Henry Rzepa's Blog Chemistry with a twist

June 12, 2013

Mechanistic arrow pushing. A proposed addition to its rules.

Filed under: Curly arrows — Tags: , , — Henry Rzepa @ 9:56 am

A little while ago, I set out some interpretations of how to push curly arrows. I also appreciate that some theoretically oriented colleagues regard the technique as neither useful nor in the least rigorous, whereas towards the other extreme many synthetically minded chemists view the ability to push a reasonable set of arrows for a proposed mechanism as of itself constituting evidence in its favour.[1] Like any language for expressing ideas, the tool needs a grammar (rules) and a vocabulary, and perhaps also an ability to carry ambiguity. These thoughts surfaced again via a question asked of me by a student: “is the mechanism for the hydrogens in protonated benzene whizzing around the ring a [1,2] or a [1,6] pericyclic sigmatropic shift?”. 



  1. M.J. Gomes, L.F. Pinto, P.M. Glória, H.S. Rzepa, S. Prabhakar, and A.M. Lobo, "N-heteroatom substitution effect in 3-aza-cope rearrangements", Chemistry Central Journal, vol. 7, 2013. http://dx.doi.org/10.1186/1752-153X-7-94

May 29, 2013

Mechanism of the Van Leusen reaction.

Filed under: Uncategorised — Tags: , , , — Henry Rzepa @ 2:23 pm

This is a follow-up to comment posted by Ryan, who asked about isocyanide’s role (in the form of the anion of tosyl isocyanide, or TosMIC): “In Van Leusen, it (the isocyanide) acts as an electrophile”. The Wikipedia article (recently updated by myself) shows nucleophilic attack by an oxy-anion on the carbon of the C≡N group, with the isocyanide group acting as the acceptor of these electrons (in other words, the electrophile). In the form shown below, one negatively charged atom appears to be attacking another also carrying a negative charge. Surely this breaks the rules that like charges repel? So we shall investigate to see if this really happens.


May 22, 2013

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

Filed under: Uncategorised — Tags: , , , — Henry Rzepa @ 9:13 am

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.


May 20, 2013

Woodward’s symmetry considerations applied to electrocyclic reactions.

Sometimes the originators of seminal theories in chemistry write a personal and anecdotal account of their work. Niels Bohr[1] was one such and four decades later Robert Woodward wrote “The conservation of orbital symmetry” (Chem. Soc. Special Publications (Aromaticity), 1967, 21, 217-249; it is not online and so no doi can be given). Much interesting chemistry is described there, but (like Bohr in his article), Woodward lists no citations at the end, merely giving attributions by name. Thus the following chemistry (p 236 of this article) is attributed to a Professor Fonken, and goes as follows (excluding the structure in red):



  1. N. Bohr, "Der Bau der Atome und die physikalischen und chemischen Eigenschaften der Elemente", Zeitschrift f�r Physik, vol. 9, pp. 1-67, 1922. http://dx.doi.org/10.1007/BF01326955

May 11, 2013

Concerted 1,4-addition of thioacetic acid: a (requested) reality check.

Filed under: Interesting chemistry — Tags: — Henry Rzepa @ 4:07 pm

Lukas, who occasionally comments on this blog, sent me the following challenge. In a recent article[1] he had proposed that the stereochemical outcome (Z) of reaction between a butenal and thioacetic acid as shown below arose by an unusual concerted cycloaddtion involving an S-H bond. He wrote in the article “…this scheme … recommends itself for evaluation by in silico methods“. I asked if the answer could be posted here, and he agreed. So here it is.



  1. L. Hintermann, and A. Turočkin, "Reversible Generation of Metastable Enols in the 1,4-Addition of Thioacetic Acid to α,β-Unsaturated Carbonyl Compounds", The Journal of Organic Chemistry, vol. 77, pp. 11345-11348, 2012. http://dx.doi.org/10.1021/jo3021709

May 8, 2013

Transition states for the (base) catalysed ring opening of propene epoxide.

Filed under: Uncategorised — Tags: , — Henry Rzepa @ 7:30 pm

The previous post described how the acid catalysed ring opening of propene epoxide by an alcohol (methanol) is preceded by pre-protonation of the epoxide oxygen to form a “hidden intermediate” on the concerted intrinsic reaction pathway to ring opening. Here I take a look at the mechanism where a strong base is present, modelled by tetramethyl ammonium methoxide (R4N+.OMe), for the two isomers R=Me; R’=Me, R”=H and R’=H, R”=Me.


May 6, 2013

Hidden intermediates in the (acid catalysed) ring opening of propene epoxide.

In a previous post on the topic, I remarked how the regiospecific ethanolysis of propene epoxide[1] could be quickly and simply rationalised by inspecting the localized NBO orbital calculated for either the neutral or the protonated epoxide. This is an application of Hammond’s postulate[[2] in extrapolating the properties of a reactant to its reaction transition state. This approach implies that for acid-catalysed hydrolysis, the fully protonated epoxide is a good model for the subsequent transition state. But is this true? Can this postulate be tested? Here goes.



  1. H.C. Chitwood, and B.T. Freure, "The Reaction of Propylene Oxide with Alcohols", Journal of the American Chemical Society, vol. 68, pp. 680-683, 1946. http://dx.doi.org/10.1021/ja01208a047
  2. G.S. Hammond, "A Correlation of Reaction Rates", Journal of the American Chemical Society, vol. 77, pp. 334-338, 1955. http://dx.doi.org/10.1021/ja01607a027

April 29, 2013

Why diphenyl peroxide does not exist.

A few posts back, I explored the “benzidine rearrangement” of diphenyl hydrazine. This reaction requires diprotonation to proceed readily, but we then discovered that replacing one NH by an O as in N,O-diphenyl hydroxylamine required only monoprotonation to undergo an equivalent facile rearrangement. So replacing both NHs by O to form diphenyl peroxide (Ph-O-O-Ph) completes this homologous series. I had speculated that PhNHOPh might exist if all traces of catalytic acid were removed, but could the same be done to PhOOPh? Not if it continues the trend and requires no prior protonation at all!


April 28, 2013

How to predict the regioselectivity of epoxide ring opening.

I recently got an email from a student asking about the best way of rationalising epoxide ring opening using some form of molecule orbitals. This reminded me of the famous experiment involving propene epoxide.[1]



  1. H.C. Chitwood, and B.T. Freure, "The Reaction of Propylene Oxide with Alcohols", Journal of the American Chemical Society, vol. 68, pp. 680-683, 1946. http://dx.doi.org/10.1021/ja01208a047

April 14, 2013

Intermediates in oxime formation from hydroxylamine and propanone: now you see them, now you don’t.

Filed under: Interesting chemistry — Tags: — Henry Rzepa @ 7:26 pm

A recent theme here has been to subject to scrutiny well-known mechanisms supposedly involving intermediates. These transients can often involve the creation/annihilation of charge separation resulting from  proton transfers, something that a cyclic mechanism can avoid. Here I revisit the formation of an oxime from hydroxylamine and propanone, but with one change. In the earlier post, I used two molecules of water to achieve the desired proton transfer. Now I look to see what effect replacing those two water molecules by a guanidine has.NH2OH+Guanidine


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