Well it’s been one year since I started this “feature” and I have enjoyed doing it, I hope you have enjoyed reading it. Of course, it has reflected my own interests but I think the selection of ASAPs was reasonably broad in scope. At least I had to read the papers in detail instead of skimming through them and it’s there that you will find the little bits and pieces which make a paper worth the effort to read, or not, as the case may be.

One of the most controversial was the paper about the “Drug-printer” which was subsequently withdrawn by the author. This proposed the 3D printing of “drugs” using a reactor chamber based upon a Chinese egg-cake oven with optical tweezers picking up individual atoms from an atom pot (which replaces the printer cartridges) with the computer directing their placement within the chamber. All good stuff and lots of comments.

I enjoyed the various publications from the Baran group at Scripps who have an interest in efficient natural product synthesis, especially the concept of C-H activation/functionalisation within this setting. Along the way developing new reagents such as Palau’chlor, a new guanidine based chlorinating agent, or examining the selective C-H oxidation in complex systems such as the Lupane triterpene family in order to improve the physical properties of such systems to take advantage of their significant biological activity. The scope of this groups work is very wide, from electrochemical oxidation to delivering a 14 step total synthesis of (+)-ingenol with intermediates which can be used for SAR studies.

One worrying trend is the use of the word “scalable” The latest example I found here. As a development chemist scalable means something more than running your  reaction at 1g,  going up from the 0.1mmol scale! That is something everyone can do, scalable means going from doing 1g reactions to multiple kilogram reactions. So really there is no basis for a paper, presented by a research group, to use the word scalable. Especially when no thermodynamic data is presented.

Imagine you discovered this shit hot reagent, HOCW. Your boss tells you to investigate its reactions thoroughly. This means that you are going to need lots of it, especially as you have observed some interesting biological effects from some of the compounds you have initially made. OK. You decide to make a couple of kilos, if done on a 1g scale you can either do 2000 1g reactions or you can make the entire lot at once. Off you go, after 30 minutes into the reaction you notice a few bubbles forming suddenly the whole reaction mass gets very hot and comes flying out towards you. You have a runaway, which you don’t get time to do! After changing your underpants and cleaning up the mess you find that your HOCW undergoes an autocatalytic decomposition, oops never saw that before on the 1g scale! Proper thermochemical evaluation is therefore crucial to your understanding of the reaction.

The example I mentioned above deals with TMS-phosphonites and their reaction with aldehydes. Now I have done these reactions of scales considerable larger than 1g, also with TMS-phosphinites. I made quantities of the reagent(s) and kept them in cold storage under argon. After some monthsI observed in both types of compound an orange/reddish precipitate had formed. So being a good chemist I decided to filter it off. No sooner had I started than an incredible stench appeared accompanied by flames. These compounds are known for this. No-one really knows what is going on here, maybe redox process, maybe slight impurities, who knows. But it was enough to make me change the synthesis route because such a happening in a pilot plant is not welcome.

So please, dear academics, be careful how you use the word scalable. I know it’s not your job to investigate the system completely, but basic stability data would be welcome, especially if you want the world to use your wonderful reagent/reaction or whatnot. We don’t want anymore unfortunate incidents like the explosion of TMS-azide where people get seriously damaged.

Wishing you another successful year of research, may all your reactions produce 99.999% yield on, at least, a 1g scale.

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