Imines and Enamines

Concept: Concept: General Reactions

3m
Video Transcript

In this next page, we’re going to talk about the nucleophilic addition of neutral amines to carbonyls and this is going to yield imines and enamines.
The difference between an imine and an enamine is simply going to be type of amine that the carbonyl is reacting with. As you can see, when you react a carbonyl with primary amine, you’re going to get an imine. An imine has a functional group of basically a nitrogen with a double bond on it and possibly an R group on the top. Think about an imine is like a carbonyl but with a nitrogen. If it would have been a carbonyl with an oxygen, that’s an imine with a nitrogen on it. Notice that when they react a secondary amine, I get a different looking compound. This amine has two R groups. Instead of getting the double bond directly on the N, I actually get it down towards one of the R groups.
We’re going to go through both of these mechanisms completely. But I just want to ask you guys, why do you think that double bond might move? Why do you think it might be towards the bottom? Because if you have two R groups on your N, that means that if I were to put the double bond on the N, I would get a formal charge. To eliminate the formal charge, I'm going to have to move the double bond down to one of the R groups. That’s the biggest difference between an imine and an enamine. In fact, they’re pretty much the same exact reaction except for the final step. What we’re going to do is we’re going to through both of these mechanisms and I do want to say one thing really quick, that both of these mechanisms are going to pass through a very important intermediate. That intermedia is called the iminium cation. The iminium cation looks like this. It's a nitrogen with a double bond and with two things on it, either Hs or Rs and a plus charge, so two of these and a plus charge. We're always going to pass through the iminium cation and then how we resolve that cation is we determine whether it's going to be an imine or an enamine. Let's go ahead and look into the mechanism of an imine. 

Concept: Concept: Imine Mechanism

7m
Video Transcript

An imine is created when a carbonyl reacts with a primary amine and acid. You can also use ammonia. Ammonia would be considered as 0-degree amine. It’s the same thing. Either 0 degree or primary would both make an imine. You need an acid so I’m going to put H+ here.
For the purposes of this mechanism, I personally like it if I combine my proton with my solvent so that I don’t have multiple types of reagents I’m trying to work with. Can you guys just go ahead and assume with me that NH3 plus H+ would give me NH4+. That’s what I’m actually going to react with. For all of my reactions, for both of these mechanisms, I’m just going to use NH4+, which is fine. You can use any acid you want, whatever acid professor or your textbook gives you. I'm going to go ahead and draw it like this.
What do you guys think is the first step of this acid-catalyzed mechanism? You got it, protonation. How did you guess? Now I’m going to use reversible arrows, not forward arrows. I’m going to draw that I have a double bond H carbon. This has a positive charge. I'm going to go ahead and draw a resonance structure. I’m going to draw this structure so that I can understand what this positive charge is doing. Just so you know, disclaimer, your professor may not draw this resonance structure and that's okay because it’s still valid.
What I’m trying to say here is that there may be minor differences between my mechanism and the one that you learned in class, but again this is a valid mechanism and if you want to throw in a resonance structure, it's totally fine. Your professor isn’t going to dock you for doing this because all the arrows are going to the same place eventually. Now what this is going to do, since I have a positive charge, this is going to yield a nucleophilic attack. Let’s go ahead and take our NH¬3. It has a lone pair, so it's very attracted to that positive charge. We’re going to do a nucleophilic attack and what we're going to get is a compound that looks like this. We’re going to get OH, RR. Those are just R groups and then NH3+. Does it look familiar at all? If you guys have gone through the hemiacetal and acetal mechanism, pretty much everything has been the same up until this point.
The difference is going to happen here. We're going to consolidate a few steps. Instead of deprotonating this thing, we're just going to go ahead and start trying to get rid of that alcohol. The way we could do that is through a proton exchange. A better way to write this NH3+ would be to take the 3, change it to a 2 and then draw one H out. That’s going to allow me to do a proton exchange. This is going to yield a compound that now looks like, this OH2+, NH2, RR. Let me go ahead and backtrack and write down all the steps.
We said that this first one was protonation. The next one was nucleophilic attack. Now we just got proton transfer and now we're about to kick out the leaving group. But instead of it just leaving, we could actually use the electrons from my nitrogen to kick it out. What I could do is I could make a double bond and kick out the water. What this is going to make is a double bond N.
I just realized that my nitrogen is at the bottom. I wanted to face it up. If you don’t mind. I’m going to flip this molecule. I’m going to flip it so that now my Nh2 is at the top and it was making a double bond so I’m going to draw the double bond facing down. There's two R groups. I’m going to put the R groups facing down, positive charge. Do you recognize this intermediate? This is the iminium cation, plus we would also get water leaving. Now that is my compound, that’s my imunium cation. How do you think we can get rid of one of those Hs? We can use the conjugate base. Remember I had NH3 hanging around. I’m going to use NH3 and I’m going to deprotonate. I’m going to take away an H, give the elections to the N and what I'm going to get is my imine plus my catalytic acid and plus yeah, we did make a water. We lost a water like that. Now my product is an imine. How do I know this is an imine? Because it looks like a carbonyl except that has a nitrogen in it. Does that make sense?
This has a lot of steps but if you've watched the hemiacetal or acetal mechanism, this is extremely similar. If you haven’t watched those mechanisms yet, then when you get to them it will seem very similar to this. I'm just trying to show you guys how the mechanisms are very, very related. Also, I think I messed up on an arrow up here. This is supposed to be reversible. Sorry about that. I get too excited with this mechanism. But you have to make sure to go back if you make mistakes, always change it before you submit your exam. We're done with this one. Let’s move on to enamines.

Imines and Enamines Additional Practice Problems

Provide the missing product. Show only one most preferred product. Consider only monosubstitution for EAS where appropriate.

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Write a detailed mechanism that explains the following reaction of 6 to furnish piperidine 7 and cyclohexanone 8. Show all intermediates! Transfer protons intramolecularly!

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Complete the following reaction by drawing the structure of the principal major product. Indicate relative stereochemistry where necessary. If there is no reaction, write NR.

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Complete the following reaction by drawing the structure of the principal major product. Indicate relative stereochemistry where necessary. If there is no reaction, write NR.

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One of the following reactions are incorrect as written. Choose which reaction, A or B is incorrect and draw the correct product. Then fill in the 2 sentences below. 

 

Reaction           is incorrect. The correct product should be a                      .

Reaction           is correct because we formed a                     

 

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Predict the product when cyclopentanecarbaldehyde reacts with phenylhydrazine (PhNHNH2) in the presence of an acid catalyst. 

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What product will result from the reaction shown?

a. enamine

b. imine

c. hydroxylamine

d. amino acid

e. hydrazine

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Predict the product for the following reaction sequence.

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An iminium can be turned into an enamine in one step. Draw the mechanism of this below. Draw all the arrows to indicate movement of the all electrons, write all lone pairs, all formal charges, and all products.

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Complete the following reaction. Pay careful attention to the stereochemistry of the product.

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Indicate the order in which the intermediates would appear during the conversion of   1 into 2.

1) 1 → I → IV → II → 2

2) 1 → III → II → 2

3) 1 → V → III → I → IV → 2

4) 1 → V → III → II → 2

5) 1 → II → I → III → IV → 2

 

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Which compound would react with  A to give product B?

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The reaction of an amine with a carbonyl compound leads to an iminium ion, which can often convert into an imine or an enamine. Which combination below cannot form an enamine or an imine (i.e., must remain as an iminium ion)?

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What is the product of the following reaction?

 

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Which carbonyl compounds cannot form an enamine with amine 1?

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Provide a complete mechanism for the following transformation.

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Draw the major organic product in the box provided. 

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What combination of reactants can be used to form the product shown?

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What combination of reactants can be used to form the product shown?

 

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