Cyanohydrin - Online Tutor, Practice Problems & Exam Prep

Nucleophilic addition to carbonyls can produce cyanohydrins, where cyanide (CN^-) acts as a nucleophile. The reaction involves forming a negatively charged intermediate, followed by protonation, yielding a cyanohydrin. Cyanohydrins, containing a hydroxyl (OH) and a nitrile (CN), can undergo hydrolysis to form carboxylic acids or be reduced to primary amines using reducing agents like lithium aluminum hydride (LAH) or catalytic hydrogenation. Understanding these transformations is crucial for grasping the behavior of carboxylic acid derivatives and nitriles in organic synthesis.

Addition of Cyanide

Now that we understand the general mechanism of nucleophilic addition, it's important to really understand those specific nucleophiles that can attack carbonyls and make substituted alcohols. One of the most famous of these is cyanide. Cyanide is a negatively charged nucleophile that's used to make a functional group called the cyanohydrin. You might already kind of be able to guess what that is just by the name but I'll show you. Typically, CN is reacted as a negatively charged anion. I mean NaCN is very common. We could also see KCN. This is a very common way to represent it as well. As you can imagine, this is just straight up nucleophilic addition. I've got my CN negative. I've got my very strong partial positive charge. I get a nucleophilic addition mechanism. What this is going to make is a negatively charged oxide and my CN substituent. That is what I get after the first step. Then there's always going to be a protonation step that you can use. You can use water or some kind of mild acid to protonate. Obviously, that's not the mechanism for protonation. It would be something like this and like that. You would get your functional group. Your functional group, whenever you have a CN and an OH on the same geminal to each other, that's called a cyanohydrin.

Now, I wanted to inform you that there's another form of CN that's actually pretty common as well that doesn't require a protonation step. That one, I'm going to erase a few arrows if you don't mind. You can keep the ones that you have on your page. But just want to show you guys another example would be if I used or if I used HCN. HCN is a really interesting compound because if you just look at it, you might think, "Oh, that's a source of CN negative. But remember that the carbon-hydrogen bond is actually a very strong bond. Usually, carbon and hydrogen don't just ionize like that. That's actually a covalent bond. Covalent bonds usually don't just dissociate to make H⁺ and CN^-. That's kind of strange. Why would it do such a thing? The answer has to do with acidity, guys. It turns out that it's not that it's a weak bond in terms of polarity or that there's a dipole but it turns out that there's a very acidic bond. It turns out that HCN, if you guys remember your pKa's way back in the day, has a pKa of about 10. In normal aqueous environments, it's going to be ionized. It's going to be in an ionized form. Now the advantage of using HCN is that look what you got. You've got the CN^- and you've also got your proton to protonate. You could do NaCN and then water or you could just do HCN. Gosh. That's not what I meant to do. Or you could just use HCN and HCN will take care of both steps. It will do the nucleophilic addition and you'll go ahead and you'll add your hydrogen for the protonation step.

Now what I want to do is, I specifically want to talk about 2 other reactions that happen with cyanohydrins that really have nothing to do with the nucleophilic addition. But as a functional group, we should be aware of what you can do to a cyanohydrin. That's what we're going to do in the next two videos. Let's go ahead and start off with the first cyanohydrin reaction.

Nitrile Hydrolysis

Now that we know what a cyanohydrin is, let's go ahead and draw that in. We've got an OH on one side and a CH₃OH on the other. The first thing you guys should be aware of is that we have a nitrile. That's the name of the functional group. The CN is called a nitrile. Altogether, this is called a cyanohydrin. It turns out that nitriles are actually in a category of molecules called carboxylic acid derivatives. If this is something that you've already learned at this point in your course, then this is going to make perfect sense. If not, that's fine. I'm just going to help you guys understand it now. But it turns out that carboxylic acid derivatives are a category of molecule that by definition can be hydrolyzed to carboxylic acid. I'll just draw it out. It's in a category of molecule that can be hydrolyzed. There's a whole section of organic chemistry just dealing with carboxylic acid derivatives. Obviously, if you want more information, go there. But right here, we're just going to summarize it to say that there's acid and base catalyzed mechanisms for this to happen. Any combination of acid and water or base is going to get this to hydrolyze. You can see here I have water with acid, with base and heat. Heat can always help with these reactions. It can always help to hydrolyze something. What you're going to get is nothing happens to the alcohol. That stays the same. But we would just expect since it's the carboxylic acid derivative, I'm going to get a carboxylic acid here. Really that's it. This is not specific to cyanohydrins. It's specific just to nitriles. If you understand that nitrile is a carboxylic acid derivative, then this reaction really isn't anything new. It's just an application of a carboxylic acid derivative reaction. Awesome guys. That's it for that one. Let's move on to another.

Provide the major product for the following reaction. 

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Here’s what students ask on this topic:

What is a cyanohydrin and how is it formed?

A cyanohydrin is an organic compound that contains both a hydroxyl group (OH) and a nitrile group (CN) attached to the same carbon atom. It is formed through the nucleophilic addition of cyanide (CN^-) to a carbonyl compound (such as an aldehyde or ketone). The reaction involves the cyanide ion attacking the electrophilic carbon of the carbonyl group, forming a negatively charged intermediate. This intermediate is then protonated, typically using water or a mild acid, to yield the cyanohydrin.

What are the common reagents used to form cyanohydrins?

Common reagents used to form cyanohydrins include sodium cyanide (NaCN) and potassium cyanide (KCN). These reagents provide the cyanide ion (CN^-) necessary for the nucleophilic addition to the carbonyl compound. Another reagent that can be used is hydrogen cyanide (HCN), which provides both the cyanide ion and the proton needed for the protonation step in a single compound. HCN is particularly useful because it simplifies the reaction process by combining both steps into one.

How can cyanohydrins be converted to carboxylic acids?

Cyanohydrins can be converted to carboxylic acids through hydrolysis. This process involves breaking down the nitrile group (CN) in the presence of water and either an acid or a base. The hydrolysis can be acid-catalyzed or base-catalyzed, and heat is often applied to facilitate the reaction. The nitrile group is transformed into a carboxyl group (COOH), while the hydroxyl group (OH) remains unchanged. The overall reaction converts the cyanohydrin into a carboxylic acid.

What reducing agents are used to convert cyanohydrins to primary amines?

To convert cyanohydrins to primary amines, common reducing agents include lithium aluminum hydride (LiAlH₄) and catalytic hydrogenation. Lithium aluminum hydride is a strong reducing agent that can reduce the nitrile group (CN) to a primary amine (CH₂NH₂). Catalytic hydrogenation involves using hydrogen gas (H₂) in the presence of a metal catalyst such as nickel, palladium, or platinum. Both methods effectively reduce the nitrile group while leaving the hydroxyl group (OH) intact.

Why is HCN considered a useful reagent for forming cyanohydrins?

HCN (hydrogen cyanide) is considered a useful reagent for forming cyanohydrins because it provides both the cyanide ion (CN^-) and the proton (H⁺) needed for the reaction in a single compound. This dual functionality simplifies the reaction process by combining the nucleophilic addition and protonation steps into one. Additionally, HCN has a pKa of about 10, making it sufficiently acidic to ionize in aqueous environments, which facilitates the formation of the cyanohydrin.