Welcome to the Fold, Antimony

Now, I'm not the kind of guy who goes out of my way to try some fancy, exotic transition-metal catalyst. However, there are some I will trumpet from the tops of the mountains (such as ytterbium (III) triflate, which I used at my old job to do just about everything). When I come across a method for making something that I can't get done under some other, simpler way, I will use the new and exotic method. Plus, it's cool when you can use something new. In the back of my mind, I've kept a running tab of all the spots on the periodic table where I've used an element. It's sadly nerdy, but I am a chemist, after all.

In light of my inability to do certain types of palladium-based coupling reactions, I've had to find a new route to developing the SAR around our superduperriffic compound that we've been making and testing. One way, instead of coupling the free amine sticking off a heterocycle with an aryl bromide, is to try displacing a chloride off the heterocycle SNAr-style with an aniline or an aliphatic amine. The problem is, how does one go from an amino group to a displacable aryl halide?

Simple: you diazotize the amine in an aqueous acid and then convert the hydroxy group to a chloride using the appropriate reagent. I was doing this in two steps using NaNO2 in HOAc followed by stirring in warm POCl3 for a couple of hours. This was working great...until someone else in my company decided to paint the inside of their hood bright-ass yellow by means of an angry flask of POCl3 (hence known as "Pockle-3"). My safety-conscious company has decided to start making sure such volatile reagents, such as Pockle-3, are in the hands of people who know how to handle them. This is not a bad thing; at my old company, the procedure was to cool the Pockle-3 in an ice bath and then chuck in whole chunks of ice while stirring to induce things to crash out and then pour off the Pockle-3/ice/water solution from HELL. Usually into a mixture of halogenated and non-halogenated solvents. My old company wasn't big on safety. Or chemistry.

I digress. Now, enter me, who is staring at the dubious task of trying to make multiple grams of material with the chloride in place (a fluoride would probably work better, but I REALLY don't want to work with DAST). This would mean several multi-milliliter reactions featuring Pockle-3. Not wanting to have to do a safety review on each of the reactions, I decided to find a way around this mess. As it turns out, you can treat the amine in question with t-butyl nitrite in DCM with a little bit of dichloroacetic acid around to diazotize the amine and then addition of antimony(III)chloride will substitute the diazocompound with a chlorine (this can also be done with bromines, as well, using the appropriate brominated compounds). Boom. There it is. One step. Sure, the process takes two days, but between diazotizing, purifying and then hitting the hydroxy with Pockle-3 also takes about two days. Unfortunately, my compound, as unyielding as the relentless pounding of the surf against the shore, only formed the chloride in ~20%. ~70% was the hydroxy with ~10% left over as unreacted starting material. So much for great strokes of genius.

So now I've decided to just put up with the safety committee and go before them, goggles in hand, to be educated as to the ways of dealing with Pockle-3. In the meantime, this was the first time I had ever used an antimony compound. I know that salts of antimony can be used to kill the worms that cause leishmaniasis (I actually asked a girl out in high school whose name was Laurie Leish); unfortunately, the antimony salts also kill the people infected with the disease.

However, this allowed me to fill in one more spot on my "I've used that!" periodic table. Behold:


Sure, some of them are cop-outs, such as I use carbon everyday and most of the time nitrogen is in a ring, or some such. I've never actually taken nitrogen and tried to get it to bond with a transition metal or something. However, I have used the nitrate to do the diazotization reaction. Likewise, I've only ever used cesium in cesium carbonate form (damned fine base, by the way), but it's still cesium. You'll note I highlighted technecium; I'm not sure what technecium can be used for, since it's radioactive and (mostly) man-made. However, I had it shot into me, as outline in the first part of The Ordeal that I wrote about months ago.

So, there you have it. One more box colored in. I'm half tempted to color in thorium, since I've nicknamed my rotovap "The Mighty Thor". I feel that rotovaps work better if you stroke their egos before using them.