Chemistry," Chem. Rev. 2012, 112, 1839–1862, DOI: href="http://dx.doi.org/10.1021/cr200106v">10.1021/cr200106v.

(3) Bally, T.; Rablen, P. R. "Quantum-Chemical Simulation of 1H NMR Spectra. 2. Comparison of DFT-Based Procedures for Computing Proton-Proton Coupling Constants in Organic Molecules," J. Org. Chem. 2011, 76, 4818-4830, DOI: 10.1021/jo200513q.>

(4) Jain, R.; Bally, T.; Rablen, P. R. "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem. 2009, 74, 4017-4023, DOI: 10.1021/jo900482q.

(5) Smith, S. G.; Goodman, J. M. "Assigning the Stereochemistry of Pairs of Diastereoisomers Using GIAO NMR Shift Calculation," J. Org. Chem. 2009, 74, 4597-4607, DOI: 10.1021/jo900408d.

(6) Smith, S. G.; Goodman, J. M. "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI: 10.1021/ja105035r.

(7) Willoughby, P. H.; Jansma, M. J.; Hoye, T. R. "A guide to small-molecule structure assignment through computation of (1H and 13C) NMR chemical shifts," Nat. Protocols 2014, 9, 643-660, DOI: 10.1038/nprot.2014.042.

Twisting a benzene ring

Aromaticity Steven Bachrach 26 Jan 2015 No Comments

Here’s another cruel and unusual punishment applied to the poor benzene ring. Hashimoto,et al. have created a molecule that is a fused double helicene, where the fusion is about a single phenyl ring.1 Compound 1 has two [5]helicenes oriented in opposite directions. This should provide a twist to the central phenyl ring, and the added methyl groups help to expand that twist.

They prepared 1 and its x-ray crystal structure is reported. The compound exhibits C2 symmetry. The twist (defined as the dihedral of four consecutive carbon atoms of the central ring) is 28.17°, nearly the same twist as in [2]paraphenylene.

The B3LYP/6-31G(d) structure of 1 is shown in Figure 1. This geometry is very similar to the x-ray structure. The calculated NICS value for the central ring is -4.9 (B3LYP/6-311+G(d,p)/B3LYP/6-31G(d)) and -4.3 (B3LYP/6-311+G(d,p)/x-ray structure). This diminished value from either benzene or C6(PSH2)2(CH3)4 indicates reduced aromaticity of this central ring, presumably due to the distortion away from planarity. Nonetheless, the central ring of 1 is not oxidized when subjected to MCPBA to oxidize to the bis phosphine oxides.

1

Figure 1. B3LYP/6-31G(d) optimized structure of 1.

References

(1) Hashimoto, S.; Nakatsuka, S.; Nakamura, M.; Hatakeyama, T. "Construction of a Highly Distorted Benzene Ring in a Double Helicene," Angew. Chem. Int. Ed. 2014, 53, 14074-14076, DOI: 10.1002/anie.201408390.

InChIs

1: InChI=1S/C50H32P2S2/c1-25-17-21-29-9-5-13-33-41(29)37(25)45-46-38-26(2)18-22-30-10-7-15-35(42(30)38)52(54)36-16-8-12-32-24-20-28(4)40(44(32)36)48(50(46)52)47-39-27(3)19-23-31-11-6-14-34(43(31)39)51(33,53)49(45)47/h5-24H,1-4H3

o-Phenylene conformations

Aromaticity Steven Bachrach 21 Jan 2015 No Comments

In solution ortho-phenylenes preferentially coil into a helix with the phenyl rings stacked. However, 25-50% of these chains will typically misfold. Hartley and coworkers have reported the use of substituents to increase the percentage of perfectly folded chains.1

They synthesized two isomeric o-phenylenes, differing in the substitution pattern (1 and 2), with chain length of 6 to 10 phenyl rings. Substituents included methoxy, acetoxy, nitrile, and triflate. They principally employed 1H NMR to assess the conformational distribution, and used computations to confirm the conformation.

Ideally folded conformations of 1 and 2 with eight phenyl rings are shown in Figure 1. The dihedral angle formed by two adjacent phenyl rings are typically about ±55° or ±130°.

1

2

Figure 1. Idealized folding of 1 and 2 with X=OH.
Hydrogens omitted in these images, but full structures available, through Jmol, by clicking on the image.)

Given the size of these systems, and the conformation flexibility not just of the chain but with each substituent, a full search to identify the global minimum was not undertaken. Rather, a library of conformations was generated with MM, the lowest 200 conformations were then reoptimized at PM7 and then the energies were determined at PCM/B97-D/TZV(2d,2p). The lowest energy conformer was then reoptimized at this DFT level. Three conformations of 3 and 4 are shown in Figure 2 with triflate as the substituent with six phenyl rings. The first conformer has optimal stacking (perfect folding), the second conformer as one misfold at the end, and the third conformer has no stacking at all.

3
– ideal fold

3
– one misfold

3 – all misfold

4 – ideal fold

4
– one misfold

4
– all misfold

Figure 2. Optimized geometries of conformers of 3 and 4.
(Remember that clicking on one of these images will bring up the JMol applet allowing you to rotate and visualize the molecule in 3-D – a very useful feature here!)

NMR chemical shifts were then computed using these geometries at PCM/WP04/6-31G(d). In all cases examined, the chemical shifts of the major conformation was confirmed to be the perfect folding one by comparison with the computed chemical shifts. The examined substituents enhanced the proportion of properly folded chains in all cases, often to the extent where no minor conformer was observed at all.

References

(1) Mathew, S.; Crandall, L. A.; Ziegler, C. J.; Hartley, C. S. "Enhanced Helical Folding of ortho-Phenylenes through the Control of Aromatic Stacking Interactions," J. Am. Chem. Soc. 2014, 136, 16666-16675, DOI:10.1021/ja509902m.

InChIs

3: InChI=1S/C42H26F18O18S6/c43-37(44,45)79(61,62,63)23-5-1-21(2-6-23)29-13-9-25(81(67,68,69)39(49,50)51)17-33(29)35-19-27(83(73,74,75)41(55,56)57)11-15-31(35)32-16-12-28(84(76,77,78)42(58,59)60)20-36(32)34-18-26(82(70,71,72)40(52,53)54)10-14-30(34)22-3-7-24(8-4-22)80(64,65,66)38(46,47)48/h1-20H,(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)
InChIKey=BOCNJIZJHQKUNK-UHFFFAOYSA-N

4: InChI=1S/C42H26F18O18S6/c43-37(44,45)79(61,62,63)23-6-4-21(5-7-23)33-17-25(81(67,68,69)39(49,50)51)9-13-30(33)35-19-27(83(73,74,75)41(55,56)57)11-15-32(35)36-20-28(84(76,77,78)42(58,59)60)10-14-31(36)34-18-26(82(70,71,72)40(52,53)54)8-12-29(34)22-2-1-3-24(16-22)80(64,65,66)38(46,47)48/h1-20H,(H,61,62,63)(H,64,65,66)(H,67,68,69)(H,70,71,72)(H,73,74,75)(H,76,77,78)
InChIKey=YKSIXAVDGFBUIZ-UHFFFAOYSA-N

Benchmarking π-conjugation

DFT Steven Bachrach 14 Jan 2015 2 Comments

With the proliferation of density functionals, selecting the functional to use in your particular application requires some care. That is why there have been quite a number of benchmark studies (see these posts for some examples). Yu and Karton have now added to our benchmark catalog with a study of π-conjugation.1

They looked at a set of 60 reactions which involve a reactant with π-conjugation and a product which lacks conjugation. A few examples, showing examples involving linear and cyclic systems, are shown in Scheme 1.

Scheme 1.

The reaction energies were evaluated at W2-F12, which should have an error of a fraction of a kcal mol-1. Three of the reactions can be compared with experimental values, and difference in the experimental and computed values are well within the error bars of the experiment. It is too bad that the authors did not also examine 1,3-cyclohexadiene → 1,4-cyclohexadiene, a reaction that is both of broader interest than many of the ones included in the test set and can also be compared with experiment.

These 60 reactions were then evaluated with a slew of functionals from every rung of Jacob’s ladder. The highlights of this benchmark study are that most GGA and meta-GGA and hybrid functionals (like B3LYP) have errors that exceed chemical accuracy (about 1 kcal mol-1). However, the range-separated functionals give very good energies, including ωB97X-D. The best results are provided with double hybrid functionals. Lastly, the D3 dispersion correction does generally improve energies by 10-20%. On the wavefunction side, SCS-MPs gives excellent results, and may be one of the best choices when considering computational resources.

References

(1) Yu, L.-J.; Karton, A. "Assessment of theoretical procedures for a diverse set of isomerization reactions involving double-bond migration in conjugated dienes," Chem. Phys. 2014, 441, 166-177, DOI: 10.1016/j.chemphys.2014.07.015.

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