Practice: Predict the product(s) for the following reaction. Provide the mechanism of the imine hydrolysis step if required.
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|Monosaccharides - O-Glycoside Hydrolysis|
We know that aldose aldehydes are susceptible to the same nucleophilic addition reactions that we learned in carbonyl chemistry. Let's now learn a reaction that involves the formation of a cyanohydrin. The neat thing about this reaction is that the cyano group can then be reduced and hydrolyzed to form a new, chain-lengthened aldehyde.
Hey guys. in this video I'm going to show you guys how to make monosaccharides chains longer through a process called the Kiliani-Fisher synthesis. Alright, guys so you have to love saccharides because saccharides have alcohol they have carbonyls there's so many different things you can do with them they're so versatile and one thing that you should always keep in mind is that the reaction that we learned about aldehydes and ketones back in your carbonyl section of organic chemistry apply, many of those reactions apply to saccharide because we have an aldehyde present, okay? So, just keep in mind that many of the same nucleophilic addition reactions that we learned in your carbonyl chemistry chapter are going to apply to that aldehyde, okay? Now, specifically, when we expose an aldehyde to HCN hydrogen cyanide, aldoses can reversibly transform into cyanohydrin, okay? Now, guys this shouldn't be a shock to you because this is exactly what we learned back when we did carbonyl chemistry, okay? What we learned is that if you react in aldehyde or a ketone with HCN what's going to end up happening is that you get a CN negative that comes in and attacks and kicks electrons up to the O, right? So, we're just drawing out the cyano hydrogen mechanism right now and then what would happen, this is called a nucleophilic addition the fan would attack the positive of the carbonyl, kick the electrons up to the O, what you would get now is a C triple bond n attached to that carbonyl carbon and then you would get a C other than an O minus and that O minus would later on get protonated by this h that disassociated it. So, eventually this becomes an OHA and guys, this is what we call a cyanohydrin functional group, okay? So, everything that I just showed you is 100% based on other videos, if you want to type in cyanohydrin into your search bar right now, you will find the same back mechanism, just instead of working with sugar, we were just working with a regular aldehyde, okay? So, there's 0 new information here. Now, what's interesting is that we can take advantage of the fact that cyano groups have an extra carbon, we can take advantage of that fact to length in the chain and if we can keep adding cyano groups, we can keep lengthening this chain. So, ideally we could turn a pentose into a hexose by just adding more and more cyanohydrins, okay? Now, the way that we do this is that we're going to have to hydrolyze that CN and turn it into, turn into a carbonyl in some way, okay? So, let's go ahead and figure out how to do that, okay?
So it says, the cyano group can then be reduced and hydrolyzed to form a new chain length in aldehyde, okay? So, guys it turns out that we have learned in the past how to reduce nitriles or cyano groups, okay? But, when we have studied reduction of cyano groups in the past, it's usually been with catalytic hydrogenation, and what catalytic hydrogenation does is it adds hydrogens to every pi bond. So, if we just use, for example, h2 and palladium, let's say, if we just use that as catalytic hydrogenation, what we would expect to get is ch2, don't draw this by the way because this is the wrong answer, NH2, okay? It was completely reduced, we would add a ton of H's. Now, it turns out that we don't want this because we only want to reduce it to a double bond not to a single bond because we want to keep a carbonyl, okay? So, what we're going to do is we're going to, we're going to develop some kind of reduction, not this one, but we're going to build some kind of reduction some weaker form of reduction to leave it as a CN double bond. So, we're going to do this, C double bond NH, okay? And then obviously this H is still present. Now, you don't know what this reducing agent is but I'm just letting you know that, that's going to be part of the synthesis is to find a reducing agent that only reduces it one step and not two steps, cool? Then once you have this functional group, this is called an amine and guys we learn in back in the carbonyl, in the carbonyl chapter, that amines can be reversibly hydrolyzed into carbonyls using just water and acid, through hydrolysis it's possible to turn that N into an O, okay? Now, if you're wondering, Johnny, this is just going over my head, I don't know any of these reactions, I have all these on video. So, if you type in amine and you'll see all the amine actions and you'll see mechanisms of how we can turn a double bond N into a double bond O, if you search cyanohydrins you can look at the first step. So, really the steps that you should already know from what we've already learned in organic chemistry are this step and this step, both of these steps come from carbonyl chemistry, the only set that should still be a big question mark for you, is this step, and that's fine because I'm going to explain that step more in a little bit okay, cool? So, just before I go into the specific reagent and the specific mechanisms, I'm trying to give you the big picture, and one thing I want to show you, oh by the way, I'm sorry, this would still be an h, but one thing I want to show you is that this synthesis can be repeated multiple times because notice that at the end we end up with an aldehyde that is now one carbon longer than before, right? Before starting with ribose, which is a pentose, right? Now, I have one, two, three, four, five, six, carbons and I still have an aldehyde present, what can aldehydes do when you expose them to a CN negative, they can react again and they can do another cyanohydrin, so the whole idea here is that you can repeat this cycle as many times as you want and get your carbon chain to be longer, longer and longer and you can theoretically just keep on going forever, okay? Now, one thing to keep in mind though is that the chirality at carbon 2 is always going to be a mixture, it's never going to be a solid like diastereomer or solid configuration and the reason guys is because this carbon here is the same as this carbon here, it never had chirality, it started off as a chiral because it was trigonal planar and now after we've added the alcohol we don't know which side the alcohol added to it, it could have added from the right it could have added from the left, so the one limitation of Kiliani-Fischer is even though it's a great way to lengthen the chain, you're going to continue to get mixtures of configurations at every carbon as you go up, the more time you do it the more uncertain carbons you're going to have where you don't know if the OH faces towards the right or if the Oh faces towards the left, we're actually going to get is a mixture of both and actually as it's not even 50/50 because these are diastereomers. So, they tend to have different properties so it could be a mess, it could be like 60% of the right and 40% of the left like you don't really know. So, that's just one of the limitations of Kiliani-Fischer, does that make sense so far? cool. So, in the next video, what I want to do is I want to talk about some specific reagents and I want to talk about why, why in my title it's modern Kiliani-Fischer and I'll explain that in the next video.
The original Kiliani-Fischer synthesis required two additional steps after cyanohydrin addition, and resulted in poor yields. However, an improved reducing agent, (H2, Pd/BaSO4), was developed to form imines instead of amines.
So, why did I call this reaction the modern Kiliani-Fischer synthesis? Well guys, that's because when doctors Kiliani and Fischer first made this reaction they were using slightly different reagents, so the first set was the same. it was still done through a cyanohydrin. So, what they would do is, just as I explained in the first step on the previous video, they would add a CN group here and this would become an OH and they would form a cyanohydrin, so that part was identical but the reagents that they used afterwards to hydrolyze that CN were actually very different, it required more steps, so it required two additional steps and it resulted in poor yields, okay? So, it was a very important reaction at the time back in the 1800's but we had 150 years to improve it and now the new set of reagents is what would be referred to as the modern Kiliani-Fischer okay, cool? So, what are these newer reagents. So guys, it turns out that we were able to design a better reducing agent that would work on the CN and turn it into an amine, okay? And this reducing agent you've never really seen this exact reducing agent before but it's similar to other ones that we've seen because what this is it's h2, palladium. So, this looks like catalytic hydrogenation but it's not exactly palladium, it's Palladium on barium sulfate. So, Pd over BaSo4, this combination you're just going to memorize it probably put it on a flash card, this is what we call a poisoned reducing agent and why, what poison means guys, if you ever hear the term poisoned, it means weaker, okay? So, whenever you hear poison that means it's weaker than normal, normal. So, another term of a poisoned, another poisoned hydrogenation is Lindlar catalysts. Remember, how Lindlar instead of going from triple bond to single bond it goes to a C's double bond, this goes all the way to organic chemistry one? Well, in the similar way this is a poison catalyst because instead of turning my CN into CH2 and NH2, which is what we would expect from a regular catalytic hydrogenation, what it's going to turn it into is remember, this is a triple bond, right? So, I'm going to just write it again, it's going to turn it into C double bond NH and then this is a CH, okay? And once again, let's just go ahead and write the reagents in, it's going to be H2 palladium and barium sulfate, cool? And once again, this is important because it turns it into an amine and once we have that amine, we can use any hydrolysis, which is a reaction that we learned a long time ago in carbonyl chemistry, to turn this into a carbon needle. So, then it will look like this it's going to go back to being an aldehyde and as we know this h is still there. So, we're just going to get an alcohol there and as we already talked about, this is the reason this is squiggly is because it's going to be a mixture of diastereomers because we don't know exactly where that OH is going to attach from, okay? So, guys, what you need to know is that the modern Kiliani-Fischer uses this palladium and Barium sulfate and you should probably know each intermediate step, how you're reducing to an amine and then how an amine is being hydrolyzed in an aqueous solution back to the aldehyde, cool? Awesome guys, so we're done with this video, let's move on to the next.
Ready for a practice problem?
Practice: Predict the product(s) for the following reaction. Provide the mechanism of the imine hydrolysis step if required.
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