Archive for October, 2014

QM reflection off a barrier

Organic chemists are beginning to recognize that tunneling may be more pervasive than previously thought. This blog has noted a number of interesting occurrences of tunneling, and here’s one more, by Karmakar and Datta.1

The barrier for the intramolecular earrangement (Reaction 1) taking the carbene 1 into 2 is estimated to be 44.1 kcal mol-1 at M06-2X/6-31+G(d,p), prohibitively large. However, the intermolecular rearrangement (Reaction 2) has a much smaller barrier of 11.4 kcal mol-1. The structures of the transition states for these two reactions are shown in Figure 1.



Figure 1. M06-2X/6-31+G(d,p) optimized transition states for Reactions 1 and 2.

Given that the barrier width is likely to be very small for the intramolecular route, perhaps tunneling may play a role. The rate predicted with canonical variational transition-state theory (CVT) and small curvature tunneling (SCT) at 298K is negligible. However, for the intermolecular process, the rate at 298K including tunneling is 3.56 x 104 s-1, more than 10 times great than predicted with CVT alone, and tunneling makes a dramatically larger difference at lower temperatures.

The intermolecular barrier for the rearrangement of 3 into 4 is very small, only 1.6 kcal mol-1.
This manifests in a very interesting rate prediction: the reaction is actually predicted to be slower at temperatures above 150K when tunneling is included than when tunneling is omitted. This is a result of quantum mechanical reflection off of the barrier, and this becomes noticeable with the very small barrier. In addition, the kinetic isotope effects are smaller than expected when D is substituted in for H. These predictions await experimental confirmation.


(1) Karmakar, S.; Datta, A. "Tunneling Assists the 1,2-Hydrogen Shift in N-Heterocyclic Carbenes," Angew. Chem. Int. Ed. 2014, 53, 9587-9591, DOI: 10.1002/anie.201404368.


1: InChI=1S/C3H6N2/c1-2-5-3-4-1/h4-5H,1-2H2

2: InChI=1S/C3H6N2/c1-2-5-3-4-1/h3H,1-2H2,(H,4,5)

3: InChI=1S/C3H2F2N2/c4-2-3(5)7-1-6-2/h6-7H

4: InChI=1S/C3H2F2N2/c4-2-3(5)7-1-6-2/h1H,(H,6,7)

Tunneling Steven Bachrach 27 Oct 2014 No Comments

The unusual PES of (CO)3

As recently explicated by Wang and Borden using NIPE spectroscopy and computations, the potential energy surface of cyclopropyl-1,2,3-trione 1 is remarkably complex.1 (U)CCSD(T)//aug-cc-pVTZ computations of the D3h singlet (the 1A1’ state shown in Figure 1) is actually a hilltop, possessing two imaginary frequencies. Distorting the structure as indicated by these imaginary frequencies and then optimizing the structure leads directly to dissociation to three CO molecules. Thus, (CO)3 does not exist as a stable minima on the singlet surface.

The D3h triplet (the 3E” state shown in Figure 1) is not a critical point on the surface; due to the Jahn-Teller effect is distorts into two different states: the 3B1 state which is a local energy minimum, and the 3A2 state which is a transition state between the symmetry-related 3B1 states.

So, this implies the possibility of a very interesting NIPE experiment. If the radical anion (CO)3-.
loses an electron and goes to the singlet surface, it lands at a hilltop(!) and should have a very short lifetime. If it goes to the triplet surface, it lands at either a transition state (3A2) and again should have a short lifetime, or it can land at the 3B1 state and perhaps have some lifetime before it dissociates by losing one CO molecule.






Figure 1. (U)CCSD(T)//aug-cc-pVTZ optimized geometries of 1 and its radical anion.

The NIPE spectrum identifies three transitions. By comparing the energies of the electron loss seen in the experiment with the computations, along with calculating the Franck-Condon factors using the computed geometries and vibrational frequencies, the lowest energy transition is to the 1A1’ state, and the second transition is part of the vibrational progression also to the 1A1’ state. This is the first identification of vibrational frequencies associated with a hilltop structure. The third transition is to the 3A2 state. No transition to the 3B1 state is found due to the large geometric difference between the radical anion and the 3B1 state; the Franck-Condon factors are zero due to no overlap of their wavefunctions.

Once again, the power of the symbiotic relationship between experiment and computation is amply demonstrated in this paper.


(1) Chen, B.; Hrovat, D. A.; West, R.; Deng, S. H. M.; Wang, X.-B.; Borden, W. T. "The Negative Ion Photoelectron Spectrum of Cyclopropane-1,2,3-Trione Radical Anion, (CO)3•– — A Joint Experimental and Computational Study," J. Am. Chem. Soc. 2014, 136, 12345-12354, DOI: 10.1021/ja505582k.


1: InChI=1S/C3O3/c4-1-2(5)3(1)6

Borden Steven Bachrach 21 Oct 2014 No Comments

A Triple-Möbius Aromatic Molecule

Herges and co-workers have prepared a triply-twisted Möbius molecule. 1 The key element is recognizing that most of the “twisting” needs to be accomplished through writhe, a twisting that produces figure-8-like crossing, the way an old-school phone cord twists about itself or the way a pretzel is formed. Herges employs three bi-naphthelene subunits to provide the template for the writhe needed. The prepared compound is 1. A clever, relatively straightforword synthesis produces this amazing molecule, along with the single-twisted 2.

The B3LYP/6-31G* optimized geometries of 1 and the single-twisted analogue 2 are shown in Figure 1. Table 1 presents the key topological parameters of 1 and 2, comparing the computed and X-ray crystal structure. The absolute value of the linking number Lk is 3, indicating the three twists, and the reason that this highly twisted molecule can be made is that half of the twist actually results from writhe.



Figure 1. B3LYP/6-31G* optimized geometries of the two diastereomers if 1. (Be sure to click on these images to launch JMol and interactively manipulate the structures!)

Table 1. Topological parameters of 1. a





X-ray, 1




Comp, 1




Comp, 2




aLk is the linking number, Tw is the twist number, and Wr is the writhe number, with the condition that Tk + Wr = Lk.


(1) Schaller, G. R.; Topić, F.; Rissanen, K.; Okamoto, Y.; Shen, J.; Herges, R. "Design and synthesis of the first triply twisted Möbius annulene," Nat. Chem. 2014, 6, 608-613, DOI: 10.1038/nchem.1955.


1: InChI=1S/C72H36/c1-2-26-56-44-38-50-20-8-14-32-62(50)68(56)70-58(46-40-52-22-10-16-34-64(52)70)28-5-6-30-60-48-42-54-24-12-18-36-66(54)72(60)71-59(47-41-53-23-11-17-35-65(53)71)29-4-3-27-57-45-39-51-21-9-15-33-63(51)69(57)67-55(25-1)43-37-49-19-7-13-31-61(49)67/h7-24,31-48H/b69-67-,70-68-,72-71-

Aromaticity Steven Bachrach 13 Oct 2014 6 Comments

History of the development of ChemDraw

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!


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

Uncategorized Steven Bachrach 08 Oct 2014 3 Comments

Dynamics in a photorearrangement

The di-π-methane photorearrangement has been known for many years, first studied by Zimmerman.1,2 The triplet photorearrangement gives an interesting rearranged product; and the mechanism of this photorearrangement of 1 into 2 has now been examined by the Houk group using computational techniques, including trajectory analysis. The proposed mechanism is that excitation to the triplet state 1* is followed by rearrangement to the triplet intermediate INT1* which then rearranges to the triplet INT2*. Intersystem crossing then leads to the singlet product 2.

The PES for this rearrangement was explored3 at CASMP2(10,10)/6-31G(d)//CASSCF(10,10)/6-31G(d), with geometries and relative energies shown in Figure 1, as well as at (U)M06-2x/6-31G(d) and (U)B3LYP/6-31G(d); they all give qualitatively the same result. The first TS is the rate limiting step, and the second TS lies only 1-2 kcal mol-1 above the intermediate INT1. So, the reaction appears to be two steps, but with such a low barrier for the second step, dynamic effects might be important as trajectories might cross INT1* and go over TS2* without residing in the intermediate well for any appreciable time – a seemingly one step reaction. Note than no TS for directly traversing from 1* to INT2* was found.






Figure 1. CASSCF(10,10)/6-31G(d) geometries and CASMP2 energies in kcal mol-1.

Now in a follow-up study, Houk and co-workers4 performed trajectories analysis on the M06-2x/6-31G(d) PES. A total of 256 trajectories were initiated at TS1* and 241 ended at INT2* within 1500fs. Of these, 24 trajectories resided for less than 60fs within the region of INT1, a time less than a C-C vibration. Furthermore, the lifetime of INT1 that is predicted by RRKM is much longer (about 500fs) than what is observed in the trajectories (about 200 fs). Thus, there is significant dynamic effects in this excited state rearrangement, though INT1 is always sampled.


(1) Zimmerman, H. E.; Grunewald, G. L. "The Chemistry of Barrelene. III. A Unique Photoisomerization to Semibullvalene," J. Am. Chem. Soc. 1966, 88, 183-184, DOI: 10.1021/ja00953a045.

(2) Zimmerman, H. E.; Binkley, R. W.; Givens, R. S.; Sherwin, M. A. "Mechanistic organic photochemistry. XXIV. The mechanism of the conversion of barrelene to semibullvalene. A general photochemical process," J. Am. Chem. Soc. 1967, 89, 3932-3933, DOI: 10.1021/ja00991a064.

(3)  Matute, R. A.; Houk, K. N. "The Triplet Surface of the Zimmerman Di-π-Methane Rearrangement of Dibenzobarrelene," Angew. Chem. Int. Ed. 2012, 51, 13097-13100, DOI: 10.1002/anie.201208002.

(4) Jiménez-Osés, G.; Liu, P.; Matute, R. A.; Houk, K. N. "Competition Between Concerted and Stepwise Dynamics in the Triplet Di-π-Methane Rearrangement," Angew. Chem. Int. Ed. 2014,
53, 8664-8667, DOI: 10.1002/anie.201310237.


1: InChI=1S/C16H12/c1-2-6-12-11(5-1)15-9-10-16(12)14-8-4-3-7-13(14)15/h1-10,15-16H

2: InChI=1S/C16H12/c1-3-7-11-9(5-1)13-10-6-2-4-8-12(10)15-14(11)16(13)15/h1-8,13-16H

Dynamics Steven Bachrach 06 Oct 2014 1 Comment