Imperial College London

Henry Rzepa

Recently, the 100th anniversary of the birth of the famous chemist Derek Barton was celebrated with a symposium. One of the many wonderful talks presented was by Tobias Ritter and entitled “

 Late-stage fluorination for PET imaging

” and this resonated for me. The challenge is how to produce C-F bonds under mild conditions quickly so that

 18

F-labelled substrates can be injected for the PET imaging.

Concerted Nucleophilic Aromatic Substitution Mediated by the PhenoFluor Reagent.

In the last post, IH

 7

was examined to see if it might exhibit true hypervalency. The iodine, despite its high coordination, turned out

 not

to be hypervalent, with its (s/p) valence shell not exceeding eight electrons (and its d-shell still with 10, and the 6s/6p shells largely unoccupied). Instead, the 14 valence electrons (7 from H, 7 from iodine) fled to the H…H regions.

Hypervalency: I(CN)7 is not hypervalent!

Zosurabalbin[cite]10.1038/s41586-023-06873-0[/cite],[cite]10.1093/ofid/ofad500.1754[/cite], is receiving a great deal of attention as a new class of antibiotic which can target infections for which current treatment options are inadequate.

Macrocyclic peptide antibiotics – now Zosurabalpin – then  antibacterial  agents based on cyclic D,L-α-peptide architectures.

One thing almost always leads to another in chemistry. In the last post, I described how an antiperiplanar migration could compete with an antiperiplanar elimination. This leads to the hydroboration-oxidation mechanism, the discovery of which resulted in Herbert C. Brown (at least in part) being awarded the Nobel prize in 1979. This reaction represents a fairly steep learning curve for new students of organic chemistry.

The hydroboration-oxidation mechanism: An updated look.

On 8th August this year, I posted on a fascinating article that had just appeared in Science[cite]10.1126/science.1188002[/cite] in which the crystal structure was reported of two small molecules, 1,3-dimethyl cyclobutadiene and carbon dioxide, entrapped together inside a calixarene cavity.

Can a cyclobutadiene and carbon dioxide co-exist in a calixarene cavity?

This editorial from Nature[cite]10.1038/d41586-023-01612-x[/cite] is a timely reminder of the importance of data.

“For chemists, the AI revolution has yet to happen”.

Egon has reminded us that adoption of ORCID (Open researcher and collaborator ID) is gaining apace. It is a mechanism to disambiguate (a Wikipedia term!) contributions in the researcher community and to also remove much of the anonymity (where that is undesirable) that often lurks in social media sites.

ORCID identifiers galore!

Harnessing FAIR data is an event being held in London on September 3rd; no doubt all the speakers will espouse its virtues and speculate about how to realize its potential.

 ♥

Admirable aspirations indeed. Capturing hearts and minds also needs lots of real life applications!

Harnessing FAIR data:  A suggested useful persistent identifier  (PID) for quantum chemical calculations.

Like benzene, its fully saturated version cyclohexane represents an icon of organic chemistry. By 1890, the structure of planar benzene was pretty much understood, but organic chemistry was still struggling somewhat to fully embrace three rather than two dimensions. A grand-old-man of organic chemistry at the time, Adolf von Baeyer, believed that cyclohexane too was flat, and what he said went.

The conformation of cyclohexane

I am a member of the  Royal Society of  Chemistry’s Historical group. Amongst other activities, it publishes two editions of a newsletter each year for its members.

Two influential textbooks – “Mee”  and “Mellor”.

A bond index (BI) approximately measures the totals of the bond orders at any given atom in a molecule. Here I ponder what the maximum values might be for elements with filled valence shells.

What are the highest bond indices for main group and transition group elements?

In my previous post on the topic, I introduced the concept that data can come in several forms, most commonly as “raw” or primary data and as a “processed” version of this data that has added value. In crystallography, the chemist is interested in this processed version, carried by a CIF file.

Raw data and the evolution of crystallographic FAIR data. Journals, processed and raw structure data.

I noted in an earlier post the hypothesized example of (CO)

 3

Fe⩸C[cite]10.1039/d0cp03436c[/cite] as exhibiting a carbon to iron quadruple bond and which might have precedent in known five-coordinate metal complexes where one of the ligands is a “carbide” or C ligand. I had previously mooted that the Fe⩸C combination might be replaceable by an isoelectronic Mn⩸N pair which could contain a quadruple bond to the nitrogen.

A reality-based suggestion for a molecule with a metal M⩸N quadruple bond.

The previous post was about an insecticide and made a point that the persistence of both insecticides and herbicides is an important aspect of their environmental properties. Water hydrolysis will degrade them, a typical residency time being in the order of a few days. I noted in passing a dioxepin-based herbicide[cite]10.1039/P29890001265[/cite] which contains a ketal motif and which in water can hydrolise to a ketone and alcohol.

A computational mechanism for the aqueous hydrolysis of a ketal to a ketone and alcohol.

Last May, I wrote an update to the story sparked by the report of the chemical synthesis of C

 2

.[cite]10.1038/s41467-020-16025-x[/cite] This species has a long history of spectroscopic observation in the gas phase, resulting from its generation at high temperatures.[cite]10.1021/acs.accounts.0c00703[/cite] The chemical synthesis however was done in solution at ambient or low temperatures, a game-changer as they say.

The chemical synthesis of C2: another fascinating twist to the story.

The quote of the post title comes from R. B. Woodward explaining the genesis of the discovery of what are now known as the Woodward-Hoffmann rules for pericyclic reactions.[cite]10.1021/ja01080a054[/cite] I first wrote about this in 2012, noting that “*for (that) blog, I do not want to investigate the transition states”.* Here I take a closer look at this aspect.    I will start by explaining my then reluctance to discuss transition states.

The thermal reactions … took precisely the opposite stereochemical course to that which we had predicted

Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!).[cite]10.1002/jhet.5570260518[/cite] Here the key intermediate proposed is a thiirenium cation (labelled

 8

in the article) and labelled

 Int3

below.

The Willgerodt-Kindler Reaction: mechanistic reality check 2.

Earlier, I constructed a possible model of hydronium hydroxide, or H3O+.OH– One way of assessing the quality of the model is to calculate the free energy difference between it and two normal water molecules and compare the result to the measured difference. Here I apply a further test of the model using isotopes.

Earlier, I constructed a possible model of hydronium hydroxide, or H

 3

O

 +

.OH^– ^One way of assessing the quality of the model is to calculate the free energy difference between it and two normal water molecules and compare the result to the measured difference. Here I apply a further test of the model using isotopes.

Deuteronium deuteroxide. The why of pD 7.435.

With AI and Machine learning needing data in abundance, interest in data discovery is intense. However, this type of discovery is somewhat different from more traditional data base searches, in that it is particularly suited for machine discovery as well as by humans. The discovery searches are conducted using an aggregated and federated metadata store, such as that curated by DataCite.

Data Discovery: A pick-n-mix library of useful FAIR Data searches &#8211; and a call for new search suggestions.

Text books often show the following diagram, famously consolidated over many years by Emil Fischer from 1891 onwards. At the top sits

 D

-(+)-glyceraldehyde, to which all the monosaccharides below are connected by painstaking chemical transformations.

The (+) in D-(+)-glyceraldehyde means it has a positive optical rotation? Wrong!

The notorious neurotoxin Tetrodotoxin is often chemically represented as a zwitterion, shown below as

 1

. This idea seems to originate from a famous article written in 1964 by the legendary organic chemist, Robert Burns Woodward.[cite]10.1351/pac196409010049[/cite] This structure has propagated on to Wikipedia and is found in many other sources.

The Structure of Tetrodotoxin as a free base.

I have had some interesting discussions recently regarding metadata. What emerges is that it can be quite a broadly defined concept and it is clear that a variety of answers might be obtained when asking the simple question “what is it useful for?” Here I set out some of my answers to that question. Metadata

 vs

Data.

Metadata. Why?

At the ACS conference, I have attended many talks these last four days, but one made some “connections” which intrigued me. I tell its story (or a part of it) here. But to start, try the following experiment. Find a Word document of .docx type on your hard drive Remove the .docx suffix and replace it with a .zip suffix. Expand as if it is an archive (it is!). A folder is created and this itself contains four further folders.

Research data: Managing spectroscopy-NMR.

The topic of open citations was presented at the PIDapalooza conference and represents a third component in the increasing corpus of open scientific information. David Shotton gave us an update on  Citations as First Class data objects – Citation Identifiers and introduced (me) to the blog where he discusses this topic.

First, Open Access, then Open (and FAIR) Data, now Open  Citations.

In the previous post, I referred to a recently published review on hypervalency[cite]10.1039/C5SC02076J[/cite] which introduced a very simple way (the valence electron equivalent γ) of quantifying the effect. Diazomethane was cited as one example of a small molecule exhibiting hypervalency (on nitrogen) by this measure.

Can any hypervalence in diazomethanes be amplified?

Michael in a comment here on the mechanism of the Masamune-Bergman reaction notes that when it occurs as part of the Calicheamicin (an antibody-drug conjugate or ADC) version of this mechanism, a pre-step is first necessary. As discussed in this review article,[cite]10.3390/ph14050442[/cite] the trisulfide linkage is reduced and the resulting thiolate undergoes a facile 1,4-addition to the adjacent enone.

Mechanism of the Masamune-Bergman reaction. Part 4. Why was the DFT energy barrier too high for the Calicheamicin reaction?

An N-B single bond is iso-electronic to a C-C single bond, as per below. So here is a simple question: what form does the distribution of the lengths of these two bonds take, as obtained from crystal structures?  The Conquest search query is very simple (no disorder, no errors).  When applied to the Cambridge structure database (CSD) the following two distributions are obtained.

Elongating an N-B single bond  is much easier than stretching a C-C single bond.

I noted in my WATOC conference report a presentation describing the use of calculated reaction barriers (and derived rate constants) as mechanistic reality checks. Computations, it was claimed, have now reached a level of accuracy whereby a barrier calculated as being 6 kcal/mol too high can start ringing mechanistic alarm bells.

Dyotropic Ring Expansion: more mechanistic reality checks.

In 2023, we very much take for granted that everyone and pretty much everything is online. But it was not always so and when I came across an old plan indicating how the chemistry department at Imperial College was connected in 1989, I was struck by how much has happened in the 34 years since. Nowadays all the infrastructures needed are effectively “built in” to the building when it is constructed and few are even aware of them.

A trip down memory lane: An online departmental connection map from 1989.

Bees are having a tough time around the world. Oddly, they are surviving very well in cities. One reason are the wild flower meadows in London and for some summer relief I thought I would tell you the story of the one shown below. We live in west London, in an area that was farmland as recently as the 1930s and used to produce vegetables and milk for the population of London.

Wild flowers in West London.

A previous post was triggered by Peter alerting me that interactive electronic supporting information (

 IESI

) we had submitted to a journal in 2005[cite]10.1021/ic0519988[/cite] appeared to be strangely missing from the article landing page. This set me off recollecting our journey, which had started around 1998, and to explore what the current state of these ancient

 IESI

s were in 2022.

Four stages in the evolution of interactive ESI as part of articles in chemistry journals.

In 2006[cite]10.1021/ic0519988[/cite] we published an article illustrating various types of pseudorotations in small molecules. It’s been cited 20 times since then, so reasonable interest! We described rotations known as Lever and Turnstile as well as the better known Berry mode. Because the differences between these rotations are quite subtle, we included an interactive electronic supporting information to illustrate them.

Web page decay and Journals: How an interactive  “ESI” from 2006 was rescued.

I have long been fascinated by polymers of either carbon dioxide,

 †

or carbon monoxide, or combinations of both. One such molecule, referred to as dioxane tetraketone when it was featured on the ACS molecule-of-the-week site and also known as the anhydride of oxalic acid, or more formally 1,4-dioxane-2,3,5,6-tetraone, has been speculated upon for more than a century.[cite]10.1002/cber.19080410335[/cite] The history of chemistry

Dioxane tetraketone – an ACS molecule of the week with a mystery.

The previous examples of four atom systems displaying two layers of aromaticity illustrated how 4 (B

 4

), 8 (C

 4

) and 12 (N

 4

) valence electrons were partitioned into 4n+2 manifolds (respectively 2+2, 6+2 and 6+6). The triplet state molecule B

 2

C

 2

with 6 electrons partitioned into 2π and 4σ electrons, with the latter following Baird’s aromaticity

C2N2: a 10-electron four-atom molecule displaying both Hückel 4n+2 and Baird 4n selection rules for ring aromaticity.

The number of repositories which accept research data across a wide spectrum of disciplines is on the up. Here I report the results of conducting an experiment in which chemical modelling data was deposited in six such repositories and comparing the richness of the metadata describing the essential properties of the six depositions. The repositories are as follows:

 Figshare

as a repository dates from 2012.

A comparison of descriptive metadata across different data repositories.

In 2016, the world heard that gravitational waves had been detected and now a third instance is reported.

 ‡

Given that the data associated with these detections are perhaps amongst the most important instances in recent times, I thought I might take a peek at how it was managed. The original report in 2016[cite]10.1103/PhysRevLett.116.061102[/cite] cited (Ref 116) data as DOI: 10.7935/K5MW2F23.

FAIR Research data: Gravitational waves as an example from the astrophysics community.

In Internet terms, 23 years ago is verging on pre-history. Much of what was happening around 1997 on the Web was still highly experimental and so its worth taking a look at some of this to see how it has survived or whether it can be “curated” into a form that would still be useful.

Internet Archeology: an example of a revitalised molecular resource  with a new activity now built in.

Increasingly, individual small molecules are having their structures imaged using STM, including cyclo[18]carbon that I recently discussed. The latest one receiving such treatment is Kekulene.[cite]10.1021/jacs.9b07926[/cite]  As with cyclo[18]carbon, the point of interest was which of the two resonance structures shown below most closely resembled the measured structure.

Does Kekulene have Kekulé vibrational modes? Yes!

This post arose from a comment attached to the post on Na

 2

He and relating to peculiar and rare topological features of the electron density in molecules called non-nuclear attractors. This set me thinking about other molecules that might exhibit this and one of these is shown below.

The H4 (2+) dication and its bonding.

This, the fourth candidate provided by C&amp;EN for a vote for the molecule of the year as discussed here, lays claim to the World’s most polar neutral molecule (system

 1

shown below).[cite]10.1002/anie.201508249[/cite] Here I explore a strategy for extending that record.

Molecules of the year? The most polar neutral compound synthesized…

This last month, as a follow-up to the preceding post on the colour of flowers, I have been moonlighting by blogging elsewhere. Do go visit my “guerrilla blog” at perivalepark.london. Part of this project involves visiting two “physic or botanic” gardens, which originate from early 17th century explorations of herbs and other botanicals as medicines. Both are very old and their chemistry is indeed fascinating; more of which later.

Chemistry (and music) in the Park.

I started this story by looking at octet expansion and hypervalence in non-polar hypercoordinate species such as S(-CH

 3

)

 6

, then moved on to S(=CH

 2

)

 3

. Finally now its the turn of S(≡CH)

 2

.

 ‡

As the triple bonds imply, this seems to represent twelve shared valence electrons surround the sulfur, six from S itself and three from each carbon.

Octet expansion and hypervalence in dimethylidyne-λ6-sulfane.

Ammonium hydroxide (NH4+…OH–) can be characterised quantum mechanically when stabilised by water bridges connecting the ion-pairs.

Ammonium hydroxide (NH

 4


 +

…OH

 –

) can be characterised quantum mechanically when stabilised by water bridges connecting the ion-pairs.

Hydronium hydroxide: the why of pH 7.

Deltamethin is a pyrethroid insecticide for control of malaria which has been used for a little while. Perhaps inevitably, mosquitoes are developing resistance to it. So what could be done about countering this? Well, perhaps surprisingly, form a polymorph![cite]10.1073/pnas.2013390117[/cite] These crystal structure isomers are often highly undesirable;

Deltamethrin – a polymorphed insecticide.

The phenomenon of

 bond stretch isomerism

, two isomers of a compound differing predominantly in just one bond length, is one of those chemical concepts that wax and occasionally wane.[cite]10.1016/S1631-0748(02)01380-2[/cite] Here I explore such isomerism for the elements Ge, Sn and Pb. In one earlier post, I noted a form of bond stretch isomerism that can arise from a Jahn-Teller distortion ending in two different geometries

Bond stretch isomerism. Did this idea first surface 100 years ago?

Another conference, a Cambridge satellite meeting of OpenCon, and I quote here its mission: “OpenCon is a platform for the next generation to learn about Open Access, Open Education, and Open Data, develop critical skills, and catalyze action toward a more open system of research and education” targeted at students and early career academic professionals. But they do allow a few “late career” professionals to attend as well!

OpenCon (2016)

This is sent from the Pidapalooza event in Reykjavik, Iceland, and is a short collection of notable things I learnt or which attracted my attention. Firstly, what IS

 PIDapalooza

[cite]10.5438/11.0001[/cite]? Well, it’s all about persistent identifiers, but don’t let that put you off! Another way of putting it is that it’s a way of finding things scientific on the Web.

Pidapalooza!

Allotropes are differing structural forms of the elements. The best known example is that of carbon, which comes as diamond and graphite, along with the relatively recently discovered fullerenes and now graphenes. Here I ponder whether any of the halogens can have allotropes. Firstly, I am not aware of much discussion on the topic.

Allotropic halogens.

The traditional structure of the research article has been honed and perfected for over 350 years by its custodians, the publishers of scientific journals. Nowadays, for some journals at least, it might be viewed as much as a profit centre as the perfected mechanism for scientific communication. Here I take a look at the components of such articles to try to envisage its future, with the focus on molecules and chemistry.

Re-inventing the anatomy of a research article.

In the beginning (taken here as prior to ~1980) libraries held five-year printed consolidated indices of molecules, organised by formula or name (Chemical abstracts). This could occupy about 2m of shelf space for each five years. And an equivalent set of printed volumes from the Beilstein collection.

One molecule, one identifier: Viewing molecular files from a digital repository using metadata standards.

In the preceding post, a nice discussion broke out about Kekulé’s 1872 model for benzene.[cite]10.1002/jlac.18721620110[/cite] This model has become known as the

 oscillation hypothesis

between two extreme forms of benzene (below). The discussion centered around the semantics of the term

 oscillation

compared to

 vibration

(a synonym or not?) and the timescale implied by each word.

Benzene: an oscillation or a vibration?

Steve Bachrach has just blogged on a recent article (DOI: 10.1002/anie.200903969) claiming the isolation of a compound with a C≡S triple bond; A compound with a C≡S triple bond  Steve notes that Schreiner and co claim a “structure with a rather strong CS double bond or a weak triple bond”. With this size of molecule, the proverbial kitchen sink can be thrown at the analysis of the bonding.

The nature of the C≡S triple bond

My previous post related to the aromatic electrophilic substitution of benzene using as electrophile phenyl diazonium chloride. Another prototypical reaction, and again one where benzene is too inactive for the reaction to occur easily, is the catalyst-free bromination of benzene to give bromobenzene and HBr.

Aromatic electrophilic substitution. A different light on the bromination of benzene.

The

 1

H NMR spectrum of an aromatic molecule such as benzene is iconic; one learns that the unusual chemical shift of the protons (~δ 7-8 ppm) is due to their deshielding by a

 diatropic

ring current resulting from the circulation of six aromatic π-electrons following the Hückel 4n+2 rule.

The NMR spectra of methano[10]annulene and its dianion. The diatropic/paratropic inversion.

Andy Extance at the Chemistry World blog has picked up on a fascinating article[cite]10.1021/jz401578h[/cite] on the dimer of SF

 2

. This molecule has three F atoms on one S, and only one on the other; FSSF

 3

. But all four S-F bonds are of different length.

The dimer of SF2: small is beautiful (and weird).

It is always interesting to observe conference experiments taking place. The traditional model involves travelling to a remote venue, staying in a hotel, selecting sessions to attend from a palette of parallel streams and then interweaving chatting to colleagues both old and new over coffee, lunch, dinner or excursions.

Chemical Bonds at the 21st Century – 2017:  the Bond Slam.

The period 1951–1954 was a golden one for structural chemistry; proteins, DNA, Ferrocene (1952) and the one I discuss here, a bonding model for Zeise’s salt (

 3

). In “A review of π Complex Theory”,

 Bull. Soc. Chim. Fr.

,

 1951

, 1 8 , C79 (it is not online) M. J. S. Dewar sets out his theory of the role of π-complexes in (mostly) organic chemistry.

The π-complex theory of metal-alkene compounds.

This is a recently published[cite]10.5560/ZNB.2012-0189[/cite] (hypothetical) molecule which has such unusual properties that I cannot resist sharing it with you. It is an annulene with 144 all-cis CH groups, being a (very) much larger cousin of (also hypothetical) systems mooted in 2009[cite]10.1021/ja710438j[/cite],[cite]10.1021/jp902176a[/cite].    A 144-carbon annulene.

Anapolar ring currents: a [144]-Annulene.

The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. Each achieves its chiral magic by control of the geometry at the transition state for the reaction, and the stabilizations (or destabilizations) that occur at that geometry.

Non covalent interactions in the Sharpless transition state for asymmetric epoxidation.

Birch reduction of benzene itself results in 1,4-cyclohexadiene rather than the more stable (conjugated) 1,3-cyclohexadiene. Why is this?

The mechanism of the Birch reduction. Part 3: reduction of benzene

A game chemists often play is to guess the mechanism for any given reaction. I thought I would give it a go for the decomposition of the

 tris-peroxide

shown below.

The “unexpected” mechanism of peroxide decomposition.

Blogging in chemistry remains something of a niche activity, albeit with a variety of different styles. The most common is commentary or opinion on the scientific literature or conferencing, serving to highlight what their author considers interesting or important developments. There are even metajournals that aggregate such commentaries. The question therefore occasionally arises;

The status of blogging as scientific communication.

The reaction described in the previous post (below) is an unusual example of nucleophilic attack at an sp

 2

-carbon centre, reportedly resulting in inversion of configuration[cite]10.1021/ja00765a062[/cite]. One can break it down to a sequence of up to eight individual steps, which makes teaching it far easier. But how real is that sequence?

Secrets of a university tutor. An exercise in mechanistic logic: first dénouement.

One thing leads to another. Thus in the previous post, I described a thermal pericyclic reaction that appears to exhibit

 two

transition states resulting in

 two

different stereochemical outcomes.

An unusual [1,6] shift in homotropylium cation exhibiting zones of aromaticity.

In the previous posts, I explored reactions which can be flipped between two potential (stereochemical) outcomes. This triggered a memory from Alex, who pointed out this article from 1999[cite]10.1070/MC1999v009n02ABEH000995[/cite] in which the nitrosonium cation as an electrophile can have two outcomes

 A

or

 B

when interacting with the electron-rich 2,3-dimethyl-2-butene.

Computationally directed synthesis:  2,3-dimethyl-2-butene + NO(+).

ELNs (electronic laboratory notebooks) have been around for a long time in chemistry, largely of course due to the needs of the pharmaceutical industries. We did our first extensive evaluation probably at least 15 years ago, and nowadays there are many on the commercial market, with a few more coming from opensource communities. Here I thought I would bring to your attention the potential of an interesting new entrant from the open community.

Electronic notebooks: a peek into the future?

An extensive discussion developed regarding my post on a fascinating helical [144]-annulene.

Helically conjugated molecules. A follow-up to [144]-annulene.

Nucleophiles are species that seek to react with an electron deficient centre by donating a lone or a π-bond pair of electrons. The ambident variety has two or more such possible sources in the same molecule, an example of which might be hydroxylamine or H

 2

NOH.

σ or π? The ambident nucleophilic reactivity of imines: crystallographic and computational reality checks.

Previously, I had noted that Corey reported in 1963/65 the total synthesis of the sesquiterpene dihydrocostunolide. Compound

 16

, known as

 Eudesma-1,3-dien-6,13-olide

was represented as shown below in black; the hydrogen shown in red was implicit in Corey’s representation, as was its stereochemistry. As of this instant, this compound is just one of 64,688,893 molecules recorded by Chemical Abstracts.

Validating the chemical literature heritage. Eudesma-1,3-dien-6,13-olide.

The blog post by Rich Apodaca entitled “

 The Horrifying Future of Scientific Communication

” is very thought provoking and well worth reading. He takes us through disruptive innovation, and how it might impact upon how scientists communicate their knowledge. One solution floated for us to ponder is that “

 supporting Information, combined with data mining tools, could eliminate most of the need for manuscripts in the first place

”.

Research data and the “h-index”.

The outcome of pericyclic reactions con depend most simply on three conditions, any two of which determine the third. Whether the catalyst is Δ or hν (heat or light), the topology determining any stereochemistry and the participating electron count (4n+2/4n). It is always neat to conjure up a simple switch to toggle these; heat or light is simple, but what are the options for toggling the electron count?

Using a polar bond to flip the (stereochemical) outcome of a pericyclic reaction.

In my earlier post on the topic, I discussed how inverting the polarity of the C-X bond from X=O to X=Be could flip the stereochemical course of the electrocyclic pericyclic reaction of a divinyl system. An obvious question would be: what happens at the half way stage, ie X=CH

 2

? Well, here is the answer.

Using a polar bond to flip: a follow up project.

C

 2

(dicarbon) is certainly interesting from a theoretical point of view. Whether or not it can be described as having a

 quadruple bond

has induced much passionate discussion[cite]10.1038/nchem.1263[/cite],[cite]10.1002/anie.201208206[/cite],[cite]10.1002/anie.201301485[/cite],[cite]10.1002/anie.201302350[/cite]. Its occurrence in space and in flames is also well-known.

Is dicarbon (C2) a molecule of chemical interest?

William Henry Perkin is a local chemical hero of mine. The factory where he founded the British (nay, the World) fine organic chemicals industry is in Greenford, just up the road from where we live. The factory used to be close to the Black Horse pub (see below) on the banks of the grand union canal.

William Henry Perkin: The site of the factory and the grave.

In this post, I looked at some hydrogen bonds formed by interaction of a π-system with an acidic hydrogen. Unlike normal lone pair donors, π-systems can involve more than two electrons, most commonly four or six. Here I look at examples of both these higher-order donors.

 FIMNEU

FIMNEU.

NCI (non-covalent-interaction) analysis for some π-hydrogen bonded systems.

A dichotomy is a

 division into two mutually exclusive, opposed, or contradictory groups.

Consider the reaction below*.* The bicyclic pentadiene on the left could in principle open on heating to give the monocyclic [12]-annulene (blue or red)

 via

what is called an

 
 electrocyclic reaction
 

as either a six (red) or eight (blue) electron process. These two possibilities represent our dichotomy;

A pericyclic dichotomy.

I was intrigued by one aspect of the calculated transition state for di-imide reduction of an alkene; the calculated NMR shieldings indicated an diatropic ring current at the centre of the ring, but very deshielded shifts for the hydrogen atoms being transferred. This indicated, like most thermal pericyclic reactions, an aromatic transition state. Well, one game one can play with this sort of reaction is to add a double bond.

Di-imide reduction with a twist: A Möbius version.

A few years ago, we published an article which drew a formal analogy between chemistry and iTunes

 (sic

)[cite]10.1021/ci060139e[/cite]. iTunes was the first really large commercial digital music library, and a feature

 under-the-skin

was the use of meta-data to aid discoverability of any of the 10 million (26M in 2013) or so individual items in the store.

 ‡

The analogy to digital chemistry and discoverability of

What can chemistry learn from photos?

Astronomers who discover an asteroid get to name it, mathematicians have theorems named after them. Synthetic chemists get to name molecules (Hector’s base and Meldrum’s acid spring to mind) and reactions between them. What do computational chemists get to name? Transition states! One of the most famous of recent years is the Houk-List.

Stereoselectivities of Proline-Catalyzed Asymmetric Intermolecular Aldol Reactions.

The previous post explored why E2 elimination reactions occur with an

 antiperiplanar

geometry for the transition state. Here I have tweaked the initial reactant to make the overall reaction

 exothermic

rather than

 endothermic

as it was before. The change is startling. The exothermicity is of course due to the aromatisation of the ring. The IRC is however quite different from before. IRC for E2 elimination.

An exothermic E2 elimination: an unusual intrinsic reaction coordinate.

The tetrahedral intermediate is one of those iconic species on which the foundation of reaction mechanism in organic chemistry is built. It refers to a (normally undetected and hence merely inferred) species formed initially when a nucleophilic reagent attacks a carbonyl compound. Its importance to understanding the activity of enzymes cannot be overstated.

The

 
 tetrahedral intermediate
 

is one of those iconic species on which the foundation of reaction mechanism in organic chemistry is built. It refers to a (normally undetected and hence merely inferred) species formed initially when a nucleophilic reagent attacks a carbonyl compound. Its importance to understanding the activity of enzymes cannot be overstated.

Secrets of a university tutor: tetrahedral intermediates.

There are many treasures in Woodward and Hoffmann’s (WH) classic monograph. One such is acetolysis of  the

 endo

chloride (green), which is much much faster than that of the

 exo

isomer (red). The explanation given in their article (p 805) confines itself to succinctly stating that only loss of the

 endo

halogen can be concerted with a required disrotatory ring opening of the cyclopropane.

Mechanistic morphemes. Perisolvolysis of a cyclopropyl chloride.

Following on from Armstrong’s almost electronic theory of chemistry in 1887-1890, and Beckmann’s radical idea around the same time that molecules undergoing transformations might do so via

 
 a reaction mechanism
 

involving unseen intermediates (in his case, a transient enol of a ketone) I here describe how these concepts underwent further evolution in the early 1920s.

The dawn of organic reaction mechanism: the prequel.

How one might go about answering the question: do alkenes promote anomeric effects? A search of chemical abstracts does not appear to cite any examples (I may have missed them of course, since it depends very much on the terminology you use, and new effects may not yet have any agreed terminology) and a recent excellent review of hyperconjugation does not mention it. Here I show how one might provide an answer.

Spotting the unexpected. Anomeric effects involving alkenes?

Most representational chemistry generated on a computer requires the viewer to achieve a remarkably subtle transformation in their mind from two to three dimensions (we are not quite yet in the era of the 3D iPad!). The Cahn-Ingold-Prelog convention was a masterwork (which won the Nobel prize). It is shown in action for the molecule on the left below.

The perception of stereochemistry. A challenging case.

A staple of introductory undergraduate teaching in organic chemistry is Markovnikov’s rule, which states: “

 the addition of a protic acid HX to an alkene results in the acid hydrogen (H) becoming attached to the carbon with fewer alkyl substituents and the halide (X) group to the carbon with more alkyl substituents

”. Shortly thereafter, students are exposed to the “anti-Markovnikov” addition of borane to

 e.g.

The wrong trousers: the anti-Markovnikov addition of borane to 2-methylpropene.

In the previous post, I found intriguing the mechanism by which methane (CH

 4

) inverts by transposing two of its hydrogens. Here I take a look at silane, SiH

 4

. It appears it is a three-stage process! Firstly, silane eliminates molecular hydrogen to form a molecular complex between H

 2
 
 and SiH
 
 2

(DOI: 10.14469/hpc/2290). The barrier (~60 kcal/mol) is very much lower than with methane.

How does silane invert (its configuration)?

In my first post on the topic, I discussed how inverting the polarity of the C-X bond from X=O to X=Be (scheme below) could flip the stereochemical course of the electrocyclic pericyclic reaction of a divinyl system.

Using a polar bond to flip: on the knife-edge!

Continuing my hunt, here is a candidate for a strong(est?) halogen bond, this time between Se and I.[cite]10.1021/ic50038a006[/cite].  The features of interest include:  The six-membered ring is in the chair conformation.

Halogen bonds 4: The  strongest (?) halogen bond.

The conformational analysis of cyclohexane is a mainstay of organic chemistry. Is there anything new that can be said about it? Let us start with the diagram below: This identifies the start of the process as a chair conformation of cyclohexane, with D

 3d

symmetry.

Ring-flipping in cyclohexane in a different light

The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers

 A-D

, each in two conformations (

 1/2

) were calculated at the ωB97D/6-311G(d,p)/SCRF=ethanol level, and are shown here relative to

 A1

(kcal/mol) as free energies.

Updating a worked problem in conformational analysis. Part 2: an answer.

Moving (chemical) data around in a manner which allows its (automated) use in whichever context it finds itself must be a holy grail for all scientists and chemists.

Data-round-tripping: wherein the future?

The Wikipedia page on hypervalent compounds reveals that the concept is almost as old as that of normally valent compounds.

Hypervalency: Is it real?

Since I have gotten into the habit of quoting some of my posts in other contexts, I have started to also archive them using WebCite. One can quote the resulting archive as: Rzepa, Henry. Quintuple bonds.  2010-04-18. URL:http://www.ch.ic.ac.uk/rzepa/blog/?p=1722. Accessed: 2010-04-18. (Archived by WebCite

 ®

at http://www.webcitation.org/5p5BtuzSH) There is one issue though.

WebCite and Jmol

One of the (not a few) pleasures of working in a university is the occasional opportunity that arises to give a new lecture course to students.

Conformational analysis of biphenyls: an upside-down view

In this follow-up to the previous post, I will try to address the question

 what is the nature of the bonds in penta-coordinate carbon

? This is a difficult question to answer with any precision, largely because our concept of a bond derives from trying to define what the properties of the electrons located in the region between any two specified atoms are.

Capturing penta-coordinate carbon! (Part 2).

In the previous two posts, I noted the recent suggestion of how a stable frozen S

 N

2 transition state might be made. This is characterised by a central carbon with five coordinated ligands.

It’s penta-coordinate carbon Spock- but not as we know it!

In 1988, Wilke[cite]10.1002/anie.198801851[/cite] reported molecule 1 It was a highly unexpected outcome of a nickel-catalyzed reaction and was described as a 24-annulene with an unusual 3D shape. Little attention has been paid to this molecule since its original report, but the focus has now returned!

In 1988, Wilke[cite]10.1002/anie.198801851[/cite] reported molecule

 1

A 24-annulene. Click for 3D. It was a highly unexpected outcome of a nickel-catalyzed reaction and was described as a 24-annulene with an unusual 3D shape. Little attention has been paid to this molecule since its original report, but the focus has now returned!

Henry Rzepa's Blog

Helically conjugated molecules. A follow-up to [144]-annulene.