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  • >> I want to move on and start talking

  • about 2-D NMR spectroscopy and what we're going

  • to do we'll be using this as a tool very,

  • very useful for structure solving.

  • There's a whole sort of alphabet soup of different techniques

  • but rather than just unleashing a torrent,

  • I mean people do research in this area just

  • like they do research in organic chemistry

  • and so big thing is invent a new technique

  • to solve specialized problems, but rather than trying to sort

  • of talk broadly about everything we're going to focus

  • on getting a few tools in our toolbox and see how

  • to use these techniques to address different problems.

  • We'll start out with 2 tools in the toolbox that will be HMQC

  • and COSY techniques and then we'll add some more tools

  • and I'll try to put them into some sort of context.

  • There are 2 additional lectures that aren't specifically on 2-D

  • that will come in either possibly next time or the time

  • after that so we'll be talking specifically

  • about the Nuclear Overhauser effective, which applies

  • to 1-D NMR as well and we'll be talking about dynamic NMR

  • and dynamic effects in NMR spectroscopy,

  • but we're going to start.

  • Our next homework set will start to bring in 2-D and I'd

  • like to get you familiar with the tools.

  • All right theory I'm going to start really simple minded

  • and I think this is actually a good way to think about things.

  • So, in 1-D, we said the basic idea was your pulse

  • and then you observe, that's your 90-degree pulse.

  • The observe is your FID.

  • Have you now seen your FID on the spectrometers?

  • Have you seen the little wiggly, squiggly cosine wave

  • with a die off [phonetic].

  • So this is your FID and, of course,

  • what you've got here is an amplitude domain and then

  • over here you have time.

  • This is literally your signal dying off with time

  • and the cosine wave that corresponds to the periodicity

  • of the various nuclei.

  • So the whole idea in 1-D Fourier transform is this time domain

  • on the X axis ends up getting transformed

  • to a frequency domain and that's your parts per million

  • and so your spectrum still has amplitude on the vertical axis

  • and it has frequency in the units of PPM

  • on the horizontal dimension

  • and the reason we call this 1 dimensional NMR spectroscopy is

  • not because this is a 1-D graph, it's not,

  • you'd say this is a 2-D graph.

  • It's because you have 1 time dimension

  • and that gets transformed to a frequency dimension.

  • Now, in 2-D NMR, you get 2 time domains, 2 time dimensions

  • in the FID and they get transformed

  • into 2 frequency domains.

  • So I'm going to give you just

  • as I have given you my simplified version

  • of an NMR spectrometer, an IR spectrophotometer

  • and a mass spectrometer and so forth.

  • I'll give you my simplified version of a 2-D pulse sequence.

  • A 2-D pulsate sequence is going to be pulse weight pulse observe

  • and so what you do when you do this is you get 2 time

  • dimensions because the weight is you're waiting for some time,

  • you're going to vary the weight and then you observe.

  • So this first weight becomes time 1 and we'll call that t1

  • and the second weight becomes t2.

  • Now these are not to be confused

  • with the capital Ts we talked about for relaxation.

  • Remember we talked about Capital T1 is vertical is spin

  • relaxation where the magnetization returns

  • to the Z axis and Capital T2 is spin lattice relaxation

  • where the magnetization spreads out in the X, Y plane.

  • These are lower case ts and they in turn transform

  • when you do a 2-D ft they transform to 2 frequency domains

  • and so you get a spectrum that might look like this

  • where you have 1 domain here and this is called your f2 domain

  • and then another domain here and that's called your f1 domain.

  • Now what does this mean?

  • As you're varying, well, you understand here, of course,

  • in t2, you're collecting a signal

  • and it's dying off with time.

  • So you understand that basic transform

  • that if the periodicity of this signal is 1 cycle per second,

  • we get a line at 1 hertz and if the periodicity

  • of this line is 2 cycles per second, you get a line

  • at 2 hertz and if it's a composite of 1 cycle per second

  • and 2 cycles per second

  • and others you get a spectrum consisting of many lines.

  • Now similarly as you vary this t1 let's say starting

  • with hypothetically a millisecond

  • in the first experiment,

  • then the next experiment 2 milliseconds,

  • the next experiment 3 milliseconds, the next 4.

  • Another periodicity occurs.

  • In other words, your FID what you observe

  • in this time also shows variation that occurs in time.

  • Variation, amplitude, a periodic variation.

  • Those variations transform to the second frequency domain

  • and so you get a spectrum now that consists

  • of 2 frequency domains.

  • It is, of course, plotted 2 dimensionally

  • but it is really just as this is actually a 2-D graph this is 3-D

  • graph if you will and typically these days the way we express it

  • is as a topological map so you'll typically see a series

  • of contours that's just like if you've ever seen a topographical

  • map of the mountains each contour represents a

  • certain height.

  • So a very tall peak has many contours

  • and a short peak has fewer contours.

  • So it's 3 dimensions being represented being projected

  • in two, but again the reason we call this 2-D NMR is not

  • because there are 2 dimensions in the graph but rather

  • because there are 2 time dimensions.

  • All right that's what I want to say about sort

  • of the basic mechanics of the experiment.

  • There are 2 general types of 2-D NMR experiments.

  • One of these experiments is one of these families the one

  • that we'll be talking mostly about,

  • is correlation experiments.

  • Correlation means connectivity.

  • It means literally what's connected to what.

  • Another way of thinking of this is coupling.

  • It can be proton-proton coupling,

  • it can be proton-carbon coupling,

  • that's what correlation experiments give you

  • information on.

  • You've already been using this type of information

  • from coupling patterns and coupling constants.

  • When you see a triplet here, you say, oh, that's a methyl group

  • and then it integrates the 3 hydrogens you say, oh,

  • that's a methyl group that's next to a CH2 group.

  • When you see a quartet here and it integrates to 2 hydrogens,

  • you say, oh, that's a methyl group that's next

  • to 3 hydrogens.

  • Maybe it's next to a methyl group and correlations give

  • that same type of information.

  • When you see a 17 hertz coupling in a trans alkene, you say, oh,

  • that 17 hertz coupling must have a partner somewhere.

  • Ah, here is its partner that also has a 17 hertz coupling.

  • So you're already using connectivity information

  • in helping to deduce your structures.

  • Two-D experiments provide that information

  • in a more general term.

  • The other type of 2-D experiment that we'll be talking

  • about are Overhauser effect experiments.

  • We'll be talking more about the Nuclear Overhauser Effect

  • in a couple of lectures.

  • Those give rise to information on spatial proximity.

  • [ Writing on board ]

  • These can be very useful for information

  • about stereochemistry and conformation.

  • All right my philosophy on teaching 2-D NMR spectroscopy

  • as I said before there's a whole alphabet soup

  • of techniques out there.

  • My philosophy is not to bombard us but to give us a small box,

  • a small tool box of what I'll call core techniques.

  • In other words, techniques that if we are good at we can use

  • to solve a variety of problems and then if you're good

  • with those techniques you'll be able to say oh here's a whole

  • in my tools where I have a very specialized problem

  • that isn't being solved by these tools and you can go

  • to Phil [phonetic] or go to the NMR manual and say, oh,

  • I'm encountering this particular problem with a COSY

  • and A Toxi [phonetic] isn't helping me out

  • but I remember him saying something

  • that there was some type of technique called a relay COSY

  • and saying I can add that to my toolbox.

  • So, okay, the first 2 tools that we'll be talking about are COSY,

  • which was really the first main 2-D technique.

  • It stands for correlation spectroscopy.

  • So this is typically proton-proton

  • or let's just say homo-nuclear coupling

  • and then the second technique that we're going to add

  • to the toolbox is HMQC and this is heteronuclear correlation.

  • Well, I should say something.

  • So we're learning about the modern versions

  • of the experiments.

  • HMQC uses something that's inverse detection.

  • That means on the f2 dimension you're detecting proton

  • and on the f1 dimension you're detecting carbon.

  • The older, less sophisticated version

  • of this experiment was called het core [phonetic].

  • I'm going to put it in parentheses

  • but that's not really, it's not the same thing.

  • Het core was heteronuclear correlation spectroscopy

  • and now that's what you'd call HMQC.

  • Het core was an experiment where you would collect carbon data

  • on the f2 dimension and proton data on the f1 dimension

  • and it was a slower, less-efficient experiment.

  • So we're going to start with these 2 techniques

  • as our initial starting point for building our toolbox

  • and we'll see that they're extremely powerful.

  • We're then going to add in Toxi [phonetic].

  • Toxi is what stands for total correlation

  • and I'll put that in quotes.

  • It's like a super COSY that gives cross peaks

  • with all other nuclei in the spin system.

  • I'll show it to you today but you won't have the, you won't

  • yet have the experience to see where it's useful.

  • We'll bring in some problems later on, but I don't want

  • to bombard you with too much and HMBC is sort

  • of a long range het core.

  • In fact, that's the version

  • of the experiment that it used to be.

  • It is basically these two experiments are conceptually

  • more complicated because initially you're going

  • to say what do I need them for and it gives you a ton of data

  • but when you start to encounter specific problems of overlap

  • in the case of the former and in the case of the latter fragments

  • that you can't put together they'll be very helpful.

  • So all of these are correlation techniques

  • and then we will also throw into the mix

  • of core techniques NOSY and ROSY.

  • These are both Overhauser effect experiments.

  • [ Writing on board ]

  • They both give rise to information on proximity.

  • NOSY is good for molecules that are small and molecules

  • that are very large, but there's a whole right in the middle

  • of medium-sized molecules that don't work well in it

  • and ROSY ends up working well with medium-sized molecules.

  • [ Pause ]

  • All right.

  • Let's start with COSY and HMQC

  • and let me just show you the general gist

  • of the 2 experiments.

  • So let's start with COSY.

  • Imagine for a moment that you have propanol and so

  • if you think of your H1 NMR spectrum

  • of propanol you'll probably think

  • of something that looks like this.

  • You'll see a triplet with a 1 to 2 to 1 triplet

  • for the CH2 that's next to the oxygen.

  • You'll see a singlet for the OH typically unless you're very

  • free of acid or very free of water and the singlet is going

  • to correspond to the OH that's going to be exchanging rapidly

  • and not coupling unless you, as I said, are very acid free.

  • You'll see something that looks kind of sort of like a sextet

  • in a 1 to 5 to 10 to 10 to 1 ratio.

  • I guess that's not the prettiest of sextets.

  • Let me make my outer peaks a little smaller.

  • Then you'll see something that looks like a triplet

  • in a 1 to 2 to 1 ratio.

  • As I said, you already know correlation.

  • You know that when I see this triplet here downfield it's

  • telling us that I have 2 hydrogens, it's telling us

  • that I have a CH2 next to a CH2 and when I see this triplet

  • up field I see, I know that I'm having a methyl group and I need

  • to go off 3 hydrogens.

  • I'm having a methyl group and it's next to a CH2.

  • When I have this sextet here,

  • you know that I'm having one methyl group is it's 2 hydrogens

  • and by being a sextet I know it's coupling

  • with equal coupling constants to find different hydrogens.

  • So for this simple problem you're very good

  • at reading this.

  • COSY is providing exactly this type of information

  • but in a more systematic fashion.

  • Now similarly if I have a carbon NMR spectrum let's say

  • for the same molecule, I may have something that looks kind

  • of sort of like this with let's say 3 lines in it

  • and what HMQC is going to do is it's going

  • to correlate the proton signals with the carbon signals.

  • In other words, it's going to say, ah,

  • this proton signal is connected is coupled

  • with that carbon signal this proton signal is coupled

  • with this carbon signal, this proton signal isn't coupled

  • with any carbon signals and this proton signal is coupled

  • with that carbon signal.

  • All right let me give you a handout that sort of starts us

  • on all of the core correlation techniques both these 2

  • and the COSY and the Toxi and het core

  • and let me show you schematically what I'm

  • talking about.

  • [ Pause ]

  • Plug in the machine doesn't it?

  • That's better.

  • All right.

  • So this is not a real spectrum.

  • This is a sketch of the COSY spectrum of propanol.

  • [ Pause ]

  • So it's my little pigeon, pigeon sketch of it

  • and so a COSY is going to give us all of our couplings,

  • it's going to give us our J33, in other words, our vicinal,

  • our geminal, our vicinal couplings, and our J3s

  • and our J2s, in other words, our geminal coupling.

  • Any case you have coupling you'll get long-range coupling

  • as well like allylic coupling.

  • In general, if you're coupling constants are small,

  • the signals are going to be weaker.

  • So if you have a very small coupling

  • like an allylic coupling, it may not show up as strongly

  • or if you don't go down in

  • that topographical map enough you may not see it.

  • Later on we'll talk about some tricks to help bring

  • up those signals, but right now basically anything that's

  • coupling is going to give you a peak.

  • Now remember I talked about our axes so this is our f2 axis,

  • this is our f1 axis and these technically are not part

  • of the spectrum.

  • These are actually 1 dimensional spectra added for reference.

  • So you typically and you'll be doing this,

  • we'll take a 1-D spectrum and you will use it as a projection

  • on the axis so that you see how things line up.

  • Now in terms of the anatomy of a COSY spectrum,

  • this is what we call the diagonal.

  • [ Pause ]

  • And the diagonal basically is just the spectrum.

  • In other words, it's the methyl peak here, the methylene here,

  • the OH here and the methylene next to the oxygen.

  • These are the peaks that are interesting.

  • These are called the cross peaks, there are 4 of them here,

  • the cross peaks if you'll notice are symmetrical about the axis

  • and what I always liked to do in naming my spectra

  • and we'll be doing this as a convention

  • in class is we'll identify all of the peaks in the 1-D spectra

  • and we'll letter them starting at the left of the spectrum.

  • So I will call this Peak A, this Peak B, this Peak C

  • and this Peak D. We'll do the same over here, A, B, C,

  • D. What the COSY is telling us is that A, notice it lines

  • up with A, is crossing with C. So you see this peak

  • and so we have this cross peak for A cross C

  • and you get the same thing over here

  • and then you have another cross peak here and that's C crossing

  • with D. I like to go ahead and basically keep the idea

  • of my peaks and my cross peaks before we assign

  • where those peaks are in the molecule so, of course,

  • now we know that in this molecule this is HB, this is HA,

  • this is HC and this is HD and I'll show you

  • as we progress we'll learn more and more how

  • to systematically extract this from unknown structures

  • but you can see, for example, that A crosses C

  • and so that's corresponding to this coupling, this correlation,

  • and we can see that C crosses with D, that's corresponding

  • to this coupling, this correlation, and we can see

  • in this particular simulated spectrum,

  • this particular I should say sketch of a spectrum,

  • B because it's not J coupled isn't coupling to anything.

  • If B were a triplet if it were J coupling,

  • then we would expect it to give a cross peak with A

  • and so we would see a separate peak

  • over here associated with that coupling.

  • All right so that's our COSY spectrum.

  • So now let me show you our HMQC coupling spectrum.

  • All right so this is your HMQC spectrum,

  • your HMQC spectrum picks up one bond CH coupling and in picking

  • up 1 bond CH coupling, of course, now we have no diagonal

  • because we've got on our f1 domain we've got C13

  • and on our f2 domain we've got our proton spectrum.

  • So there's no diagonal and what instead we have is a series

  • of cross peaks and, again, if I transcribe the structure

  • of the molecule and I call this HBOCH2A CH2C CH3D

  • for the molecule now what we're going to do is

  • to correlate these carbon peaks with the proton peaks and,

  • again, I like to very, very slavishly label my peak.

  • So I'm going to go through every time I encounter a spectrum I'm

  • going to go through start at the left and go A, B, C,

  • D for each of my peaks and if I start

  • at the carbon I'll do 1, 2, 3 and so forth.

  • One of the reasons I'm so dogmatic about this is

  • because when you get to larger molecules it's very easy

  • to start to get confused.

  • You'll have 1 expansion here and 1 expansion there.

  • If you take the time to do this, it'll always help you keep track

  • of what's going on particularly when you have many spectra.

  • So, now we have these cross peaks here 1A.

  • So in other words, I look across 1A, I look across 2C here,

  • and I look across 3D and nothing is crossed with B

  • and so I can say, okay, this is C1, this is C2, this is C3.

  • [ Pause ]

  • Thoughts or questions at this point?

  • [ Inaudible question ]

  • You mean reverse it and have up field?

  • [ Inaudible question ]

  • Oh, yeah, it is possible and, in fact, well,

  • let's see which way is it typically plotted.

  • I think it's typically plotted this way

  • because you could envision picking this

  • up and putting it here.

  • So, I think you will always see down field

  • down here but I could be wrong.

  • It's of no consequence.

  • Let me put it this way it's of no consequence whether we go

  • from 0 PPM to high PPM or we go from 0 PPM to I PPM.

  • You will also see maybe

  • in the textbook you may see a few het core spectra given

  • for some of the compounds.

  • In a het core spectrum, the C13 is going to be up here

  • and the proton will be down here.

  • Other thoughts or questions?

  • All right.

  • I want to throw into the mix, I don't yet expect you

  • to assimilate it because we're throwing out a lot

  • of information, I want to throw

  • yet into the mix the Toxi and HMQC.

  • So the big difference in Toxi and, I'm sorry, HMBC,

  • let me again make our little schematic molecule here.

  • Okay, in our little schematic molecule in a Toxi spectrum,

  • you still get all the cross peaks of the COSY

  • but now you get new cross peaks.

  • So we get this cross peak here

  • and we get the cross peak corresponding

  • to this coupling here, but in the Toxi spectrum,

  • what you also get is a cross peak between these 2 protons.

  • You don't get a cross peak with this OH if it's exchanging

  • because if it's exchanging it's not part of the spin system

  • but what you get is cross peaks with all other protons

  • in the spin system and at this point it's hard for you

  • to see why in the heck you'd want that?

  • The COSY already seems very information rich,

  • but it's very good for dealing with overlap

  • where your COSY can't walk you through and you can break

  • through overlap with the Toxi where you have peaks on top

  • of each other and the other thing that's extremely good

  • for is biopolymers.

  • Oligosaccharides, nucleic acids and proteins and peptides

  • because each residue

  • in a biopolymer typically is 1 spin system.

  • So I'll give you a quick schematic of the Toxi.

  • We'll have a separate lecture on this later on but I just want

  • to just introduce you to the basic anatomy here.

  • [ Pause ]

  • All right.

  • So this is again our sketch of a spectrum

  • and it looks just like a COSY.

  • In other words, you have your diagonal,

  • everything is the same as the COSY.

  • You have, if I again go and slavishly label our peaks A, B,

  • C, D, A, B, C, D, you have all the peaks

  • that you would have seen in the COSY.

  • You have your AC peak, you have your AD peak,

  • your CD peak rather, but now you get this 1 additional

  • cross peak.

  • So you get A to D that's unique to the Toxi and that's

  • that cross peak between these 2 here.

  • [ Inaudible response ]

  • You can do that and you'll find

  • if I do the same thing here I could call this either C to A

  • or A to C and I could call this D to A and I could call this D

  • to C it's providing no additional information.

  • The only thing that I use this

  • and it doesn't matter whether you use this half or that half,

  • the thing that I use it for is basically to check

  • if I'm confused if something is a real peak, if there's a lot

  • of noise or some artifacts, I'll check if it's there in both.

  • Sometimes things will be clearer in one or clearer in the other.

  • [ Inaudible response ]

  • That's for homonuclear.

  • Homonuclear, right, you don't have a diagonal,

  • you don't have this element of symmetry.

  • All right.

  • The last one in our schematic now we come to our HMBC

  • and let me again sort of show you in my simple minded view

  • on the blackboard here.

  • So, again, we'll come back to our molecule.

  • HMBC can be like drinking from a fire hose.

  • There's a ton of information there and what you end

  • up needing to do is use it in a very focused fashion

  • because you'll just drown in peaks.

  • So, remember HMQC was our 1 bond CH couplings.

  • In HMBC, we get 2 and 3 bond CH couplings.

  • Not always in a predictable or guaranteed fashion.

  • So in other words, this hydrogen will be coupling

  • with this carbon, this hydrogen will be coupling

  • with this carbon, this hydrogen will also be coupling

  • with this carbon.

  • This hydrogen will be coupling with this carbon,

  • this hydrogen will be coupling with this carbon,

  • this hydrogen will also be coupling with that carbon.

  • So you're getting this tremendous amount

  • and if OH is exchanging rapidly it won't be coupling with any

  • of them and, again, right now it's too overwhelming for you

  • at this point to just throw all these spectra

  • at you and say use them.

  • So, what I'm going to put it is just

  • like I say this is particularly, Toxi is particularly good

  • for overlap and biopolymers.

  • What I'm going to do is say that HMBC is particularly useful

  • for what I'll call putting the pieces together.

  • You know how in the homework I'm telling you to write

  • down fragments, things that you know I know this molecule has an

  • ethyl group, I know this molecule has an isolated methyl

  • group, when you're getting to that point

  • and you have these fragments and you're saying now how

  • in heck do I systematically put them together?

  • This is where HMBC shines where you say, oh, now I can see

  • that this fragment is somehow connected to that fragment

  • where you have these isolated spin systems

  • and you're trying to put them together.

  • So I'll give you the schematic of an HMBC right now.

  • >> There's no single bond?

  • >> Ah, great question, James.

  • Yes. You will sometimes see single bond coupling

  • and your textbook actually removed it from a few

  • of their problems and I put it back in.

  • I basically took out.

  • [Laughter] Well, the reason is what good is it to have spectrum

  • in the textbook that are doctored

  • when you then encounter real spectra.

  • To put it another way you encounter them in your research

  • or the exam, which may be on people's mind more

  • and it looks different and you're

  • like what the hell is going on?

  • So you can see those and we will get used

  • to that, we will see that.

  • >> Are they rare?

  • >> They are, yeah, rare and usually in the case

  • of strong peaks and you'll know because I will refer to them as,

  • you will see them as these, hey, it's Halloween,

  • vampire bites around the peak.

  • They are, you will see the J1CH splitting .

  • All right.

  • So if we again go back to our system here.

  • So you notice now we're getting this very rich piece

  • of information here.

  • So, for example, if this is our molecule, OHB CH2 ACH2C CH3D

  • and we already know these are carbons 1, 2 and 3.

  • So let's just, we're just talking 2 of these.

  • So, this cross peak here of 1 to D that's telling us

  • that we're seeing and, again, this is just my sketch.

  • That's showing us that we're seeing this long range

  • heteronuclear correlation.

  • This cross peak here of 2 and that's my scrawl of a 2,

  • this cross peak here of 2 to D is telling us

  • that now we are seeing this correlation over here

  • and you will see how to use this very,

  • very information-rich system in the future.

  • [ Inaudible response ]

  • Yeah, it's not so much how far.

  • Remember how I said that J2CH and J3CH are typically 0 to 20

  • and they're going to depend 0 to 10 they're going

  • to depend on hybridization?

  • They will have different intensities based

  • on the J value.

  • If your J value is very, very small,

  • you won't pick it out no matter what.

  • If you've got a J of like 1 hertz,

  • good luck finding that coupling.

  • So it's, and this is the killer on HMBC is

  • that you can't tell your J2CHs from your J3CHs.

  • So you get this information

  • but there's always these question marks.

  • Are they direct, you know, are they neighbors

  • or are they nearest neighbors

  • or are they neighbors 1 down the road?

  • But don't worry about this right now.

  • We're going to spend a week or two not using HMBC.

  • What I do want to start us out now is on an example with HMQC

  • and COSY and show you how beautifully they work together

  • and show you how I solve a simple problem

  • and this is a problem from not this week's homework

  • but next weeks' homework so it'll be sort

  • of a demo problem for you.

  • [ Pause ]

  • If anyone didn't get one, there's enough to go around.

  • Now the other thing I would

  • like to give you is a tool that's useful particularly

  • when you get more crowded spectra and that's these grids.

  • They're very useful in helping you line things up.

  • They're yours to keep and you can print more

  • on transparency film or if your lab mates are envious of you

  • and steal them, you can go ahead and get them.

  • All right now, what the heck?

  • Ah, okay. So, I want to whip

  • through this kind of, sort of quickly.

  • So, okay, this is a spectrum and we have a mass spectrum,

  • we have an IR spectrum.

  • Now the reason I have been pushing on you write fragments,

  • write pieces of information,

  • is it helps you organize your thoughts and it helps me

  • and you get an answer wrong it helps me figure

  • out what your thinking was

  • because often there's good thinking in a wrong answer.

  • All right.

  • So I look at this spectrum, I see a carbonyl, I see something

  • at 1743, I work out the formula from the mass it's C7H14.

  • O2 works out for the mass there's 1 degree

  • of unsaturation.

  • It sure looks like it's an ester,

  • 17.43 is about the right position for an ester.

  • Here there happens it's a small molecule, very small molecule,

  • and I happen to see the CO single bond stretch.

  • If I look in the proton NMR spectrum,

  • I see some downfield peaks that look

  • like it's consistent with an ester.

  • So take it as a given right now that it's an ester.

  • I go ahead and I look at my peaks and, again, I really,

  • really, really like to get in the habit of labeling them

  • and just walking across this spectrum A, B, C, D, E, F,

  • G. It's a little confusing here.

  • If I look closely, it looks like I see a doublet.

  • Can you see the pattern of the doublet on top

  • of a triplet you see the 1 to 2 to 1 triplet.

  • So it looks like I have G is probably a doublet and H

  • so that's probably G and that's probably H right over here.

  • Now, you really, really, really want to be diligent

  • about putting a ruler, measuring the height of your integrals,

  • I like to be good, I like to take this height, this height,

  • this height, this height, this height, this height,

  • this height, everything I'm sure of divide by the number

  • of protons and get the most accurate height per

  • proton possible.

  • This one is pretty obvious to follow by inspection.

  • If I really feeling lazy,

  • I could always just even use my grid as some sort of uber ruler

  • and I say, oh, 1.7, 1.7, 5 point looks like about 5.3, 5.4, yeah,

  • 5.4, 1.7 or 1.8 I guess if I want to be good

  • about it I will even try to line up my grid a little bit better.

  • About 1.7, 1.7, 1.7, about 2 point, let's see about 10.6

  • and if I work this out, I'm getting about 1.7 for hydrogen,

  • about 1.7 for hydrogen, this ruler, by the way, is graduated

  • in tenths of an inch is the small tick marks

  • in case you're wondering.

  • All right.

  • So I can very quickly go through and say 1 hydrogen, 1 hydrogen,

  • 3 hydrogens, 1 hydrogen, 1 hydrogen,

  • 1 hydrogen and this is 3 and 3.

  • It looks like it's 6 hydrogens.

  • [ Pause ]

  • Similarly I like to look at the carbon NMR spectrum

  • and if I have a depth spectrum, I'm very happy and, again,

  • I'll go and number my peaks 1, 2, 3, 4, 5, 6, 7,

  • and I look at my peaks and I say it looks like 1 is a quat,

  • carbon, 2 looks like a methylene,

  • I may have to make judgment calls

  • if my depth isn't completely clean, 3 is CH, 4 is a CH2,

  • and 5 through 7 are CH3s.

  • Now with these data alone I'm going to have,

  • this is at the harder end of a molecule

  • to solve with just 1-D data.

  • It's not that you can't.

  • You could easily puzzle out the structure,

  • but I want to show us how 2-D data is going to help us.

  • Usually at this point I sort

  • of jot some ideas down as fragments.

  • I see I have a methyl group, a 2, I don't know,

  • maybe a methyl group at 2 might be indicative of CH3.

  • Carbonyl might be something.

  • I think I have, it looks like I have 2 methyl groups here.

  • One of them is a triplet, one of them is a doublet.

  • So I probably have if I'm just tallying

  • up fragments I probably have a CH3 CH2 fragment

  • and I probably have another CH3, CH fragment and honestly

  • if you puzzled around now you could probably put the structure

  • together, but I want to show you this way

  • of putting the structure together that we're going

  • to do here using HMQC and COSY in a systematic fashion.

  • All right I actually liked to start with my HMQC spectrum

  • and the reason I do is that's going to help me,

  • first of all it's going to avoid having me waste a lot

  • of time getting stuck on geminal couplings and it's going

  • to give me a very systematic way of naming things and, again,

  • I'm going to be very slavish, A, B, C, D, E, F, G, H, E, F, G,

  • H. You notice we've left out of the carbonyl,

  • we left out the carbonyl at about 100, oh,

  • that's another thing that clued me into an ester.

  • The carbonyl was at 170 something PPM?

  • Typical ester so it's not a methyl ketone,

  • it's not an aldehyde, right a methyl ketone I'd expect

  • at like 205 to 220 and aldehyde It'd expect at like 190 or 200.

  • So I am pretty darn sure this is an ester.

  • Anyway, but we don't need in HMQC it's not going

  • to correlate anything because it's a quat carbon it's

  • not coupled.

  • So, I start my numbering 2, 3, 4, what am I doing here?

  • It's hard staring in the light, 5, 6, 7.

  • [ Pause ]

  • Now I just look at my cross peaks and so 2 is crossing

  • with A and B, 3 is crossing with D; 4 is crossing with E

  • and F. Every time I get one of these carbons crossing

  • with 2 methylenes I know it's a diastereotopic methylene.

  • Six is crossing with, now this is where it's hard to see

  • and I have you have trouble particularly

  • in a crowded spectrum, put just slap a grid on it

  • and you can see 1 cross peak lines up kind of centered

  • with H, the other cross peak lines

  • up with G. They've included and expansion here.

  • I believe they have actually forged their data here.

  • I think this cross peak actually should be spread out

  • and they were trying to make it easy for students

  • by showing it just under here, but again what good is

  • that going to do for you when you encounter your own real data

  • and you say, oh, it doesn't look like it looked in the problem.

  • So, here I look and I see, oh, yeah,

  • you see how nicely you can see with the grid lines this lines

  • up with G, this lines up with H. So, we get 6G and 7H

  • and now I'm going to be very, this is going

  • to become my Rosetta Stone for the problem.

  • I'm just writing all

  • of my numbers here right over the letters.

  • Two A and 2B, 5C, 3D, 4E, 4F and 6G and 7H.

  • All right here's where all of this work pays off.

  • Now we go to the COSY spectrum and what I do again I'm very,

  • very, very mechanical about this.

  • I go ahead and I transcribe from my other axis 2A, 2B, 5C, 3D,

  • 4E, 4F, 6G, 7H and I do, if I had another axis

  • up here I would do the same.

  • They only gave us 1 edge projection.

  • That's not going to matter.

  • All right we' now all set to put this molecule together.

  • All right so I literally I go

  • through now I identify my diagonal, I draw a line

  • through my diagonal so I don't get confused, ruler is better

  • than the side of my grid but if the grid is what I have

  • on me then I use the grid.

  • David always comes prepared, he has his ruler, all right.

  • Now we're ready to look at our cross peaks.

  • Two A crossing with 2B.

  • That's just I'm taking the 2A

  • and the 2B diagonal they're crossing with each other.

  • Normally I go up and over but here because they're all

  • on this side I go over and over.

  • So, okay, tell us something we don't know, right?

  • That's our, that's our C2HA, HB.

  • The only thing I really do know at this point that's the carbon

  • at 70 parts per million so I know

  • that that carbon probably is connected to an oxygen.

  • I think I have an ester in here.

  • All right here's where we start to get some new information

  • because 2A and 2B each cross with 3D.

  • See I can go up and over so that's useful;

  • 2A with 3D and 2B with 3D.

  • Okay, that's useful because now I know I have C3HD

  • and it's connecting and I'm starting

  • to put this thing together in a systematic fashion

  • and I'm just going to continue to read my spectrum.

  • So we go over here and we say, oh, here we get 3D cross 4E

  • and 3D crossed 4F and you say, oh, okay, that's useful.

  • I have this methylene C4 with E and F connected it's got

  • to connect up, C4, HE, HF and I'm building

  • up this chain that's harder to put together

  • than a usual coupling where we can just read off

  • and see what's coupled with what.

  • You say hey this is useful.

  • I look up here and I say okay I've got this cross peak maybe I

  • need to slap a grid on it to help see how things line up

  • and I look at my grid and I say, ah, it looks like that aligns

  • with 6G and so now I say, ah, okay, so I have 3D lining

  • up also crossing with 6G.

  • Ah. Okay. So 3D also has to cross with C6 H3G.

  • Now I have almost the entire chain built up.

  • I have this cross peak here.

  • Does that tell me anything useful?

  • What's that cross peak?

  • So I go over, normally I would go over

  • and up but it's 4E cross 4F.

  • Well, that's fine and dandy,

  • but it isn't telling me anything useful

  • for E cross 4F that's just the diastereotopic one

  • but now I come to the last ones and I get 4E with 7H.

  • You notice this one is lining up with the full edge.

  • So 4E to 7H and this one is 4F to 7H.

  • That gives me the last of my chain, C7 H3H.

  • [ Pause ]

  • All I have left now is I have this isolated methyl, C5, H3C.

  • He's not correlating with anything here.

  • If I had an HMBC I could put them in systematically.

  • I have 1 carbon left that C1 which is part of a carbonyl,

  • that was in my other one and you can see how it comes

  • together now.

  • We had 2 valences on the carbonyl that needed

  • to be filled, we had a valence on C5H3C that needed

  • to be filled, we had a valence on the oxygen

  • that needed to be filled.

  • The only way to put the molecule together was to connect

  • that valence from C5H3C to C1 and the valence,

  • the other valence on C1 to the valence on oxygen

  • and bingo you have the whole structure systematically

  • worked out.

  • Obviously it's not as easy the first time

  • around as I make it look here, but the same strategy will start

  • with a simple problem set next week, the same strategy

  • of going ahead and working the HMQC

  • and in working the COSY is going to take you very far. ------------------------------f5df921dc12e--

>> I want to move on and start talking

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