Concept: Concept: Addition of Cyanide4m
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 may 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. NaCN is very common but you 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 so I get a nucleophilic addition mechanism. What this is going to make is a negatively charge 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. We’ll do something like this and like that and 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.
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. I just wanna show you guys another example would be if I use 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 doesn't just ionize like that. that’s actually a covalent bond. Covalent bonds usually don't just disassociate to make H plus and CN negative. That's kind of strange.
Why would it do such a thing? The answer has to do with acidity. It turns out that it's not that it's a weak bond in terms of polarity, that there's a dipole. But it turns out that this is a very acidic bond. It turns out that HCN, if you guys remember your pKas way back in the day, it 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.
The advantage of using HCN is that look what you’ve got. You’ve got the CN negative and you’ve also got your proton to protonate. You could do NaCN and then water 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 two 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 can you 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.
Concept: Concept: Nitrile Hydrolysis3m
Now that we know what a cyanohydrin is, let's go ahead and draw the N. We’ve got an OH on one side in a C triple bond N on the other.
The first thing you should be aware of is that we have a nitro. That's the name of the functional group. The CN is called a nitro. Altogether this is called a cyanohydrin. It turns out that nitriles are actually in a category of molecules 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 hope you understand it now.
But it turns out that carboxylic acid derivatives are a category molecule that by definition can be hydrolyzed to carboxylic acid. 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 for 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 the alcohol, that stays the same. But we would just expect since this is a 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. That's it for that one. Let's move on to another.
Concept: Concept: Nitrile Reduction3m
Once again, since we know what a cyanohydrin is, let's draw it. I've got my O H, I've got my C triple bond N and what is cyanohydrin reduction? Well again guys, this has to do really with nitriles not with cyanohydrins. Just that since you have a nitrile present, nitriles have the ability to be reduced and nitriles are very often reduced to primary amines. So if you want more information on the specific reaction then you could go to the amine section of our clutch videos because there I'm going to discuss in much more depth the exact reducing reagents that could be used for all types of nitrogen derivatives that can be turned into amines but for right now since we're here anyway let's just reinforce that there are a few very popular reducing agents that could be used to turn the C N compound into a primary amine. The number one being with lithium aluminum hydride. When in doubt use LAH. That thing for pretty much everything it blasts like pretty much all double bonds.
So lithium aluminum hydride works also do you guys recognize these reagents? That's catalytic hydrogenation so obviously it doesn't have to be nickel. It could be called palladium or platinum and catalytic hydrogenation would also take out the triple bond and what you get instead is nothing happens to the alcohol it's actually very difficult to reduce and alcohol but the C N is very easy to reduce. So this is going to become, I'm going to need to go off the screen a little or off the box a little bit, it's going to be C H 2 N H 2. Now what's really important guys is that you remember that this carbon exists so don't just turn the C N group into a nitrogen. That would be a big mistake if you did something like this, you draw it as C N and then when you reduce it you draw it as N H 2. I've seen tons of students make that mistake that's wrong because if you're reducing C N you're actually reducing it to C H 2 N H 2 because there's a carbon and there's a nitrogen. So make sure to do that correctly but other than that, really easy reaction again this really comes from your amines section of organic chemistry. I'm just reinforcing that here since we're learning how to make a cyanohydrin. Awesome, so let's move on to the next topic.
Problem: Provide the major product for the following reaction.3m
Show how you would accomplish the following syntheses.
(a) acetophenone acetophenone cyanohydrin
(b) cyclopentanecarbaldehyde 2-cyclopentyl-2-hydroxyacetic acid
(c) hexan-1-ol 2-hydroxyheptanoic acid
Propose a mechanism for each cyanohydrin synthesis just shown.
Can a cyanohydrin be prepared by treating a ketone with sodium cyanide?
In the mechanism for cyanohydrin formation, why is HCN the acid that protonates the alkoxide ion, instead of HCl?
Give the appropriate reagent to achieve the indicated two-step transformation.
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.
Suggest efficient reaction sequence for the synthesis of each of the compound starting from the designated reactant and any necessary organic or inorganic reagent:
Predict the products for the following reaction.
Based on the principles of acidic and basic cleavage as well epoxidation determine the necessary reagents for the each of the following transformations.
What product is formed in the reaction shown?
Which of the following compounds will have the smallest equilibrium constant (Keq) for the reversible reaction with HCN?
Given the following reaction:
Keq will be:
a) greater than one
c) less than one
d) cannot be determined
What is the final product of the following synthesis?