字幕表 動画を再生する 英語字幕をプリント >> All right. Well, I will leave these and get started then, I guess. All right, so I think I want to finish up what I'll call basic NMR spectroscopy today. In other words, things that all sort of fall at the level of basic interpretation of structures, and in turn things that we'll get on the mid-term. I think probably where I'll pick up next time is going to be introducing 2D NMR and then our next homework set, not Monday's, but the one after that, we'll start using 2D NMR spectroscopy. So what I wanted to do today was to talk more about carbon 13 chemical shifts. And I gave you, when we talked last time, I gave you this sort of general information that just like proton NMR, carbon NMR, aliphatics tend to be upfield, aromatics tend to be downfield, things that are next to electron withdrawing groups, particularly oxygen, tend to be mid -- we'll call it mid field, sort of in that 50 to 70 range. I also indicated -- and we said that the range is a lot, lot bigger. It's about 20 times bigger in ppm for C13 NMR. In other words, an aldehyde CH is at roughly 10 ppm whereas in carbon NMR an aldehyde carbonyl is at roughly 200 ppm. So it's sort of like 20 times bigger range. Now, C13 shifts have a bigger range. And there's also more richness. In other words, when we talked about proton NMR, it was pretty easy. And we were able to come up with some really simple, you know, back of the envelope calculations where you could typically peg the chemical shift to within, you know, a few tenths of a ppm. We talked about if you're next to an ester, you know, let's -- or if you're next to an oxygen, figure you're going to be about 2 ppm downfield of where you'd normally be. If you're next to a benzene ring or a double bond or a carbonyl, figure you're about 1 ppm further downfield. And I gave you several ways of thinking about this. And you should all be able to pretty much estimate things. We talked about the effects of alpha substituents and said that alpha substituents have a really big effect being next to a CH next to a halogen next to a nitrogen next to an oxygen shifts you down, you know, a couple of tenths -- a couple of ppm. We talked about beta effects. And we said that they're smaller. Beta effects in proton NMR shift you down by like .2 to .5 ppm. C13 NMR is a little bit more subtle and a little bit -- I won't say less predictable, because we're going to see it's actually quite predictable. But the factors, there are more factors. For example, gamma effects as well as beta effects tend to be big. And there are some really interesting steric effects. Now, along with this richness comes tremendous power. Because this means that carbon NMR also can give you tons of rich information about structure and can be really useful for figuring out structures, confirming structures, disproving structures, and at the end I'll show you a beautiful example of fraudulent work that was disproven by Professor Rychnovsky's laboratory. And also going ahead and basically having a tool that can get you a lot more information than meets the eye. So, I want to show you some of the factors that contribute to these sorts of general ranges, and particularly now, perturb them. And let's start with something pretty simple, inductive effects and resonance effects. [ Writing on Board ] And electron density, of course, plays a huge role in chemical shift because electrons contribute to the shielding or de-shielding if they're absent, of various nuclei. So, if you have substituents that increase or decrease the electron density in a carbon, you're going to shift that carbon upfield or downfield. Let me show you what I mean. We'll start with a simple benzene example. Now, the easiest way to, in your mind, think about chemical shifts is to start with a base value and then perturb it. So a great way to think about benzene is the normal position for benzene is 128.5 ppm. And then if you put substituents on it, you perturb things in a rational way. So let me show you what I mean. If we put a methoxy on the benzene, the oxygen is electron withdrawing through the sigma bond. And so the carbon attached to the oxygen shifts substantially downfield. So you go to 160 ppm. In other words, you shift downfield by 30 ppm, more than 30 ppm by putting that oxygen there. Now, what's interesting, then, is the ortho carbons end up having by resonance extra electron density at them. In other words, the two ortho carbons you can push your arrows, and you see they're electron rich. It's the same reason why electrophilic aromatic substitution occurs ortho and para when you have a methoxy group on there. So, the ortho carbons appear at 114 ppm in methoxybenzene. You don't get a big effect at the meta carbons, which makes sense because you have inductive effects that are now quite removed. So it's very small. And resonance doesn't pump up the electron density at the meta carbon. You go to the para carbon, and now you also see an upfield shifting, although it'll be at a smaller upfield shifting of 121 ppm -- at 121 ppm. Now, I'll come in a moment to empirical additivity relationships, but one way to think about this is to think about it if you have a methoxy group or an alkoxy group on a benzene, that it shifts the ortho protons upfield by about 14 or 14 1/2 ppm. And if you have a methoxy group, it shifts the para protons upfield by about 7 1/2 ppm. And if you have a methoxy group or an alkoxy group, it shifts the meta protons downfield by just a fraction of a ppm. And what we'll see in a moment is that you can add up all these effects and then calculate for different aromatics, the effects of different substituents. All right, let's take a look at some other examples of electron -- of inductive and resonance effects. So, let's take an alkene. And I'll give you cyclohexene as a base value. In cyclohexene, your alkene is at 128 -- 127.4 ppm. Let's compare that to cyclohexanone. And in cyclohexanone, we see a very big effect at the beta position and just a little effect, just a little inductive effect at the alpha position. The beta position is 151 ppm and the alpha position is just shifted downfield by a hair. And that makes sense because you look at this and you say okay, now you can think of a resonance structure in which you're electron deficient, right? We all know that enones are Michael acceptors. That nucleophiles like to attack at the beta position. Are you doing this with orbitals in Van Vranken's class now? >> Yes. >> Yeah, so you know about frontier orbitals and electron density. And so you see, the effect is actually very substantial, right? Both of these carbons, they're symmetrical, they're at 127. You go more than 20 ppm downfield by decreasing the electron density. These effects can be absolutely humongous. And one of the things that I've tried to emphasize when I've talked about these ranges here are these are general ranges. These are not carved in stone. And so you already see, for example, that this one inductive oxygen here brings us even outside of this very generic range here. Let me show you just how huge the effects can be. So, ketene acetal is a good example, right? Alkenes are normally like 110 to 150 ppm. But if hugely perturb the electron density, you can have huge effects. So it probably doesn't surprise you too much if I tell you that you now, by having two methoxys on an alkene can shift it downfield to 169.7. But what's really huge is you look at the position here, the beta position on the alkene, and now we're so electronic rich, this thing is so nucleophilic at this position, there's so much electron density at that position, that we're at 45.5 ppm. You look at a spectrum of that and you wouldn't even know it's an alkene because you'd say, oh, that's got to be aliphatic. That's got to be somewhere over here. And we've just pumped up the electron density hugely. The most radical example I know off the top of my head is this sort of push me, pull you system here, where you have two electron-donating groups and then two electron-withdrawing groups, two cyano groups. And so this alkene, you go to 39.1 ppm. And then this carbon here is at 171. And 171, you'd say all right, well, it's really downfield. But you'd say it makes sense. You've got these beta electron withdrawing groups. But you look, 39.1, who would of thunk that that is an alkene. [ Erasing Board ] >> Can I ask you a question? >> Yeah. >> What is that letter to the -- CW, or CN? >> CN. >> Okay. >> So these are two nitrile groups. These are two cyano groups, CN groups. >> Okay. >> All right. So, substituents have substantial effects whether they're alpha, whether they're beta, whether they're gamma. And you can really see this. I'll give you -- we're going to walk through this and I'll give you some examples. So first let's talk about alpha alkyl substitution. And if I want to give you a general principle, in general, alpha alkyl substitution leads to more downfield shifting. So if we, again, take our benzene example, and remember we said that benzene was at 128.5. If we put a methyl group on it and make it into toluene, now we go to 137. The point is we shift downfield by about 9 ppm by putting on a methyl group onto benzene. Let's take a look at alkyl systems. So, we'll look at propane. And we'll look at the central methylene of the central carbon of propane. You put on an alkyl group onto propane and you get isobutane. And now you're down at 25 ppm. And so you notice, it's kind of about the same. Here we moved down by about 8 or 9 ppm. And here we, again, moved down by about 9 ppm. So in other words, we're talking on the order of, eh, 10 ppm or thereabouts. All right, you put on another alkyl substituent and the effect isn't as dramatic. But again, you move further downfield. Now we're at 28 ppm. Now, what's nice about this is these ideas are generalizable. There is really science here to it. And this is the point, that you can take little bits of knowledge and generalize and build up in your mind what's going on. So let me compare us, say, to ethanol. If we start at 58 for ethanol, and now we envision going to isopropanol, what would you predict your carbon to be at here? >> 67. >> 67 would be a very good prediction, because we say, okay, we take 16, we add 9, we get to 25. You add 9, you get to 67. And that's a very good guess. 64 is the answer. All right. Now imagine we go further and we go to tert-butanol. Now what do you think, for tert-butanol? >> 66. >> 66? >> I don't think it's going to change. >> You don't think it's going to change. Okay. Other guesses on that this estimates? >> 67. >> 67. All right.