Nucleophilic Addition - Online Tutor, Practice Problems & Exam Prep

Nucleophilic addition is a key mechanism in organic chemistry involving carbonyl compounds. It occurs when a nucleophile, typically negatively charged or with a lone pair, attacks the electrophilic carbon of a carbonyl group, leading to the formation of a tetrahedral intermediate. This intermediate is crucial for subsequent steps, often resulting in a substituted alcohol. Various nucleophiles, such as hydride (H^-), cyanide (CN^-), and alkynides, can participate, demonstrating the versatility of this mechanism in reactions like reductions and organometallic chemistry.

Nucleophilic Addition

Now I want to introduce a new mechanism that's going to be really important for this chapter. This mechanism is really completely unique. You haven't seen anything like it in this course so far. And the name of it is nucleophilic addition. So, what is nucleophilic addition? Well, nucleophilic addition is actually one of the most important ways that carbonyl compounds can participate in organic reactions. Okay. And how does this work? Well, basically, if you look at a typical carbonyl, what you always have is you have a carbon attached to an oxygen and 2 groups on both sides. This is always going to produce a very predictable partial charge. That partial charge you should be looking for is a partial positive. Notice that if I were to assign a positive and a negative charge to this molecule, I would say that the O is going to have my negative charge and the carbon is going to have my positive. Nucleophilic addition is going to be the addition of nucleophiles or negatively charged species to that electrophilic carbon. So the reason this thing is so reactive and the reason that carbonyls are so good at this is because the carbonyl carbon is electrophilic. Electrophilic means that it's going to react with negatively charged things very, very well. Does that make sense so far?

So let's go ahead and look at the general mechanism for nucleophilic addition so this can get a better idea of what's going to happen. Nucleophilic addition, in general, involves a carbonyl. It could really be any carbonyl compound and a nucleophile that has a negative charge. It doesn't always have to have a negative, but most of the time, it will. Sometimes it may be neutral just with a lone pair. As long as it has the ability to donate electrons, it can be a nucleophile. So, in our first step, if we were to try to predict the first arrow here, where do you think we would start the arrow from? Would we start from the carbonyl? Would we start from the nucleophile? Do you guys remember these rules for mechanisms? Pretty sure you guys remember that you always start from the area of high density to the area of low density, meaning that your electron flow is going to start from your nucleophile to somewhere because that's the thing with the most electrons. Now, where are we going to go? Are we going to want to go to a partial negative? Hell no. We're going to go ahead and attack the bottom carbon, the electrophilic carbon. That makes sense because now I have a negative and a positive interacting. But we've got a problem. Does carbon like to have 5 bonds? Remember that each mechanism arrow represents a new bond that's going to be created? No. So if we make a bond, we have to break a bond. Can you think of the easiest bond to break here? It wouldn’t be to kick out one of those R groups. Notice that right now, I’m dealing with a ketone. These are R groups, but it could also be an H like an aldehyde. Regardless, do we have something that's easy to kick out? No. R groups hate to be broken off and get a negative charge. They're terrible leaving groups. So, this is the bond that we’re going to break. We’re going to break the double bond to the O making a negatively charged species with a nucleophile on it. Now, this intermediate is going to be very important throughout the course of this topic because you have to pass through this stage every single time. This is called a tetrahedral intermediate. This is actually an intermediate we’re going to see a lot in Orgo 2. In Orgo 2, we are going to deal a lot with this mechanism, but for right now, you don’t have to know it super in-depth. You just need to know the basics. We've got this negative charge. What do you think we can do after that? Well, your final product should never have a formal charge on it. Our last step here is going to be to protonate. So I'm going to go ahead. I’m going to use some kind of acid. There always will be some kind of protonating agent that you can extract a proton from. So now I've got my proton. What do I get at the an alcohol? A substituted alcohol. Why? Because there's an alcohol in the final product and you have one extra substituent afterward. Sometimes, that's going to be an R group, but it really depends on whatever your nucleophile is whatever your nucleophile is, that’s going to be what’s attached. Make sense so far? Cool. So now what I want to do is I want to show you guys some general you know the general mechanism now. This is the mechanism that we’re going to follow pretty much throughout all of the topics that include nucleophilic addition. But now I want to show you guys some specific additions

Here’s what students ask on this topic:

What is nucleophilic addition in organic chemistry?

Nucleophilic addition is a fundamental mechanism in organic chemistry where a nucleophile, which is typically negatively charged or has a lone pair of electrons, attacks the electrophilic carbon of a carbonyl group. This results in the formation of a tetrahedral intermediate. The carbonyl carbon is electrophilic due to the partial positive charge it carries, making it highly reactive towards nucleophiles. The final product of nucleophilic addition is often a substituted alcohol, depending on the nucleophile used. This mechanism is crucial for various reactions, including reductions and organometallic chemistry.

How does the mechanism of nucleophilic addition work?

The mechanism of nucleophilic addition involves several steps. First, the nucleophile, which has a high electron density, attacks the electrophilic carbon of the carbonyl group. This attack forms a new bond, creating a tetrahedral intermediate. Since carbon cannot have five bonds, the double bond between carbon and oxygen breaks, resulting in a negatively charged oxygen. This intermediate is then protonated by an acid or protonating agent, leading to the formation of a substituted alcohol. The general mechanism can be represented as:

$R_2(C=O)+Nu\to R_2(C-O)-Nu\to R_2(C-\mathrm{OH})-Nu$

What are some common nucleophiles used in nucleophilic addition reactions?

Common nucleophiles used in nucleophilic addition reactions include hydride (H-), cyanide (CN-), and alkynides. Hydride is often used in reductions, where it adds two hydrogens across a double bond. Cyanide adds a cyano group (CN) to the carbonyl carbon, forming a substituted alcohol. Alkynides, which are strong nucleophiles and bases, add an alkynyl group (C≡CH) to the carbonyl carbon. These nucleophiles demonstrate the versatility of nucleophilic addition in forming various substituted alcohols and other products.

What is a tetrahedral intermediate in nucleophilic addition?

A tetrahedral intermediate is a key structure formed during the nucleophilic addition mechanism. When a nucleophile attacks the electrophilic carbon of a carbonyl group, the carbon-oxygen double bond breaks, and a new bond forms between the carbon and the nucleophile. This results in a carbon atom bonded to four different groups, creating a tetrahedral geometry. The intermediate is crucial for the reaction's progression and is often protonated in the final step to form the product, typically a substituted alcohol.

How does nucleophilic addition relate to reduction reactions?

Nucleophilic addition is closely related to reduction reactions, particularly when the nucleophile is a hydride (H-). In such cases, the hydride nucleophile adds two hydrogen atoms across the carbonyl double bond, reducing the carbonyl compound to an alcohol. This process is known as a reduction because it increases the hydrogen content of the molecule. The general mechanism involves the hydride attacking the electrophilic carbon, forming a tetrahedral intermediate, which is then protonated to yield the final alcohol product.