Addition of Water, Alcohol & Cyanide
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MannoseArgininColaminBaseStickstofffixierungMagnetometerBockbierBraunes FettgewebeBaseSäureElektron <Legierung>ReaktionsmechanismusCobaltoxideChlorideWasserChemische ReaktionChemische VerbindungenChemische StrukturHydroxylgruppeReplikationsursprungOperonAcetonSetzen <Verfahrenstechnik>Funktionelle GruppeMesomerieGradingAcetateComputeranimation
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LipopolysaccharideInsulinMannoseMagnetometerEinschlussArgininVerhungernHomöopathisches ArzneibuchApplikation <Medizin>PhasengleichgewichtOktanzahlCobaltoxideChemische ReaktionAlterungGangart <Erzlagerstätte>HydroxylgruppeAtomsondeStickstoffatomFunktionelle GruppeDehydratisierungFülle <Speise>ExplosionKohlenstofffaserSäureGesundheitsstörungWasserstoffbrückenbindungÜbergangszustandHydrocarboxylierungReaktionsmechanismusWassertropfenQuerprofilWasserstoffAmineQuelle <Hydrologie>FunkeDeprotonierungOrdnungszahlEinsames ElektronenpaarIminiumsalzeSetzen <Verfahrenstechnik>ImineLevomethadonEntfestigungComputeranimation
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Computeranimation
Transkript: Englisch(automatisch erzeugt)
00:09
Good afternoon we're going to get started. We're going to continue with chapter twenty one, are there any questions before we get started? Anyone?
00:20
Alright. It's the third week already, we have a test next week. I hate that. I hate tests just as much as you do by the way. Someday what I'm hoping for is that they have this thing you walk up and it's a brain scanner and it will just you know give you your grade.
00:42
They'll see how much you have in your brain and then we won't have to do tests, right? You'll still have to study though, I don't know, it's my dream.
01:00
Okay so we're talking about the acetal mechanism last time and I told you there was a very high likelihood that I would put the acetal mechanism on the test. Okay so we went through the base catalyzed reaction and with the base catalyzed reaction you can't make an acetal with base. It stops at a hemiacetal. So something to keep in mind.
01:21
So we stop right here at the hemiacetal. In the acid catalyzed reaction I generally can't stop it right here so if you want to make a hemiacetal you should use base. Generally not isolable, it will go all the way to the acetal so we went through the base catalyzed mechanism to form the hemiacetal and then we went through the
01:41
acid catalyzed mechanism to form the hemiacetal and here we are. We stopped at the hemiacetal and then on the next page we were continuing with acetal formation. Alright so there are two ways to do this. On both methods you protonate the hydroxyl here because that's going to leave.
02:01
And the way it turns out with these acid catalyzed mechanisms that we're going to be doing over the next several weeks, in an acid catalyzed mechanism you always protonate the leaving group first. Okay so here we're going to protonate first and then the way I do it is I have the electrons on oxygen come down and kick off water but you can certainly show it
02:20
this way. It makes you draw one more thing here, this leaves, and then we can draw the resonance structure here. So these are two resonance structures for the same compound here so let me just put brackets around there and that is also fine. Okay and then we want to keep going don't we because we're not done yet.
02:45
So then methanol is going to come in and attack. So we're basically we're replacing a methoxy group with a hydroxyl group but we're not doing it by an SN2 reaction.
03:07
So as you can see we are one step away from a hemiacetal.
03:21
What do we have to do? What's our last step? Our last step is to deprotonate so I'm going to just deprotonate with methanol. So in an acetalase mechanism we're deprotonating and then we're actually going to regenerate
03:40
our catalyst. So it looks like that. Questions on the acetal mechanism? Anybody? Yes.
04:04
I don't grade reversible arrows so you don't need to worry about these guys. On the exam I grade curvy arrows. So don't get worried about this part right here I don't grade that. More questions? Anybody?
04:23
Alright important points about hemiacetal and hemiacetal formation. Hemiacetals cannot be converted into acetals with base, we mentioned that already. So there we're making that point again. Use aciketalases to go all the way to the acetal. Hemiacetals are difficult to isolate unless the hemiacetal is part of a five or a six
04:41
membered ring. Alright so if you had something like this and you did an intramolecular reaction you can actually isolate this compound. And hemiacetal is favored.
05:07
So in this case hemiacetal is favored so we don't have to drive the equilibrium it wants to be in a six membered ring. So most of the time the aldehyde or the ketone is favored but in this case the hemiacetal is favored.
05:22
And the best example here this is glucose as a hydroxy aldehyde and only a very small percentage of glucose is in what we call the open chain form.
05:42
So it's the open chain form. It likes to be in a ring. And so long arrow to the right, short arrow to the left. And this is going to be, we're going to talk about this more in depth in the very last chapter in 51C and you'll get really good at drawing these.
06:06
So you thought you were done with drawing chairs, no. So notice all these hydroxyls are in the equatorial position so that certainly makes it easier to remember the structure of glucose. Harder is to actually pick out the hemiacetal carbon.
06:24
So remember when we look for a hemiacetal we want a carbon that's bonded to a hydroxyl and a methoxy. So right here this carbon is only bonded to a hydroxy so that's an alcohol. Likewise that's an alcohol, that's an alcohol, that's an alcohol. This one right here and I kind of drew that a little weird it looks like there's, I
06:43
got to fix that. This carbon right here is bonded to a hydroxyl and an OR. And so it's a hemiacetal so that's our hemiacetal carbon. So let me go back and fix that. Kind of looks like I have an extra bond, oh now look at that.
07:03
So now things are really going to be, is that better? Yeah. And now let's label that hemiacetal carbon.
07:22
So there's a question on Sapling you might have already run across where they asked you to say what's our hemiacetal, acetal, you know by the way there is a small, there's a small issue here with the words hemiacetal and acetal. Some of our O chem textbooks use hemiacetal and acetal for everything.
07:43
Other textbooks that we've used in the past use ketal if it's from a ketone and acetal if it's from an aldehyde. Okay so there's a distinction there and I use, I learned that hemiacetal, hemiacetal, ketal, acetal but then you know the books that we've had over the years don't do
08:05
the ketal anymore but if you see that that's what they're talking about. So we just use hemiacetal in this book for anything that has a carbon bonded to a hydroxyl and an OR group whether it came from a ketone or an aldehyde. Okay so there's this little bit, you might run across hemiketal and it's just the same
08:23
thing it just comes from a ketone. Alright so hemiacetal carbon and so this is glucose in the hemiacetal form and I think that at equilibrium, this is definitely greatly favored at equilibrium, I think there's like
08:44
less than one percent in the open chain form. So this is greatly favored at equilibrium. So with these guys where you have the acetal in a six or a five membered ring you can stop
09:09
at the hemiacetal with acid because that's what's favored. Questions on that point there, anybody? Same factors that govern equilibrium in hydrate formation also govern equilibrium
09:23
in hemiacetal and acetal formation so you can go back and review that. The more stable the carbonyl the less favorable the addition and addition is favored for formaldehyde and aldehydes with electron withdrawing groups just exactly like with hydrates. So we can follow the same principles.
09:42
Reaction must generally be driven to completion using Le Chatelier's principles and so and to drive the equilibrium you typically use a large excess of alcohol or remove water as it's being formed or both, you can do both things. So there would be a large excess here.
10:06
Let's draw the product, our OR prime, OR prime, we've got two of them here. Our side product is water which we want to be paying attention to if we're trying
10:20
to figure out how to drive equilibrium. So a large excess of water or remove water as a, a large excess of alcohol or remove water as it's being formed.
10:41
So those are the two most common ways. Standard way to remove water as it's formed is to azeotrope with benzene or toluene. Alright so let me show you what the setup looks like for that and this is using a
11:04
Dean-Stark trap, kind of a really cool reaction. I did this reaction and I thought oh this is so cool I'm actually synthesizing water in this reaction. So that's on the next page and I'm going to show you what that looks like. So this is from a Brown and Foote book that we used to use, it's a really great
11:24
drawing of this. I would love to do this in the undergraduate labs but the Dean-Stark traps are really expensive. Alright so here's the idea here. Here's your reaction, you have let's just say aldehyde, what are they using?
11:40
They're using aldehyde or ketone and you're using alcohol. You've got to have two alcohols because you're incorporating two alcohols in your product and then you mix that with benzene or toluene. Why benzene or toluene? In this case they're using benzene because benzene forms an azeotrope with water. So what's an azeotrope? It forms a, in the gas state it forms a structure, the boiling point is different
12:04
than benzene and different than water it's at some intermediate value. So they actually go, they co-distill. So you're doing this reaction, you're boiling benzene, benzene as the water's formed is forming an azeotrope and so it comes up here, it comes up here, it comes up here and
12:23
then it goes into this condenser right here right? So this condenser, once it condenses the benzene and the water don't mix anymore do they? They form a separate layer. So what happens is it comes down here and it drips down in here but what's more dense
12:44
benzene or water? Water goes to the bottom. So these, as soon as this condenses they're no longer together and so the water goes to the bottom, the benzene goes to the top. And so once you get too much benzene here if this overflows it just drips benzene right
13:04
back into the reaction. So that allows you to, you can actually measure the amount of water you have here, the one that I used had gradations on here so you could measure how much water am I actually forming in this reaction and then you'll know when you're done here.
13:21
And then if this gets too full of water you don't want the water to go all the way up here or else it'll go back in here you can just drain it with a stopcock. So this is how you, the very common way to drive water off as it's formed. And that's a Dean-Stark apparatus or you can call it a Dean-Stark trap. So really really nice drawing of that.
13:41
Alright so by the same token if an acetal is placed in excess water with a trace of acid the ketone will recover from the reaction mixture, this is known as a hydrolysis. So this is a reversible reaction, we have the reversible arrows right here. At equilibrium the ketone is the thing that's favored so without driving it it's
14:05
going to want to go back to the ketone. Okay so once you put that acetal on it comes off very easy. So this is what it looks like.
14:22
So here's our acetal that we just made above, reversible arrows here, H3O+, H2O. And you really only need catalytic H3O+, that's all you need. And it wants to go back to the ketone.
14:45
Same mechanism but reverse direction. You need to know the mechanism in both directions.
15:02
Next week in discussion we will do the reverse reaction. Okay so know both mechanisms. And then so this will be discussion week four as we'll do that.
15:26
So you may want to try it on your own before next week and see if it matches what you would talk about in discussion. Alright so some more points we want to make since acetals can be hydrolyzed under very mild conditions to regenerate the original carbonyl they're often used as protecting
15:41
groups for aldehydes and ketones. They make great protecting groups for aldehydes and ketones. Aldehydes and ketones only. So you can make an acetal from an aldehyde, you can make it from a ketone, you cannot make an acetal from an ester, an amide, an acid chloride, a carboxylic acid, this
16:03
is only aldehydes and ketones. And more commonly rather than making this type of acetal is to make a cyclic acetal when you're using this as a protecting group. So this one's the most common. And this would be the conditions, tosic acid.
16:28
You could also use catalytic sulfuric acid but more commonly tosic acid. So very similar to sulfuric acid. So that's what tosic acid is. Toluene, Dean-Stark apparatus, why toluene?
16:41
Toluene's more common than benzene now because benzene's a pretty bad carcinogen so we try to avoid it if we can. And this would look like this and we'll look at the mechanism for this reaction in discussion also next week. So that's a cyclic acetal.
17:01
Side product is water. So we would drive this the exact same way using that Dean-Stark trap. Questions? Anybody on acetal formation? So a little bit more about acetals.
17:25
The reason why a cyclic acetal is used more commonly as a protecting group is for two reasons. Number one, recall that we have, recall this formula from GCAM.
17:40
Delta G equals delta H minus T delta S. And mostly we have been ignoring, we've been assuming if delta G is favorable then delta H is favorable, but we've been mostly ignoring this entropy component. But the entropy component
18:01
can play a role in some reactions. We've just been pretty much ignoring it. It's been off our radar. So this reaction is when you make a cyclic acetal it's more favored because if you think about it we have three reagents here. And if you look at the products, two products.
18:29
So we're decreasing entropy here. So decrease in entropy is not good.
18:44
Decrease in entropy disfavors reaction. And if we make a cyclic acetal we have two reagents here. And we get two reagents in our products.
19:02
So not as bad change here. So similar entropy.
19:22
So that's reason number one. Reason number two is that intramolecular reactions are more probable. So if you go through the mechanism to make the cyclic acetal, which we will do in discussion in the forward and reverse direction, you're gonna get an intermediate that looks like this.
19:49
And then you're gonna have the alcohol attack here. Okay, so that would be intramolecular.
20:02
And remember, making a five or six membered ring is very favored. This is gonna make a five membered ring. And if you compare that to making a non-cyclic acetal, this is what it would look like.
20:22
If you go through the mechanism you're going to get the alcohol attacking like this. This would be intermolecular. So in the intermolecular reaction
20:41
you have to wait for those two species to collide. You have to wait till they collide with enough energy and you have to wait till they collide in the right orientation. If it's intramolecular, you don't have to wait for the two species to collide. It's a much faster reaction, much more probable reaction. And remember, this is an uphill reaction. We are forming a product
21:02
that's less stable than our reactants. So this is more probable. All right, so for all those reasons, that's the typical protecting group that we're gonna use for aldehydes and ketones. Any questions on acetals?
21:24
So that's our second reaction. We did hydrates first, we did acetal second, and now we're gonna have addition of cyanide. So cyanide ionizes the carbonate group of an aldehyde or ketone to form a tetrahedral intermediate called a cyanohydrin. So yet another new functional group for you.
21:40
So here's what it would look like. Cyanide ion in step one. This is a good nucleophile.
22:02
It attacks carbonyl directly. And then once it attacks the carbonyl, what do we get? We get a deprotonated cyanohydrin,
22:20
so we have a negative charge on oxygen. We've just formed a new carbon-carbon bond, so this reaction needs to go on your carbon-carbon bond forming page. And then in the second step, we add acid to protonate.
22:51
So a cyanohydrin is a carbon that is attached to a hydroxyl and a cyano group, a cyanide group.
23:13
So and again, add this to your carbon-carbon bond forming page. This is a new carbon-carbon bond forming reaction.
23:32
All right, so we make a couple points about this reaction on the next page. Aside from it being a new carbon-carbon bond forming strategy for aldehydes and most aliphatic,
23:43
remember what aliphatic means? Not aromatic. Aliphatic means not aromatic. For aldehydes and most aliphatic ketones, the position of equilibrium favors cyanohydrin formation, so cyanohydrins are more favored than acetals or hydrates.
24:02
For many aryl ketones, so that aryl means we're remaining right here that we have aromatic ketones. For many aryl ketones and sterically hindered aliphatic ketones, the position of equilibrium favors starting materials. So sterically hindered aliphatic ketone.
24:22
Let's show an example here. Maybe a ketone with a tert-butyl group on one side and a methyl on the other or maybe a tert-butyl group on both sides. So when you start getting steric hindrance there, you slow the reaction down quite a lot.
24:43
All right, so here's an example, benzaldehyde cyanohydrin, also known as mandelinitrile. This is synthesized by millipedes. This is a reversible reaction. It's in our reversible reaction chapter, so it's synthesized by millipedes.
25:02
It's also found in bitter almonds and peach pits. So if you have a bag of almonds and one of the almonds is bitter, you probably want to spit it out because you're going to get a little bit of cyanide if you don't.
25:21
And peach pits. Okay. You also don't want to chew on peach pits, okay? So I had a student one time and they turned white as a ghost and they said, I chew on peach pits a lot. I said, okay, and I'm like, you're here a lot, you're alive, you're fine, right? You haven't died, so you're fine.
25:43
Anyway, so when threatened, it's released, okay? So millipedes release this when threatened. Inside the animal that it gets shot on,
26:07
it undergoes enzyme-catalyzed reverse cyanohydrin formation. It undergoes enzyme-catalyzed
26:23
reverse cyanohydrin formation. So it goes back to benzaldehyde and the side product is hydrogen cyanide.
26:45
Not enough hydrogen cyanide to kill an adult, but enough to kill a small mouse. So a little interesting fact about cyanohydrins.
27:04
Questions on cyanohydrins, anybody? Okay, we have another functional group we're going to talk about and that is imines and then we're going to talk about enamines. So a bunch of new functional groups in this chapter. So addition of primary imines to give imines,
27:22
imines are also known as shift bases. I didn't learn them as shift bases so I don't call them shift bases, but I know when I went to grad school and so this one guy was talking about, oh shift bases, I'm like, what is he talking about? I had no idea until I looked it up. So it's just an interchangeable word for imines. And so here's what the product looks like.
27:43
Something completely different than what we've been talking about. But we ran into these in the last chapter, didn't we? This is an imine.
28:02
So it's like the nitrogen analog of a carbonyl. So instead of the oxygen, you have a nitrogen. So the nitrogen of course has three bonds because it's not oxygen, but that's an imine. Side product here is water.
28:21
And there's a couple of different ways to do this reaction. You can remove water like we talked about with an acetal, but sometimes you can precipitate the imine. So the reaction is driven by precipitation,
28:42
if applicable, if you can do that, precipitation of the imine or a removal of water as it's formed. So this is another uphill reaction. The product is actually less stable than the reactant.
29:03
Okay, so you will have to drive it if you want to get any decent amount of imine in this reaction. Followed compounds related to ammonia also react from similar compounds. So you can, if you use a hydroxyl imine, it forms something called an oxime.
29:21
You don't need to know these names, but you may run across these. If you use hydrazine, it forms a hydrazone. If you use phenylhydrazine, it forms a phenylhydrazone.
29:50
If you use 2,4-dinitrophenylhydrazine, it forms something with a short name, a short abbreviation. It forms 2,4-dNPH is the abbreviation.
30:08
And so these are very, very similar. So very similar to an imine. So if you had, if you used hydroxyl imine, okay, instead of this, in the place of the methyl,
30:20
you'd have an OH right here, okay? If you used hydrazine in the place of the methyl, you'd just have another nitrogen. You'd just have another amine. So it's just like that. The mechanism's gonna be exactly the same. So let's do the mechanism.
30:55
You're only gonna have an acid-catalyzed mechanism for this, we're not gonna do a base-catalyzed mechanism and I'll show you why in just a minute.
31:01
Acid-catalyzed, pH five is the best. pH five is the best. So what happens is, so what that means is you're gonna have, at pH five,
31:21
you're gonna have some of the amine protonated but not all of the amine protonated. Now is nitrogen a good nucleophile? Yeah, it is actually. So since it's a good nucleophile, it's going to attack directly.
31:41
We are not going to protonate first, even though we have a slight amount of acid in here. We have a mildly acidic conditions. We're not gonna protonate first because the nitrogen's a really good nucleophile, only a small amount of the amine is protonated and we're not gonna protonate the oxygen first. So a good nucleophile,
32:03
so this is really our exception here. Good nucleophile attacks carbonyl directly, right.
32:22
Again, reversible arrows. Let's see what happens when we do that. We have two things that we need to do here. We need to, nitrogen's gonna have a positive charge,
32:41
we need to deprotonate nitrogen and we need to protonate oxygen. Could we do that intramolecularly? What do you think? Let's count atoms. You have to make a five or six number transition state. One, two, three, four. No, it can't reach. So we have to turn this into two steps.
33:02
All right, so at pH five, we have some protonated amine. I'm gonna do this step first, but it's okay if you don't do this step first. Definitely, I'm gonna do this step first, so I'm gonna deprotonate nitrogen
33:22
and then I'm gonna use the protonated nitrogen to protonate oxygen in the next step. So in that last step, I just used,
33:41
I just made protonated amine and that's what I'm gonna use for this. All right, so it's gonna come and grab a hydrogen. We're gonna break the nitrogen hydrogen bond.
34:21
This is what we call a carbanolamine. Another functional group, how about that? Carbanolamine, analogous to a hemiacetal.
34:45
So carbanolamine, that's the first phase of the reaction. In the second phase of the reaction, we're gonna do a dehydration. So we're gonna, we need to lose that hydroxyl group and our rule of thumb for all these reactions is
35:00
in an acid-catalyzed reaction, we always protonate the leaving group before it leaves. So we're gonna protonate that leaving group before it leaves. So I'm gonna redraw the carbanolamine here and I'm gonna protonate oxygen.
35:31
And this is the whole reason why we have acid in this reaction, slightly acidic conditions is because we really want to protonate
35:40
this leaving group before it leaves.
36:09
All right, and then what's gonna happen is the lone pairs of nitrogen are gonna come down and we're gonna kick off our leaving group. So we've got a lot of mechanisms in this chapter
36:20
but they're very, very similar. Each one of them is very similar. And as you can see, once we do that, we're one step away. So this is an iminium ion and now we just need
36:41
to deprotonate to make the imine. So I'm just gonna deprotonate with imine
37:07
and we're done. Oh, that's a positive charge, isn't it? Let's fix that.
37:23
All right, so think you can do that on a test? Yeah? All right, so that's imine formation. Special points, the reaction runs best when it runs slightly acidic. I was gonna draw a graph for you, I have it already drawn in here, but I didn't.
37:40
So we're gonna draw a graph right now. I just ran out of time during that non-break, that non-spring break that they like to call a break. Okay, so let's do rate of the reaction as a function of pH. So pH down here, we're gonna have one,
38:02
two, three, four, five, six, seven, let's go to eight and nine, okay? See what happens to this reaction as a function of pH. All right, so it starts off here,
38:21
really small rate of reaction right here, starts down right here, and then it peaks at somewhere, it's right around, we're gonna say five, it's probably closer to 4.5, and then it drops down to nothing at eight. So does that look centered at five?
38:41
Sort of, hopefully yours looks better than mine. So this is about pH 4.5, you'll see it on some, it looks more like five and some looks like five, and I just say five just to round it. All right, so let's look at this. Why would the reaction be zero at a pH of one?
39:03
Essentially zero, why do you think? So let's go back and look at the first step here. What has to happen in the first step? The amine has to attack the carbonyl.
39:22
If that amine is completely protonated, can it attack the carbonyl? No, so that's why we have zero rate of reaction. Okay, zero rate of reaction. And so as we raise the pH, we have more and more amine that's not protonated and the reaction can go quickly.
39:41
Why does it drop down? What happens at eight? Why do we have zero reaction at eight? If we're at pH eight, we're not protonating the hydroxyl when it leaves, okay? Now maybe that doesn't mean a lot to you because we've seen hydroxyl leave before
40:01
in certain instances, but in amine, and we can have a hydroxyl leave when we're making a carbonyl, but an amine is not as stable as a carbonyl. So the reaction goes way down. So that's why we're doing an acid catalyzed mechanism because that maximizes the rate of the reaction. So what you really need to write
40:20
if you're making an amine on an exam is you write your amine and then you can just write pH five and I'll know exactly what you're talking about, okay? So slightly acidic so that leaving group can leave. So we're gonna label and we're gonna say all the things I just said so you don't have to go back and look at the podcast to get that down. So at a lower pH than five,
40:50
methyl amine is significantly protonated.
41:09
All right, so what it's gonna look like is this
41:22
and that's no longer a nucleophile. We've just, when we protonate that, we change that amine into an electrophile. So no longer nucleophilic, no lone pair to attack with.
41:51
And then our second thing is at high pHs, at higher pH than five,
42:07
the leaving group is not protonated. The leaving group is not protonated. It drops pretty rapidly here. And the hydroxide is not gonna leave.
42:21
The hydroxide can leave to form a carbonyl. We'll see that in chapter 21, but the, in chapter 22, but the hydroxide is not gonna leave to form an amine.
42:41
All right, so that's point number one. Questions about that aspect of the reaction? Anybody? And the second point I want to make about this, in most of these acid-catalyzed reactions, we've protonated oxygen first and we don't here.
43:01
So why is that? So in previous acid-catalyzed reactions, we protonate the carbonyl first and then we have the nucleophile attack.
43:32
Okay, and so in this reaction, that doesn't happen. We said because the amine is strong enough to deprotonate the carbonyl, I mean the amine is strong enough
43:42
to attack the carbonyl without protonation, but the other reason is is that this is not formed because the amine will be deprotonated first and the amine will be protonated first.
44:02
Sorry about that. So methyl amine is a stronger base than ketone and that's not erasing very well.
44:30
NH, the methyl amine is a stronger base than ketone. In this case, acetone. All right, and if we were to make this protonated carbonyl
44:44
and the amine came nearby, what would the amine do first? Would it attack the carbonyl or would deprotonate the oxygen? It would deprotonate the oxygen. So this is the one reaction, amine formation, enamine, where we don't protonate the carbonyl first.
45:03
Questions on amine formation? Anybody? Yes? Not usually. So it's like hemiacetal, yeah. Addition of secondary amines to give enamine. So yeah, one more. I think we're done with functional groups here after this.
45:21
I think so. We'll see if there's something I'm forgetting. So to make an amine, you use a primary amine. This uses a secondary amine. So secondary amine gives enamine instead.
45:43
All right, so let's draw the structure of an enamine.
46:02
Double bond between two carbons now. Side product is water, so you can drive this the same way we did enamines. You can drive this the same way we did acetals. So very common to have this removed as it's formed
46:25
to drive the equilibrium. All right, so mechanism, the first step of the mechanism formation of the carbonyl amine is exactly the same.
46:40
So same as step one for amine formation. The second step is dehydration
47:00
and every step except for the very last one is also gonna look like amine formation. So let's go through that in the last minute. We'll see how far we can get. So let's draw our carbonyl amine that we get and you'll see why this is different.
47:22
We're going to protonate our carbonyl amine. We're gonna protonate oxygen so it can leave. You don't see any oxygen in an enamine, so we know that that group has to leave. So we're gonna grab a proton from protonated.
47:40
This is also pH five or catalytic acid. So, so far the same. This next step is the same.
48:01
Electrons on nitrogen come down, kick off water. Only the very last step is different. Now in the last step of amine formation, we deprotonated nitrogen.
48:21
Can we deprotonate nitrogen here? No, there's no proton to deprotonate. So that's why this is different. So what we do instead is we eliminate what we call a beta hydrogen. So this is gonna come in. We're gonna grab this proton.
48:42
We're gonna move electrons over here and up onto nitrogen and that's our enamine. So that's the difference here. If we had a proton to remove on nitrogen, we would have done it but we didn't.
49:01
So we're stuck with the enamine. All right, that's time. We'll stop right there and we will continue this on Friday.