Nitrile to Ketone - Online Tutor, Practice Problems & Exam Prep

Nitriles can be converted into ketones through nucleophilic addition using Grignard reagents in an acidic environment. The mechanism involves the Grignard reagent attacking the electrophilic carbon of the nitrile, forming an intermediate imine. An acid workup then protonates the nitrogen, facilitating the conversion back to a carbonyl group. This process highlights the reversibility of carbonyl reactions and the importance of understanding imine formation and hydrolysis in organic synthesis.

General Reaction

In this video, we're going to talk about how you can make ketones from nitriles. Like carbonyls, nitriles have a very strong dipole along the carbon-nitrogen bond, which is going to make the carbon highly electrophilic. This is very similar to carbonyls. That means that when you react a nitrile with a nucleophile, you can expect to get nucleophilic addition. Very popular nucleophiles that we've used in this section are organometallics like Grignards, R-MgBr, and RLi. Remember that these reagents have full negative charges on them. What's also advantageous about them is that they have alkyl groups so that they can add Rs. It turns out that if you use one of these reagents on a nitrile in an acidic environment, you're going to get a ketone. The R group here is actually coming from the Grignard or the organolithium. That R gets added to the carbon and winds up turning into a carbonyl. You might be a little bit confused because you're thinking, Johnny, what happened to the nitrogen? We had a nitrogen. It really looks nothing like the original compound. For this, we're going to have to go into the mechanism which yes, I'll show you the whole mechanism. But it turns out that this mechanism is going to make a lot more sense to you than you think because it's really just a variation of stuff we've learned before. In the next video, I'm going to show you the full mechanism for how you can turn a nitrile into a ketone.

Mechanism

For this mechanism, I'm just going to bring down the exact compound that we had, the exact nitrile. We just have to choose what R group we want to add to it. Let's just make it a methyl group to make it really easy. I'm going to use CH₃MgBr. Keep in mind that we kind of separate these regions. We react with the Grignard first and then we have our H₃O⁺ acid workup. The mechanism for the Grignard is so easy that everyone here should know it regardless of whether your professor likes mechanisms or not. You should know the first part. The second part, the acid work up, I'm going to show you anyway because I'm just that kind of guy. But it's a mechanism that you probably don't need to be able to draw but we'll just do it in case. The negative attacks the carbon. The electrons go up to the nitrogen. What we make is a compound that looks like this, NR₂. This looks a lot like a ketone but it's got a nitrogen with a negative charge on it. How do we

Here’s what students ask on this topic:

What is the mechanism for converting nitriles to ketones using Grignard reagents?

The mechanism for converting nitriles to ketones using Grignard reagents involves two main steps. First, the Grignard reagent (R-MgBr) attacks the electrophilic carbon of the nitrile (R-C≡N), forming an intermediate imine (R-C=N-R'). This intermediate has a nitrogen with a negative charge. In the second step, an acid workup (H₃O⁺) protonates the nitrogen, converting the imine into a carbonyl group (R-C=O-R'). This process highlights the reversibility of carbonyl reactions and the importance of understanding imine formation and hydrolysis in organic synthesis.

Why is an acid workup necessary in the conversion of nitriles to ketones?

An acid workup is necessary in the conversion of nitriles to ketones to protonate the nitrogen in the intermediate imine. After the Grignard reagent attacks the nitrile, the resulting imine has a nitrogen with a negative charge. The acid workup (H₃O⁺) protonates this nitrogen, facilitating the conversion of the imine back to a carbonyl group. This step is crucial for completing the transformation from a nitrile to a ketone.

What role do Grignard reagents play in the conversion of nitriles to ketones?

Grignard reagents (R-MgBr) play a crucial role in the conversion of nitriles to ketones by acting as nucleophiles. They attack the electrophilic carbon of the nitrile (R-C≡N), forming an intermediate imine (R-C=N-R'). The R group from the Grignard reagent adds to the carbon, which eventually becomes part of the ketone after the acid workup. This nucleophilic addition is the key step in transforming the nitrile into a ketone.

Can you explain the importance of understanding imine formation and hydrolysis in organic synthesis?

Understanding imine formation and hydrolysis is crucial in organic synthesis because these reactions are reversible and play a significant role in various transformations. Imines are intermediates in the conversion of nitriles to ketones and can be formed by the reaction of carbonyl compounds with ammonia or amine derivatives. Hydrolysis of imines back to carbonyl compounds is essential for completing reactions like the nitrile to ketone conversion. Mastery of these concepts allows chemists to manipulate and design synthetic pathways effectively.

What are some common nucleophiles used in the conversion of nitriles to ketones?

Common nucleophiles used in the conversion of nitriles to ketones include organometallic reagents such as Grignard reagents (R-MgBr) and organolithium reagents (R-Li). These reagents have a full negative charge on the carbon, making them highly nucleophilic. They attack the electrophilic carbon of the nitrile, forming an intermediate imine, which is then converted to a ketone through an acid workup.