April 17th, 2015
The knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old.[1] Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. Here I try to recover some of this information by searching crystal structures.
I conducted the following search:
- Any electron donating group as a ring substituent, defined by any of the elements N, O, F, S, Cl, Br.
- A distance from the H of an OH fragment (as a hydrogen bonder to the aryl ring) to the ortho position relative to the electron donating group.
- A similar distance to the meta position.
- The |torsion angle| between the aryl plane and the C…H axis to be constrained to 90° ± 20.
- Restricting the H…C contact distance to the van der Waals sum of the radii -0.3Å (to capture only the stronger interactions)
- The usual crystallographic requirements of R < 0.1, no disorder, no errors and normalised H positions.
The result of such a search is seen below. The red line indicates those hits where the distance from the H to the ortho and meta positions is equal. In the top left triangle, the distance to ortho is shorter than to meta (and the converse in the bottom right triangle). You can see that both the red hot-spot and indeed the majority of the structures conform to ortho direction (of π-facial ) hydrogen bonding.
Here is a little calculation, optimising the position that HBr adopts with respect to bromobenzene. You can see that the distance discrimination towards ortho is ~ 0.17Å, a very similar value to the “hot-spot” in the diagram above.
This little search of course has hardly scratched the surface of what could be done. Changing eg the OH acceptor to other electronegative groups. Restricting the wide span of N, O, F, S, Cl, Br. Probing rings bearing two substituents. What of the minority of points in the bottom right triangle; are they true exceptions or does each have extenuating circumstances? Why do many points actually lie on the diagonal? Can one correlate the distances with the substituent? Is there a difference between intra and intermolecular H-bonds? What of electron withdrawing groups?
The above search took perhaps 20 minutes to define and optimise, and it gives a good statistical overview of this age-old effect. It is something every new student of organic chemistry can try for themselves! If you run an introductory course in organic aromatic chemistry, or indeed a laboratory, try to see what your students come up with!
References
- H.E. Armstrong, "XXVIII.—An explanation of the laws which govern substitution in the case of benzenoid compounds", J. Chem. Soc., Trans., vol. 51, pp. 258-268, 1887. https://doi.org/10.1039/ct8875100258
Tags: above search, Aromatic compounds, aromaticity, Birch reduction, Chemistry, electron donating, Electrophile, Electrophilic aromatic substitution, Ether, Functional groups, little search, Organic chemistry, Physical organic chemistry, Substitution reactions
Posted in Chemical IT, crystal_structure_mining | 1 Comment »
April 12th, 2015
Sodium borohydride is the tamer cousin of lithium aluminium hydride (LAH). It is used in aqueous solution to e.g. reduce aldehydes and ketones, but it leaves acids, amides and esters alone. Here I start an exploration of why it is such a different reducing agent.
Initially, I am using Li, not Na (X=Li), to enable a more or less equal comparison with LAH, with water molecules to solvate rather than ether (n=2,3,5) and R set to Me. First, n=2, for which the IRC is shown below. In this model, we will assume that the carbonyl has not first reacted with water to form a gem-diol. The free energy barrier is 9.6 kcal/mol (ωB97XD/6-311+G(d,p)/SCRF=water) which corresponds to a very fast reaction at room temperatures.
The immediate product is, if anything, more interesting than the transition state[1] with quite a stretched length for the newly formed C-H bond and predicted stretching wavenumber for this bond of 2137 cm-1. This effect is similar to that seen for the LAH reduction of cinnamaldehyde, and is due to stereoelectronic antiperiplanar alignment of the oxyanionic oxygen lone pair with the C-H bond. This species is also some 6.5 kcal/mol higher in energy than the reactant, and is clearly not the final product of the reaction (which must contain e.g. B-O bonds), the mechanism for which will not be investigated here immediately.
For n=3, we see new solvation patterns, including a dihydrogen bond formed between water and the borohydride at the transition state; ΔG† is 10.0 kcal.mol.
Click for 3D.
Finally, n=5, where the TS is showing a cage-like structure of complex weak interactions, ΔG† is 11.3 kcal.mol. We see a model where inclusion of explicit solvent molecules can have a significant influence on the size of the barrier obtained.
Click for 3D
NCI surface. Click for 3D. Blue=strong attractions, green=weak.
| n |
ΔG298‡ |
FAIR Data citation |
| 2 |
9.6 |
[2] |
| 3 |
10.0 |
[3] |
| 5 |
11.3 |
[4] |
With a mechanistic prototype now identified, it is time to start varying some of the parameters, such as X and R. This will enable us to assess the models built here to see if they reflect reality.
References
- H.S. Rzepa, and H.S. Rzepa, "C 2 H 12 B 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191186
- H.S. Rzepa, and H.S. Rzepa, "C 2 H 12 B 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191188
- H.S. Rzepa, and H.S. Rzepa, "C 2 H 14 B 1 Li 1 O 4", 2015. https://doi.org/10.14469/ch/191189
- H.S. Rzepa, and H.S. Rzepa, "C 2 H 18 B 1 Li 1 O 6", 2015. https://doi.org/10.14469/ch/191192
Tags: aqueous solution, Chemical bond, chemical bonding, Chemistry, Electronic effect, energy, final product, free energy barrier, Hydride, Hydrogen bond, immediate product, Lithium aluminium hydride, reduction
Posted in reaction mechanism | 2 Comments »
April 10th, 2015
Previously on this blog: modelling the reduction of cinnamaldehyde using one molecule of lithal shows easy reduction of the carbonyl but a high barrier at the next stage, the reduction of the double bond. Here is a quantum energetic exploration of what might happen when a second LAH is added to the brew (the usual ωB97XD/6-311+G(d,p)/SCRF=diethyl ether).
In a comment at the end of the first post on this theme, I had noted some crystal structures containing in effect HxAl.Li(OR)y units (x=3,4; y=0-3), noting the variety of structural motifs. The current exploration does not even attempt to cover this range of possibilities, but it is informed by the types of weak interaction that these structures reveal. I will nevertheless accept that whatever pathway is revealed here is likely to represent an energetic upper bound and recognise that lower energy pathways may well exist but are yet to be explored.
- At the I12 stage, a second AlH4–.Li(OMe)2 is added and hydride transfer occurs antiperiplanar across the C=C bond (TS34-1). The computed free energy barrier ΔG298† is ~24 kcal/mol. The magnitude of this barrier corresponds to a relatively slow reaction occurring around room temperatures or slightly higher.
TS. Click for 3D
NCI Isosurface (green regions are dispersion stabilizing) Click for 3D
- A transient shallow intermediate I34-1 is formed in which the benzylic anion is stabilised by an adjacent solvated Li centre. The energy of this species (Table below) needs some explanation.‡ Can its free energy really be 1.5 kcal/mol higher than that of the preceding transition state? Yes, because its entropy is lower! The transition state is located on a total energy surface, which does not include thermal and entropic corrections; these are always applied AFTER the stationary points are located. If one inspects these total energies, I34-1 emerges as 1.2 kcal/mol lower than the preceding transition state. This sort of result serves to remind us of the dynamic nature of a potential energy surface, and that static energies may on occasion lead to odd results. Its geometry is shown below, and this too has an interesting feature. The C-H bond just created from the LAH is antiperiplanar to the benzylic anion (locked anti by the Li) and the resulting stereoelectronic effect reduces its C-H calculated[1] stretching wavenumber from the normal value of ~3100 cm-1 to 2231 cm-1, a remarkable reduction.
I34-1. Click for 3D
- The C-O-AlH3.Li(OMe)2 ligand now needs to rotate to I34-2 so that metal exchange on the benzylic carbon can occur, with Al displacing Li at that position. As with I34-1, the free energy of this species is actually slightly higher than that of TS34-1. Two AlH3 groups now exist at this stage (each of them formed by hydride donation as part of the reduction process, see below). A hydride transfer metathesis between them (H2Al-H-Al3 is actually a stable bridged species) will generate an AlH2 as part of the 5-ring aluminate ester in P34 and regenerate a molecule of LAH. Transition states for these processes (i.e. TS34-2) proved difficult to locate;† it may be that the ligand rotation and the hydride metathesis are part of the same concerted process but that is not proven yet.
I34-2. Click for 3D
- The final product prior to hydrolysis is appropriately exoenergic.
- I would also remark that many aspects of this reaction remain unexplored. For example, AlH4 can deliver up to four hydrides, becoming progressively substituted as Al(OR)nHy and in the process loosing Al-H…Li weak interactions. What influence this has on the barriers remains unknown.
In summary, the first step in the reduction of cinnamaldehyde to cinnamyl alcohol requires just one molecule of “LiAlH4” as reductant and has a very low barrier to reaction. To construct a reasonable model to account for the slower further reduction of the C=C bond requires adding a further LiAlH4, the key feature being the availability of a lithium centre to stabilise out the forming benzylic carbanion. No doubt even better models might include the effects of adding e.g. a third molecule of LAH, and a much more extensive exploration of the various conformational options. But I think the present model might be good enough to augment the apparently relatively limited mechanistic speculations found in text books on the topic.
†You sometimes see this phrase in articles reporting transition state location. What is means it that I tried a half-dozen what I thought were reasonable possibilities, and none of them satisfactorily converged. This semi-random exploration of the potential energy surface revealed a very flat energy potential, with lots of conformational possibilities. At this point, you have to decide whether it is worth the time to continue hunting.
References
- H.S. Rzepa, and H.S. Rzepa, "C 17 H 40 Al 2 Li 2 O 5", 2015. https://doi.org/10.14469/ch/191178
- H.S. Rzepa, and H.S. Rzepa, "C 17 H 40 Al 2 Li 2 O 5", 2015. https://doi.org/10.14469/ch/191172
- H.S. Rzepa, and H.S. Rzepa, "C 17 H 40 Al 2 Li 2 O 5", 2015. https://doi.org/10.14469/ch/191177
- H.S. Rzepa, and H.S. Rzepa, "C 17 H 40 Al 2 Li 2 O 5", 2015. https://doi.org/10.14469/ch/191181
- H.S. Rzepa, and H.S. Rzepa, "C 17 H 40 Al 2 Li 2 O 5", 2015. https://doi.org/10.14469/ch/191171
Tags: computed free energy barrier, energy, energy surface, final product, flat energy potential, free energy, lower energy pathways, metal exchange, pence, potential energy surface, reduction, Yes
Posted in reaction mechanism | No Comments »
April 8th, 2015
Last August, I wrote about data galore, the archival of data for 133,885 (134 kilo) molecules into a repository, together with an associated data descriptor[1] published in the new journal Scientific Data. Since six months is a long time in the rapidly evolving field of RDM, or research data management, I offer an update in the form of some new observations.
Firstly, 131 kilo molecules are now offered in a new different form; http://gdb.koitz.info/gdbrowse/ and it is worth comparing the differences between the presentation of the two sets of otherwise identical data.
- The original archive had a single assigned DOI[2] from where you could download a ZIP file to be unpacked and navigated on your own computer. The exposed metadata for the deposition (by which I mean in this case, metadata registered with DataCite, the registration authority used by Figshare) was limited to general information about the 133,885 molecules such as the authorship and license. The granularity is coarse, not extending to descriptions of individual molecules.
- The new version forgoes the ZIP archive, replacing it with a proper database (based on MongoDB) containing information about 130,832 molecules. This allows one to search the data at the individual molecule level (formula, InChI descriptor, mass, etc) using the tools provided. To the end-user, this is much more useful; the data is both discoverable and re-usable.
This is no overlap between these two presentations of the data. There also appears to be no API (application programming interface) which might allow one to write code to construct one’s own searches. The apparent absence of an API also means that really only a human navigating the set menus can discover and re-use that data; the data might not be mineable by a machine for example. The absence of an API is not that unusual, only some of the best known molecular databases offer this; the RCSB Protein Data Bank is a good example. More significantly, each instance of such a molecule-based database is likely to have its own way of accessing the data and even if a documented API were available, one would still have to write specific code for each such resource.
So the first bowl contains what I suggest is cold porridge and the second is perhaps equivalent to a table d’hôte menu. Does Goldilocks have a third option? I would argue yes, she could have:
- We recently published data for 158 kilo molecules[3] for which each molecule carries its own metadata. That metadata can be queried using any search engine that supports the basic metadata standards:
http://search.datacite.org/ui?q=has_media:true&fq=prefix:10.14469
is an example. Or armed with the metadata schema, one could also write one’s own search engine and in theory at least, that code should serve to query ANY repository that supports these standards.
You could argue that all that has happened is one has simply replaced a specific database API (if it exists) with a specific metadata schema. But these metadata schemas are controlled standards, the components of which should be self-describing (and one can see the schema components by invoking the link above).
As the archival of data (RDM) becomes increasingly important, communities will have to start making decisions about which flavour of data-porridge to offer Goldilocks. For molecular data at least, I suggest the third option is highly desirable and perhaps likely to be the most persistent. Parochial databases very much depend on a specialised team of people to maintain them in perpetuity, which I gather now means 20 years. At very least, we should start to have a debate about how the future will evolve. Let us not leave this debate merely in the hands of a small number of large organisations that are likely to make decisions based on their own business models. After all, it starts off at least as our data, not theirs! Arguably, we as authors have now largely lost control over how our stories (journal articles) are managed, let us not cede the same for data.
References
- R. Ramakrishnan, P.O. Dral, M. Rupp, and O.A. von Lilienfeld, "Quantum chemistry structures and properties of 134 kilo molecules", Scientific Data, vol. 1, 2014. https://doi.org/10.1038/sdata.2014.22
- Raghunathan Ramakrishnan., P. Dral, P.O. Dral, M. Rupp, and O. Anatole Von Lilienfeld., "Quantum chemistry structures and properties of 134 kilo molecules", 2014. https://doi.org/10.6084/m9.figshare.978904
- Y. Zhang, H.S. Rzepa, J.J.P. Stewart, P. Murray-Rust, M.J. Harvey, N. Mason, A. McLean, and Imperial College High Performance Computing Service., "Revised Cambridge NCI database", 2014. https://doi.org/10.14469/ch/2
Tags: API, RCSB Protein Data Bank, search engine
Posted in Chemical IT | No Comments »
April 1st, 2015
The reduction of cinnamaldehyde by lithium aluminium hydride (LAH) was reported in a classic series of experiments[1],[2],[3] dating from 1947-8. The reaction was first introduced into the organic chemistry laboratories here at Imperial College decades ago, vanished for a short period, and has recently been reintroduced again.‡ The experiment is really simple in concept; add LAH to cinnamaldehyde and you get just reduction of the carbonyl group; invert the order of addition and you additionally get reduction of the double bond. Here I investigate the mechanism of these reductions using computation (ωB97XD/6-311+G(d,p)/SCRF=diethyl ether).
The mechanism can be envisaged as proceeding through a 1,4-hydride attack (TS14) with a hidden intermediate (HI14) on the reaction path, or instead finding a pathway involving either one or two consecutive 1,2-attacks; TS12-1, TS12-2 via an explicit intermediate I12. Experiment shows that quenching with D2O at the end of the reduction to replace a C-Al with a C-D bond certainly seems to rule out the 1,4 route, since that would not lead to incorporation of deuterium at the benzylic position. So does the computational model reflect this reality?
I have chosen a model in which two dimethyl ether molecules solvate the lithium cation. The reactant itself has an interesting structure, in which two of the Al-H bonds form bridges to the Li, which ends up being five-coordinated. Further weak C-H…O=C hydrogen bonding is also observed. The NCI (non-covalent-interaction) surfaces are well worth inspecting (inspection notes: the NCI surrounding the Al has artefacts, since the value of the electron density surrounding the metal is lower than covalent density for the other elements. Click on the image below to load the 3D model).
Click for 3D
TS14 retains that C-H…O=C hydrogen bond, but the double Al-H-Li bridge is lost. The 8-ring for the TS allows the hydride transfer to be approximately linear, and the Bürgi-Dunitz angle of approach of the hydride to the double bond is 107.4°. Whilst the barrier is acceptably low, the reaction reaches a cul-de-sac down this path; it has no low energy escape route.
Click for 3D
TS12-1 loses the C-H…O=C hydrogen bond, but being 3.3 kcal/mol lower in free energy than TS14 fortunately provides a lower energy alternative to that cul-de-sac! The Bürgi-Dunitz angle is 112.0°.
TS12-2 is required to proceed further to the dihydrocinnamyl alcohol reduction product P12, and now we have to confront the nub of the problem. Why does this further reduction only proceed when the LAH is in excess? TS12-2 itself corresponds to an Al-H addition across a C=C double bond.[11]†, with a similar barrier to TS12-1. The answer to this conundrum is to recognise that I12 forms what is called a resting state for the reaction, and that to proceed further the reaction has to overcome the barrier from I12 to TS12-2. That barrier is 42.3 kcal/mol, far too high to proceed thermally. When one encounters an unreasonable barrier, one has to look very carefully at the model one has constructed for the process.
Click for 3D
Clearly, the model I used here is lacking something. Since the reaction only proceeds when LAH is in excess, we can formulate the hypothesis that further LAH must be added to the model, from which a more reasonable barrier might emerge. If I find out how that can be done, I will report back here.
‡ LAH as a reagent was originally available in powder form, which could be quite tricky to handle and could cause fires if not handled properly. The lab organiser Chris tells me it now comes in standard-sized pellets which are far easier and safer to handle in a laboratory, allowing its re-introduction.
†Biographical note. This footnote is added because I spent three years as a Ph.D. student trying to construct transition state models by measuring kinetic isotope effects. My failure to do so convincingly meant I decided to spend a further three years as a Post Doc inverting the concept by learning how to model transition states using quantum mechanical computation. I first applied these skills as an independent researcher to locating the transition state for Cl-H addition (vs Al-H in this post) across a C=C double bond and computing the associated isotope effects.[12] This article ends with the assertion that “SCF-MO calculations may provide a more rational basis for interpreting kinetic isotopes than the reverse procedure of attempting to establish a transition state model from the observed kinetic data.” It is nice to see that posterity has shown that this assessment was about right.
References
- R.F. Nystrom, and W.G. Brown, "Reduction of Organic Compounds by Lithium Aluminum Hydride. I. Aldehydes, Ketones, Esters, Acid Chlorides and Acid Anhydrides", Journal of the American Chemical Society, vol. 69, pp. 1197-1199, 1947. https://doi.org/10.1021/ja01197a060
- R.F. Nystrom, and W.G. Brown, "Reduction of Organic Compounds by Lithium Aluminum Hydride. II. Carboxylic Acids", Journal of the American Chemical Society, vol. 69, pp. 2548-2549, 1947. https://doi.org/10.1021/ja01202a082
- F.A. Hochstein, and W.G. Brown, "Addition of Lithium Aluminum Hydride to Double Bonds", Journal of the American Chemical Society, vol. 70, pp. 3484-3486, 1948. https://doi.org/10.1021/ja01190a082
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191154
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191148
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191152
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191149
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191151
- H.S. Rzepa, and H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191156
- H.S. Rzepa, "C 13 H 24 Al 1 Li 1 O 3", 2015. https://doi.org/10.14469/ch/191155
- H.S. Rzepa, "Gaussian Job Archive for C2H7Al", 2015. https://doi.org/10.6084/m9.figshare.1362146
- H.S. Rzepa, "MNDO SCF-MO calculations of kinetic isotope effects for dehydrochlorination reactions of chloroalkanes", Journal of the Chemical Society, Chemical Communications, pp. 939, 1981. https://doi.org/10.1039/c39810000939
Tags: Al-H-Li bridge, dihydrocinnamyl alcohol reduction product, free energy, Imperial College, independent researcher, low energy escape route, lower energy alternative, metal, pence
Posted in reaction mechanism | 5 Comments »
March 20th, 2015
This might be seen as cranking a handle by producing yet more examples of acids ionised by a small number of water molecules. I justify it (probably only to myself) as an exercise in how a scientist might approach a problem, and how it linearly develops with time, not necessarily in the directions first envisaged. A conventional scientific narrative published in a conventional journal tells the story often with the benefit of hindsight, but rarely how the project actually unfolded chronologically.‡ So by devoting 7 posts to this, you can judge for yourself how my thoughts might have developed (and I am prepared to acknowledge this may only serve to show my ignorance).
To pick up the story where it ended in the 6th post, I set off to hunt for a strong acid that might require precisely two water molecules to ionise it. So here are some more candidates:
| Acid |
Acid…H length, Å |
OH length in 2H2O |
Data-DOI |
| bis-triflylamine |
NH=1.056 |
1.622 |
[1] |
| bis-triflylamine |
OH=1.575 |
1.007 |
[2] |
| Perchloric acid |
1.024 |
1.540 |
[3] |
| Perchloric acid |
1.514 (3H2O) |
1.026 (3H2O) |
[4] |
| Perbromic acid |
1.030 |
1.518 |
[5] |
| Fluorosulfonic acid |
1.028 |
1.504 |
[6] |
| Fluoroselenic acid |
1.025 |
1.522 |
[7] |
Of these, perchloric acid is thought to be stronger than eg HBr, and indeed whereas the latter requires four water molecules for ionization, the former seems to require only three (I include this in the table above to show what happens to the bond lengths upon ionisation). But two is not quite enough, although it does appear to be on the edge. Nor does perbromic acid achieve this, or fluorosulfonic or fluoroselenic acids.
This search also illustrates another proclivity of humans, to set themselves targets, and on occasion fairly pointless targets. But one never knows whether even an apparently pointless target at the outset might not result in the discovery of something much more unexpected (even climbing Mt Everest might have brought some benefits to humanity, although I cannot name one here). I think a fair few discoveries have gone down that route. But, sadly, the hunt for acids ionized by precisely two water molecules in the gas-phase has not (yet?) borne such fruits.
‡We recently tried to write an article in such a chronological fashion. We had a hypothesis, initially thought we might be able to prove it, did more experiments and ultimately proved the hypothesis wrong (in solution!). The referees did not take to this perhaps slightly too honest account of our efforts. Since the hypothesis was wrong, why did we need to publish the story? Well, it did get published in the end, and you can make your own mind up.[8]
References
- H.S. Rzepa, "C 2 H 5 F 6 N 1 O 6 S 2", 2015. https://doi.org/10.14469/ch/191136
- H.S. Rzepa, "C 2 H 5 F 6 N 1 O 6 S 2", 2015. https://doi.org/10.14469/ch/191137
- H.S. Rzepa, "H 5 Cl 1 O 6", 2015. https://doi.org/10.14469/ch/191139
- H.S. Rzepa, "H 7 Cl 1 O 7", 2015. https://doi.org/10.14469/ch/191138
- H.S. Rzepa, "H 5 Br 1 O 6", 2015. https://doi.org/10.14469/ch/191140
- H.S. Rzepa, "H 5 F 1 O 5 S 1", 2015. https://doi.org/10.14469/ch/191143
- H.S. Rzepa, "H 5 F 1 O 5 Se 1", 2015. https://doi.org/10.14469/ch/191141
- P. Bultinck, F.L. Cherblanc, M.J. Fuchter, W.A. Herrebout, Y. Lo, H.S. Rzepa, G. Siligardi, and M. Weimar, "Chiroptical Studies on Brevianamide B: Vibrational and Electronic Circular Dichroism Confronted", The Journal of Organic Chemistry, vol. 80, pp. 3359-3367, 2015. https://doi.org/10.1021/jo5022647
Tags: Mt. Everest, scientist
Posted in Interesting chemistry | No Comments »
March 17th, 2015
I do not play poker,‡ and so I had to look up a 5-4-3-2-1(A), which Wikipedia informs me is a 5-high straight flush, also apparently known as a steel wheel. In previous posts I have suggested acids which can be ionised by (probably) 5, 4, 3 or 1 discrete water molecules in the gas phase; now to try to track down a candidate for ionisation by the required two water molecules to form that straight flush.
As the counter-anion to quaternary ammonium cations, bis(trifluoromethylsulfonyl)imide is a component of some ionic liquids. Its conjugate acid is thought[1],[2] to protonate on the nitrogen.
Click for 3D
My first obvious attempt was to place two waters near that N-H to see if it would ionise from that position.[3] The proton remains attached to the nitrogen(-:
Next, how about re-locating the waters so that they are closer to the sulfonyl oxygens? This time we do have the characteristic hydronium cation forming.[4] However, the free energy of this isomer is +6.7 kcal/mol higher relative to the NH form. So not a 5-high straight flush in a strict sense, but it perhaps does give a hint of how one might design the missing card.
Click for 3D
‡Confession time. I did spend many a Wednesday afternoon as an undergraduate playing the card game bridge.
References
- "Structures of bis(fluorosulfonyl)imide HN(SO<sub>2</sub>F)<sub>2</sub>, bis(trifluoromethylsulfonyl)imide HN(SO<sub>2</sub>CF<sub>3</sub>)<sub>2</sub>, and their potassium salts at 150 K", Zeitschrift für Kristallographie - Crystalline Materials, vol. 213, pp. 217-222, 1998. https://doi.org/10.1524/zkri.1998.213.4.217
- Zak, Z.., and Ruzicka, A.., "CCDC 119129: Experimental Crystal Structure Determination", 1999. https://doi.org/10.5517/cc3zyww
- H.S. Rzepa, "C 2 H 5 F 6 N 1 O 6 S 2", 2015. https://doi.org/10.14469/ch/191136
- H.S. Rzepa, "C 2 H 5 F 6 N 1 O 6 S 2", 2015. https://doi.org/10.14469/ch/191137
Tags: free energy, gas phase, steel wheel
Posted in Interesting chemistry | No Comments »
March 15th, 2015
My previous posts have covered the ionization by a small number of discrete water molecules of the series of halogen acids, ranging from HI (the strongest, pKa -10) via HF (weaker, pKa 3.1) to the pseudo-halogen HCN (the weakest, pKa 9.2). Here I try out some even stronger acids to see what the least number of water molecule needed to ionize these might be.
Firstly what must surely be the ultimate acid H(CHB11Cl11), discovered by Christopher Reed[1] in 2006. This is so strong that it appears that it can even largely ionize itself; the form on the right (below) is the cationic acid, the form on the left is its anionic base. The proton itself is bridged[2] between the two in a manner similar to the structure of one form of HCl.4H2O reported in the earlier post on the topic.
Click for 3D
So it comes as no surprise‡ to find[3] that just one water molecule can also ionize H(CHB11Cl11) to the anionic form (CHB11Cl11)–.
Click for 3D
How about triflic acid, CF3SO2OH, pKa -16), which is also a fair bit more acidic than HI? Here, only three waters are needed (ωB97XD/6-311++G(2d,2p) prediction) to ionise to triflate anion.[4]
Click for 3D
So, if there a system which is ionised by precisely two water molecules I will record it here.
‡Perhaps also no surprise is that one H2S molecule can also perform this ionisation.[5] This leads us into another exploration, using molecules other than water to perform these ionisations.
References
- E.S. Stoyanov, S.P. Hoffmann, M. Juhasz, and C.A. Reed, "The Structure of the Strongest Brønsted Acid: The Carborane Acid H(CHB<sub>11</sub>Cl<sub>11</sub>)", Journal of the American Chemical Society, vol. 128, pp. 3160-3161, 2006. https://doi.org/10.1021/ja058581l
- Stoyanov, E.S.., Hoffmann, S.P.., Juhasz, M.., and Reed, C.A.., "CCDC 606170: Experimental Crystal Structure Determination", 2006. https://doi.org/10.5517/ccnbrwl
- H.S. Rzepa, "C 1 H 4 B 11 Cl 11 O 1", 2015. https://doi.org/10.14469/ch/191134
- H.S. Rzepa, "C 1 H 7 F 3 O 6 S 1", 2015. https://doi.org/10.14469/ch/191129
- H.S. Rzepa, "C 1 H 4 B 11 Cl 11 S 1", 2015. https://doi.org/10.14469/ch/191135
Tags: Christopher Reed, Ohio, pence
Posted in Interesting chemistry | 3 Comments »
March 2nd, 2015
HCN is a weak acid (pKa +9.2, weaker than e.g. HF), although it does have an isomer, isocyanic acid or HNC (pka < +9.2 ?) which is simultaneously stronger and less stable. I conclude my halide acid series by investigating how many water molecules (in gas phase clusters) are required for ionisation of this “pseudo-halogen” acid.
First some observations about the structures of these complexes. The negative charge that develops on the cyanide is no longer atom-centered but is delocalised across two atoms, and furthermore the C≡N triple bond is also quite basic. So the stabilising hydrogen bonds have more choices than with the halide anions. To characterise these weak interactions, I show the structures here with the NCI (non-covalent-interaction) function included.[1] The colour coding is blue=strong attraction, green=weaker attraction, yellow=weak repulsions.
- The 2H2O complexes have insufficient length to bridge across from the H to the developing charge on the cyanide. Hence instead you see weaker π-facial interactions. Contrast also the dark blue of the NCI interaction to NH but the lighter cyan to CH.
- The 3H2O complexes abandon the weaker π-facial interactions to form a more normal H-bond to the terminal atom of the cyanide. The angle is far from optimal, and the colour coding reflects this weakening (cyan rather than deep blue). Note the small green zone in the middle of the ring, a residual π-facial mode.
- Here we see conventional H-bonds, but note now the deep blue NCI for the CH…O interaction, and the cyan for the OH…N for the first example.
- An interesting new feature appears with five water molecules. Lots of blue-coloured NCI, but one is missing (red arrow). This is because NCI is filtered to remove electron densities above a specified threshold, since these are no longer deemed “non-covalent” but start to fall into the covalent regions. The hydrogen bond specified by the red arrow is such.
If that density threshold is raised (0.07 au), the deep blue feature can now be seen. So we have the concept here that a hydrogen bond can indeed be too strong to be “non-covalent” and it passes the (rather arbitrary) threshold into being covalent. A new way of classifying hydrogen bonds!
The surprises are not quite over yet. Below is an isomer in which the water arrangement is different. This is much more ionic, as shown by three regions of covalent hydrogen bonds (red arrows) and a fully ionised cyanide supporting two hydrogen bonds to it, not one as before. The free energy of this alternative however is 5.1 kcal mol-1 higher than the previous non-ionic form.
With the HCN isomer, the normal thresholds again apply.
- With six waters and HNC, ionisation now occurs and the NCI feature appears in the N…H region rather than the H…O. The ionic nature also manifests with four other H…O regions (red arrows) where the non-covalent NCI threshold is passed or almost passed, and the covalent one starts.
Note how much green dispersion attraction is starting to appear in this caged structure and how strong (NCI = deep blue) the C-H…O hydrogen bond has become (CH hydrogen bonds in ionic systems are indeed much stronger than they are given credit for).
The transition to ionicity can also be seen with the trend bond lengths, and the sudden discontinuity with six water molecules.
|
HCN |
HNC |
| n |
C-H |
H-O |
N-H |
H-O |
| 1 |
1.077 |
2.021[2] |
1.015 |
1.806[3] |
| 2 |
1.078 |
2.064[4] |
1.027 |
1.736[5] |
| 3 |
1.086 |
1.913[6] |
1.037 |
1.667[7] |
| 4 |
1.089 |
1.864[8] |
1.042 |
1.637[9] |
| 5 |
1.103 |
1.795[10] |
1.074
1.609 |
1.522[11]
1.021[12] |
| 6 |
1.106 |
1.767[13] |
1.525 |
1.041[14] |
To summarise, HNC is a relatively strong acid, and six water molecules are required to ionise it. In contrast, HCN is much weaker and so it is not ionised even by six waters, much like HF.
References
- A. Armstrong, R.A. Boto, P. Dingwall, J. Contreras-García, M.J. Harvey, N.J. Mason, and H.S. Rzepa, "The Houk–List transition states for organocatalytic mechanisms revisited", Chem. Sci., vol. 5, pp. 2057-2071, 2014. https://doi.org/10.1039/c3sc53416b
- H.S. Rzepa, "C 1 H 3 N 1 O 1", 2015. https://doi.org/10.14469/ch/190936
- H.S. Rzepa, "C 1 H 3 N 1 O 1", 2015. https://doi.org/10.14469/ch/190935
- H.S. Rzepa, "C 1 H 5 N 1 O 2", 2015. https://doi.org/10.14469/ch/190940
- H.S. Rzepa, "C 1 H 5 N 1 O 2", 2015. https://doi.org/10.14469/ch/190937
- H.S. Rzepa, "C 1 H 7 N 1 O 3", 2015. https://doi.org/10.14469/ch/190938
- H.S. Rzepa, "C 1 H 7 N 1 O 3", 2015. https://doi.org/10.14469/ch/190939
- H.S. Rzepa, "C 1 H 9 N 1 O 4", 2015. https://doi.org/10.14469/ch/190951
- H.S. Rzepa, "C 1 H 9 N 1 O 4", 2015. https://doi.org/10.14469/ch/190954
- H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190964
- H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190957
- H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190968
- H.S. Rzepa, "C 1 H 13 N 1 O 6", 2015. https://doi.org/10.14469/ch/190971
- H.S. Rzepa, "C 1 H 13 N 1 O 6", 2015. https://doi.org/10.14469/ch/190965
Tags: ionic systems
Posted in General, Interesting chemistry | No Comments »
February 28th, 2015
Why is this post orphaned from the previous? In order to have the opportunity of noting that treating iodine computationally can be a little different from the procedures used for F, Cl and Br.
As the nuclear charge increases proceeding down the periodic table, the inner electron shells start becoming relativistic. Iodine is the first halogen where this might really start to matter.* There are two ways in which one can compute molecules with I; the first adopts the same procedure as for the earlier halogens, whereby all the electrons are described by basis functions (called an all-electron basis). This effect does not really include the effects of relativistic contractions on the inner (1s) shell unless special relativistic Hamiltonians are also used. The second replaces these inner cores with a pseudopotential, and this does incorporate some of the relativistic effects. To find out how much this might matter, I have included both types:
|
I |
| n |
I-H |
H-O |
| 1 |
1.637†/1.623‡ |
2.032/2.060[1] |
| 2 |
1.657/1.641 |
1.863/1.889[2] |
| 3 |
1.696/1.675 |
1.641/1.670[3] |
| 4 |
2.316/2.304 |
1.014/1.015[4] |
†Non-relativistic calculation with an all-electron 6-311G(d,p) basis on I, 6-311++G(2d,2p) on O and H. ‡Def2-TZVPPD basis, with pseudopotential just on I.
As with bromine, iodine shows a precipitous ionisation when the 4th water molecule is added. In the previous post, I compared this with pKa values, and a comment posted there reminded us that a pKa is measured for macroscopic bulk water and that all sorts of new effects due to free energy/entropy, continuum solvation and much else will take hold. But qualitatively at least, the ionisation of HI in a gas-phase cluster of water molecules seems to match the bulk properties. Relativistic effects do not appear to play a major role here.
*Whilst such effects can be prominent for I, arguably they actually start at Cl via an effect called spin-orbit (SO) coupling. This manifests in the calculation of chemical magnetic shieldings. If one uses standard GIAO NMR theories, one can calculate shieldings for e.g. C pretty accurately. But with Cl, the shieldings may be SO-perturbed by about 3ppm, with Br it’s about 12 ppm and with I it reaches 50 ppm![5]
References
- H.S. Rzepa, "H 3 I 1 O 1", 2015. https://doi.org/10.14469/ch/190924
- H.S. Rzepa, "H 5 I 1 O 2", 2015. https://doi.org/10.14469/ch/190921
- H.S. Rzepa, "H 7 I 1 O 3", 2015. https://doi.org/10.14469/ch/190925
- H.S. Rzepa, "H 9 I 1 O 4", 2015. https://doi.org/10.14469/ch/190927
- D.C. Braddock, and H.S. Rzepa, "Structural Reassignment of Obtusallenes V, VI, and VII by GIAO-Based Density Functional Prediction", Journal of Natural Products, vol. 71, pp. 728-730, 2008. https://doi.org/10.1021/np0705918
Tags: chemical magnetic shieldings, free energy/entropy, gas-phase cluster, Hawaii, pence
Posted in General, Interesting chemistry | No Comments »
Here is a little calculation, optimising the position that HBr adopts with respect to bromobenzene. You can see that the distance discrimination towards ortho is ~ 0.17Å, a very similar value to the “hot-spot” in the diagram above.
