Concept: General Reaction3m
Hey guys in this page I want to talk about a base catalyzed reaction of monosaccharides, which is called epimerization, so guys in basic conditions it turns out that monosaccharides can undergo a multitude of tautomerizations and isomerizations that make life really complicated, in fact, it's for this reason that we typically don't expose monosaccharides to base because it leads to so many byproducts, let me show you one of them, so the most straightforward of these is epimerization, okay? Epimerization, remember what an epimer is, it's when you are switching just the position of one chiral Center. Now, when you are switching the chiral center of C1, that makes anomers, and that's called mutorotation but when you're switching the position of c2, that's called epimerization. So, monosaccharides will readily epimerize the C2 position, several possible mechanisms exist, this can either proceed through an enolate mechanism or an enediol mechanism, I'm going to show you both of them, but let me just show you how to the general reaction to start off with. So, once again I'm just kind of kicking on our beta D-glucopyranose because it's a molecule that you should be really familiar with by now, and I'm showing you what happens in base.
Well, we've already discussed mutorotation, right? mutorotation is essentially epimerzation of c1, okay? It's where you can get, that'll take Cl, it's where you can get carbon-1 to form to anomers to form some of the Alpha and some of the beta because, we've already discussed this, but it turns out that another reaction that can take place is epimerzation where. Now, be the, I'm sorry, beta D-glucopyranose can equilibrate into D-mannosepyranose, why is that? because it turns out that now the two position can actually switch from going down to going up, how does that happen? I'm going to show you the mechanisms but I just want to show you that both of these are going to happen at the same time and it's uncontrollable, you're going to start to get mixtures of isomers because you're going to get different anomers and now you're going to get different anomer of a completely different, completely different monosaccharides, mannose is a different monosaccharide than glucose, that's because now that OH is going to face towards the left instead of towards the right, also notice that in the epimerization the anomers are also in equilibrium with each other. So, it's just a big mess, alright? so in the next video we're going to show you the enolate mechanism and then I'm going to show you the enediol mechanism.
Concept: Enolate Mechanism5m
So, let's go through the enolate mechanism first, and actually my first question for you is, can you think of any reasons why specifically the c2 position of a monosaccharide is susceptible to epimerization in base, what we're talking about is this position right here, can you think of any other principles in organic chemistry that would make that position specifically susceptible to base? and guys, we do know of a principle that would apply here and that would be the principle of alpha carbons. Remember, that alpha carbons more than usual are uniquely acidic due to their proximity to a carbonyl, remember that the alpha carbon is always going to have hydrogen's that are much, much more easy to deprotonate than other hydrogen's while these other hydrogen's have Pk's of, I don't know, you know, around 50, this guy here is going to have a pKa of around 20, specifically, when I say this guy, I'm talking about this hydrogen right here, because that's the only alpha hydrogen. So, in the presence of base it's not going to be difficult for my OH to remove that hydrogen and form an enolate and that's exactly what we're going to do, let's go ahead and do that here, the first step is that my OH minus or my base comes in takes away an H, I make a double bond and then kick electrons up to the O.
So, what that's going to do is it's going to form an enolate that now looks like this, double bond here, oops, no, double bond here and negative charge here. Notice that now I've lost the stereochemistry of this OH, this OH is now trigonal, on a trigonal planar carbon, it could either be on the right or the left because it's now double bonded. Now, guys there may be some of you that are saying, Johnny, that's not how I usually draw a enolates, usually how I draw an enolate would just be with a double bond H and with the negative here, is that also possible? totally, that's the same thing, these are actually resonance structures of each other. So, it's totally fine if you draw that way, the only reason I do it this way is because that's the way your book tends to draw it and that would be like the major contributor of the enolate. So, your book tends to draw like that but if you, in principle this is the same exact reaction if you just draw the negative on this carbon, because once again what's going to happen is that that OH is going to be able to flip back and forth because now it doesn't have stereochemistry, okay? Does that make sense? awesome. So, now that is what happens? Well, now we would just protonate again or not protonate again, we would now protonate. So, then in the next step you have water, okay? And, what you're going to do is just reform this double bond, so that the whole bond, I'm sorry, reform the carbonyl. So, this negative charge is going to come down, make a double bond and then this go bond is going to grab a H and now, it's going to become the aldehyde once again but notice that because we lost the stereochemical information on that c2 carbon. Now, it's possible for the OH to basically racemize and go to the other side, and by the way guys, this is not unique to sugars, one thing that we learned in enolate chemistry is that enolates always racemize the Alpha position. So, essentially nothing new is happening here, all we're doing is we are racemizing the alpha position of the sugar, which happens to be the C2 position. So, this totally falls in line with all the principles that we learned about enolate from enolate chemistry from your alpha carbon chapter, okay? Awesome guys, so that was the enolate mechanism and next I want to show you guys the enediol mechanism, which is a competing mechanism that accomplishes the same thing.
Concept: Enediol Mechanism3m
Okay guys so the enediol mechanism is super, super similar, we're going to go ahead and take away the H, make the double bond, kick electrons up to the O, this is going to give me a negative charge here and a double bond here, the only difference guys is that I'm now going to protonate. So, I'm going to protonate that negative charge to give me literally what's called an enediol, enediol, meaning that I have a double bond with two alcohols on it enediol. So, that's my enediol intermediate. Now, the enediol intermediate, once again the information of c2 has been lost in terms of the stereochemical information, it could go in either direction. So, I'm just going to go back to the original enolate and back to the monosaccharide.
So, now in this next step, I'm going to take base again, I'm going to deprotonate and that's going to give me a negative charge here with a double bond and then finally I'm going to reform the carbonyl and grab an H and that's going to give me my epimer where now the OH is faced towards the other side and I now have a new monosaccharide and basically what just happened was just another route towards c2 epimerization, you might even say, Johnny, it seems unnecessary, why did you add, it's basically you're just adding a proton to take it away again and that's exactly it but this is one of the important mechanisms, one of the other important ways that epimerization can take place. So, just you know basically enediol is just a longer version of enolate because enolate I just kept it as a negative charge, you went back, here I protonated, deprotonated again and then finally went to the epimer, okay? Hope that makes sense, the same thing happened at the end, let's keep moving on.
Show how C3 of fructose can epimerize under basic conditions.
(a) Draw D-allose, the C3 epimer of glucose.
(b) Draw D-talose, the C2 epimer of D-galactose.
(c) Draw D-idose, the C3 epimer of D-talose. Now compare your answers with Figure 23-3.
(d) Draw the C4 “epimer” of D-xylose. Notice that this “epimer” is actually an L-series sugar, and we have seen its enantiomer. Give the correct name for this L-series sugar.
What sugar is the C-3 epimer of D-fructose?
a. What sugar is the C-3 epimer of D-xylose?
b. What sugar is the C-5 epimer of D-allose?
c. What sugar is the C-4 epimer of L-gulose?
d. What sugar is the C-4 epimer of D-lyxose?
Draw the mechanism for epimerization at the C2 carbon of this molecule