Org Prep Daily

October 12, 2015

Drying sieves, melting flasks

Filed under: lab destruction — milkshake @ 5:13 pm


I was going to expound on advantages of using high-temperature dry bath made of graphite flakes – cheap, good thermal conductivity, easy to clean, soft and shiny, does not scratch the glassware – and so I took this picture of half kilo of sieves baked at 380 C under vacuum, on a heating mantle filled with graphite flakes. (Btw, the thermo-probe on IKA stirrers really goes up to 400 C).

Only when I finished and cooled my sieves, I saw that the flask softened from overheating and its bottom got sucked in. Now we have a 2L Pyrex vase in our office, with a 24/40 joint on top…


August 19, 2015

How to destroy eighteen teflon Schlenk stopcocks in one go

Filed under: lab destruction — milkshake @ 11:04 am

It turns out that the teflon air-free stopcocks used in Schlenk-ware aren’t all teflon, they have little viton O-rings hidden under two teflon sleeve rings (=the green bits that provide the actual seal contact surface). And viton swells in acetone like a sponge…

After finishing a year-long scaleup project done with boiling conc. HCl, I had to overhaul my hood, because of all the corrosion. Long story short, the vacuum manifold glass parts went into a base bath, the O-rings and air-free stopcocks sat in a bucket with acetone. About an hour later, I noticed that the O-rings from manifold joints were already up to double in size. Those old swollen O-rings may eventually return close to their original size when they dry up. But all stopcocks from a long double bank manifold got ruined – the green teflon parts, stretched and lifted by the bulging viton from inside, are going to stay out of shape for good.

It is nice to learn that these teflon air free stopcocks used for all kinds of harsh chemistry actually won’t tolerate immersion in a solvent like acetone, DCM, THF. The ones I just killed cost $500 plus one week of wait-time to replace.


July 31, 2015

The End of Affair

Filed under: industry life — milkshake @ 12:43 pm


It lasted twelve months – longer than I could have hoped. I will always remember our time together: The stunning saffron, cinnamon and maroon colors of your intermediates, the lustrous shimmering of microcrystalline flakes when you precipitated; I held you in my hands so many times. Your central atom – a noble metal from the platinum group – will stay in my heart and bones forever.

I am proud when I see how far you have advanced, now that you are to become a project to someone else. I am happy for you. But who will appreciate your special properties like I do, my unstable little molecule?

July 3, 2015

Happy 4th!

Filed under: Uncategorized — milkshake @ 3:12 am

freedom search

Credit: Jiri Sliva

June 10, 2015

The power of blunder – based optimization

Filed under: industry life, procedures — milkshake @ 8:46 pm

I have been trying to optimize a difficult reaction; I thought a presence of zinc chloride might help so I gave this a try and there was an improvement: The results were getting better, week after week.

Some time later – by now with improved product purity and filtrability – I begun to wonder if the zinc chloride effect was real, or maybe something else was going on, so I finally got around to run a control. And sure enough, the reaction worked even better without zinc chloride. So, after many tries with quantities of reagents and additives, I arrived at optimized procedure which looked almost exactly like the one that I started with, except few minor details – the little changes that were incidentally co-introduced because of the ZnCl2 addition – few small changes that make a difference… I would have never tried these changes without it. And I would have given up if I had run the control experiments earlier and found out it does nothing.

It is delightful to read methodology papers, the observations and explanations arranged neatly, flowing like a good detective story, with a chain of clear logical reasoning based on the experimental evidence. But I suspect it is mostly fictional (There is no good place in a process paper to explain that after very slow reagent addition because of a clogged valve that no-one cared to inspect before the pilot run, the impurity profile improved and the troublesome sideproduct from the second step no longer buggers up the recrystallization). I worry that reading published accounts of process research can give the management a very unrealistic impression what a normal project should look like.

March 19, 2015

How to leave a strong impression

Filed under: lab destruction — milkshake @ 9:14 pm

I got a summer internship in a natural product synthetic group, a quarter century ago when I was in high school. It was a very nice lab doing medicinal chemistry on cardioglycosides and I really liked it there. But I didn’t realize that the PI from the group wasn’t thrilled to have me (he was asked to take some random kid as a community outreach initiative, and he could not turn it down.) He promptly sent me out of the way, to the library.

In those days, the literature search used to be done with printed indexes of Chemical Abstracts. It was like slogging away through a supermarket shelf filled with phone books; I spent three weeks doing this.

Undeterred, I was nagging the PI to have me try experimental chemistry. Finally, he would let me prepare an acetylated analog of a frog cardanolide, as analytical standard. He instructed me to weight out 10mg of the material, dissolve it in 1mL of pyridine, add 1mL of acetanhydride, and let it sit overnight. Then evaporate, work up with diluted sulfuric acid and DCM.

I tried to hit exactly 10.0mg and it wasn’t easy: it took me forever to weight on precision balances, and meanwhile the guy was looming over me, unimpressed, rolling his eyes. During all this, I somehow put a tip of the little spatula to my lips – the working end of the spatula – and then asked the dour PI if bufanolides were supposed to have such a bitter taste.

For a moment, it wasn’t clear who was going to suffer the heart attack first but eventually the shouting subsided, I got my face wiped clean with alcohol swabs and was ready to set up the experiment.

So I dissolved the material in exactly 1.0 mL of pyridine, then carefully added 1.0 mL of pyridine to it (I must have grabbed the wrong brown bottle, they looked the same) and isolated 9 mg of a very pure starting material a day later; it was my last experiment in that lab…

Whenever I have to work with someone young and unbearable, it helps to recall the many asinine things I did unto others.

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