Nucleophiles and Electrophiles

Nucleophiles are negatively charged or uncharged compounds that donate electrons to a positively charged species known as an electrophile forming a covalent bond.

Conversely, electrophiles are structures who seek out and accept electrons to form a chemical bond and can be positively charged or neutral.

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Breakdown of Nucleophiles and Electrophiles 

As mentioned above, nucleophiles are considered electron pair donors and electrophiles are electron pair acceptors.

With these definitions in mind, we can relate nucleophiles (abbreviated Nu-) with a type of base known as a Lewis base, which we learned about when talking about acids & bases.

Lewis Acid & Base

The opposite would then apply to electrophiles (abbreviated E+) who are synonymous with Lewis acids, because both seek out electrons to accept. This will make more sense when we get into examining structures and determining if molecules are reactive or not.

*Hint: if you see the word Lewis Acid, think Accept

2 common examples of this:

     1. Lewis Base (LB)

Lewis Base Structure

     2. Lewis Acid (LA)

Lewis Acid Structure

Big Takeaway:

• If you see the word Lewis acid, think electrophile
• If you see the word Lewis base, think nucleophile

Now, before we go into some of the most common examples of nucleophiles and electrophiles, let’s discuss another way you may interpret them.

A nucleophile, while being classified as a Lewis base due to its ability to donate electrons, may also be classified according to its ability to accept a proton (H+). This is termed Bronsted-Lowry base.

Similarly, a Bronsted-Lowry acid is also a type of electrophile. Remember that electrophiles are classified according to their ability to accept electrons, just as a Bronsted-Lowry acid is able to donate protons.

We will discuss these terms in more detail below when we learn how to distinguish between nucleophiles (Lewis definition) and bases (Bronsted-Lowry definition).

Examples of Nucleophiles:

It is easy to distinguish between nucleophile and electrophile if it has a full negative charge, but it gets trickier when there’s partial charges involved. One way to go about this is to memorize some of the most common nucleophiles and electrophiles.

However, we will also discuss ways to determine how an uncharged molecule will behave based on bonding preference (more on this below).

Easy Cases:

• For these our key indicator is a negative charge. Remember, nucleophiles have a good source of electrons and want to use them to create chemical bonds with an electrophile.
• We can also classify nucleophiles as bases, for their ability to grab protons.

Nu-: negatively charged nucleophiles

• Halogens: I-, Br-, Cl-, F-
• Hydroxide: -OH
• Cyanide: CN-
• Sulfur compounds such as thiolates: RS-
• Organometallics such as Grignard: RMgX (-R +MgX)
• Hydrogen anion: H-

More Challenging Cases: 

• A molecule doesn’t require a negative charge to be a nucleophile, but it needs to have similar properties (i.e. a source of electrons).

Nu: neutral nucleophiles 

• Ammonia: NH3
• Water: H2O
• Alcohols: ROH
• Thiols: RSH
• HX acids: HCl, HBr, etc. (specifically the X)
• Double bonds/Triple bonds (pi bonds)
• Aromatics (pi bonds)

Note: some of these may be able to act as both a nucleophile or electrophile depending on what it is reacting with (i.e. water, HX).

Big Takeaway:

While this is not a comprehensive list, these examples are meant to serve as a guide for what to look for. If no formal charges are present, we will use a rule (discussed below) to determine if the molecule wants to act as a nucleophile or electrophile.

Also, some of the groups mentioned above were specific (ammonia, hydroxide), however be aware that we can generalize these molecules to include functional groups that are similar such as amines, alcohols, organometallic compounds, etc.

Examples of Electrophiles:

If we closely examine the word electrophile we will see that word literally means “lover of electrons”. With that in mind, the next group of molecules and atoms will be devoid of electrons and therefore be attracted to them.

Just as before, we can group together electrophiles as those who bear a full positive charge and those who may have partial positive character. Nevertheless, the list below is meant to serve as a basic understanding of what to look for.

Also, keep in mind that Lewis acids are electrophiles. Therefore, compounds with empty p orbitals such as BF3 and AlCl3 fall into this category.

E+: postively charged electrophiles

• Hydrogen cation: H⁺
• Hydronium: H₃O+
• Carbocations: ⁺CH3
• Nitrosonium cation: ⁺NO

Note: The list above can be never ending. As long as the molecule has a full positive charge you can be confident it will act as an electrophile.

E: neutral electrophiles

• Lewis Acids: AlCl₃, BF₃, etc
• Water: H₂O
• HX acids: HCl, HBr, etc. (specifically the H)
• Alkyl Halides: RX (CH₃Br)
• Carbonyls: ketones, aldehydes, esters, etc.
• Diatomic Halogens: Br₂, Cl₂, etc.
• Carbon Dioxide: CO₂

*Hint – Remember, some molecules such as water can act as both a nucleophile or electrophile depending on what it is reacting with. You should draw out dipoles to determine which parts of the molecule which have a partial positive charge.  

For example:

Structure of Water

In the case where water (H₂O) is reacting with a nucleophile (Nu-), then the H will act as an electrophile due to its partial positive charges.

Determining Reactivity

Thus far we have determined whether a compound will react as a nucleophile or electrophile in a chemical reaction. However, there are cases where a molecule will not be reactive at all. Here are some basic rules to understand about what makes something reactive.

1. Formal charge

• This means an atom is not at its ideal bonding preference. This could be a result of too many or too few valence electrons. Basically, if a molecule has a formal charge (+ or -) it wants to go back to normal, which is having the right number of valence electrons according to its bonding preference.
• For these reasons, any molecule with a formal charge will be reactive.

Test: Will this molecule be reactive?

Carbocation Reactivity

2. Net dipoles 

• Here, we are concerned with having asymmetrical dipoles that do not cancel each other out. If you remember, dipoles are created by having partial charges in different places. The sum of the dipoles equals the net dipole.

For this rule, we will apply it to special cases when no formal charge is seen to determine exactly HOW the molecule will react (nucleophile or electrophile).

The rule is:

• The side of the dipole with the highest bonding preference determines if the molecule will react as a Nu- or E+.
• Another way to say this is: Which side is going to make the most bonds?

Alkyl Halides (Orgo 1) + carbonyls (Orgo 2) are very important and common electrophiles that result from having a net dipole moment.

Test: Will this molecule be reactive?

Carbon Tetrachloride Reactivity

3. Pi bonds (π-bonds)

• These are what double bonds and triple bonds are made of and are a good source of electrons. Remember that pi bonds are weaker than sigma bonds and thus are easy to break.
• If you see a pi bond in a molecule (double bond, triple bond, etc.) you know that this molecule will definitely be reactive. 

Test: Will this molecule be reactive?

Cycloalkene Reactivity

4. Steric effects

• This effect is more complex than the other 3, however it is important to learn because small rings such as cyclopropane (3-membered ring) are reactive due to having less than ideal bond angles. Normally, tetrahedral bond angles are 109.5˚, however anything above or below this creates instability, thus reactivity.

Note: Stability and reactivity have an inverse relationship. This means if a molecule is stable, it will not be reactive. Conversely, if a molecule is unstable it will be reactive.

Test: Will this molecule be reactive?

Cyclopropane Reactivity

If you see the word inert, this refers to compounds such as CCl4 which will not react with anything. This is very common for a tetrahedral, which is a type of molecular geometry.

Trick Question: Is water reactive? Yes! It has a net dipole. Remember, water can react as both an electrophile or nucleophile depending on what it is reacting with.

Answers:

1. Yes! It has a positive charge in the form of a carbocation on the C.
2. No! While the molecule has many dipole moments, the dipoles are symmetrical and perfectly cancel each other out.
3. Yes! Notice the double bond inside the cyclobutane ring (4-membered ring). Follow up question… Will this react as a nucleophile or electrophile? (Answer below)
4. Yes! Three-membered rings have 60˚ bond angles between atoms which is less than ideal (109.5˚) and thus will be reactive.  

Cyclopropane Bond Angles

As a general rule: the higher the strain, the higher the energy, the lower the stability.

Drawing Mechanisms

Above we learned how to determine reactivity using 4 principles and some of the major nucleophiles and electrophiles. Now, we will learn the basics of drawing mechanisms with electron movement.

Here it’s all about sharing electrons with other molecules to become more stable. Curved arrows are used to indicate which way electrons are moving, similar to how we show the movement of cations and anions in resonance structures.

What you need to know:

1. An arrow = 2 electrons shared.
2. Nucleophiles (high electron density) always attack electrophiles (low electron density).
3. After the reaction, we can replace that arrow with new sigma bond. Therefore, an arrow represents a fancy sigma bond being created.

When drawing mechanisms and trying to make bonds, we should always look for the atom or atoms on a molecule that have the most electron density. This will come in handy when trying to start a curved arrow mechanism with 2 molecules that have no formal charges.

In the scenario below, we have been given 2 molecules who have a formal charge present already. Based on what we learned, we start our mechanism with the atom or atoms who have the most electron density, which is the nucleophile.

Nucleophile & Electrophile Reaction

First, find the nucleophile, then you can draw an arrow from that atom to the electrophile to represent electrons being shared. (Stay tuned for the answer)

After you draw that first arrow, you can show the new sigma bond in the product. Now, once this occurs we could be done with the reaction. However, there are times where we must break a bond to preserve an atoms bonding preference.

A common example of this is when attacking a H (hydrogen) atom because H likes to create only one bond. So the question becomes: How do we break bonds?

There are actually 2 ways to break bonds:

First, there is heterolytic cleavage which produces different ions and uses a full arrow. This is the mechanism we will be using for breaking bonds with nucleophiles and electrophiles.

Heterolytic Cleavage

The other type is hemolytic cleavage where each atom gets the same amount of electrons or a radical and this uses half arrows.

Homolytic Cleavage

Therefore, when necessary we will use the heterolytic cleavage method to draw an arrow from the bond being broken to an atom. This will create as mentioned above, ions.

Here is an example of what this would look like in a reaction between a double bond (the nucleophile) and hydrochloric acid (HCl; the electrophile).

Homolytic Cleveage Example

Notice that we started the mechanism from the Lewis base (nucleophile) and finally broke the bond in the second step to preserve H’s bonding preference. What we produced was a cation, known as a carbocation and an anion, which is a chloride anion.

Note: In case you were wondering the name of this reaction, it is called hydrohalogenation and is a common way to create alkyl halides in the end.

Answer to follow up question above (#3): Nu-. Why? Because pi bonds are good sources of electrons! It will want protons.

Answer to mechanism above:

Nucleophile & Electrophile Mechanism

Nucleophiles and Basicity 

Throughout our time discussing nucleophiles, you may have heard the terms nucleophile and base being thrown around interchangeably at times. However, there is a distinction that can be made between the two.

A nucleophile can be explained best using the Lewis definition which is a molecule who can easily donate their electrons. This is consistent with what we have been describing and looking at so far.

The newer term we need to familiarize ourselves with now is the term base. This is where the Bronsted-Lowry definition plays a larger role as it describes a molecule that can easily remove (accept) a proton (H⁺).

Since these terms essentially represent a similar phenomenon, they will behave in similar fashion…. for the most part. Below we will describe the different situations that play a factor in nucleophilicity and basicity.

When we head these terms we may be confused at first, but they simply reflect how good or how bad a nucleophile/base will behave. Moving forward if we hear the term base, or basic, just think “ability to remove a proton”. This means that a base describes a nucleophile who attacks another atom, hydrogen (H).

A nucleophile then, describes an atom or compound who attacks (donates its’ electrons to) an electrophile that is an atom other than hydrogen, such as carbon.

With that in mind, certain factors may affect a bases (and a nucleophiles) ability to perform such action. Can you think of any?

Factors that contribute to nucleophilicity & basicity.  

1. First and foremost, a standard rule is that a negatively charged compound is a stronger nucleophile than a neutral compound.

• Hint: When you hear the term negative think strong, and when you hear the term neutral, think weak.
• Another way to say this is the conjugate base is always a stronger nucleophile than its neutral counterpart.

2. A bulky substrate is more basic, and less nucleophilic. This means that a bulky nucleophile (tert-butoxide ion) is worse at donating electrons because it has a difficult time approaching electrophiles.

However, it will be better at pulling off protons (acting as a base) because protons reside normally at the edge of molecules. This effect is known as steric hindrance.

3. As we move to the left on the periodic table, nucleophilicity and basicity will increase.

• This is because these compounds/atoms are more willing to give up or donate their electrons, and are less electronegative.

4. Also, moving up the periodic table (smaller in size), nucleophilicity and basicity increase only when in aprotic solvents (those which cannot hydrogen bond).

• In protic solvents the trend is a little different. That is because protic solvents actually hinder nucleophiles due to being highly solvated. What does that mean? Solvation refers to waters tendency to crowd around nucleophiles and lower their ability to react with an electrophile.

• In protic solvents, nucleophilicity actually increases going down the periodic table (larger in size) due to this effect. (i.e. I- is a better nucleophile than F-)

Nucleophilicity & Basicity Chart

Reactions involving Nucleophiles & Electrophiles

The reactions involving nucleophiles and electrophiles are endless. However, here are some of the reactions that are most recognized in Organic Chemistry I and II.

• Nucleophilic Substitution (SN1, SN2)
• Electrophilic Addition to Alkenes and Alkynes
• Nucleophilic Addition to Carbonyls 
• Electrophilic Aromatic Substitution (EAS)
• Nucleophilic Aromatic Substitution
• Nucleophilic Acyl Substitution

Did you notice anything about the names mentioned? They mostly included nucleophile or electrophile in the name, a functional group, and/or the type of reaction occurring.

While this is not always the case, it commonly applies. Therefore, without knowing the reaction you can already determine the general process that occurs.

Commonly Asked Questions: 

Besides lone pairs, and pi bonds are there any other types of nucleophiles I should know?

• Sometimes, a sigma bond can act as a nucleophile as well. One example of this is with carbocation rearrangements when doing shifts such as a hydride or methyl shift. 

What does the term nucleophilicity mean again?

• In simplest terms, nucleophilicity describes how well a nucleophile can do its job or the nucleophile strength. Above, we mentioned different trends such as electronegativity, solvent, and size effects that modified this. 

What about electrophilicity?

• Just as nucleophilicity described the reactivity of a nucleophile, electrophilicity describes the reactivity of an electrophile or the degree in which a molecule/atom can accept a lone pair. 

I’m confused as to why less electronegativity makes better nucleophiles?

• This is because when an atom is less electronegative it is more willing to share its electrons. Therefore, as we move to the left on the periodic table we achieve better nucleophiles. 

Sample Questions: T or F 

     1. I – (Iodide) is a better nucleophile than F – (Fluoride) in polar protic solvents.

     2. I - polar protic solvents a selenide anion (Se-2) is a weaker nucleophile as compared to a sulfide anion (S-2).

(See bottom of post for answers)

Major differences between Nucleophiles and Electrophiles:

Nucleophiles vs. Electrophiles

• Nucleophiles are electron rich, while electrophiles are electron poor (deficient)
• A nucleophile is similar to a Lewis base, while an electrophile is similar to a Lewis acid
• Nucleophiles are electron pair donors, and electrophiles are electron pair acceptors
• Nucleophiles can be negatively charged or neutral, while electrophiles can be positively charged or neutral
• Nucleophiles always attack electrophiles in a chemical reaction

Answers to Sample Questions:

1. True
2. False

Reason: In polar protic solvents, nucleophilicity increases as we go down the periodic table. Iodine is located below Flourine in the periodic table in group 7A which is our halogens, just as Se (selenium) is located below S (sulfur) in group 6A, known as the chalcogens.