I'm closing in towards my final target in my total synthesis, but I'm almost out of starting material for the key late stage cyclisation I've been trying to get going. Fortunately I had some more in the back of my freezer, but it was an old batch, and even though I knew it was clean because I remember running multiple columsn to separate it out from its close running diastereomer, I decided to check its purity by NMR anyway.
Sure enough, there was my starting material and all its familiar peaks, but I also saw two 2:1 ratio quartets at ~5 and ~4 ppm respectively. What the...
These peaks also reminded me of the strange peaks that I saw in the crude NMR spectrum of my previous reactions using the same compound. I knew it wasn't a degradation product of my starting material, so I simply thought it was something from the reagents and solvents. But when the same peaks kept turning up when I changed solvents and reagents, I knew something didn't really make sense. The only things common between those reactions were the starting material, and the work up procedure, and that's when I suspected that diethyl ether peroxides were in my crude.
This morning I checked my bottle of ether for peroxides using the KI solution test, and sure enough, there it was. Shaking a bit of my ether with a solution of KI resulted in a pinkish orange organic layer (due to the peroxides oxidising the iodide ions to iodine), and a yellow water layer (due to the I3- ion). Testing various bottles around the lab, it seems (from qualitative observations) that my bottle actually had much more peroxides than others. I guess it's probably due to my habit of having my own bottle of ether. B, probably due to the nature of his chemistry, almost never uses ether since it's not polar enough. P just grabs a bottle of ether on the shelf whenever he needs it, so each of the bottles on the shelf roughly gets the same exposure to air and light. Since I have my own bottle, my ether gets much more exposure to the elements than the other bottles. And since I've been doing <10mg reactions, the small amounts of peroxides show up very well in my crude NMR, as I don't necessarily scale down work up procedures proportionally. If I did I would be extracting with 0.5mL to 1mL of solvent which really isn't practical. B and I washed every single last drop (well not really) of diethyl ether in the lab with KI solution, then washed the ether with sodium thiosulfate solution. Drying with sodium sulfate then distillation gave (hopefully) peroxide free diethyl ether. The question is: why did my starting material, which was columned and dried and stored under argon in the freezer, have diethyl ether peroxides? I think it's because I wash my NMR tubes with water, acetone and diethyl ether successively before drying in a warm oven. The ether I used must have had peroxides. Either that or it was from the solvent used in the column in which I purified the starting material in the first place. All the more reason to change the purification protocol of this compound from an ethereal solvent system to a hexanes/EtOAc one. Unless an ethereal solvent system gives improved separation over a hexanes/EtOAc system, or unless there are problems with volatility, why use an ethereal solvent in the first place. Sure, you can rotavap the stuff off a bit faster, but it's so much more expensive.
Sure enough, there was my starting material and all its familiar peaks, but I also saw two 2:1 ratio quartets at ~5 and ~4 ppm respectively. What the...
These peaks also reminded me of the strange peaks that I saw in the crude NMR spectrum of my previous reactions using the same compound. I knew it wasn't a degradation product of my starting material, so I simply thought it was something from the reagents and solvents. But when the same peaks kept turning up when I changed solvents and reagents, I knew something didn't really make sense. The only things common between those reactions were the starting material, and the work up procedure, and that's when I suspected that diethyl ether peroxides were in my crude.
This morning I checked my bottle of ether for peroxides using the KI solution test, and sure enough, there it was. Shaking a bit of my ether with a solution of KI resulted in a pinkish orange organic layer (due to the peroxides oxidising the iodide ions to iodine), and a yellow water layer (due to the I3- ion). Testing various bottles around the lab, it seems (from qualitative observations) that my bottle actually had much more peroxides than others. I guess it's probably due to my habit of having my own bottle of ether. B, probably due to the nature of his chemistry, almost never uses ether since it's not polar enough. P just grabs a bottle of ether on the shelf whenever he needs it, so each of the bottles on the shelf roughly gets the same exposure to air and light. Since I have my own bottle, my ether gets much more exposure to the elements than the other bottles. And since I've been doing <10mg reactions, the small amounts of peroxides show up very well in my crude NMR, as I don't necessarily scale down work up procedures proportionally. If I did I would be extracting with 0.5mL to 1mL of solvent which really isn't practical. B and I washed every single last drop (well not really) of diethyl ether in the lab with KI solution, then washed the ether with sodium thiosulfate solution. Drying with sodium sulfate then distillation gave (hopefully) peroxide free diethyl ether. The question is: why did my starting material, which was columned and dried and stored under argon in the freezer, have diethyl ether peroxides? I think it's because I wash my NMR tubes with water, acetone and diethyl ether successively before drying in a warm oven. The ether I used must have had peroxides. Either that or it was from the solvent used in the column in which I purified the starting material in the first place. All the more reason to change the purification protocol of this compound from an ethereal solvent system to a hexanes/EtOAc one. Unless an ethereal solvent system gives improved separation over a hexanes/EtOAc system, or unless there are problems with volatility, why use an ethereal solvent in the first place. Sure, you can rotavap the stuff off a bit faster, but it's so much more expensive.
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And that is precisely the reason I avoid small scale reactions like the plague.
ReplyDeleteSmall scale reactions make you strong. But also insane
ReplyDeleteThe trick is to keep the oil out of your ether is put h ethr in a 2 or 1.5 litre bottle, add about half as mucj hot water and a couple drops of dawn dish soap, shake vigorously for a couple mins, and let set, for a day, the dawn dish soap attaches to the oils in the ethr, and pulls it out, hence the cloudy layer in the middle. The bottom layer is water, and the top is clean ether. Use polar its the best, since prestone started putting in upercilinder lubricant in it, but ur top layer is clean, no oil ethuer, siphen it off, if anny clowdy liqiud comes through ur siphen hose , pack cotton balls in a funnel and filter it through that, ittl pull the oil in the cotton balls w/o lettin it go though. Pack the cotton balls tight.
ReplyDelete