Nucleophiles and Electrophiles

What are Nucleophiles and Electrophiles?

It is scientifically well-known that opposites tend to come together to balance each other out. Hot water will mix with cold water, air will try to fill a vacuum, and negative charges will go towards positive charges. The restoration of balance is a common theme in this universe, which is responsible for polar reactions.

• Ionic reactions occur when two species try to restore a balance in charge.
• When an atom or molecule is saturated with electrons, it is referred to as being negatively charged.
• Conversely, when a molecule has fewer electrons, it is known as being positively charged.
• When these charges, negative or positive, are centered in a specific area, they are described as polar.

Effects of Polarity in Reactions

When describing polar molecules, we use the general term Polarity, which is described in detail elsewhere. As a quick refresher, recall that covalent bonds are not always equal, as they are shown in Lewis diagrams. Electrons are typically centered on one spot more than another. Differences in Electronegativity affect how electrons are held, and often result in an imbalance in the bond.

In a typical bond line, electrons are not shown. However, it is easy to forget that electrons are not held at equal distances between the two atoms. In the H–F bond, fluorine is much more electronegative. Fluorine will thus preferentially hold the electrons a lot closer to it. This creates a polarity difference since there will be a directional difference in electron density.

Just like how ions and cations will come together to balance charges, different electron densities also tend to come together to balance charges. It is important to note that this can happen in polar and nonpolar molecules. The takeaway here is that molecules will try to balance differences in electron density. But how do we know when there are differences in electron density?

It was mentioned that electronegativity differences contribute to differences in electron density. This is perfectly illustrated by the molecule methane, CH₄. This molecule is nonpolar with 4 equal C–H bonds. Since carbon is the most electronegative, the electron density is mostly held on carbon, with 4 hydrogens donating electrons. However, replace one of the hydrogens with another atom, and the electron density changes. The image below is called an electrostatic potential map. Areas in red show a high electron density, and areas in blue show areas of low electron density. In other words, red areas are more likely to have electrons.

On the left, you can see that more electron density is held on the chloride than on the carbon. This is because chlorine is more electronegative (3.16) compared to carbon (2.55). In the diagram on the right, carbon is pulling electrons away from lithium, which is less electronegative (0.98). Just by replacing one bond in methane, there can be extreme differences in electron density. This example shows two very different carbon atoms. The carbon on the left is behaving as an electrophile, and the carbon on the right is a nucleophile.

• A nucleophilic center can donate electrons to an area of less electron density.
• In contrast, an electrophilic center can accept electrons from an area of higher electron density.

In the example above, if the two molecules were to come into contact, the nucleophilic center (C–Li) would likely donate electrons to the electrophilic center (C–Cl), causing a chemical reaction. These reactions typically occur via the donation of an electron pair. So, the two electrons in the C–Li bond would be donated to the C atom of the C–Cl bond. This particular reaction would be known as an S_N2 reaction, which is discussed in Organic Chemistry Reactions.

Nucleophiles and Electrophiles Characteristics

The characteristics which are attributed to nucleophiles and electrophiles are opposite in their behavior. As we saw before, a nucleophile has a high amount of electron density, while an electrophile has a low amount of electron density. Simply put:

• Nucleophiles have either full or partial negative charges
• Electrophiles have either full or partial positive charges

If you can remember that electrons are negative, then you can pick out where nucleophiles and electrophiles will exist. This is a simple and easy way to think about this concept, albeit, it is slightly more complicated than that. Without going too deep into it, we will take a brief look at how these species react with each other to form a new bond.

Orbitals of Nucleophiles and Electrophiles

Determining the identity of a molecule can be done by recognizing differences in electron densities around certain atoms. However, it is also important to understand what orbitals of nucleophiles and electrophiles look like. We will now take a brief look at Molecular Orbital Theory.

We discussed how a nucleophile will donate electrons to an electrophile. The electrons it uses for that reaction are located in the HOMO (highest occupied molecular orbital). The electrons which are highest in energy will always react first. They will try to overlap with the LUMO (lowest unoccupied molecular orbital) of the electrophile. If the orbitals are close enough in energy, they can interact and form a new bond. When orbitals overlap to form a bond, they will form a new orbital that is lower in energy than the previous two. This is why the bond stays together. If the product is higher in energy than the reactants, it will be unlikely to stay that way and will revert to its previous state.

Orbital energies are often the real explanation for why reactions occur. However, it is unlikely that you will be able to determine a molecule's orbital energies just by looking at it. That is why we have other arguments for whether a reaction will occur.

Types of Nucleophiles and Electrophiles

Now that we understand what they are, it may be useful to look at some types of nucleophiles and electrophiles. Earlier we discussed polar molecules and how these look in electrostatic potential maps. This is one way to identify whether a molecule is nucleophilic, electrophilic or neither. If a bond is polarized (electrons are pulled in one direction), it can have a big effect on how it behaves.

Larger atoms, like iodine, have numerous electrons held far away from the nucleus. Large atoms, like iodine, have many protons (53, to be exact). To balance this, iodine also has 53 electrons, which float around the nucleus. Since electrons repel each other, iodine's valence electrons are very far away from the nucleus. This means that they are held looser than the electrons in a smaller atom are, like fluorine.

As a result, they can be unevenly distributed a lot easier. Iodide anions can do this in the presence of electrophiles, and thus behave as nucleophiles. An atom's polarizability has a lot to do with its strength as a nucleophile, which will be explored a bit later.

Nucleophiles

Iodide anions are an example of a nucleophilic atom. Typically, nucleophiles are seen in molecules, like with the C–Li example. This is a nucleophile that is formed due to inductive effects. Essentially, the different pull of electrons between the two atoms creates a carbon nucleophile. Carbon is holding the electron pair so close to it, that it can donate it to something else without lithium having a say in the matter. This is observed anytime carbon is bonded to a metal.

Another type of nucleophile is one that uses lone pairs. Some atoms, like nitrogen and oxygen, carry lone pairs (non-bonded electron pairs) which can attack electrophiles.

In the example above, the nitrogen atom has a lot more electron density than the carbon atom. This means that it can donate its lone pair in a nucleophilic attack. Lone pairs are often used by nucleophiles since they are not already shared with another atom.

One final example of nucleophiles is observed with π-bonds. In a C=C bond, one of the electron pairs held between the carbons can be donated to an electrophile forming a bond between one or both of the carbons and the electrophile.

In this example, the π-bond acts as a nucleophile and attacks one of the bromine atoms. This results in the bromine forming a bond with both carbon atoms.

Electrophiles

Electrophiles can be formed due to polarizability as well. However, this is observed in ways opposite to that of nucleophiles. Just as an anion may act as a nucleophile, cations may behave as electrophiles since they are missing electrons. Electrophiles are usually present as molecules, with carbon being a very common example. Carbon cations (known as carbocations) are electrophilic and will easily be attacked by nucleophiles.

The carbon has only 3 bonds, giving it a positive charge, and making it an excellent electrophile. The oxygen atom of the hydroxide ion subsequently donates a lone pair, forming CH₃OH.

You can also find carbon behaving as an electrophile in examples such as the one shown with C–Cl. When carbon has a bond that is pulling electrons away from it, it craves electron density from some other source. This is often observed with C=O bonds. The more electronegative oxygen pulls electrons away from carbon with two bonds, leaving it especially electrophilic.

In this example, the carbon atom has 3 different bonds with oxygen. It has most of its valence electrons being pulled away from it, making it electrophilic. The ester (molecule on the left) is open to attack. Water, which is a weak nucleophile, can attack it to form acetic acid, a.k.a. vinegar. This is a classic example of an electrophilic reaction, which will come up a lot more in organic chemistry.

It is pretty clear at this point that nucleophiles and electrophiles are pretty diverse topics. We have explored how to identify each and what some examples look like. The next step is to look at what makes these strong or weak, which is covered in Nucleophilicity and Electrophilicity. After that, be sure to check out some Reactions of Nucleophiles and Electrophiles.

Now that you understand what nucleophiles and electrophiles are, do you think Paula Abdul was right? Do opposites attract?

Strong and Weak Nucleophiles and Electrophiles

To discuss the properties of strong and weak nucleophiles and electrophiles, we must discuss nucleophilicity.

So, the strength of a nucleophile is determined by how quickly it will attack an electrophile. This is why it can be tricky to predict the strength of a nucleophile that has not been experimentally observed. Predicting the strength of a nucleophile can be done by identifying a few criteria:

• Does the nucleophile have a negative charge?
• Is the nucleophile highly polarizable?
• Is the solvent affecting the nucleophile?

By using the above-mentioned list, we can reasonably predict the reactivity of a nucleophile. There are other factors which affect nucleophilicity, like R groups, and HSAB (hard soft acid base) theory, but those will be ignored for now. We will start our analysis with electrical charge.

Nucleophilicity

Nucleophilicity is heavily dependent on the charge of a molecule. A nucleophile with a negative charge will be dramatically more reactive than one with a neutral charge. Previously, we discussed how negative and positive charges will come together. Well, a nucleophile with a full negative charge can balance a positive charge a lot better than one with a partial negative charge.

In the example, hydroxide reacts exponentially faster than water does. That is because the oxygen in hydroxide has a full negative charge compared to the partial negative charge in water. Consequently, anionic nucleophiles are often strong nucleophiles.

Along with anionic charges, polarizability also affects nucleophilicity. For example, halides can redistribute their electron density quite well, which allows them to act as strong nucleophiles. This is the case for I^-, Br^-, and Cl^-. However, F^- can behave as either a strong or a weak nucleophile. The behavioral changes of fluoride are purely dependent on the solvent.

Solvent Effects on Nucleophilicity

Differing solvents can play a big role in nucleophilicity, either activating or deactivating a nucleophile. Nucleophiles are often ions, as are the leaving groups in reactions. To stabilize the ionic species which are participating in the reaction, organic chemists use polar solvents to run the reactions in. This is crucial for the reaction, since these species are often not soluble in non-polar solvents.

When organic chemists choose a polar solvent to use in a reaction, there are two types of solvents which they consider:

• Polar protic solvents
• Polar aprotic solvents

This may seem hard to visualize, so let's look at some examples of some common solvents.

The protic solvents have at least one hydrogen bonded to an electronegative atom. In the aprotic solvents, there can be electronegative atoms, but they won't have any bonds to hydrogen. This has consequences for certain species in a solution.

Solvents will affect the rate of nucleophilic attacks in certain reactions. Essentially, some solvents will increase or decrease the strength of the nucleophile. But how do we go about predicting this behavior? Well, as you may have guessed, polar protic and polar aprotic solvents differ in how they interact with nucleophiles.

Solvation

To understand how nucleophiles will behave in solution, we must first discuss a phenomenon known as solvation. When water contains ionic compounds, such as NaCl, the ions are present as Na⁺ and Cl^-. To help keep energies at a minimum, water molecules surround these ions.

The Na⁺ ions are surrounded by the partial negative oxygen atoms. Cations in solution are always well-solvated, which means that they have a tight shell of solvent molecules surrounding them. In water, the Cl^- ions hydrogen bond with the water molecules, which helps to lower their energy.

Hydrogen bonding plays a pivotal role in nucleophile solvation. If an anionic nucleophile forms hydrogen bonds with the solvent, it limits the nucleophile's ability to move around and react. Since the nucleophile is surrounded by solvent molecules, it can't attack an electrophile as quickly. This results in a slower reaction rate, and ultimately, a weaker nucleophile.

So, in a polar protic solvent, which has potential to form hydrogen bonds, nucleophiles react slower. This is not the case in polar aprotic solvents, since they don't solvate nucleophiles as effectively.

Electrophilicity

Identifying an electrophilic center is slightly more complicated than identifying a nucleophilic center. Mostly because doing so sometimes requires a more in-depth understanding of organic chemistry. For now, we will just review what we mentioned before. The two main factors which influence electrophilicity are charge and polarization.

If an atom has a positive charge, it will be lacking in electrons, and can then accept them from a nucleophile. To be a little more precise, it will have an empty electron orbital. Atoms with empty orbitals are higher in energy, and thus become a lot more reactive. The more unhappy an atom is, the more reactive it becomes. It becomes less picky with what it will react, and as a result, reacts quicker. This effect results in a greater electrophilicity.

This is also observed with partial positive charges. When an atom is sharing an uneven bond, with a more electronegative atom, it will have fewer electrons on it. The more positive an atom becomes, the more reactive it will become. So, the more uneven bonds that it has, the more unstable it will become. This is especially relevant with double or triple bonds to electronegative atoms, such as in C=O. The second bond to the same oxygen atom makes carbon more electrophilic than it would be with two bonds to two different oxygens.

There are many other determinants of electrophilicity, but we won't address those here. For now, just remember that cations, and polarizable atoms, can make strong electrophiles.

Polymer Reactions with Nucleophiles and Electrophiles

Polymers, or plastics, are produced on an incredible scale. They are essential to the way of life as we know it. The types of polymers that exist are as diverse as their use. As such, there are many different methods to synthesize these polymers to provide different properties. It may come as no surprise that nucleophiles and electrophiles can be used in polymer reactions. The synthesis of polymers is something that could occupy its own article, so we will just take a very brief look at them.

Anionic Polymerization

Have you ever used superglue? It is a liquid in its tube, but as soon as it is exposed to air, it begins to harden almost immediately. The reason this happens is that moisture (water, suspended in air) can act as a nucleophile to polymerize the monomer.

In anionic polymerization, a nucleophile, typically an anion, starts the cycle by attacking an electrophilic monomer. The electrophilic monomer becomes nucleophilic, which continues the propagation. This cycle happens very fast and very efficiently. It will continue until there is no more material to polymerize.

That is why superglue is so quick and strong. All the glue will polymerize from water in the air. Typically, the nucleophile will be OH^- instead of H₂O. In this example, water was depicted just for simplicity.

Cationic Polymerization

Another type of polymerization, cationic polymerization, is the opposite of anionic polymerization because it uses electrophiles to grow the polymer chain. To help illustrate what this looks like, we will take a look at the polymerization of isobutylene.

Cationic polymerization typically forms softer polymers, with shorter chain lengths, than those formed by anionic polymerization. The polymerization of isobutylene is an incredibly useful and important reaction. Polyisobutylene, also known as butyl rubber, has various applications.² Some of its uses include:

• Rubber Gloves.
• Chewing Gum.
• Footballs.
• Tires.
• Explosives.

It's hard to imagine that one polymer could have that many applications, and more! It goes to show how much we rely on polymers. They are essential to our society, with many pros and cons. Despite this, it is clear how important it is to understand some reactions of nucleophiles and electrophiles.

By now, hopefully, it is clear how important nucleophiles and electrophiles are. These reactions happen in our bodies, in the world around us, and in chemistry laboratories. Without them, life on earth as we know it would cease to exist. Next time you look at an organic molecule, can you pick out the nucleophilic and electrophilic centers?