Nucleophile

Brønsted and Lowry have given us a simple definition of acids and bases: An acid is a proton donor and a base is a proton acceptor. Consequently, electrophiles and nucleophiles are species in organic chemistry that interact very much like acids and bases.

Electrophiles are “electron poor”, therefore, are electron-loving compounds. Nucleophiles are “electron rich” compounds, also known as “positive-charge loving”, or “nucleus loving”.

It is a nucleophile reactant that provides a couple of electrons to form a new covalent bond, we can say that it acts as a Lewis base. A Lewis base contains at least one lone pair of electrons, and a Lewis acid is a species that contains an atom that is at least two electrons short of a closed outer shell.

 

 

Nucleophiles all have pairs of electrons to donate and tend to be rich in electrons. As you can see, they can be neutral or charged (of course, negative).

Therefore, there are three types of nucleophiles:

1. Lone pairs

Each of these examples above has lone pairs on an electronegative atom (C, N, O, S, X). Some bear a negative charge and is, therefore, more nucleophilic than neutral. Nevertheless, neutral molecules can still function as a nucleophile, because the lone pairs in these molecules represent regions of high electron density. Any atom that possesses a localized lone pair can be nucleophilic.

2. π bonds

The π bonds can also function as nucleophiles because a π bond is a region in space of high electron density (above and below the plane).

3. σ bonds

Finally, the pair of electrons in a σ bond can, on occasion, also act as nucleophiles. This class of nucleophiles is probably more subtle and less commonly encountered than the previous two, but you might recognize it when you see it.

 

Here are four factors that make a good nucleophile:

1. Charge

As already mentioned, a stronger nucleophile is the one with a negative charge. Nucleophiles are a species that is donating a pair of electrons and, of course, with an increase in the number of electrons and its nucleophilicity, it will increase. So, as the electron density increases, nucleophilicity also increases. And therefore, the conjugate base is always a better nucleophile.

 

2. Electronegativity

Nucleophilicity increases as you go to the left along the Periodic Table i.e. as electronegativity increases, nucleophilicity decreases. This makes sense when you think about it, electronegativity – “greed for electrons” – is the opposite of nucleophilicity – “giving away electrons”. Note: It’s important to restrict the application of this trend to atoms in the same row of the periodic table; for instance, C, N, O, F, or Si, P, S, Cl.

 

3. Solvent

If we have a polar protic solvent (such as water, alcohol, carboxylic acids) it comes to hydrogen bonding between nucleophile and hydrogen from solvent.

For example, if we have a fluoride ion (nucleophile) in a alcohol (solvent), this alcohol will participate in hydrogen bonding with a fluoride ion, creating a “shell” of solvent molecules around it. The fluoride will be significantly less reactive, as its individual pairs of electrons will interact with the electron-poor hydrogen atoms of the solvent.

 

 

If we compare fluoride and iodide, iodide will also form hydrogen bonds with alcohol. But iodide is bigger than fluoride, and therefore, it’s going to be less tightly packed. On the of that, iodide is more polarizable. The strength of a nucleophile is also affected by polarizability. Polarizability describes the ability of an atom to distribute its electron density unevenly in response to external influences. Polarizability is directly related to the size of the atom and the number of electrons that are distant from the nucleus. So, if we look at halogens in the Periodic Table, the iodide will be the best nucleophile, and fluoride will be the worst.

The ability of nucleophiles to participate in hydrogen bonding decreases as we go down the periodic table. Hence fluoride is the strongest hydrogen bond acceptor, and iodide is the weakest. In a polar protic solvent iodide is the best nucleophile, followed by bromide, followed by chloride, and then last of all is the fluoride.

I‾ > Br‾ > Cl‾ > F‾

BUT the opposite is true in aprotic solvents. A polar aprotic solvent doesn’t hydrogen bond to nucleophiles to a significant extent, meaning that the nucleophiles have greater freedom in solution. Under these conditions, nucleophilicity correlates well with basicity. Basicity and nucleophilicity are related but they don’t have the same concept. When discussing nucleophilicity we’re specifically talking about donating a pair of electrons to an atom other than hydrogen (usually carbon). When a species is donating a pair of electrons to a hydrogen (more specifically, a proton, H+) we call it a base. Thus, fluoride ion, being the most unstable of the halide ions, reacts fastest with electrophiles.

F‾ > Cl‾ > Br‾ > I‾

Conclusion: In polar protic solvents, nucleophilicity increases with polarizability, because hydrogen bonds form a shell around the less polarizable atoms and decrease their nucleophilicity. In polar aprotic solvents, this is not an issue, so basicity is the most important variable.

 

4. Steric hindrance

When discussing reactions in organic chemistry, we must take into account that orbitals at the carbon that participate in reactions are generally less accessible than protons are. The bulkier of the groups that are adjacent to a nucleophilic atom, the slower the reaction will be. This means that steric hindrance of the nucleophile makes it hard to react and therefore makes it a weak nucleophile.

So comparing several deprotonated alcohols, in the sequence methanol – ethanol – isopropanol – t-butanol, deprotonated methanol (“methoxide”) is the strongest nucleophile, and deprotonated t-butanol (“t-butoxide”) is the poorest (or “weakest”) nucleophile.

Carbocation stability

Carbocations often occur as intermediates in reactions in Organic Chemistry. It is therefore important to get acquainted with its characteristics. This will help you master carbocation intermediate reactions down the line including Markovnikov alkene addition reactions, unimolecular substitution SN1, β elimination E1, and so much more.

Carbocation = carbo (as carbon) + cation (positively charged ion)

This means that positive charge on the carbon atom of the molecule.

Formation of the carbocation

For example, in SN1 mechanism the carbocation forms in the first step by the loss of the leaving group. Heterolytic bond cleavage results in the ionization of a carbon atom and a leaving group. In the starting compound, the carbon atom is sp³ hybridized. When the leaving group leaves, the carbon for which it was attached, becomes sp² hybridized with an empty p orbital sitting perpendicular to the molecule.

 

 

Here’s another example – Addition of π electrons to an electrophile. One of the two carbon atoms involved in the π bond will have three bonds instead of four and bears the positive charge.

 

 

Being electron-deficient (and therefore unstable), the formation of a carbocation is usually the rate-limiting step in these reactions.

 

Carbocations

In the sp³ hybridized carbon atom, we have four attached substituents. Each of these four bonds consists of 2 electrons (the octet rule). When one pair is removed, carbon remains only 6 electrons in total. Therefore, we say that the carbon is electron-deficient. Such a carbon is sp² hybridized. Carbocations are electron-poor: they have less than a full octet of electrons.

 

 

Classification of carbocations (in brackets is the abbreviation):

  1. Primary (1°) carbocation – attached to only one carbon ⇒ least stable;
  2. Secondary (2°) carbocation – attache to two other carbon atoms;
  3. Tertiary (3°) carbocation – attached to three other carbon atoms ⇒ most stable.

 

 

Why is the tertiary carbocation the most stable?

In the tertiary carbocation, the electron-deficient carbon is surrounded by three methyl groups (the simplest example). These methyl groups are electron donating groups (EDG). As the number of these groups decreases around electron-deficient carbon, carbocations are becoming less stable. The methyl carbocation doesn’t have a methyl group to withdraw electron density from. The tertiary carbocation is plenty of electron density that can withdraw from and so it’s much more stable.

 

Carbocation stability

There are two ways to stabilize carbocations:

  1. Hyperconjugation;
  2. Resonance.

Both hyperconjugation and resonance are forms of electron delocalization. They are distinguished by the type of orbital: Resonance normally refers to the π-type overlap of p orbitals, whereas hyperconjugation incorporates overlap with the orbitals of σ bonds.

HYPERCONJUGATION
Hyperconjugation is the result of the overlap of a p orbital with a neighboring bonding molecular orbital, such as that of a C–H or a C–C bond. In a carbocation, the p orbital is empty. The alkyl group donates electron density to the electron-deficient center and thus stabilizes it.

 

 

When we compare the orbital pictures of the methyl and tert-butyl carbocations, we can see that each methyl group increase the hyperconjugation interaction. The order of stability of the carbocations is a consequence of this effect.

Another important thing to mention here is electronegativity. If you look at the C-H bond, carbon has an electronegativity value of 2.5, and hydrogen 2.1. We can see that the carbon is slightly more electronegative than hydrogen. Thus, carbon pull electron density toward itself and, therefore, this carbon is a partial negative charge (δ-), and hydrogen is a partial positive charge (δ+). When we have a carbocation next to a partially negative carbon, this carbon can donate some density to that carbocation.

RESONANCE

In organic chemistry, we also encounter molecules for which there are several correct Lewis structures or resonance structures. They have the characteristic property of being interconvertible by electron-pair movement only, the nuclear positions in the molecule remaining unchanged.

 

 

Let’s look at the following examples:

Question: How to determine the order of stability of these carbocations?

 

 

The first thing you need to do is to determine the type of carbocations, whether it is primary, secondary, or tertiary. So we have:

  1. primary
  2. secondary
  3. tertiary
  4. tertiary
  5. primary

If we know the order of stability of carbocations, we know that tertiary is the most stable, then is secondary, and primary as the least stable. But if we have more carbocations of one type, then we have to determine which of them is more stable. So, when we compare these two tertiary carbocations (3 and 4), we can see that carbocation #3 is a typical carbocation stabilizing with hyperconjugation. And the carbocation #4 is allylic carbocation (the double bond is one carbon away from positively charged carbon) which is stabilized by resonance. Here are their resonant structures:

 

 

REMEBER 1: as soon as you can draw the resonant structures of a carbocation, then this carbocation is more stable! And this is because the positive charge is shared by two atoms, not on the one. REMEBER 2: The more resonance structures you can draw, that is the carbocation more stable. In our example, the carbocation #4 is more stable than the carbocation #3.

We have one more case in this example with primary carbocations (1 and 5). The carbocation #1 is a saturated carbocation which is stabilized by hyperconjugation. But carbocation #5 is vinylic carbocation (positively charged carbon is sp² hybridized, i.e. carbon of the double bond) and this is the least stable. The reason being is the positive charge directly on a double bond so we can’t draw any the resonant structures.

The order of decrease of the stability of the carbocations is: 4 > 3 > 2 > 1 > 5.

In some literature, you will find that the compounds with heteroatoms stabilized by resonance are a separate type of stabilization, but this is a resonance no matter which atoms are in question.

pKa table

pKa table

 

The pKa table is very useful and it’s really important to become familiar with them. The pKa table tells you a lot more information than you realize. They don’t only tell you the pKa values for each set of species with certain functional groups, they also tell you the relative strength of each species. We can also predict whether a reaction will occur via the SN2 / SN1 or E2 / E1 mechanism, or it will be an acid-base reaction.

The greater the pKa, the less acidic is the proton, and the less the pKa, the more acidic is the proton.

 

 

The pKa is equal to the negative logarithm of the Ka. Because of the way the logarithm function works, a smaller pKa means a larger Ka. Ka is called the acid dissociation constant.

pKa and Ka describe the degree of ionization of an acid or base and are true indicators of acid or base strength because adding water to a solution will not change the equilibrium constant.

pKa is helpful for predicting whether a species will donate or accept protons at a specific pH value. For example, if our acid is hydrobromic acid, the pKa of its proton is approximately -9. When the base removes this proton, a conjugate base of a hydrobromic acid (bromide ion) is obtained. As already said, the less pKa, the acid is stronger. This means that hydrobromic acid is a very strong acid. It can easily donate a proton. Therefore, the resulting conjugate base of this strong acid is a very weak baseA stronger acid will tend to react with a stronger base to produce a weaker acid and a weaker base. But if we have alkanes which have pKa approximately 50, donating a proton will be very difficult. This means that alkanes are very weak acids. Actually, they are the weakest acids.

It would not be bad to remember number 16. Because he is here in the middleAlcohols and water have this value (in fact, the water has 15.7 but we can say 16). They are practically neutral. Compounds with pKa higher than 16 are bad acid, and lesser than 16 are good acids.

good acids < 16 < bad acids

 

Most acids that we will see in organic chemistry are weak. This means that they have high pKa values.

Primary, secondary, tertiary carbons

Primary, secondary, tertiary carbons

 

The nomenclature is a very important part of organic chemistry. The names are not given only to compounds but also to the carbon atoms that make up this compound.

Thus, we can classify carbon atoms as primary, secondary, tertiary, or quaternary. These terms refer to the substitution level that a given carbon has in a molecule. In other words, these terms are used to describe how many other carbons a given carbon is attached to. This classification applies only to saturated carbons.

  • Primary (1°) carbon atom – bonded to one other carbon atom,
  • Secondary (2°) carbon atom – bonded to two other carbon atoms,
  • Tertiary (3°) carbon atom – bonded to three other carbon atoms,
  • Quaternary (4°) carbon atom – bonded to four other carbon atoms.

 

 

This can be explained by one of the important properties of carbon and is its tetravalency. Carbon is a strict octet follower, which means it needs a maximum of 8 electrons to form stable compounds. Since a carbon atom has 4 valence electrons, it can form up to 4 bonds with different elements. Part of the reason why there are millions of compounds of carbon is its ability to form a very stable bond with another carbon atom.

 

 

The same terminology is used for carbocations. A primary carbocation is attached to one other carbon, a secondary to two, and a tertiary to three. A quaternary carbocation does not exist without violating the octet rule.

 

 

 

For example, you get the following compound to determine which primary, secondary, tertiary, or quaternary carbons are. As mentioned above, a primary is attached to one carbon atom, a secondary to two, a tertiary to three, and a quaternary to four other carbon atoms. For each carbon atom, you need to count how many carbon atoms next to it that particular carbon atom is connected to.

 

 

There is another rule:

  1. Primary carbon atoms are always at the end;
  2. Secondary carbon atoms are in the middle (between two other carbon atoms);
  3. Tertiary carbon atoms are branched out in three different ways;
  4. Quaternary carbon atoms have the most carbon atoms around (max 4).

 

OK. These are carbon atoms. But what about the hydrogen atoms which are bonded to these carbon atoms? Yes, they can also be primary, secondary, and tertiary. It depends on the carbon atoms they are attached to. So follow the next rule for hydrogens:

  1. Primary hydrogen atoms are attached to primary carbon atoms;
  2. Secondary hydrogen atoms are attached to secondary carbon atoms;
  3. Tertiary hydrogen atoms are attached to tertiary carbon atoms.

In our example, we have a total of 18 primary hydrogens. Because each primary carbon has 3 hydrogen atoms, and we have 6. Secondary hydrogen atoms have a total of 4 (2 hydrogens per secondary carbon atom), and tertiary 2 (1 hydrogen per tertiary carbon atom).

Let’s go back to the carbons. Let’s look at what are called carbons that are bonded to other atoms and atomic groups such as halides, hydroxides, amines.

 

Alkyl halides

 

 

It should also count here how much carbon atoms are attached to a particular carbon. Halides (fluorine, chlorine, bromine, or iodine) are not counted. Thus, the primary alkyl halide is one that has only one carbon atom bound to itself. The secondary has two carbon atoms and a halide, and the tertiary has three carbon atoms and a halide bonded to itself. The quaternary alkyl halides don’t exist because that would involve breaking the octet rule.

 

Alcohols

 

The rules apply the same way for alcohols as it does for alkyl halides. For the most groups like alcohols, alkyl halides, and hydrogen atoms to determine if it’s primary, secondary, or tertiary, look at the carbon atom that bears those atoms, ignore this atom or group and count how many carbons are attached to it.

 

Amines

Here is a slightly different story. Amines are named according to the number of carbons attached to nitrogen. Primary, secondary, and tertiary amines are nitrogens bound to one, two and three carbons, respectively. They also form quaternary amines, since the nitrogen has a lone pair and it possible to form another bond to carbon. They bear a positive charge on nitrogen and are not at all basic. They are often referred to as quaternary ammonium salts.

 

 

 

Numbers of carbon atoms attached to carbon atoms also govern how they will react.

For carbocations, that is cations if carbons, carbons with more carbons attached on (i.e. tertiary) tend to be less electron-deficient due to hyperconjugation from nearby C-H bonds. Therefore, tertiary carbocations are more stable compared to secondary, primary, and methyl, respectively.

Another case is that of alcohols. Primary alcohols can be oxidized to aldehydes and carboxylic acids (two levels). Secondary alcohols can go only one level of ketones, and tertiary alcohols cannot be oxidized at all.

 

Isobutyl

Isobutyl

 

Organic chemistry is reduced to consideration of the reactions and mechanisms of organic compounds. Learning how to name organic compounds is the foundation upon which your entire organic chemistry knowledge will be based.

The nomenclature of the linear molecules is simple, but when these molecules begin to branch, the naming of organic compounds becomes very complex.

The first situation we encounter is branched alkyl substituents on alkanes. So let’s consider the simplest example, and it is butane (alkane) or butyl (alkyl group).

Butane has four carbon and thus two possible structures. These are the so-called structural isomers. One is the 4-carbon straight chain which is call n-butane (“n” like normal), and the other is the 3-carbon chain with a methyl group on C2. It is called 2-methyl propane, or isobutane.

 

 

When we remove a hydrogen from butane we get butyl group. There are four different types of “butyls”, and they all have their own name:

1-butyl (n-butyl where “n” stands for “normal”)
2-butyl (s-butyl where “s” stands for “secondary”)
2-methyl-1-propyl (isobutyl)
2-methyl-2-propyl (t-butyl)

 

 

For example, chlorination of butane would result in:

 

 

Therefore, giving a name to a branched molecule will follow the following items:

  • Identify the parent chain or the largest chain in the molecule (marked green)
  • Numerization of the parent chain – the numbering is done on one side where the branching of the molecules is closer (1-10)
  • then identify the attached group (marked blue)
  • and number the attached group (1-3)

 

 

Thus, the name of our compound in this example is 5-(2methylpropyl)decane or 5isobutyldecane.