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  • >> Yes, so as you may have noticed this is

  • from your homework, and I want to do this

  • as a demonstration regardless

  • of whether you've already solved this problem.

  • In fact, I hope that you've solved this problem

  • because what I'd like you to do is to be able

  • to think really deeply about it, and show you my perspective

  • on structure solving and in particular we're going

  • to be talking about using HMBC as a very focused tool

  • to help solve structures and specifically for the problem

  • of putting the pieces together.

  • You've seen on the templates that I've given you,

  • I've had this tremendous emphasis, or at least I've tried

  • to have this tremendous emphasis on thinking your way

  • through the problem, reading the spectrum, getting the formula,

  • writing out fragments, jotting down what you know,

  • jotting down what you don't know if possible, and then being able

  • to ask focused questions.

  • HMBC is an incredibly data rich technique,

  • it also has ambiguities to it because we get two bond

  • and three bond couplings.

  • So you've got a huge amount of information, a huge amount

  • of data and what I'd like us to do today is to learn how

  • to use it as a focus tool.

  • So I want to zip through the problem from Silverstein

  • at the beginning and then focus on the HMBC angle.

  • So this is problem 8.43 from Silverstein, and I want to jot

  • down my -- you know I've worked this problem,

  • just like you folks, and I want to jot down my impressions

  • on working the problem.

  • So I look at this problem and I generally start with --

  • I have -- I mean what's the most useful thing you can get?

  • Molecular formula and functional group.

  • That's sort of the most general stuff, and we'll be able

  • to get molecular formula in just a moment

  • because we'll actually see all the hydrogens

  • and all the carbons so we basically will get them,

  • get the oxygen's by difference.

  • So before we start with the NMR spectra though,

  • looking at the IR spectrum, I see what looks like an OH group,

  • I see what looks like a carbonyl.

  • At 1728, it's a little high for a typical ketone, right.

  • A typical ketone is a little but lower, it might be an ester.

  • I've been emphasizing it's very hard, in any sort of level

  • of complexity, to get CO single bonds stretches associated

  • with esters.

  • It's probably hiding right here at 1188.

  • You sort of get a hint at it, but we'll see in a moment,

  • there's some other hints there pointing--

  • pointing towards ester.

  • We probably have an alkene -- that's probably an alkene CH,

  • it could be an aromatic, we'll see in a moment it's not.

  • That's probably an alkene CC bond.

  • All right, mass spec it's 200 molecular weight

  • in the EI mass spectrum.

  • What I'm going to do before we --

  • before we actually get the formulas,

  • so maybe at this point I'll just jot down sort of a question mark

  • on the IR spectrum -- ester is sort of my thinking on this.

  • All right, at this point I want to go and look

  • at the proton NMR, look at the carbon NMR, and I've really,

  • really, really been emphasizing this notion

  • of keeping the resonances separate from the atoms.

  • In other words, we know resonance is something you can

  • see, we're going to be assigning those resonances

  • to the structure as we build the structure,

  • and so we have a common language, I go ahead

  • and I simply letter the peaks A, B, C --

  • it's hard staring into the light -- D, E, F, G, H, I, J,

  • and we number the carbon resonances, and I'll go 1, 2,

  • 3 -- that's our chloroform -- 4, 5, 6, 7, 8, 9, 10, 11.

  • I like to do a good job of working the integrals.

  • My philosophy, every particular integral has experimental errors

  • associated with it.

  • The best way that you can do it if you know the number

  • of hydrogens in the molecule or you know multiple hydrogens,

  • is add up a bunch and divide by the number of hydrogens.

  • If you don't or you're in a hurry, often you can get it

  • by dissection with a ruler.

  • These integrals are a little hard to read,

  • they're starting right in the baseline; they're not offset.

  • You can use a ruler and draw straight lines,

  • you can slap a grid on it.

  • I'm just using my ever, ever useful grid, and if I'm looking,

  • I start to see a ratio that's just a hair under 6,

  • a hair under 6, a hair under 3, hair under 3, hair under 3.

  • This one's just a little bit --

  • actually this just a hair under 6, hair under 9,

  • so basically we're talking about like 2 point --

  • 2.8 units, these happen to be tenths of an inch per hydrogen.

  • This guy is interesting, he's coming up a little bit,

  • this one right at 1.6 ppm, so he's coming up over .6,

  • and I'll tell you about that in a second,

  • and then we see one that's just a hair under .9,

  • and another that's just a hair under .9.

  • So you pretty much, by inspection, can go ahead

  • and get -- and again it's really hard staring in here --

  • 2H for A, 2H for B, 1H for C, 1H for D, 1H for E, 1H for F.

  • [ Inaudible ]

  • 2H for F, thank you, 3H for G. Now H is interesting, 1.6 --

  • this is in chloroform solution, and chloroform,

  • water typically shows up at about 1.6 parts per million,

  • and so you can kind of see the water peak right over here.

  • So you have this multiplate that's reasonably symmetrical,

  • and then you'll have a little bit

  • of water off on this side here.

  • I would go in if I were at my own spectrometer --

  • I'd go in, and zoom in and get a better look and see,

  • but I think you can see the integral just gives a little

  • extra kick up for the water.

  • So H is 2H, I is 3 -- 3H, J is 3H.

  • So in other words, our molecular formula has a total

  • of H20 in it.

  • Now it's certainly possible, if I had an amine or something,

  • that the amine NH would not show up or an alcohol NH.

  • So I'm not immediately locking it in,

  • and this is really important,

  • you have to be keeping your wits about you.

  • Secondary amine NH is aliphatic.

  • Secondary NH's are terribly hard to see.

  • Alcohols can be broad.

  • Alcohols can be with the water peak.

  • Carboxylic acids can be broad as well, and can be disappeared,

  • particularly if you're in chloroform

  • versus DMSO due to exchange.

  • If we look at the carbon NMR here, peak number one is

  • at about 170, just a hair down of 170, about 173 ppm

  • where you would expect for an ester,

  • not where you'd expect for a ketone.

  • We've got a couple of peaks over here, if I want to go ahead

  • at this point, I'll say, one is a quat, two is a quat,

  • looking at the depth, three is a CH2, four is a quat,

  • five is a CH2, six is a CH2, seven and eight are all CH2's,

  • and then nine, 10, and 11 are all CH3's.

  • So basically if we do this, we see we have C11H20.

  • If we have symmetry in a molecule, which you've gotten

  • in a couple of homework problems this week,

  • of course you might end up with a count that's lower,

  • if your carbons aren't all different,

  • or you could have overlapping peaks,

  • but symmetry's a typical reason.

  • If you have a plain phenyl group, you're going

  • to see four carbon peaks, but you're going to get six carbons.

  • If you have a ring like a cycle propane ring,

  • and there's no stereo center in the molecule,

  • you may if you have one point of attachment have two methylene's

  • that are the same, but if I look here, I'm suspecting an alcohol,

  • I'm suspecting an ester.

  • I have 200, if I take away C12, C11,

  • and H20 from that, I get O3.

  • So I'm reasonably happy at this point,

  • I think I have a molecular formula.

  • Now, the next thing I do

  • with the molecular formula is I'll start to --

  • it's nice to have a scorecard here, so I might, for example,

  • over here, jot down some thoughts; ester, alcohol,

  • alkene as some of the group that we're seeing in the molecule.

  • If I want, I can calculate degrees of unsaturation,

  • another very useful thing.

  • Remember, I don't do it by formula,

  • I just say, C11would be H24.

  • I'm at H20 so we have two degrees of unsaturation.

  • So I can help keep my wits about me.

  • That also tells me if I have a carbonyl,

  • and I have an alkene I know I have no rings in the molecule.

  • All right, now the next place --

  • any questions or thoughts at this point?

  • >> So it doesn't matter [inaudible]?

  • >> Does it?

  • Let's see.

  • >> Maybe I'm doing my math -- I'm doing my math wrong.

  • >> And this is actually a good point in checking yourself.

  • I have an incredible ability to screw up arithmetic on my feet

  • which means go ahead and double check yours.

  • >> I think you're actually right I calculated the formulas wrong.

  • >> All right.

  • >> [Inaudible] C could and D would be the OH.

  • So we've got some interesting points here you can already see.

  • So if you're reasonably experienced,

  • I'm going to bet anything

  • that we have a stereo center in the molecule.

  • Now, even though I haven't measured the coupling constants,

  • I could measure the coupling constants,

  • they very conveniently give me a scale here

  • and you get a peak print out, but very conveniently,

  • a typical aliphatic CH coupling constant is about 7 hertz.

  • A methyl group next to a methylene is really very typical

  • for this, you'll -- a methyl group next to just

  • about anything is going to give you about 7 hertz.

  • So immediately if I'm eye-balling this,

  • even if I don't know I'm at 600 megahertz,

  • and I see this triplet here that's obviously a CH3 next

  • to a CH3 next to a CH2.

  • In fact I can write this as one of my fragments here

  • because I think we're pretty obvious at that point for this

  • and this here, but if I'm looking at that, I see okay,

  • these guys are leaning into each other, we have an AB pattern,

  • it's obviously a big coupling constant.

  • This separation is at least twice the separation

  • in the triplet, so it's like a 14 hertz

  • or 15 hertz coupling constant.

  • That is very typical for a germinal coupling.

  • So in the back of my mind I'm thinking stereo center,

  • something with the methylene that's diastereotpic.

  • If I have a stereo center, every methylene

  • in the molecule is going to be diastereotopic,

  • but usually the ones that are further

  • from the stereo center behave as if things are coincident.

  • So we look here, we have what looks like an ethyl group,

  • it wouldn't have surprised me

  • to see a more complicated coupling pattern

  • for this ethyl group, but it doesn't necessarily surprise me

  • to see a less coupling constant.

  • I'm pretty [inaudible] less complicated coupling pattern

  • just to see a plain old quartet.

  • I'm pretty certain I have an ethyl ester at this point.

  • Pretty confident I have an ethyl ester because that sure looks

  • like an OCH2CH3 off of an ethyl ester,

  • but it could be something else that's shifting it downfield.

  • All right, at this point it's time to get analytical,

  • and where I'd like to go next is actually the HMQC rather

  • than the COZ.

  • As I was saying in discussion the other day,

  • the problem is you're drowning in data in the COZ quite often,

  • and a lot of the data isn't particularly useful.

  • You'll have two diastereotopic protons, and they'll both couple

  • to another two diastereotopic protons or even to one proton,

  • and you're getting more information than you need

  • because you'll get the diastereotopic protons are

  • coupling with each other, okay, big whoop.

  • You'll get that each one is coupling to one of the protons,

  • all right that gives you some new information,

  • but that's redundant.

  • If you have two diastereotopic protons coupled

  • to two diastereotopic protons, now you've got lots and lots

  • of data points that basically just tells you you have a CH2

  • next to a CH2.

  • So in order to help make sense of the data,

  • I got next to the HMQC, and I'm very, very rigorous about trying

  • to transcribe stuff, and I'm not super neat,

  • but I tend to really try to be analytical.

  • So I'm going to copy all of my numbers here to the carbon axis,

  • and I'll copy all of my letters to the proton axis.

  • And at this point, again, a grid is extremely useful,

  • if you're working on your own spectrometer you might want

  • to do an expansion, you might want to expand this region just

  • so you can get a close look and see what's lining up,

  • but if you're having trouble following with your eye,

  • and things aren't completely obvious, slapping a grid

  • on the spectrum is a very useful way, for example,

  • to see that this peak at nine here is actually crossing