Hetero-substituted corranulene

Aromaticity Steven Bachrach 20 Jul 2015 1 Comment

A heterosubstituted corranulene analogue has now been prepared. Ito, Tokimaru, and Nozaki report the synthesis of 1 and compare it with corranulene.1 The x-ray structure of 1 shows it to be a deeper bowl than corranulene, and the bond distances suggest the Kekule structure with a central pyrrole and five Clar-type phenyl rings.

The B3LYP/6-311+G(2d,p) optimized structure of 2, then analogue of 1 missing the t-butyl group, is shown in Figure 1. Its geometry is very similar to that of 1 observed in the crystal structure. The NICS(0) values are shown in Scheme 1. These values support the notion of a central (aromatic) pyrrole surrounded by a periphery of five aromatic phenyl rings.

Scheme 1. NICS(0) values

An interesting feature of bowl compounds is their inversion. The inversion barrier, through the planar TS shown in Figure 2, is computed to be 17.0 kcal mol-1 at B3LYP/6-311+G(2d,p). This is 6-7 kcal mol-1 larger than the inversion barrier of corranulene, which is not surprising given the additional phenyl groups about the periphery.

2

bowl inversion TS

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

References

(1) Ito, S.; Tokimaru, Y.; Nozaki, K. "Benzene-Fused Azacorannulene Bearing an Internal Nitrogen Atom," Angew. Chem. Int. Ed. 2015, 54, 7256-7260, DOI: 10.1002/anie.201502599.

InChI

1: InChI=1S/C38H23N/c1-38(2,3)18-16-27-25-14-6-12-23-21-10-4-8-19-20-9-5-11-22-24-13-7-15-26-28(17-18)35(27)39-36(31(23)25)33(29(19)21)34(30(20)22)37(39)32(24)26/h4-17H,1-3H3
InChIKey= JJPREOOFFSVARV-UHFFFAOYSA-N

2: InChI=1S/C34H15N/c1-6-16-17-7-2-9-19-21-11-4-13-23-25-15-5-14-24-22-12-3-10-20-18(8-1)26(16)30-31(27(17)19)34(29(21)23)35(32(24)25)33(30)28(20)22/h1-15H
InChIKey= FFFUKUDWQMOFQQ-UHFFFAOYSA-N

Hypercoordinated carbon revisited

Isotope Effects &Tunneling Steven Bachrach 14 Jul 2015 No Comments

Last year I wrote a post on the possibility of a stable hypercoordinated carbon in the C(CH3)5+ molecule as proposed by Schleyer and Schaefer.1 Kozuch has re-examined this molecule with an eye towards examining the lifetime of this proposed “fleeting” molecule.2

The computed barriers for either (1) loss of a methane molecule leaving behind the (CH3)2C+CH2CH3 cation or (2) loss of an ethane molecule leaving behind the t-butyl cation are small: 1.65 and 1.37 kcal mol-1, respectively. Kozuch employed canonical variational theory with and without small curvature tunneling (SCT). Without the tunneling correction, the pentamethylmethyl cation is predicted to have a long (millennia) lifetime at very low temperatures (<20 K). However, when tunneling is included, the half-life is reduced to 6 and 40 μs for degradation along the two pathways. Clearly, this is not a fleeting molecule – its lifetime is really too short to consider it as anything.

Interestingly, perdeuterating the molecule ((CD3)5C+) substantially increases the half-life to 4 ms, a thousand-fold increase. Tritium substitution would further increase the half-life to 0.2 s – a long enough time to really identify it and perhaps justify the name “molecule”. What is perhaps the most interesting aspect here is that H/D substitution has such a large effect on the tunneling rate even though no C-H bond is broken in the TS! This results from a mass effect (a CH3 vs. a CD3 group is migrating) along with a zero-point vibrational energy effect.

References

(1) McKee, W. C.; Agarwal, J.; Schaefer, H. F.; Schleyer, P. v. R. "Covalent Hypercoordination: Can Carbon Bind Five Methyl Ligands?," Angew. Chem. Int. Ed. 2014, 53, 7875-7878, DOI: 10.1002/anie.201403314.

(2) Kozuch, S. "On the tunneling instability of a hypercoordinated carbocation," Phys. Chem. Chem. Phys. 2015, 17, 16688-16691, DOI: 10.1039/C5CP02080H.

InChIs

C(CH3)5+: InChI=1S/C6H15/c1-6(2,3,4)5/h1-5H3/q+1
InChIKey=GGCBGJZCTGZYFV-UHFFFAOYSA-N

Inverted Carbon Atoms

Schreiner Steven Bachrach 06 Jul 2015 8 Comments

Inverted carbon atoms, where the bonds from a single carbon atom are made to four other atoms which all on one side of a plane, remain a subject of fascination for organic chemists. We simply like to put carbon into unusual environments! Bremer, Fokin, and Schreiner have examined a selection of molecules possessing inverted carbon atoms and highlights some problems both with experiments and computations.1

The prototype of the inverted carbon is propellane 1. The ­Cinv-Cinv bond distance is 1.594 Å as determined in a gas-phase electron diffraction experiment.2 A selection of bond distance computed with various methods is shown in Figure 1. Note that CASPT2/6-31G(d), CCSD(t)/cc-pVTZ and MP2 does a very fine job in predicting the structure. However, a selection of DFT methods predict a distance that is too short, and these methods include functionals that include dispersion corrections or have been designed to account for medium-range electron correlation.

CASPT2/6-31G(d)

CCSD(T)/cc-pVTZ

MP2/cc-pVTZ

MP2/cc-pVQZ

B3LYP/6-311+G(d,p)

B3LYP-D3BJ/6-311+G(d,p)

M06-2x/6-311+G(d,p)

1.596

1.595

1.596

1.590

1.575

1.575

1.550

Figure 1. Optimized Structure of 1 at MP2/cc-pVTZ, along with Cinv-Cinv distances (Å) computed with different methods.

Propellanes without an inverted carbon, like 2, are properly described by these DFT methods; the C-C distance predicted by the DFT methods is close to that predicted by the post-HF methods.

The propellane 3 has been referred to many times for its seemingly very long Cinv-Cinv bond: an x-ray study from 1973 indicates it is 1.643 Å.3 However, this distance is computed at MP2/cc-pVTZ to be considerably shorter: 1.571 Å (Figure 2). Bremer, Fokin, and Schreiner resynthesized 3 and conducted a new x-ray study, and find that the Cinv-Cinv distance is 1.5838 Å, in reasonable agreement with the computation. This is yet another example of where computation has pointed towards experimental errors in chemical structure.

Figure 2. MP2/cc-pVTZ optimized structure of 3.

However, DFT methods fail to properly predict the Cinv-Cinv distance in 3. The functionals B3LYP, B3LYP-D3BJ and M06-2x (with the cc-pVTZ basis set) predict a distance of 1.560, 1.555, and 1.545 Å, respectively. Bremer, Folkin and Schreiner did not consider the ωB97X-D functional, so I optimized the structure of 3 at ωB97X-D/cc-pVTZ and the distance is 1.546 Å.

Inverted carbon atoms appear to be a significant challenge for DFT methods.

References

(1) Bremer, M.; Untenecker, H.; Gunchenko, P. A.; Fokin, A. A.; Schreiner, P. R. "Inverted Carbon Geometries: Challenges to Experiment and Theory," J. Org. Chem. 2015, 80, 6520–6524, DOI: 10.1021/acs.joc.5b00845.

(2) Hedberg, L.; Hedberg, K. "The molecular structure of gaseous [1.1.1]propellane: an electron-diffraction investigation," J. Am. Chem. Soc. 1985, 107, 7257-7260, DOI: 10.1021/ja00311a004.

(3) Gibbons, C. S.; Trotter, J. "Crystal Structure of 1-Cyanotetracyclo[3.3.1.13,7.03,7]decane," Can. J. Chem. 1973, 51, 87-91, DOI: 10.1139/v73-012.

InChIs

1: InChI=1S/C5H6/c1-4-2-5(1,4)3-4/h1-3H2
InChIKey=ZTXSPLGEGCABFL-UHFFFAOYSA-N

3: InChI=1S/C11H13N/c12-7-9-1-8-2-10(4-9)6-11(10,3-8)5-9/h8H,1-6H2
InChIKey=KTXBGPGYWQAZAS-UHFFFAOYSA-N

Dyotropic rearrangement

Houk Steven Bachrach 29 Jun 2015 1 Comment

Houk and Vanderwal have examined the dyotropic rearrangement of an interesting class of polycyclic compounds using experimental and computational techniques.1 The parent reaction takes the bicyclo[2.2.2]octadiene 1 into the bicyclo[3.2.1]octadiene 3. The M06-2X/6-311+G(d,p)/B3LYP/6-31G(d) (with CPCM simulating xylene) geometries and relative energies are shown in Figure 1. The calculations indicate a stepwise mechanism, with an intervening zwitterion intermediate. The second step is rate determining.

1
(0.0)

TS1
(35.6)

2
(21.9)

TS2
(40.1)




3
(-4.2)

Figure 1. B3LYP/6-31G(d) and relative energies (kcal mol-1) at M06-2X/6-311+G(d,p).

Next they computed the activation barrier for the second TS for a series of substituted analogs of 1, with various electron withdrawing group as R1 and electron donating groups as R2, and compared them with the experimental rates.

Further analysis was done by relating the charge distribution in these TSs with the relative rates, and they find a nice linear relationship between the charge and ln(krel). This led to the prediction that a cyano substituent would significantly activate the reaction, which was then confirmed by experiment. Another prediction of a rate enhancement with Lewis acids was also confirmed by experiment.

A last set of computations addressed the question of whether a ketone or lactone would also undergo this dyotropic rearrangement. The lactam turns out to have the lowest activation barrier by far.

References

(1) Pham, H. V.; Karns, A. S.; Vanderwal, C. D.; Houk, K. N. "Computational and Experimental Investigations of the Formal Dyotropic Rearrangements of Himbert Arene/Allene Cycloadducts," J. Am. Chem. Soc. 2015, 137, 6956-6964, DOI: 10.1021/jacs.5b03718.

InChIs

1: InChI=1S/C11H11NO/c1-12-10(13)7-9-6-8-2-4-11(9,12)5-3-8/h2-5,7-8H,6H2,1H3
InChIKey=MNYYUIQDOAXLTK-UHFFFAOYSA-N

3: InChI=1S/C11H11NO/c1-12-10(13)6-9-3-2-8-4-5-11(9,12)7-8/h2-6,8H,7H2,1H3
InChIKey=OHEBSZKLNGLATD-UHFFFAOYSA-N

Structure of 2-oxazoline

MP &vibrational frequencies Steven Bachrach 15 Jun 2015 1 Comment

A recent reinvestigation of the structure of 2-oxazoline demonstrates the difficulties that many computational methods can still have in predicting structure.

Samdal, et al. report the careful examination of the microwave spectrum of 2-oxzoline and find that the molecule is puckered in the ground state.1 It’s not puckered by much, and the barrier for inversion of the pucker, through a planar transition state is only 49 ± 8 J mol-1. The lowest vibrational frequency in the non-planar ground state, which corresponds to the puckering vibration, has a frequency of 92 ± 15 cm-1. This low barrier is a great test case for quantum mechanical methodologies.

And the outcome here is not particularly good. HF/cc-pVQZ, M06-2X/cc-pVQZ, and B3LYP/cc-pVQZ all predict that 2-oxazoline is planar. More concerning is that CCSD and CCSD(T) with either the cc-pVTZ or cc-pVQZ basis sets also predict a planar structure. CCSD(T)-F12 with the cc-pVDZ predicts a non-planar ground state with a barrier of only 8.5 J mol-1, but this barrier shrinks to 5.5 J mol-1 with the larger cc-pVTZ basis set.

The only method that has good agreement with experiment is MP2. This method predicts a non-planar ground state with a pucker barrier of 11 J mol-1 with cc-pVTZ, 39.6 J mol-1 with cc-pVQZ, and 61 J mol-1 with the cc-pV5Z basis set. The non-planar ground state and the planar transition state of 2-oxazoline are shown in Figure 1. The computed puckering vibrational frequency does not reproduce the experiment as well; at MP2/cc-pV5Z the predicted frequency is 61 cm-1 which lies outside of the error range of the experimental value.

Non-planar

Planar TS

Figure 1. MP2/cc-pV5Z optimized geometry of the non-planar ground state and the planar transition
state of 2-oxazoline.

References

(1) Samdal, S.; Møllendal, H.; Reine, S.; Guillemin, J.-C. "Ring Planarity Problem of 2-Oxazoline Revisited Using Microwave Spectroscopy and Quantum Chemical Calculations," J. Phys. Chem. A 2015, 119, 4875–4884, DOI: 10.1021/acs.jpca.5b02528.

InChIs

2-oxazoline: InChI=1S/C3H5NO/c1-2-5-3-4-1/h3H,1-2H2
InChIKey=IMSODMZESSGVBE-UHFFFAOYSA-N

Making superacidic phenols

Acidity &Kass Steven Bachrach 02 Jun 2015 No Comments

Kass and coworkers looked at a series of substituted phenols to tease out ways to produce stronger acids in non-polar media.1 First they established a linear relationship between the vibrational frequency shifts of the hydroxyl group in going from CCl4 as solvent to CCl4 doped with 1% acetonitrile with the experimental pKa in DMSO. They also showed a strong relationship between this vibrational frequency shift and gas phase acidity (both experimental and computed deprotonation energies).

A key recognition was that a charged substituent (like say ammonium) has a much larger effect on the gas-phase (and non-polar solvent) acidity than on the acidity in a polar solvent, like DMSO. This can be attributed to the lack of a medium able to stable charge build-up in non-polar solvent or in the gas phase. This led them to 1, for which B3LYP/6-31+G(d,p) computations of the analogous dipentyl derivative 2 (see Figure 1) indicated a deprotonation free energy of 261.4 kcal mol-1, nearly 60 kcal mol-1 smaller than any other substituted phenol they previously examined. Subsequent measurement of the OH vibrational frequency shift showed the largest shift, indicating that 1 is extremely acidic in non-polar solvent.

Further computational exploration led to 3 (see Figure 1), for which computations predicted an even smaller deprotonation energy of 231.1 kcal mol-1. Preparation of 4 and experimental observation of its vibrational frequency shift revealed an even larger shift than for 1, making 4 extraordinarily acidic.

2

Conjugate base of 2




3




Conjugate base of 3

Figure 1. B3LYP/6-31+G(d,p) optimized geometries of 2 and 3 and their conjugate bases.

Reference

(1) Samet, M.; Buhle, J.; Zhou, Y.; Kass, S. R. "Charge-Enhanced Acidity and Catalyst Activation," J. Am. Chem. Soc. 2015, 137, 4678-4680, DOI: 10.1021/jacs.5b01805.

InChI

1 (cation only): InChI=1S/C23H41NO/c1-4-6-8-10-12-14-20-24(3,21-15-13-11-9-7-5-2)22-16-18-23(25)19-17-22/h16-19H,4-15,20-21H2,1-3H3/p+1
InChIKey=HIQMXPFMEWRQQG-UHFFFAOYSA-O

2: InChIKey=WMOPRSHYZNVZKF-UHFFFAOYSA-O

3: InChI=1S/C6H7NO/c1-7-4-2-3-6(8)5-7/h2-5H,1H3/p+1
InChIKey=FZVAZYLFYPULKX-UHFFFAOYSA-O

4 (cation only): InChI=1S/C13H21NO/c1-2-3-4-5-6-7-10-14-11-8-9-13(15)12-14/h8-9,11-12H,2-7,10H2,1H3/p+1
InChIKey=HSFRKOBOATYXAH-UHFFFAOYSA-O

Host-guest complexes

Grimme &host-guest Steven Bachrach 12 May 2015 1 Comment

Grimme and coworkers have a featured article on computing host-guest complexes in a recent ChemComm.1 They review the techniques his group has pioneered, particularly dispersion corrections for DFT and ways to treat the thermodynamics in moving from electronic energy to free energy. they briefly review some studies done by other groups. They conclude with a new study of eight different host guest complexes, three of which are shown in Figure 1.

1

2

3

Figure 1. TPSS-D3(BJ)/def2-TZVP optimized structures of 1-3.

These eight host-guest complexes are fairly large systems, and the computational method employed means some fairly long computations. Geometries were optimized at TPSS-D3(BJ)/def2-TZVP, then single point energy determined at PW6B95-D3(BJ)/def2-QZVP. Solvent was included using COSMO-RS. The curcurbituril complex 2 includes a counterion (chloride) along with the guest adamantan-1-aminium. Overall agreement of the computed free energy of binding with the experimental values was very good, except for 3 and the related complex having a larger nanohoop around the fullerene. The error is due to problems in treating the solvent effect, which remains an area of real computational need.

An interesting result uncovered is that the binding energy due to dispersion is greater than the non-dispersion energy for all of these complexes, including the examples that are charged or where hydrogen bonding may be playing a role in the bonding. This points to the absolute necessity of including a dispersion correction when treating a host-guest complex with DFT.

As an aside, you’ll note one of the reasons I was interested in this paper: 3 is closely related to the structure that graces the cover of the second edition of my book.

References

(1) Antony, J.; Sure, R.; Grimme, S. "Using dispersion-corrected density functional theory to understand supramolecular binding thermodynamics," Chem. Commun. 2015, 51, 1764-1774, DOI: 10.1039/C4CC06722C.

Uthrene, the smallest diradical graphene fragment

Aromaticity Steven Bachrach 04 May 2015 1 Comment

Uthrene 1 is the smallest formally diradical fragment of graphene; it cannot be expressed in a closed shell, fully electron-paired Kekule form. Its isomer zethrene 2 on the other hand, can be expressed in closed shell form.

Melle-Franco has examined these, and related, polycyclic aromatic hydrocarbons with DFT.1 The optimized structure of singlet and triplet 1 at CAM-B3LYP/6-31g(d,p) are shown in Figure 1. The singlet-triplet energy gap of 2 is 16.5 kcal mol-1 with a ground state singlet. However, for 1 the triplet is predicted to be lower in energy than the singlet by 7.7 kcal mol-1. And this gap increases to 10.9 kcal mol-1 at CASSCF(14,14)/6-31g(d,p)//CAM-B3LYP/6-31g(d,p). Natural orbital population analysis of the singlet of 1 at CASSCF identifies two orbitals with populations around 1 e.

Interestingly, both the singlet and triplet of 1 are not planar, exhibiting a twist to avoid the clashing of the hydrogens in the bay region. (This twisting is best seen by clicking on the structures in Figure 1, and viewing the molecules interactively through Jmol.)

singlet

triplet

Figure 1. CAM-B3LYP/6-31g(d,p) optimized geometries of the singlet and triplet of 1.

References

(1) Melle-Franco, M. "Uthrene, a radically new molecule?," Chem. Commun. 2015, 51, 5387-5390, DOI: 10.1039/C5CC01276G.

InChIs

1: InChI=1S/C24H14/c1-5-15-7-3-11-20-22(15)17(9-1)13-19-14-18-10-2-6-16-8-4-12-21(23(16)18)24(19)20/h1-14H
InChIKey=WAKUAPLTIMTENF-UHFFFAOYSA-N

2: InChI=1S/C24H14/c1-5-15-7-3-11-19-22-14-18-10-2-6-16-8-4-12-20(24(16)18)21(22)13-17(9-1)23(15)19/h1-14H
InChIKey=UXUXNGMSDNTZEC-UHFFFAOYSA-N

Fluorenyl cation

Aromaticity Steven Bachrach 13 Apr 2015 1 Comment

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

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