Posts Tagged ‘Ion-Pair Mechanisms’

Janus mechanisms (the past and the future): Reactions of the diazonium cation.

Saturday, December 11th, 2010

Janus was the mythological Roman god depicted as having two heads facing opposite directions, looking simultaneously into the past and the future. Some of the most ancient (i.e. 19th century) known reactions can be considered part of a chemical mythology; perhaps it is time for a Janus-like look into their future.

Reaction of the diazonium cation with cyanide.

The phenyl diazonium ion is often introduced early in most chemistry teaching; it is used to produce spectacularly coloured solutions from colourless starting materials and makes an immediate impression.1 The reaction of this species with cyanide salts often appears in introductory courses of aromatic chemistry as a means of producing aryl cyanides. It entered the text books around a century ago as the Sandmeyer reaction (using copper(I)cyanide, but it is also reported as occurring using more ionic cyanide salts as well).2 The mechanism of the ionic reaction however has been given little attention recently. One common representation is as a unimolecular reaction to lose nitrogen gas forming an arene cation, which is mechanistically then followed by fast quenching with cyanide anion to replace the diazo group with the cyano group.

Computational modelling of such ion-pair reactions has now become possible,3 and is going to be used here to peek into the future. A B3LYP/6-311G(d,p)/SCRF calculation shows a transition state involving C-N cleavage, with an adjacent cyanide ion doing rather more than merely spectating. The dipole moment of the transition state is 11D (in acetonitrile as solvent). The structure shows the ion-pair endeavouring to minimise the charge separation, with the cyanide approaching at a rather different angle from the departing diazo group. This sort of SN2 displacement at an sp2 (as opposed to sp3) carbon centre is mechanistically quite unusual.4 The free energy of activation for this mechanism is calculated as 24.9 kcal/mol, which is slightly worryingly high for what is considered a room-temperature reaction (the same method gave quite reasonable barriers for another ion-pair mechanism3).

Phenyldiazonium cation + cyanide anion; substitution mechanism. Click for 3D

So time to see if all is what it might seem. There are many other mechanisms that might be explored; below is what seems quite a reasonable one, the elimination of the diazo-group with accompanying proton abstraction to form a benzyne. This transition state has an activation free energy of 17.8 kcal/mol, a much more reasonable value for a room temperature reaction. The dipole moment is 17.1D (the reactant ion-pair is 19.7D).

Benzyne mechanism, in acetonitrile solvent. Click for 3D

So could it be that this veritable reaction actually proceeds via a different mechanism from that in the text books? Benzyne would be formed as a very reactive intermediate, and presumably in the presence of cyanide anions, it would react by nucleophilic addition to form benzonitrile, the same product as before. How could this be verified? Well, if the carbon atom carrying the diazonium group were to be labelled as say 14C, the original mechanism would carry all that label at one carbon in the benzonitrile product. But the benzyne mechanism would scramble the label between two carbons. Janus therefore sees the future in the shape of a useful experiment which could be done to distinguish the two alternative mechanisms.

It is also noteworthy that the two alternative transition states have different dipole moments, and so are affected differently by solvent polarity. Thus in water, the activation free energies are respectively (substitution/elimination) 25.1 and 17.9, whilst in benzene as solvent they are much higher: 48.7 and 39.0 kcal/mol. The effect of the solvent upon the structure of the transition state is also considerable. Below is shown the benzyne elimination mechanism as calculated in the non polar benzene as solvent. Note how the proton transfer is much more advanced, and the C…N cleavage is less advanced than in acetonitrile as solvent.

Benzyne transition state, in benzene solvent. Click for 3D

We are seeing something of a revolution here. Gradually, the mechanisms of the reaction library built up over the last 100 years or so are increasingly being explored using quantitative calculations. It seems entirely likely that more surprises will crop up.

  1. At the age of ~12 I was introduced to chemistry via this reaction, an exposure at least in part why almost 50 years later I am still doing chemistry and why I write this blog.
  2. Kazitsyna, L. A.; Gruzdneva, V. N. Vestnik Moskovskogo Universiteta, Seriya 2: Khimiya, 1975, 16, 331-7.
  3. The ion-pair mechanism of the racemisation of iso-bornyl chloride, another ancient and almost mythological reaction, has recently been studied in this manner; J. Kong, P. v. R. Schleyer and H. S. Rzepa, “Successful Computational Modeling of Iso-bornyl Chloride Ion-Pair Mechanisms”, J. Org. Chem., 2010, DOI: 10.1021/jo100920e
  4. Z. Wu and R. Glaser, “Ab Initio Study of the SN1Ar and SN2Ar Reactions of Benzenediazonium Ion with Water. On the Conception of “Unimolecular Dediazoniation” in Solvolysis Reactions”,  J. Am. Chem. Soc., 2004, DOI: 10.1021/ja047620a



Archived as Henry Rzepa, Janus mechanisms (the past and the future): Reactions of the diazonium cation, URL:http://www.ch.ic.ac.uk/rzepa/blog/?p=3003. Accessed: 2010-12-12. (Archived by WebCite® at http://www.webcitation.org/5uv90cJnU)

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(Hyper)activating the chemistry journal.

Monday, September 7th, 2009

The science journal is generally acknowledged as first appearing around 1665 with the Philosophical Transactions of the Royal Society in London and (simultaneously) the French Academy of Sciences in Paris. By the turn of the millennium, around 10,000 science and medical journals were estimated to exist. By then, the Web had been around for a decade, and most journals had responded to this new medium by re-inventing themselves for it. For most part, they adopted a format which emulated paper (Acrobat), with a few embellishments (such as making the text fully searchable) and then used the Web to deliver this new reformulation of the journal. Otherwise, Robert Hooke would have easily recognized the medium he helped found in the 17th century.

In 1994, a small group of us thought that one could, and indeed should go further than emulated paper. We argued [1] that journals should be activated by delivering not merely the logic of a scientific argument, but also the data on which it might have been based. Of course, we encountered the usual problem; doing this might cost publishers more in production resources, and in the absence of a market prepared to pay the extra, the business model did not make sense (to the publishers). Well, 15 years later, and most publishers are indeed now thinking about how their journals can be enhanced. A number of interesting projects (the RSC’s Project Prospect is one which strives to bring science alive) have emerged. Another is the topic of this blog; the activation of the journal with molecular coordinates and data using the Jmol applet.

Initially (~2005), this project met with resistance from publishers, and the issue really amounted to what the definitive version of a scientific article should be. Should that definitive version be printable? That model, after all had served the community well for more than 300 years! And journals from the very beginning are still as readable now as when first published. In other words, print lasts! But print is pretty limiting after all. For a start, it is limited to 2D static representations. Molecules, by and large, do their magic in a dynamic three dimensions (4D in an Einsteinian sense). But print is also expensive; not merely to produce, but to transport paper around the world.

From the turn of the millennium, a number of publishers, amongst them the American Chemical Society, started to evolve the scientific article such that the pre-eminent version would now be considered to be the HTML form (perhaps as a prelude to phasing out print entirely? See an interesting commentary by a journal editor) and perhaps a digital Acrobat form which would be deemed to loose some of its functionality once printed (again see here for how Acrobat can be used to enhance things). Again however, a chicken-and-egg scenario resulted. To enhance the articles with extra functionality (such as data), they would need to find authors prepared to put the extra work into preparing the material. In fact, most authors already do that, but they call it supporting information. This is often highly data rich, covering materials such as spectra, coordinates and other information nowadays provided to researchers for analysis. Unfortunately, what has been missing is the education of authors to provide this information in a proper digital form which can be easily re-used by others, and on a Web page, converted automatically to nice interactive models. Most spectra which form part of the supporting information are in fact still scanned versions of printed spectra!

Enter computational chemists. Nowadays, they live in a world that truly does not need printing! Almost all of their data is already suitably digital. So perhaps it is no surprise to find that when enhanced journal articles started appearing around 2005, many were produced by this group of chemists. By now perhaps you are wondering what such an article might look like. Well, the remainder of this blog will be devoted to listing some examples. You will also notice that they come exclusively from our own publications. Perhaps someone will find the time to collect a far more representative set to better illustrate the diversity of this form, and how it is evolving. Meanwhile, you might wish to take a look at the following.

Part 1: The early days: 1994 onwards

These examples all relied on a browser plugin called Chime, which is no longer with us! Hence the pages designed to invoke it no longer display properly. But the data associated with the articles is still there!

  1. An early 1994 example of (hyper)activating a journal article can be seen here as the preliminary communication and
  2. in 1995 here as the final full article. I am told that this was the article that actually inspired the developers of Chime to enhance (Netscape) with a chemical plugin.
  3. This one from 1998 illustrates how articles can decay in functionality when Chime is no longer available.
  4. An ab initio and MNDO-d SCF-MO Computational Study of Stereoelectronic Control in Extrusion Reactions of R2I-F Iodine (III) Intermediates, M. A. Carroll, S. Martin-Santamaria, V. W. Pike, H. S. Rzepa and D. A. Widdowson, Perkin Trans. 2, 1999, 2707-2714 with the supporting information here.
  5. Huckel and Mobius Aromaticity and Trimerous transition state behaviour in the Pericyclic Reactions of [10], [14], [16] and [18] Annulenes. Sonsoles Martên-Santamarêa, Balasundaram Lavan and H. S. Rzepa, J. Chem. Soc., Perkin Trans 2, 2000, 1415. with the supporting information here.
  6. Peter Murray-Rust, H. S. Rzepa and Michael Wright, “Development of Chemical Markup Language (CML) as a System for Handling Complex Chemical Content”, New J. Chem., 2001, 618-634. DOI: 10.1039/b008780g. This article broke new ground in that the supporting information was something of a misnomer. It was expressed entirely in XML, including all the chemistry data, and used XSLT transforms on the fly to regenerate the article. In that sense, it was actually a superset of the published article. It would be fair to say that this article was rather ahead of its time (although it does seem appropriate to publish it in a new journal!).
  7. M. Jakt, L. Johannissen, H. S. Rzepa, D. A. Widdowson and R. Wilhelm, “A Computational Study of the Mechanism of Palladium Insertion into Alkynyl and Aryl Carbon-Fluorine bonds”, Perkin Trans. 2, 2002, 576-581 and supporting information.
  8. P. Murray-Rust and H. S. Rzepa, chapter in “Handbook of Chemoinformatics. Part 2. Advanced Topics.”, ed. J. Gasteiger and T. Engel, 2003, Vol 1, was not enhanced per se, but did lay out the principles of how it might/should be done.
  9. K. P. Tellmann, M. J. Humphries, H. S. Rzepa and V. C. Gibson, “An experimental and computational study of β-H transfer between organocobalt complexes and 1-alkenes”, Organometallics, 2004, 23, 5503-5513. DOI: 10.1021/om049581h and supporting information.

Part 2: 2005.

These four examples all now invoke Jmol, which downloads upon request and hence does not rely on the presence of any browser plugin. The four articles were submited with supporting information in the form of HTML. These were associated with the main article, but were not formal part of that article. In that sense, they represent an incarnation of the traditional model, with all the data firmly resident in the supporting information.

  1. Gibson, Vernon C.; Marshall, Edward L.; Rzepa, H. S. ” A computational study on the ring-opening polymerization of lactide initiated by β-diketiminate metal alkoxides: The origin of heterotactic stereocontrol”, J. Am. Chem. Soc., 2005, 127, 6048-6051. DOI: 10.1021/ja043819b and supporting information.
  2. H. S. Rzepa, Mobius aromaticity and delocalization”, Chem. Rev., 2005, 105, 3697 – 3715. DOI: 10.1021/cr030092l and supporting information.
  3. H. S. Rzepa, “Double-twist Mšbius Aromaticity in a 4n+2 Electron Electrocyclic Reaction”, 2005, Chem Comm, 5220-5222. DOI: 10.1039/b510508k The supporting information is also available directly.
  4. H. S. Rzepa, “A Double-twist Mobius-aromatic conformation of [14]annulene”, Org. Lett., 2005, 7, 637 – 4639. DOI: 10.1021/ol0518333 and supporting information.

Part 3: 2006 onwards

The supporting information has now been assimilated into the main body of the article proper, and within these confines contribute components such as enhanced figures or tables (i.e. enhanced with data)

  1. A. P. Dove, V. C. Gibson, E. L. Marshall, H. S. Rzepa, A. J. P. White and D. J. Williams, “Synthetic, Structural, Mechanistic and Computational Studies on Single-Site β-Diketiminate Tin(II) Initiators for the Polymerization of rac-Lactide”, J. Am. Chem. Soc., 2006,128, 9834-9843. DOI: 10.1021/ja061400a The enhancement can be seen in Figure 11.
  2. O. Casher and H. S. Rzepa, “SemanticEye: A Semantic Web Application to Rationalise and Enhance Chemical Electronic Publishing”, J. Chem. Inf. Mod., 2006, 46, 2396-2411. DOI: 10.1021/ci060139e
  3. H S. Rzepa and M. E. Cass, “A Computational Study of the Nondissociative Mechanisms that Interchange Apical and Equatorial Atoms in Square Pyramidal Molecules”, Inorg. Chem., 2006, 45, 3958–3963. DOI 10.1021/ic0519988. Interactive table at 10.1021/ic0519988/ic0519988.html
  4. M. E. Cass and H. S. Rzepa, “In Search of The Bailar Twist and Ray-Dutt mechanisms that racemize chiral tris-chelates: A computational study of Sc(III), V(III), Co(III), Zn(II) and Ga(III) complexes of a ligand analog of acetylacetonate”, Inorg. Chem., 2007, 49, 8024-8031. DOI: 10.1021/ic062473y The enhancement can be seen in Figure 2
  5. H. S. Rzepa, “Lemniscular Hexaphyrins as examples of aromatic and antiaromatic Double-Twist Möbius Molecules”, Org. Lett., 2008, 10, 949-952.DOI:10.1021/ol703129z The enhancement can be seen in Web Table 1.
  6. D. C. Braddock and H. S. Rzepa, “Structural Reassignment of Obtusallenes V, VI and VII by GIAO-based Density functional prediction”, J. Nat. Prod., 2008, DOI: 10.1021/np0705918 and WEO1.
  7. S. M. Rappaport and H S. Rzepa, “Intrinsically Chiral Aromaticity. Rules Incorporating Linking Number, Twist, and Writhe for Higher-Twist Möbius Annulenes”, J. Am. Chem. Soc., 2008, 130,, 7613-7619. DOI: 10.1021/ja710438j and WEO1 to 4
  8. C. S. M. Allan and H. S. Rzepa, “AIM and ELF Critical point and NICS Magnetic analyses of Möbius-type Aromaticity and Homoaromaticity in Lemniscular Annulenes and Hexaphyrins”, J. Org. Chem., 2008, 73, 6615-6622. DOI: 10.1021/jo801022b and WEO1
  9. C. S. M. Allan and H. S. Rzepa, “Chiral aromaticities. Möbius Homoaromaticity”, J. Chem. Theory. Comp., 2008, 4, 1841-1848. DOI: 10.1021/ct8001915 and WEO1
  10. C. S. M Allan and H. S. Rzepa, “The structure of Polythiocyanogen: A Computational investigation”, Dalton Trans., 2008, 6925 – 6932. DOI: 10.1039/b810147g and enhanced Table
  11. H. S. Rzepa, “Wormholes in Chemical Space connecting Torus Knot and Torus Link π-electron density topologies”, Phys. Chem. Chem. Phys., 2009, 1340-1345. DOI: 10.1039/b810301a and enhanced Table.
  12. H. S. Rzepa, “The Chiro-optical properties of a Lemniscular Octaphyrin”, Org. Lett., 2009, 11, 3088-3091. DOI: 10.1021/ol901172g
  13. C. S. Wannere, H. S. Rzepa, B. C. Rinderspacher, A. Paul, H. F. Schaefer III, P. v. R. Schleyer and C. S. M. Allan, “The geometry and electronic topology of higher-order Möbius charged Annulenes”, J. Phys. Chem., 2009, DOI: 10.1021/jp902176a and enhanced table
  14. H. S. Rzepa, “The distortivity of π-electrons in conjugated Boron rings.”, Phys. Chem. Chem. Phys., 2009, DOI: 10.1039/B911817A and enhanced table.
  15. H. S. Rzepa, “The importance of being bonded”, Nature Chem., 2009, DOI: 10.1038/nchem.373 and the exploratorium.
  16. King Kuok Hii, J.L.Arbour, H.S.Rzepa, A.J.P.White, “Unusual Regiodivergence in Metal-Catalysed Intramolecular Cyclisation of γ-Allenols”, Chem. Commun, 2009, DOI: 10.1039/b913295c and enhanced table.
  17. L. F. V. Pinto, P. M. C. Glória, M. J. S. Gomes, H. S. Rzepa, S. Prabhakar, A. M. Lobo. “A Dramatic Effect of Double Bond Configuration in N-Oxy-3-aza Cope Rearrangements – A simple synthesis of functionalised allenes”, Tet. Lett., 2009, 50, 3446-3449. DOI: 10.1016/j.tetlet.2009.02.228 and interactive table.
  18. H. S. Rzepa and C. S. M. Allan, “Racemization of isobornyl chloride via carbocations: a non-classical look at a classic mechanism”, J. Chem. Educ., 2010, DOI: 10.1021/ed800058c and interactive table.
  19. K. Abersfelder, A. J. P. White, H. S. Rzepa, and D. Scheschkewitz “A Tricyclic Aromatic Isomer of Hexasilabenzene”, Science, 2010, DOI: 10.1126/science.1181771 and interactive table.
  20. A. C. Spivey, L. Laraia, A. R. Bayly, H. S. Rzepa and A. J. P. White “Stereoselective Synthesis of cis- and trans-2,3-Disubstituted Tetrahydrofurans via Oxonium−Prins Cyclization: Access to the Cordigol Ring System”, Org. Lett., 2010, DOI 10.1021/ol9024259 and interactive table.
  21. J. Kong, P. v. R. Schleyer and H. S. Rzepa, “Successful Computational Modeling of Iso-bornyl Chloride Ion-Pair Mechanisms”, J. Org. Chem., 2010, DOI: 10.1021/jo100920e and interactive table.
  22. A. Smith, H. S. Rzepa, A. White, D. Billen, K. K. Hii, “Delineating Origins of Stereocontrol in Asymmetric Pd-Catalyzed α-Hydroxylation of 1,3-Ketoesters”, J. Org. Chem., 2010, 75, 3085-3096. DOI: 10.1021/jo1002906 and interactive table.
  23. H. S. Rzepa “The rational design of helium bonds”, Nature Chem., 2010, 2, 390-393. DOI: 10.1038/NCHEM.596 and web enhanced table.
  24. P. Rivera-Fuentes, J. Lorenzo Alonso-Gómez, A. G. Petrovic, P. Seiler, F. Santoro, N. Harada, N. Berova, H. S. Rzepa, and F. Diederich, “Enantiomerically Pure Alleno–Acetylenic Macrocycles: Synthesis, Solid-State Structures, Chiroptical Properties, and Electron Localization Function Analysis”, Chem. Eur. J., 2010, DOI: 10.1002/chem.201001087 and interactive figure
  25. H. S. Rzepa, “The Nature of the Carbon-Sulfur bond in the species H-CS-OH”, J. Chem. Theory. Comput., 2010, 49, DOI: 10.1021/ct100470g and interactive table.
  26. H. S. Rzepa, “Can 1,3-dimethylcyclobutadiene and carbon dioxide co-exist inside a supramolecular cavity?”, Chem. Commun., 2010, DOI: 10.1039/C0CC04023A and interactive table
  27. M. R. Crittall, H. S. Rzepa, and D. R. Carbery, “Design, Synthesis, and Evaluation of a Helicenoidal DMAP Lewis Base Catalyst”, Org. Lett., 2011, DOI: 10.1021/ol2001705 and interactive table
  28. H. S. Rzepa, “The past, present and future of Scientific discourse”, J. Cheminformatics, 2011, 3, 46. DOI: 10.1186/1758-2946-3-46 and interactive figure 3, figure 4 and figure 5.
  29. H. S. Rzepa, “A computational evaluation of the evidence for the synthesis of 1,3-dimethylcyclobutadiene in the solid state and aqueous solution”, Chem. Euro. J., 2012, in press.
  30. J. L. Arbour, H. S. Rzepa, L. A. Adrio, E. M. Barreiro, P. G. Pringle and K. K. (Mimi) Hii, “Silver-catalysed enantioselective additions of O-H and N-H to C=C bonds: Non-covalent interactions in stereoselective processes”, Chem. Euro. J., 2012, in press, Web table 1 and Web table 2.
  31. H. S. Rzepa, “Chemical datuments as scientific enablers”, J. Chemoinformatics, submitted.
  32. A. P. Buchard, F. Jutz, F. M. R. Kember, H. S. Rzepa, C. K. Williams, C.K., “Experimental and Computational Investigation of the Mechanism of Carbon Dioxide/Cyclohexene Oxide Copolymerization Using A Dizinc Catalyst”, in press. Interactivity box
  33. D. C. Braddock, D. Roy, D. Lenoir, E. Moore, H. S. Rzepa, J. I-Chia Wu and P. von R. Schleyer, “Verification of Stereospecific Dyotropic Racemisation of Enantiopure d and l-1,2-Dibromo-1,2-diphenylethane in Non-polar Media”, Chem. Comm., 2012, just published. DOI: 10.1039/C2CC33676F and interactivity box.
  34. K. Leszczyńska, K. Abersfelder, M. Majumdar, B. Neumann, H.-G. Stammler, H. S. Rzepa, P. Jutzi and D. Scheschkewitz, “The Cp*Si+ Cation as a Stoichiometric Source of Silicon, Chem. Comm., 2012, 48, 7820-7822. DOI: 10.1039/c2cc33911k. Cites links to 10042/to-13974, 10042/to-13982, 10042/to-13969, 10042/20028, 10042/to-13973, 10042/to-13985
  35. H. S. Rzepa, “A computational evaluation of the evidence for the synthesis of 1,3-dimethylcyclobutadiene in the solid state and aqueous solution”, Chem. Euro. J., 2013, 4932-4937. DOI: 10.1002/chem.201102942 and WebTable
  36. H. S. Rzepa, “Chemical datuments as scientific enablers”, J. Chemoinformatics, 2013, 4, DOI: 10.1186/1758-2946-5-6. The interactivity box is integrated into the body of the article.
  37. M. J. Cowley, V. Huch, H. S. Rzepa, D. Scheschkewitz, “A Silicon Version of the Vinylcarbene – Cyclopropene Equilibrium: Isolation of a Base-Stabilized Disilenyl Silylene”, 2013, Nature Chem., in press and Webtable.
  38. M. J. S. Gomes, L. F. V. Pinto, H. S. Rzepa, S. Prabhakar, A. M. Lobo, “N-Heteroatom Substitution Effects in 3-Aza-Cope Rearrangements”, Chemistry Central, 2013, 7:94. doi:10.1186/1752-153X-7-94 and Table.
  39. H. S. Rzepa and C. Wentrup, “Mechanistic Diversity in Thermal Fragmentation Reactions: a Computational Exploration of CO and CO2 Extrusions from Five-Membered Rings”, J. Org. Chem., DOI: 10.1021/jo401146k and Table.
  40. D. C. Braddock, J. Clarke and H. S. Rzepa “Epoxidation of Bromoallenes Connects Red Algae Metabolites by an Intersecting Bromoallene Oxide – Favorskii Manifold”, Chem. Comm., 2013, DOI: 10.1039/C3CC46720A and Table.
  41. M. J. Fuchter, Ya-Pei Lo and H. S. Rzepa, “Mechanistic and chiroptical studies on the desulfurization of epidithiodioxopiperazines reveal universal retention of configuration at the bridgehead carbon atoms”, J. Org. Chem., 2013, in press. doi: 10.1021/jo401316a and table.

References

  1. H.S. Rzepa, B.J. Whitaker, and M.J. Winter, "Chemical applications of the World-Wide-Web system", Journal of the Chemical Society, Chemical Communications, pp. 1907, 1994. https://doi.org/10.1039/c39940001907

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