Monosaccharides - Osazones: Videos & Practice Problems

Monosaccharides undergo a reaction with primary amine derivatives, such as phenylhydrazine, leading to the formation of phenylhydrazones through nucleophilic addition to the carbonyl group. When excess phenylhydrazine is present, these derivatives tautomerize to form osuzones, specifically C1, C2 diphenylhydrazone derivatives. This reaction is significant in carbohydrate chemistry, historically aiding Emil Fischer in distinguishing between glucose and mannose epimers. Understanding this mechanism is crucial for grasping the structural analysis of monosaccharides and their derivatives.

Monosaccharides - Osazones

What's up? In this video, we're going to talk about a carbonyl site reaction of monosaccharides called osazones. So guys, one of the reasons that you've got to love monosaccharides is because they have so many functional groups. They have so many alcohols, they have carbonyls. And in this video, we're going to talk about a specific reaction that happens to the carbonyl of a monosaccharide. It turns out that aldose aldehydes, so the aldehydes at the top of an aldose, are susceptible to the same exact nucleophilic addition reactions that we learned back for carbonyl chemistry. Okay? So you can't forget those reactions. Those reactions are very relevant to monosaccharides because monosaccharides will have carbonyls that can react in those reactions.

Do you guys remember what would happen when you expose a ketone or an aldehyde to a primary amine in acid? What you would get is an imine. You would get a functional group called an imine that had a double bond to the carbon. Okay? Now, remember that similarly, if you exposed a carbonyl to a primary amine derivative, meaning it's not exactly ammonia, it's not exactly a primary amine, maybe it has some group on it like alcohol or a benzene ring or something like that, that benzene ring would stick off the end, but you would still get an imine. So that product would be called an imine derivative. And guys, if you're getting a little bit lost by what I'm saying, maybe you've just started watching this chapter. I have a whole section in carbonyl chemistry talking about imines and imine derivatives. Okay? You can go back and watch all those videos.

Anyway, what I'm trying to do is remind you of what we already know so that we can move on and understand osazones. So when the specific primary amine derivative Phenylhydrazine is used, the product is referred to as a Phenylhydrazone, and these are again things we've already discussed from the carbonyl chemistry chapter. So when I talk about Phenylhydrazine, what I'm talking about is this molecule right here. Now this is called a primary amine derivative. Why? Because notice I have a primary amine here. This is a nitrogen with 2 H's and 1 benzene ring as a Z group instead of a usual R group. Okay?

Now, let's move to what happens if you react a primary amine derivative with the carbonyl in acid. According to our rules of using an imine derivative, we should expect a double bond from the nitrogen to the carbon with the benzene ring coming off. So, let's plug that in. What we would get is a double bond N with another N and the benzene ring. And this N, the attached nitrogen, requires an H to complete its 3 necessary bonds. This is what we would expect even if I hadn't taught you anything new, if you had just seen this reagent with acid a carbonyl, you should know from carbonyl chemistry that the aldehyde would make a Phenylhydrazone or a Phenylhydrazone derivative because in this case, it's not just a Phenylhydrazone; it has a sugar attached to it.

But now, this is where things get interesting. When exposed to additional equivalents of Phenylhydrazine, meaning that instead of just using a 1:1 mole ratio, what if we use 3 moles or excess moles of Phenylhydrazine? Your imine derivative, the phenylhydrazone derivative, is going to continue to tautomerize and react. The resulting product is going to be something utterly new, completely new that you've never learned before, and that's why we need to learn it here. That product is a C1, C2 Diphenylhydrazone derivative that we call an osazone.

Last point—this reaction was very important for Emil Fischer, who's really the father of carbohydrate chemistry. In 1888, he used osazones to prove that glucose and mannose were epimers of each other. Surprisingly, these compounds were very toxic; he ended up dying because he was exposed to so much Phenylhydrazine and osazones in his experiments that he developed cancer. But his legacy is tremendous, as his discoveries in sugar chemistry paved the way for identifying monosaccharide structures long before modern techniques were available. We don't use osazones much now, but their role in scientific history is why they continue to be taught.

Awesome, guys. So hopefully this made sense. Let's go ahead and move on to the next video.

Here’s what students ask on this topic:

What is the osazone formation reaction in monosaccharides?

Osazone formation is a reaction where monosaccharides react with excess phenylhydrazine to form C1, C2 diphenylhydrazone derivatives called osazones. Initially, the carbonyl group of the monosaccharide reacts with phenylhydrazine to form a phenylhydrazone. With additional phenylhydrazine, the phenylhydrazone tautomerizes and reacts further to form the osazone. This reaction is significant in carbohydrate chemistry for distinguishing between different sugars, such as glucose and mannose, which form distinct osazones.

Why is phenylhydrazine used in the osazone formation reaction?

Phenylhydrazine is used in the osazone formation reaction because it is a primary amine derivative that reacts with the carbonyl group of monosaccharides to form phenylhydrazones. When used in excess, phenylhydrazine facilitates the tautomerization and further reaction of phenylhydrazones to form osazones. This reagent is particularly useful for identifying and distinguishing between different monosaccharides based on the unique osazones they form.

What is the significance of osazone formation in carbohydrate chemistry?

Osazone formation is significant in carbohydrate chemistry because it was historically used by Emil Fischer to distinguish between different monosaccharides, such as glucose and mannose. Osazones crystallize out of solution easily, allowing for the identification of sugars based on their unique crystalline structures. This reaction played a crucial role in determining the structures of monosaccharides and understanding their epimeric relationships.

How does the reaction mechanism of osazone formation proceed?

The reaction mechanism of osazone formation begins with the nucleophilic addition of phenylhydrazine to the carbonyl group of a monosaccharide, forming a phenylhydrazone. With excess phenylhydrazine, the phenylhydrazone undergoes tautomerization, allowing for further reaction at the C2 position. This results in the formation of a C1, C2 diphenylhydrazone derivative, known as an osazone. The detailed mechanism involves multiple steps and is complex, but the key takeaway is the formation of the osazone through the reaction of the carbonyl group with phenylhydrazine.

What are the historical contributions of Emil Fischer to osazone chemistry?

Emil Fischer made significant contributions to osazone chemistry by using osazone formation to distinguish between different monosaccharides. In 1888, he demonstrated that glucose and mannose were epimers by forming distinct osazones. Fischer's work with osazones helped establish the structures of various monosaccharides and laid the foundation for modern carbohydrate chemistry. His research was pivotal in understanding the structural relationships between sugars.