I just need to blow off some steam. Without going into great detail (and summarizing weeks and months of work):
I have a compound that is a liquid (more like an oil) at room temp.
I need definitive evidence that it is what it is; basically, I need an x-ray crystal structure cause the NMR is just too ugly to definitively say what is what.
Therefore, I need a solid derivative that will form a nice, pretty crystal.
Looking over my options and what I have on hand, I decide creating an oxime is the way to go.
After a lot of hard work, I think I have it. I take carbon and proton NMRs–Woohoo! Great, clean spectra that are showing the right functional groups and the right amount of carbons. Time to go see if I can recrystallize it.
I get most of my sample recrystallizing, but I put a bit aside for further GC and GC-MS analysis.
I start to see crystals! Woohoo!
I put my other stuff into the GC-MS. Wait–why am I getting such an ugly GC spectrum? And why am I getting a molecular ion of 173 when it should be 191?
I put more sample into the GC I normally use for monitoring reactions. I’m not seeing my normal starting material peak. This is a good thing. I’m seeing later peaks that are fairly large. This is also a good thing. However, I have to really yank it out of the baseline (not too surprising in this case) and I start having massive baseline creep problems.
So, this is where I am. I have one instrument that says one thing. I have another instrument that is suggesting something else. The only way I can reconcile them is if the hydroxyl part of the oxime falls off so easily that you wouldn’t see the correct molecular ion. Problem is, I’m not sure I can prove that using published spectra of other oximes. I have a third instrument which suggests I don’t have any starting material left. I have something crystallizing out that might be want I want, but it might be something else that I haven’t managed to get rid of yet. That would still be okay, because then I’d have an even cleaner sample, but it still doesn’t get me a nice pretty crystal. In any case, I can’t do anything else tonight because I want to see what else happens with the recrystallization and I need to talk with my research advisor.
And to top it all off, I have to a nice pretty crystal by the end of the week so I can ship it off for analysis so that I have something worth presenting at the ACS meeting in March. And no way in hell am I ever making an oxime again. I’ll make a semicarbazone next time.
Actually, now that I think a bit more about it, the mass spec. isn’t all that ominous. I’m supposed to have something at 291. I have something at 273. The starting material is 276. There is no easy way to have a loss of 3 in an organic molecule unless a nitrogen is involved somewhere. So now I think I’ve got the right molecule. It still doesn’t explain the GCs, though.
Tell me about it. I once spent 9 months thinking I had found a new type of bond for aromatic rings on silver island films (I was doing SERS). 9 months chasing this damn vibrational mode that should not be there unless the pyridine ring in my nicotinic acid was bonded to the monatomic silver layer in a as yet unseen configuration. It turned out to be contamination of my vacuum system by some Grad student who stuck some icky organic solvent in it 6 months earlier.
It was a miracle that I was able to get high vacuum at all. I would call it a wasted year except now I stay as far away from chemistry as possible (in fact I now remember nothing about it, which is somewhat unfortunate) and it changed the whole course of my education and career. From material science/quantum optics to optoelectronics/signal processing. This had made my life much better as chemistry was invented by the devil to drive people crazy.
Ah, remind me again why I left the last day of class of O-Chem II singing and telling the world that a weight had been lifted (even if I did almost fail the course) and then chose not to go into O-Chem?
You nerdy-assed bastards that wrecked the curve and made my own o-chem experience a living hell can have fun. Actually, I don’t mean to be this personal when it comes to o-chem, it’s just because I really hated the class, and I sincerely hope that you get some meaningful results from all of this. Just think of all the o-chem you know that 99.97% of the world could never grasp.
That’s what I was thinking and kinda getting at in an earlier post (though I didn’t come right out and say it.) I just found it a little odd that that OH could pop off so easily. I suppose I could bring down the ionization energy, but at this point I don’t think it really matters. I wish I could go LC-MS (well, actually, I don’t, because every single time I’ve tried to use an HPLC or the like it has been a complete pain in the ass and never works) but we don’t have one here. In any case, it’s the GC part of the GC-MS that’s got me kinda worried, because that is one ugly spectrum.
Well, I could go into my big long spiel on my research advisor’s overall project, and how this particular molecule is a sidebar, and into Michael-aldol tandem reactions and the like, but I don’t think that it’d help you have any idea what I’m talking about. Plus, organic chemistry needs pictures, and I have no way of showing you pictures.
So, suffice it to say, by pure accident we made this unpublished molecule in a somewhat unorthodox way (base-catalyzed Michael-aldol tandem reactions are fairly common, but it’s not often you do it using acid catalysis like we did.) The NMR spectra, often a very good way to tell what your molecule is, are pretty ugly, especially the proton spectrum, and we can’t say definitively from that what we have. In any case, journals generally want an x-ray crystal structure if possible, plus this way I have conclusive proof of the molecule (getting a solid derivative x-ray structure means that I must have this original structure because of the way I made the derivative.) So basically, I’m dealing with this molecule because it looks kind interesting (if probably useless) and was made in an interesting way, is unpublished, and we think we can get a paper–more like a letter or communication–out of it. I have to have a crystal ready for x-ray crystallography now because the ACS (American Chemical Society) national meeting in San Diego is in March and I’m giving an undergraduate poster. Plus, this is part of a for-credit class, and the best way to get an A is to either publish something (not likely given the time it takes to peer-review and all) or at least have something that is publishable even if it’s not been submitted yet.
Well, I need to go get some breakfast then it’s back into lab. I wonder how that crystal looks now.
Well, I went through my graduate career with a small-but-respectable Development paper to show for it - then, as I was wrapping up some odds and ends before leaving the lab, my project exploded in three new directions, all of which promise to go into better journals. So now I’ve put off potential new post-docs and I’m continuing in my current lab, trying to shepherd three simultaneous major projects with no help whatsoever (except the lovely lady who does my paraffin sectioning for me). I mean, I’m in a pretty good position, with exciting work and promising results, but come on, doesn’t anyone want to help out here in return for a peice of the pie?
I just spent three months chasing down acetaminophen on HPLC, and though frustrating at times, I have enjoyed the learning experience. I have limited experience with GC. But like every other instrument I’ve worked on, if you tear it down and rebuild it, it works fine. The trick to HPLC is 1) PURGE!!! get rid of the air bubbles first thing, and used de-gassed mobile phase, and you’ll eliminate a lot of headaches; 2) use a PDA. It gives you a lot of information; 3) Gradients are your friend! and 4) there’s more to life than just ACN and water.
I’m going on 4 years in research, and I’m still having fun.
That crystal formation? Never increased even after 20 hrs in the freezer, so I filtered it off. Probably hydroxylamine hydrochloride that hung around. I started adding water to the stuff dissolved in methanol until I got a precipitate that wouldn’t dissolve back in. Then it was back and forth between hot water and hot methanol until I had it as saturated as I thought possible. It started dropping out as soon as it started cooling down, and I’ve got it in the freezer now to get as much out as possible. It won’t give me nice pretty crystals, but if the NMR agrees with me that it is what I think it is and it won’t dissolve in ether, I can do the methanol/ether in a closed vial trick and that will give my pretty crystals.
Gotta tell my research advisor as soon as I get out of class. (And no, I’m not in class now. I’ve got class at 10:30.)
Good luck with the crystals. If they don’t work out throw the book at it NMR-wise. If COSY and HSQC spectra don’t pin it down, an HMBC experiment will nail any carbon/hydrogen connectivity problem for a small molecule like this. If you’re after stereochemistry a positive NOESY is also reliable, and would be perfectly acceptable on a poster. If the NOESY is negative (ie, the absence of a cross-peak indicates that two protons are not close in space) this is less satisfactory.
Fingers crossed for the crystals.
Has it struck any of you that it might just be easier to make up the NMR data for this stuff and just lie about the compounds you’ve made?
By the time that the editors of Nature or Cell decide to go all Ninja-on your ass and show up in the dedicated Nature biz-jet at your frontdoor, you’d be surrounded by beautiful women, filfthy rich, and living in hiding in Argentina.
Yup, in fact I finally got the last term of my main equation (spontaneous emission term in a Quantum Boltzmann model of a semiconductor laser) correct about 2 weeks before my defence. I had similar experiences for my BSc and MSc theses. I’m the king of slipping it in under the wire.
and 4) there’s more to life than just ACN and water.