Setting the record for the shortest non-bonded H^…H contact has become an active contest. Following on the report of a contact distance of only 1.47 Å that I blogged about here, Firouzi and Shahbazian propose a series of related cage molecules with C-H bonds pointed into their interior.¹ The compounds were optimized with a variety of computational methods, and many of them have H^…H distances well below that of the previous record. The shortest distance is found in 1, shown in Figure 1. The H^…H distance in 1 is predicted to be less than 1.2 Å with a variety of density functionals and moderate basis sets.

1

Figure 1. Optimized geometry of 1 at ωB97X-D/cc-pVDZ.

References

(1) Firouzi, R.; Shahbazian, S. "Seeking Extremes in Molecular Design: To What Extent May Two “Non-Bonded” Hydrogen Atoms be Squeezed in a Hydrocarbon?," ChemPhysChem 2016, 17, 51-54, DOI: 10.1002/cphc.201501002.

InChIs

1: InChI=1S/C41H44/c1-7-13-25-17-9-3-40-5-11-19(35(17)40)27-15-8-2-39(1,33(13)15)34-14(7)26-18-10-4-41-6-12-20(36(18)41)28(16(8)34)32(27)30-23(11)37(40)21(9)29(31(25)26)22(10)38(41)24(12)30/h7-38H,1-6H2
InChIKey=DMWSEJFKSWCSLI-UHFFFAOYSA-N

I don’t really have anything to say about this recent paper by Anderson, et al.¹ They have simply prepared a very beautiful structure, an aryllated analogue of 1. They even optimized the structure of 1 at BLYP/6-31G(d) and it’s shown in Figure 1. That must have taken some time!

Figure 1. BLYP/6-31G(d) optimized structure of 1.
(Remember that you can manipulate this structure by simply clicking on in, which will launch the JMol app.)

References

(1) Neuhaus, P.; Cnossen, A.; Gong, J. Q.; Herz, L. M.; Anderson, H. L. "A Molecular Nanotube with Three-Dimensional π-Conjugation," Angew. Chem. Int. Ed. 2015, 54, 7344-7348, DOI: 10.1002/anie.201502735.

Three-dimensional objects can be projected into four-dimensional objects. So for example a cube can be projected into a hypercube, as in Scheme 1.

Scheme 1.

Pichierri proposes a hydrocarbon analogue of the hypercube. The critical decision is the connecting bridge between the outer (exploded) carbons. This distance is too long to be a single carbon-carbon bond. Pichierri opts to use ethynyl bridges, to give the hypercube 1.¹

Now, unfortunately he does not supply any supporting materials. So I have reoptimized this O_h geometry at B3LYP/6-31G(d), and show this structure in Figure 1. Pichierri does not report much beyond the geometry of 1 and the perfluoronated analogue. One interesting property that might be of interest is the ring strain energy of 1, which I will not take up here.

But a question I will take up is just what bridges might serve to create the hydrocarbon hypercube. A more fundamental choice might be ethanyl bridges, to create 2. However, the O_h conformer of 2 has 13 imaginary frequencies at B3LYP/6-31G(d). Lowering the symmetry to D₃ give a structure that has only real frequencies, and it’s shown in Figure 1. An interesting exercise is to ponder other choices of bridges, which I will leave for the reader.

1

2

Figure 1. B3LYP/6-31G(d) optimized structures of 1 and 2.
As always, be sure to click on the image to enable Jmol for interactive viewing of these interesting structures!

References

(1) Pichierri, F. "Hypercubane: DFT-based prediction of an O_h-symmetric double-shell hydrocarbon," Chem. Phys. Lett. 2014, 612, 198-202, DOI: j.cplett.2014.08.032.

InChIs

1: InChI=1S/C40H24/c1-2-26-7-9-29-15-11-27-5-3-25(1)4-6-28-12-16-30(10-8-26)20-23-32(22-19-29)24-21-31(17-13-27,18-14-28)39-35(27)33(25)34(26)37(29,35)40(32,39)38(30,34)36(28,33)39/h1-24H
InChIKey=FFMFUIDOGFAUOP-UHFFFAOYSA-N

2: InChI=1S/C40H48/c1-2-26-7-9-29-15-11-27-5-3-25(1)4-6-28-12-16-30(10-8-26)20-23-32(22-19-29)24-21-31(17-13-27,18-14-28)39-35(27)33(25)34(26)37(29,35)40(32,39)38(30,34)36(28,33)39/h1-24H2
InChIKey=MCSZKKKJCDSRIV-UHFFFAOYSA-N

I suspect that the majority of my readers have no experience in drawing chemical structures by hand for publication purposes. That’s because of one software product: ChemDraw. I remember using the Fieser triangle (unfortunately no longer sold by Aldrich – click to see a pic and product description!), a plastic template that had standard-sized rings, like nice pentagons and hexagons, and chair and boat conformations of cyclohaxane, and you’d take your fancy ink pen and careful follow the template. Then you moved the template to draw say a bond off of the ring and hoped to god that the ink didn’t smudge. There were other templates for drawing letters and numbers – or you used scratch-off transfer decals. (By this point all of you under 40 are thinking “what the hell is he talking about?”)

Well all of that changed with three seminal events for organic chemists: the introduction of the original Macintosh computer, the introduction of the Apple LaserWriter and the introduction of ChemDraw. The Mac allowed one to sketch in a much more intuitive way – again for those less than 50, computers use to come without a mouse! Imagine trying to draw a chemical structure using a keyboard. That’s why there were no structure drawing tools prior to the Mac. The LaserWriter meant that you could print an output that looked as good as what you had on the screen, and could thus be submitted for publication. And ChemDraw – well this was just astonishing! I still remember the day during my post-doc when the Mac and LaserWriter arrived and we launched ChemDraw and were able to quickly draw molecules – steroid, and conformations, and stereoisomers and they all looked beautiful and we could get them done in a flash!

When I started my first academic position at Northern Illinois University in August 1987 I purchased a Mac and a LaserWriter and ChemDraw as part of my start-up – and I was the first in the department to have a Mac – but that changed rapidly!

So, why all of the teary reminiscences? Well David Evans has just published¹ a nice romp through the mid-1980s recalling how Stewart Rubinstein, aided by Evans and his wife, developed ChemDraw and started CambridgeSoft, and as Stuart Schreiber says “ChemDraw changed the field in a way that has not been replicated since.”

Today, there are other chemical structure drawing tools available, and in fact I no longer use ChemDraw, but it is still a wonder to be able to create drawings so easily and so nicely. Maybe one day I’ll reminisce about the day I got EndNote and my life changed again!

References

1) Evans, D. A. “History of the Harvard ChemDraw Project,” Angew. Chem. Int. Ed. 2014, 53, 1521-3773, DOI 10.1002/anie.201405820.

This paper is a bit afield from the usual material I cover but this is an interesting reaction. Shoji and coworkers have prepared the two-coordinate boron species 1,¹ and confirmed its geometry by an x-ray crystal structure. What I find interesting is its reaction with CO₂, which gives 2 and organoboranes that are not identified, though presumably derived from 3.

M06-2x/6-311+G(d,p) computations support a hypothetical mechanism whereby first a complex between 1 and CO₂ is formed (CP1), that is 4.4 kcal mol^-1 above isolated reactants. Then passing through TS1, which is 4.2 kcal mol^-1 above CP1, an intermediate is formed (INT), which is almost 6 kcal mol^-1 below starting materials. A second transition state is then traversed (about 1 kcal mol^-1 below starting materials), to form an exit complex between 2 and 3, which can then separate to the final products with an overall exothermicity of 10.6 kcal mol^-1. The structures of these critical points are shown in Figure 1.

1 (0.0)	CP1 (4.4)
TS1 (8.6)	INT (-5.7)
TS2 (-1.1)	CP2 (-9.0)

Figure 1. M06-2x/6-311+G(d,p) optimized structures. Relative energy in kcal mol^-1.

References

(1) Shoji, Y.; Tanaka, N.; Mikami, K.; Uchiyama, M.; Fukushima, T. "A two-coordinate boron cation featuring C–B⁺–C bonding," Nat. Chem. 2014, 6, 498-503, DOI: 10.1038/nchem.1948.

InChIs

1: InChI=1S/C18H22B/c1-11-7-13(3)17(14(4)8-11)19-18-15(5)9-12(2)10-16(18)6/h7-10H,1-6H3/q+1
InChIKey=WLUJABFTLHAEMI-UHFFFAOYSA-N

2: InChI=1S/C10H11O/c1-7-4-8(2)10(6-11)9(3)5-7/h4-5H,1-3H3/q+1
InChIKey=CUJVTHUIQVMVHD-UHFFFAOYSA-N

3: InChI=1S/C9H11BO/c1-6-4-7(2)9(10-11)8(3)5-6/h4-5H,1-3H3
InChIKey=ZJKBFARYTPYYGV-UHFFFAOYSA-N

The structure of [2,2]paracyclophane 1 has been somewhat controversial for some time. Early x-ray structures indicated that the molecule was quite symmetric, D_2h with the phenyl rings and the ethyl bridges eclipsed. Subsequent low-T experiments suggested a lower symmetry form D₂ with a twist that relieves some of the unfavorable eclipsing interactions in the ethano bridges. High-level computations by Grimme¹ and then some by myself² indicated that the D₂ structure is the lowest energy conformation, with however a low barrier through the D_2h structure.

The suggestion of the D₂ minimum was vehemently criticized by Dodziuk, et al. on the basis of NMR analysis.³

Now, a low temperature x-ray experiment of 1 brings clarity to the situation.⁴ (The introduction provides a nice summary of the previous 70 year history regarding the structure of 1.) At temperatures below 45 K, 1 is found as a single structure of D₂ symmetry (with space group P4n2). The structure is shown in Figure 1. A phase change occurs at about 45 K, and above 60 K the crystal has P4₂/mnm symmetry. The structure of 1 at the high temperature appears as D_2h with somewhat broader thermal motion of the ethano carbons than the phenyl carbons. The low T structure is in excellent accord with the previous theoretical studies, and the phase transition helps bring into accord all of the previous x-ray crystallographic work.

Figure 1. X-ray structure at 15K of 1.

References

(1) Grimme, S. "On the Importance of Electron Correlation Effects for the π-π Interactions in Cyclophanes," Chemistry Eur. J. 2004, 10, 3423-3429, DOI: 10.1002/chem.200400091.

(2) Bachrach, S. M. "DFT Study of [2.2]-, [3.3]-, and [4.4]Paracyclophanes: Strain Energy, Conformations, and Rotational Barriers," J. Phys. Chem. A 2011, 115, 2396-2401, DOI: 10.1021/jp111523u.

(3) Dodziuk, H.; Szymański, S.; Jaźwiński, J.; Ostrowski, M.; Demissie, T. B.; Ruud, K.; Kuś, P.; Hopf, H.; Lin, S.-T. "Structure and NMR Spectra of Some [2.2]Paracyclophanes. The Dilemma of [2.2]Paracyclophane Symmetry," J. Phys. Chem. A 2011, 115, 10638-10649, DOI: 10.1021/jp205693a.

(4) Wolf, H.; Leusser, D.; R. V. Jørgensen, M.; Herbst-Irmer, R.; Chen, Y.-S.; Scheidt, E.-W.; Scherer, W.; Iversen, B. B.; Stalke, D. "Phase Transition of [2,2]-Paracyclophane – An End to an Apparently Endless Story," Chem. Eur. J. 2014, 20, 7048–7053, DOI: 10.1002/chem.201304972.

InChIs

1: InChI=1S/C16H16/c1-2-14-4-3-13(1)9-10-15-5-7-16(8-6-15)12-11-14/h1-8H,9-12H2
InChIKey=OOLUVSIJOMLOCB-UHFFFAOYSA-N

What is the closest non-bonding H^…H distance within a single molecule? The world record had been 1.617 Å in a pentacyclodecane.¹ This record now appears to be broken by the preparation of the disilane 1.² The ¹H NMR and IR suggest the interior hydrogens are very close. The x-ray structure of 1 indicates a very short Si-Si distance of 4.433 Å, a distance that must accommodate two S-H bonds, typically about 1.48 Å and the H^…H non-bonded distance, which might be as short then as 1.47 Å! The crystal is unfortunately not large enough for a neutron diffraction study, which would enable precise location of the hydrogens.

1

However, computations can help here, and they suggest a H^…H separation of only 1.57 Å: this is the distance obtained with B3PW91/6-311+G(2d,p), M062x/6-311+G(2d,p) and MP2/6-31G(d). The M062x/6-311+G(2d,p) structure is shown in Figure 1.

Figure 1. The M062x/6-311+G(2d,p) optimized structure of 1.

Any ideas for a compound with an even shorter non-bonded H^…H distance?

References

(1) Ermer, O.; Mason, S. A.; Anet, F. A. L.; Miura, S. S. "Ultrashort nonbonded hydrogen^…hydrogen distance in a half-cage pentacyclododecane," J. Am. Chem. Soc. 1985, 107, 2330-2334, DOI: 10.1021/ja00294a023.

(2) Zong, J.; Mague, J. T.; Pascal, R. A. "Exceptional Steric Congestion in an in,in-Bis(hydrosilane)," J. Am. Chem. Soc. 2013, 135, 13235-13237, DOI: 10.1021/ja407398w.

InChI

1: InChI=1S/C39H32S3Si2/c1-7-19-34-28(13-1)25-40-31-16-4-10-22-37(31)44-38-23-11-5-17-32(38)41-26-29-14-2-8-20-35(29)43(34)36-21-9-3-15-30(36)27-42-33-18-6-12-24-39(33)44/h1-24,43-44H,25-27H2
InChIKey=SBEUQCUCKCNPCC-UHFFFAOYSA-N

Jacobsen reports on another application of thiourea-based organocatalysts, this time for the
catalysis of hydroamination.¹ To support the synthetic effort, he examined the uncatalyzed intramolecular hydroamination that takes 1, through TS1 into product 2. The geometry of TS1 optimized at B3LYP/6-31+G(d,p) is shown in Figure 1. The computed barrier for this reaction is 22.2 kcal mol^-1. Using a model thiourea as the catalyst (MeHN)₂C=S, 3), Jacobsen locates a
catalyzed transition state TS2 shown in Figure 1. The activation barrier for this catalyzed reaction is 19.1 kcal mol^-1, suggesting that a thiourea can afford a real catalytic effect.

TS1

TS2

Figure 1. B3LYP/6-31+G(d,p) optimized geometries of TS1 and TS2(the catalyzed transition state).

Jacobsen then goes on to show that 4 can act as both an excellent catalyst for the hydroamination reaction along with inducing significant enantioselectivity. An example is Reaction 1, where 10 mol% of catalyst 3 gives an overall yield of 83% and an ee of 91%, while in the absence of catalyst the yield is only 8%.

References

(1) Brown, A. R.; Uyeda, C.; Brotherton, C. A.; Jacobsen, E. N. "Enantioselective Thiourea-Catalyzed Intramolecular Cope-Type Hydroamination," J. Am. Chem. Soc. 2013, 135, 6747-6749, DOI: 10.1021/ja402893z.

InChIs

1: InChI=1S/C5H11NO/c1-2-3-4-5-6-7/h2,6-7H,1,3-5H2
InChIKey=JUMXQRNWLGIKEI-UHFFFAOYSA-N

2: InChI=1S/C5H11NO/c1-5-3-2-4-6(5)7/h5,7H,2-4H2,1H3
InChIKey=YVBPNYXAQNAMLH-UHFFFAOYSA-N

3: InChI=1S/C3H8N2S/c1-4-3(6)5-2/h1-2H3,(H2,4,5,6)
InChIKey=VLCDUOXHFNUCKK-UHFFFAOYSA-N

4: InChI=1S/C44H49N3OS/c1-44(2,3)42(41(48)36-25-15-24-35(36)34-23-14-21-30-16-10-11-22-33(30)34)46-43(49)45-37-26-12-13-27-40(37)47-38(31-17-6-4-7-18-31)28-29-39(47)32-19-8-5-9-20-32/h4-11,14,16-23,28-29,35-37,40,42H,12-13,15,24-27H2,1-3H3,(H2,45,46,49)/t35-,36?,37-,40-,42-/m1/s1
InChIKey=OJMZMPGOFWBKAF-FDGFXIECSA-N

After much delay, the second edition of my book Computational Organic Chemistry has been sent off to the publisher! This edition is an update from the first, including many new examples of the major themes covered in the first edition. In addition there are some entirely new sections and chapters, extending the scope of the book into areas not mentioned in the first edition. There are also some new interviews of major players in the field. Comments from this blog where helpful in guiding my choices for what new materials to include in the book.

I suspect that editing of the book and making it all ready for print will take through the rest of the year. Later on this year I will discuss in the blog the new features of the book in some detail.

I intend to continue to blog on new papers through the publication of the second edition and beyond. So continue to monitor this blog for new papers and for information on where and when to purchase the second edition!

Nanotubes are currently constructed in ways that offer little control of their size and chirality. The recent synthesis of cycloparaphenylenes (CPP) provides some hope that fully controlled synthesis of nanotubes might be possible in the near future. Jasti has now made an important step forward in preparing dimers of CPP such as 1.¹

They also performed B3LYP-D/6-31G(d,p) computations on 1 and the directly linked dimer 2. The optimized geometries of these two compounds in their cis and trans conformations are shown in Figure 1. Interestingly, both compounds prefer to be in the cis conformation; cis–1 is 10 kcal mol^-1 more stable than trans–1 and cis–2 is 30 kcal mol^-1 more stable than the trans isomer. While a true transition state interconnecting the two isomers was not located, a series of constrained optimizations to map out a reaction surface suggests that the
barrier for 1 is about 13 kcal mol^-1. The authors supply an interesting movie of this pseudo-reaction path (download the movie).

cis–1	trans–1
cis–2	trans–2

Figure 1. B3LYP-D/6-31G(d,p) optimized geometries of the cis and trans conformers of 1 and 2. (Be sure to click on these images to launch a 3-D viewer; these structures come to life in 3-D!)

References

(1) Xia, J.; Golder, M. R.; Foster, M. E.; Wong, B. M.; Jasti, R. "Synthesis, Characterization, and Computational Studies of Cycloparaphenylene Dimers," J. Am. Chem. Soc. 2012, 134, 19709-19715, DOI: 10.1021/ja307373r.

InChIs

1: InChI=1S/C106H82/c1-5-13-79-21-9-17-76-29-37-85(38-30-76)95-59-63-98(64-60-95)103-71-69-101(82(16-8-4)24-12-20-77-27-35-84(36-28-77)90-51-55-94(56-52-90)91-45-41-86(79)42-46-91)73-105(103)99-65-67-100(68-66-99)106-74-102-70-72-104(106)97-61-57-88(58-62-97)81(15-7-3)23-10-18-75-25-33-83(34-26-75)89-49-53-93(54-50-89)92-47-43-87(44-48-92)80(14-6-2)22-11-19-78-31-39-96(102)40-32-78/h5-16,21-74H,1-4,17-20H2/b21-9-,22-11-,23-10-,24-12-,79-13+,80-14+,81-15+,82-16+
InChIKey=WFVBBCVHFBTQRK-VPGVYKRGSA-N

2: InChI=1S/C100H78/c1-5-13-75-21-9-17-72-29-37-81(38-30-72)91-59-63-94(64-60-91)97-67-65-95(78(16-8-4)24-12-20-73-27-35-80(36-28-73)86-51-55-90(56-52-86)87-45-41-82(75)42-46-87)69-99(97)100-70-96-66-68-98(100)93-61-57-84(58-62-93)77(15-7-3)23-10-18-71-25-33-79(34-26-71)85-49-53-89(54-50-85)88-47-43-83(44-48-88)76(14-6-2)22-11-19-74-31-39-92(96)40-32-74/h5-16,21-70H,1-4,17-20H2/b21-9-,22-11-,23-10-,24-12-,75-13+,76-14+,77-15+,78-16+
InChIKey=HOODCSIDKUJYKE-XJQPCHFNSA-N