Posts Tagged ‘free energy barrier’

Another Woodward pericyclic example dissected: all is not what it seems.

Wednesday, May 22nd, 2013

Here is another example gleaned from that Woodward essay of 1967 (Chem. Soc. Special Publications (Aromaticity), 1967, 21, 217-249), where all might not be what it seems.


Hidden intermediates in the benzidine rearrangement. The monoprotonated mechanism.

Tuesday, January 8th, 2013

Eagle-eyed footnote readers might have spotted one at the bottom of the post on the benzidine rearrangement. I was comparing the N-N bond lengths in crystal structures of known diprotonated hydrazines (~1.45Å) with the computed N-N bond length at the start point of the intrinsic reaction coordinate for the [5,5] sigmatropic rearrangement of di-N-protonated diphenylhydrazine (the active species in the benzidine rearrangement itself), which was some 1Å longer. This post explores the implications of this oddity.


The mechanism of the Birch reduction. Part 2: a transition state model.

Monday, December 3rd, 2012

I promised that the follow-up to on the topic of Birch reduction would focus on the proton transfer reaction between the radical anion of anisole and a proton source, as part of analysing whether the mechanistic pathway proceeds O or M.


Transition state models for Baldwin’s rules of ring closure.

Saturday, June 2nd, 2012

The Baldwin rules for ring closure follow the earlier ones by Bürgi and Dunitz in stating the preferred angles of nucleophilic (and electrophilic) attack in bond forming reactions, and are as famous for the interest in their exceptions as for their adherence. Both sets of rules fundamentally explore the geometry of the transition states involved in the reaction, as reflected in the activation free energies. Previous posts exploring the transition states for well-known reactions have revealed that the 4th dimension (the timing of the bond formations/breakings) can often spring surprises. So this post will explore a typical Baldwin ring formation in the same way.


Chemistry in an attosecond.

Friday, November 4th, 2011

An attosecond is 10-18s. The chemistry that takes place on this timescale is called electron dynamics. For example, it is the time taken for an electron to traverse the 1s orbit in a hydrogen atom. And chemists are starting to manipulate electrons (and hence chemistry) on this timescale; for example a recent article (DOI: 10.1021/ja206193t) describes how to control the electrons in benzene using attosecond laser pulses.


The Sn1…Sn2 mechanistic continuum. The special case of neopentyl bromide

Monday, May 9th, 2011

Introductory organic chemistry invariably features the mechanism of haloalkane solvolysis, and introduces both the Sn1 two-step mechanism, and the Sn2 one step mechanism to students. They are taught to balance electronic effects (the stabilization of carbocations) against steric effects in order to predict which mechanism prevails. It was whilst preparing a tutorial on this topic that I came across what was described as the special case of neopentyl bromide, the bimolecular solvolysis of which has been identified (DOI: 10.1021/ja01182a117) as being as much as 3 million times slower than methyl bromide. This is attributed to a very strong steric effect on the reaction, greater even than that which might be experienced by t-butyl bromide! Time I thought, to take a look at what might make neopentyl bromide so special, and what those supposed electronic and steric effects were really up to.


Do electrons prefer to move in packs of 4, 6 or 8 during proton exchange in a calixarene?

Friday, January 7th, 2011

This story starts with a calixarene, a molecule (suitably adorned with substituents) frequently used as a host to entrap a guest and perchance make the guest do something interesting. Such a calixarene was at the heart of a recent story where an attempt was made to induce it to capture cyclobutadiene in its cavity.


Combichem: an introductory example of the complexity of chemistry

Sunday, December 19th, 2010

Chemistry gets complex very rapidly. Consider the formula CH3NO as the topic for a tutorial in introductory chemistry. I challenge my group (of about 8 students) to draw as many different molecules as they can using exactly those atoms. I imply that perhaps each of them might find a different structure; this normally brings disbelieving expressions to their faces.


Rate enhancement of the Diels-Alder reaction inside a cavity

Saturday, October 30th, 2010

Reactions in cavities can adopt quite different characteristics from those in solvents. Thus first example of the catalysis of the Diels-Alder reaction inside an organic scaffold was reported by Endo, Koike, Sawaki, Hayashida, Masuda, and Aoyama[1], where the reaction shown below is speeded up very greatly in the presence of a crystalline lattice of the anthracene derivative shown below.



  1. K. Endo, T. Koike, T. Sawaki, O. Hayashida, H. Masuda, and Y. Aoyama, "Catalysis by Organic Solids. Stereoselective Diels−Alder Reactions Promoted by Microporous Molecular Crystals Having an Extensive Hydrogen-Bonded Network", Journal of the American Chemical Society, vol. 119, pp. 4117-4122, 1997.

Reactions in supramolecular cavities – trapping a cyclobutadiene: ! or ?

Sunday, August 8th, 2010

Cavities promote reactions, and they can also trap the products of reactions. Such (supramolecular) chemistry is used to provide models for how enzymes work, but it also allows un-natural reactions to be undertaken. A famous example is the preparation of P4 (see blog post here), an otherwise highly reactive species which, when trapped in the cavity is now sufficiently protected from the ravages of oxygen for its X-ray structure to be determined. A colleague recently alerted me to a just-published article by Legrand, van der Lee and Barboiu (DOI: 10.1126/science.1188002) who report the use of cavities to trap and stabilize the notoriously (self)reactive 1,3-dimethylcyclobutadiene (3/4 in the scheme below). Again sequestration by the host allowed an x-ray determination of  the captured species!