xmas trip

I kept forgetting to post this, but better late than never.

This last holiday season my girlfriend and I went to visit my parents for a few days. My girlfriend and I live in different states, and see each other only once every two or three months. The though it's weird to have sex under my parents roof was a little disconcerting, but desperate times call for desperate measures.

On the flight there, my lady and I were discussing how we were going to pull this off with a minimum of fuss. We figured condoms were the way to go, so my mom wouldn't have to launder DNA impregnated sheets, and I grabbed a flight sickness bag so we could use it as our own personal trash bag for a later, surreptitious, disposal.

Everything went as planned, and I ended up packing the little goodie bag and bringing it back home with me. After I had landed and was commuting back, it occurred to me that I had inadvertently left a nice trap for the TSA. There wasn't a note in my bag indicating it had been searched, which actually surprised me a bit. In addition to packing the latex balloons of genetic material, I had a bunch of tools I had purchased on the trip as well.

Here is a series of me unpacking what I had flown back with.

bag full of dirty laundry

xmas socks and underwear from mom

there's some more interesting things

and the goods

In retrospect, I think it would have taken some actual effort to come up with a better trap for the TSA. Too bad they didn't fall for it.

resolution step 2

I recrystallized the material from the resolution, and the ee went up to 98.9%. Perhaps I didn't use a sufficient volume of solvent or enough wash. In any case it will be easy to recrystallize again to get the ee up enough.

I took the mother liquor from the bulk resolution, which was heavily enriched in the diasteromer salt, and free based it. The opsque, dark brown, mixture was treated with D-tartaric acid, and crashed out to give the much more enriched salt. Interestingly, when the boiling solution of base was added to the boiling solution of acid, in similar concentration to the racemic case, the salt started to come out of solution even before I was done mixing the two. The already highly enriched enantiomer gave almost optically pure material (96.8% ee) that had only a hint of color. In a typical resolution of this compound from racemic I expect to get >75% ee, so this was a pleasant surprise.



I didn't add a pic of the mother liquor because it was on the rotovap when I took this, and I expect everyone is familiar with what a flask full of tar being stripped looks like.

I recrystallized the D-tartrate salt to get the ee up, and it took nearly twice the volume of solvent it would have if it were 75% ee, presumably due to the significantly higher optical purity.

resolution

I was taking the products from the distillation and resolving them via their tartrate salts, and decided that was inefficient to do individually on a reaction by reaction basis. I saved up the products from all the remaining reactions I had, and started the resolution on a large scale today. On the left is all the product from the distillations of material in 7 volumes of solvent, and on the right is an equivalent of acid in about 7 volumes as well.



They are heated to boiling and then combined (adding the amine to the acid), and, when it works well, the salt starts to crystallize out immediately.



After cooling it is filtered and washed. One of the wonderful things about a good chiral resolution that is not often mentioned is that in addition to increasing diastereo purity, it increases chemical purity as well.


The product should be > 99.5% ee after one recrystallization, and I can take the dark mother liquor, free base the salt, and crystallize it with D-tartaric acid to get it with >99.5% ee.

art?

I was distilling some material yesterday. At the end there was a small amount of tar left that was free flowing at the distillation temperature, and the last volatile material was coming over a drop at a time. I shut off the heat to the oil bath and left, and when I came back sometime later I was greeted with this.


At first it reminded me of Eddie VanHalen's guitar, Frankenstein:


But now I think it looks more like a Jackson Pollock knock-off.

nice set up

I'm pushing a bunch of material through a known reaction that, before my boss and I improved it, sucked. It worked very well on small scale and the yield and quality of the product dropped off precipitously as it was scaled up. Now the reaction can be performed on most any scale and yields of purified product are typically 90% or above.

Now there is only one small problem, the solvent for the reaction is triglyme. I run the reaction quite concentrated, but I still have hundreds of milliliters of solvent to deal with that has 50-100 g of crude product in it. Extraction on this scale is doable, but vacuum distillation is not only easier and faster in this case, it leads to significantly more pure product.

Herein lies the issue, triglyme is a bitch to distill. It has a relatively high boiling point, typically 80-100 centigrade with the vacuum my pump generates, and is prone to bumping. By prone to bumping I mean that the shit bumps almost continuously when contaminated with a product mixture, and treated in the fashion I usually treat short path distillations.

The first time I ran this reaction at 50 g scale in 500 mL of triglyme, I distilled a significant portion of the solvent off starting with the 1 L flask the reaction took place in, rinsed into a 250 mL flask, and removed the remaining solvent, rinsed into a 100 mL flask and distilled the product. There was some bumping over of the product, but not too much, and the reaction-purification sequence took all day. All in all not too bad for a 50 g reaction, but I still needed to put a few hundred more grams through it in the coming days.

I remembered a set up my boss had mentioned to me in another context once that he used for distillation of a heat sensitive compound. Many people are aware of the falling film distillation apparatus, and they are available from places like Aldrich for the low low price of $800 for the lovely 24/40 model.

an easily broken paper weight that cost almost as much as an ounce of gold

When my boss needed to do some sensitive distillation a long time ago, he made up an exceedingly useful contraption to effect very similar conditions using common lab glassware. My target compounds are plenty stable to heat, but I thought the apparatus would be usefull to deal with the bumping issue. Here is my practice run with the apparatus.

sweetness!

It's a 3-neck 250 mL rbf fitted with a stopper, a pressure equalizing addition funnel, and a short path. Notice that the addition funnel has a glass stopcock, teflon stopcocks do not work well at all for vacuum applications. The oil bath is heated to ~150 centigrade and the mixture is added to the hot flask a little at a time. It distills rapidly, and there is never a significant amount at any one time so the bumping is inconsequential, additionally I spin the shit out of it (1,000-1,200 rpm) which helps quite a bit. This pic is a practice run, and contains the solvent from the 50 g reaction containing a trace of product, hence the slight color. I was able to distill off 500 mL water white solvent leaving the crude product in 30-40 minutes this way.

When I ran the reaction on 100 g scale I was able to distill off all the solvent, and then distill the product in less than half the time the first 50 g reaction distillation took.

Waste Disposal

Let say that hypothetically you are a member of an organic research group at a well regarded department. What would you do with this form?

Yeah, I know it's complicated. Sure you are here to get a PhD in organic chemistry, but that doesn't mean that you can fill out one of these crazy hard waste disposal forms. Good thing that we keep these forms conveniently stored in a folder with easy to follow instructions.


Where can I find instructions to dispose of wastes of space?

Dreamweaver

Brandon, Tim, and I climbed dreamweaver yesterday. Dreamweaver is my most ambitious route to date, a 1600 ft ribbon of snow, ice, and rock that leads to the summit of Mt Meeker at 13,911 ft. We left Ft Collins at 2:30 am, were on the trail by 4 am, were on the summit around noon, and back to the car at 3 pm. Why don't I feel like moving today?