Earlier, I explored the choreography or “timing”, of what might be described as the curly arrows for a typical taught reaction mechanism, the 1,4-addition of a nucleophile to an unsaturated carbonyl compound (scheme 1). I am now going to explore the consequences of changing one of the actors by adding the nucleophile to an unsaturated imine rather than carbonyl compound (scheme 2).
Archive for the ‘reaction mechanism’ Category
Choreographing a chemical ballet: what happens if you change one of the actors?
Friday, May 8th, 2020Discussion of (the) Room-temperature chemical synthesis of dicarbon – open and transparent science.
Wednesday, May 6th, 2020A little more than a year ago, a ChemRxiv pre-print appeared bearing the title referenced in this post,[1] which immediately piqued my curiosity. The report presented persuasive evidence, in the form of trapping experiments, that dicarbon or C2 had been formed by the following chemical synthesis. Here I describe some of what happened next, since it perhaps gives some insight into the processes of bringing a scientific result into the open.
References
- K. Miyamoto, S. Narita, Y. Masumoto, T. Hashishin, M. Kimura, M. Ochiai, and M. Uchiyama, "Room-Temperature Chemical Synthesis of C2", 2019. https://doi.org/10.26434/chemrxiv.8009633.v1
A databank of molecular dynamics reaction trajectories (DDT) focused on undergraduate teaching.
Wednesday, April 22nd, 2020In a previous post, I talked about a library of reaction pathway intrinsic reaction coordinates (IRCs) containing 115 examples of organic and organometallic reactions. Now (thanks Dean!) I have been alerted to a brand new databank of dynamics trajectories (DDT), with the focus on those reactions taught in undergraduate organic chemistry courses, some of which are shown below.
Choreographing a chemical ballet: a story of the mechanism of 1,4-Michael addition.
Monday, April 13th, 2020A reaction can be thought of as molecular dancers performing moves. A choreographer is needed to organise the performance into the ballet that is a reaction mechanism. Here I explore another facet of the Michael addition of a nucleophile to a conjugated carbonyl compound. The performers this time are p-toluene thiol playing the role of nucleophile, adding to but-2-enal (green) acting as the electrophile and with either water or ammonia serving the role of a catalytic base to help things along.†
Substituent effects on the mechanism of Michael 1,4-Nucleophilic addition.
Sunday, March 29th, 2020In the previous post, I looked at the mechanism for 1,4-nucleophilic addition to an activated alkene (the Michael reaction). The model nucleophile was malonaldehyde after deprotonation and the model electrophile was acrolein (prop-2-enal), with the rate determining transition state being carbon-carbon bond formation between the two, accompanied by proton transfer to the oxygen of the acrolein.
The mechanism of Michael 1,4-Nucleophilic addition: a computationally derived reaction pathway.
Wednesday, March 25th, 2020In 2013, I created an iTunesU library of 115 mechanistic types in organic and organometallic chemistry, illustrated using video animations of the intrinsic reaction coordinate (IRC) computed using a high level quantum mechanical procedure. Many of those examples first derived from posts here. That collection is still available and is viewable in the iTunesU app on an iPhone or an iPad. The realisation struck me now‡ that one of the types not described in that library was Michael-type 1,4-nucleophilic addition to an activated alkene, as described at Wikipedia. So here is that addition.
Catalytic Mitsunobu reaction.
Wednesday, October 9th, 2019If, as a synthetic chemist, you want to invert the configuration of an alcohol in which the OH group is at a chiral centre, then the Mitsunobu reaction has been a stalwart for many years. Now a catalytic version has been published, [1] along with a proposed mechanism. Here I apply computation as a reality check to see what the energetics of this mechanism might be.
References
- R.H. Beddoe, K.G. Andrews, V. Magné, J.D. Cuthbertson, J. Saska, A.L. Shannon-Little, S.E. Shanahan, H.F. Sneddon, and R.M. Denton, "Redox-neutral organocatalytic Mitsunobu reactions", Science, vol. 365, pp. 910-914, 2019. https://doi.org/10.1126/science.aax3353
An Ambimodal Trispericyclic Transition State: the effect of solvation?
Thursday, May 2nd, 2019Ken Houk’s group has recently published this study of cycloaddition reactions, using a combination of classical transition state location followed by molecular dynamics trajectory calculations,[1] and to which Steve Bachrach’s blog alerted me. The reaction struck me as being quite polar (with cyano groups) and so I took a look at the article to see what both the original[2] experimental conditions were and how the new simulations compared. The reaction itself is shown below.
References
- X. Xue, C.S. Jamieson, M. Garcia-Borràs, X. Dong, Z. Yang, and K.N. Houk, "Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity", Journal of the American Chemical Society, vol. 141, pp. 1217-1221, 2019. https://doi.org/10.1021/jacs.8b12674
- C.Y. Liu, and S.T. Ding, "Cycloadditions of electron-deficient 8,8-disubstituted heptafulvenes to electron-rich 6,6-disubstituted fulvenes", The Journal of Organic Chemistry, vol. 57, pp. 4539-4544, 1992. https://doi.org/10.1021/jo00042a039
Smoke and mirrors. All is not what it seems with this Sn2 reaction!
Thursday, April 4th, 2019Previously, I explored the Graham reaction to form a diazirine. The second phase of the reaction involved an Sn2′ displacement of N-Cl forming C-Cl. Here I ask how facile the simpler displacement of C-Cl by another chlorine might be and whether the mechanism is Sn2 or the alternative Sn1.
The reason for posing this question is that as an Sn1 reaction, simply ionizing off the chlorine to form a diazacyclopropenium cation might be a very easy process. Why? Because the resulting cation is analogous to the cyclopropenium cation, famously proposed by Breslow as the first example of a 4n+2 aromatic ring for which the value of n is zero and not 1 as for benzene.[1] Another example of a famous “Sn1” reaction is the solvolysis of t-butyl chloride to form the very stable tertiary carbocation and chloride anion (except in fact that it is not an Sn1 reaction but an Sn2 one!)
References
- R. Breslow, "SYNTHESIS OF THE s-TRIPHENYLCYCLOPROPENYL CATION", Journal of the American Chemical Society, vol. 79, pp. 5318-5318, 1957. https://doi.org/10.1021/ja01576a067
Free energy relationships and their linearity: a test example.
Sunday, January 13th, 2019Linear free energy relationships (LFER) are associated with the dawn of physical organic chemistry in the late 1930s and its objectives in understanding chemical reactivity as measured by reaction rates and equilibria.