3/04/2007

David Hasselhoff, meet No-D NMR


I don't know how well-known this particular technique is, but I have reliable sources that say it's not nearly as well-utilized as it should be, so consider this a public service announcement (since, as a blogger, I am a public servant or something). Have you ever had to titrate that old bottle of butyllithium? Kind of a pain, isn't it? There's an easier way to determine the concentration of butyllithium in solution, and it works with just about any alkyllithiums, Grignards, or anything else you decided to buy from Aldrich. It utilizes a technique called No-D NMR, and I'm sure most synthetic chemists will find it useful- nay, indispensable!

Here's what you need:
-A bottle of butyllithium in solution (essential for... finding... the concentration... of butyllithium... in solution...)
-An NMR (kids, ask your parents for $500,000 or an NSF grant!)
-An NMR tube (your NMR tech will be mad at you if you don't use an NMR tube)
-Some kind of standard with easily integrable peaks (current favorite is the cheap but stinky cyclooctadiene, affectionately known as COD)
-Ten minutes. (Just ten minutes!)

Now you can get the concentration of your butyllithium in just 6 easy steps!
Step 1. Add 600 µL of your butyllithium solution and 100 µL of COD to your NMR tube.
Step 2. Run, don't walk, to your NMR. Be sure to shove people that may or may not be in your way to really flaunt that air of urgency. (Actually, it doesn't matter. Butyllithium isn't nearly sensitive enough to ambient conditions to affect your titer.)
Step 3. Shim the NMR with the lock off. It's easier to shim the FID since the shim level is based on the deuterium lock (at least on Varian machines), and, you might have noticed, you don't have any deuterium here. (Thus the name No-D. Don't you feel smart for knowing that?)
Step 4. Set your d1 (on Varian machines. On Bruker machines, the parameter is DEUTSCHLAND ÜBER ALLES) to around 20s. This is necessary to completely relax the COD for accurate integration. Scandinavians might add a lutefisk joke here. Set the number of scans to 4-8 or so.
Step 5. Wait. Since your d1 is pretty high, it might take a while. Maybe watch the following video while you wait?
Step 6. Integrate the two COD peaks that stand out at 2.4 and 5.5 ppm. The ratios should ideally be 1:~2.03. If they're not, you fucked up. Repeat steps 3-5. Integrate the peak around -1 ppm that corresponds to two butyllithium protons. Back calculate the concentration accordingly.

And you're done! No messy Gilman doubles, one piece of glassware to clean, and an accurate titer! AND David Hasselhoff! Now go out there and titer that butyllithium! And be sure to flood the comments with boasts of how you already knew about this or how easy it is for you to do a Gilman double now that you've done it a thousand times. This IS a chemistry blog, after all.

Oh and if you're wondering about why David Hassehoff has anything to do with No-D NMR, he doesn't. I was watching that video while typing this post. Frankly, the man is a god.

13 comments:

milkshake said...

David Hasselhoff is grinning happily because he has a plug-in secretly plugged in - and now you can have it there too, in your tube, to alleviate the pain of shimming a deuterium-less sample (and then cursing your bad luck when your spectra shifts during acquisitions and every peak is there twice).

Hasselhoff's secret plugin: 1. Take Pasteur pipette, seal the tip with a torch, then elongate the sealed tip over the flame, about 1 inch in from the sealed end. 2. Fill the elongated sealed tip with d-12 cyclohexane (C6D6 also works, but more deuteriums is better)3.Freeze your deuterated solvent in the tip in liquid N2, then quickly seal by cutting the elongated tip with a torch.

You just throw this insert into your NMR tube and recover the plugin afterwards. (Don't forget to wash it before the next use.)

For BuLi, titration with isopropyl alcohol using Hamilton syringe and phenanthroline as indicator works great - I would not bother going to NMR for that.

Jokerine said...

Can't you just use "None" in the solvent field and let the NMR shim to external solvent? We do this with 31P all the time. Raw NMRs as reaction control are great, especially if your stuff is sensitive to air and water.

Oh and Bruker is austrian.

Excimer said...

milkshake: I love that plugin idea. Genius. You have a prep for that titration?

jokerine: It says on the website that bruker biospin has headquarters in germany and switzerland, but austria is close enough for me, at least for a crack on those silly Germanics.

milkshake said...

The insert trick is not my invention, I just was just reading about it few years back in discussion about shimming without deuterium (probably in letters to editor, in C&EN).

The titration: Take 50uL microsyringe, fill it with 50uL of dry isopropyl alcohol (some people use sec BuOH) weight it, then weight it empty, you get the weight difference corresponding to 50uL of iPrOH (you can calculate it of course, but at least you can re-check if your syringe is accurate - it usualy is). Calculate how much BuLi is needed to 50uL of iPrOH. Take a little less than that, say a mL or two and and add a precise volume t to few grains of phenanthroline with few mL of anh THF and micro-stirbar in a small (25mL) oven-dried flask under septa and flushed with Ar or N2. (No need to be too religious about Ar) A burgundy color should develop. Slowly keep adding iPrOH under the level of BuLi mix until sudden transition to yellow. Then add new portion of BuLi (burgundy color) and repeat the titration. You can repeat once more, to be sure.

(The first titration read tends to be a little lower than the next two - because of the phenanthroline consumption and some accidental moisture in the flask or used THF, after the first one it gets pretty reproducible.)

evgeny said...

There is no freakin' way I'm putting some BuLi in the NMR (that is not in a Young tube) after some idiot broke a corrosive sample inside the sampling chamber and it slowly oozed onto the probe. As for the goodness of BuLi, you don't really need to titrate it or do anything at all. Really.

Mostly BuLi is used as a strong base for organic reactions, which are sort of easy to get right no matter if you don't add the right amounts. You'll just take a hit on your yields, but no one cares about that in research organic chemistry. For new bottles, use 1.03-1.05 equivalents to get rid of excess moisture. If a bottle has been opened before and it's less than 1 month old and was closed well, I use 1.05 equivalents.

<2-3 months 1.1 equivalents

>3 months < 6 months 1.2-1.3 equivalents depending on how cloudy it is

Adjust accordingly for longer times and if the bottle was closed with parafilm poorly (if you're the only one who's using the bottle, this shouldn't be a problem. If you are and it is still a problem, you need to learn better BuLi storage techniques).

Also, while your reaction is going, check progress by TLC and add more BuLi accordingly. If you really need to, order a new batch and use the old stuff when the conditions call for: "add a quart of BuLi and heat to reflux until tender", which is pretty often with simple organic reactions.

No more titrations ever!

Ashutosh said...

Just splitting hairs...it's integrable, unless you deliberately meant integratable :)

Excimer said...

Splitting hairs is what chemists do. if it weren't for unsplit hairs half of us would be without a job and we'd end up solving real problems like engineers do or something. God forbid.

evgeny said...

Oh, also forgot to mention. Putting BuLi in an NMR tube is sort of alright... if it's 2.5 Molar, which is what most people use. However, the 10M stuff is just as flammable as tBuLi when you expose it to air. Don't let the people who say: 'it's more concentrated, so it reacts with air right away to form a protective coat' lead you astray onto the path of disaster. Never put it into an NMR spectrometer unless it's under an argon atmosphere inside a Young tube (not that I would use any other kind of tube for BuLi of any concentration).

Especially in the light of what happened in a department I'm familiar with a while ago, when water got into their air lines in the NMR room (actually in the entire building). All samples came out with a fine water coating since air is used to raise and lower the sample. Thank god no one was doing BuLi NMR in a normal tube (with many people having broken off glass edges of chewed up caps on their tubes)...

There are a lot of stories where people who just start out in research are too cavalier with nBuLi after 5 or 10 times using it. They get too familiar and cocky and forget to wash their syringe with solvent after adding nBuLi and then go and wash it with water right away. Or when there is just a few millilitres left and they decide to put it in the sink and aim a stream of water at the bottle to quench it... Long hospital stays to remove glass and metal embedded in flesh and/or repair burned skin ensue.

Thus, I would caution 'NOT' to do these experiments as described in the paper with secBuLi unless you are a professional. None of these things: titrations or NMR determinations, are really necessary anyways and I would never let an undergrad or first year grad student I supervise do it.

Excimer said...

Evgeny, your discretion regarding BuLi is based on personal anecdote but so is everyone else's. I would, of course, advise discretion when working with BuLi or any alkyllithium as they are highly reactive and water-sensitive, but I have never had a problem working with the stuff nor with shoving it in an NMR. We are chemists and this is a chemistry blog, and I'm not about to advertise discretion every single time I mention a compound, because I'm making the dangerous assumption that the readers of this blog aren't fucking retarded. And I will continue to make that assumption.
This is the way BuLi titers are done at my school and they are done frequently without hassle- I'm not pulling this technique out of my ass here. I frankly worry more about people who are ignorant about the BuLi solutions they add to their flasks and wonder why they don't work as well as they should.
But if you prefer I didn't tell you how I did chemistry for fear of how dangerous it is, I'll stop. I can assure you this blog will not be worth reading if I do, however. (and yes, I am severely annoyed by your comment.)

Ψ*Ψ said...

Safety concerns are always valid, but please assume that people here have SOME common sense.
Catty comments by anyone will result in an ass-kicking. It's an exam week, so I am more than happy to provide this service. :)

AC said...

This is another titration method, pretty convenient.

Burchat AF, Chong JM, Nielsen N
Titration of alkyllithiums with a simple reagent to a blue endpoint
JOURNAL OF ORGANOMETALLIC CHEMISTRY 542 (2): 281-283 SEP 20 1997

evgeny said...

I didn't think my comment was 'catty', but sorry if it was annoying. I'll stop.

Ψ*Ψ said...

More in the tone than the comment. Better to err on the side of "nice" (no matter who's commenting) :)