There are many types of compounds that have aromatic properties. When a molecule contains a benzene ring, all compounds exhibit aromatic characters.

However, there are aromatic compounds that are different from benzene rings. These are heterocyclic compounds. Aromatic heterocyclic compounds are compounds that show aromaticity but have different properties than benzene rings.

What should we pay attention to when dealing with heterocyclic compounds in organic chemistry? And what are the nature of aromatic heterocyclic compounds?

One of the major areas of organic chemistry is heterocyclic compounds. We will explain how to think about the properties of heterocyclic compounds.

What are aromatic heterocyclic compounds? Types of Heterocyclic Compounds

Before we understand heterocyclic compounds, we must learn about heteroatoms. Heteroatoms are atoms that are not carbon or hydrogen atoms. Typical heteroatoms include the following

  • Oxygen atoms (O)
  • Nitrogen atom (N)
  • Sulfur atom (S)
  • Phosphorus atom (P)

Although there are many cyclic compounds, compounds with heteroatoms are called heterocyclic compounds. There are many heterocyclic compounds that show aromatic characters, such as the following compounds.

Of course, many other aromatic heterocyclic compounds exist.

A compound is aromatic if it has (4n+2) π-electrons. For all the above heterocyclic compounds, they all have 6 or 10 π-electrons. Therefore, they are aromatic.

-There Are Many Types of Aliphatic Heterocyclic Compounds

For reference, there are many types of aliphatic heterocyclic compounds as well. A compound is an aliphatic heterocyclic compound if it does not have double bonds satisfying aromaticity but has heteroatoms in the ring compound. For example, aliphatic heterocyclic compounds include the following.

In any case, there are many types of heterocyclic compounds.

Aromatic and Basic Properties of Pyridine and Pyrrole

Even within the same aromatic heterocyclic compound, the properties of a 5-membered ring and a 6-membered ring are different. Pyridine and pyrrole are frequently used as examples of this.

For six-membered heterocyclic compounds, it is easy to understand that they have aromatic characters. Pyridine is a six-membered ring with three double bonds and six π-electrons, which makes it aromatic.

But why does pyrrole exhibit aromaticity? Pyrrole has only two double bonds. Therefore, one might think that pyrrole has only four π-electrons. If pyrrole has four π-electrons, it cannot show aromaticity.

-A Nitrogen Atom of Pyrrole is Involved in Aromaticity (2p Orbital)

In order to show aromaticity, there must be six π-electrons in the pyrrole. So if we check the nitrogen atom of the pyrrole, we can see that there is an unshared electron pair (lone pair). The nitrogen atom is bonded to two carbon atoms and one hydrogen atom. Not only that, but there are two electrons that are not involved in the bond.

In the case of pyrrole, the unshared electron pairs in the nitrogen atom are involved in the aromaticity. In addition to the four π-electrons in the double bond, two electrons (lone pairs) possessed by the nitrogen atom are involved in the aromaticity of pyrrole. This gives pyrrole an aromatic character.

Normally, when the nitrogen atom is present, it shows basicity. Therefore, the lone pair present in the nitrogen atom can nucleophilic attack other molecules.

However, the unshared electron pairs of pyrrole exist in the 2p orbitals (the orbitals involved in aromaticity). The lone pair is not on a nitrogen atom, but is distributed throughout the ring.

Because the electrons are delocalized (i.e., they are distributed in various places), the lone pair cannot attack other molecules, even though the nitrogen atoms have unshared electron pairs. In other words, there is no nucleophilic (basic) nature, and pyrrole does not show basicity.

-Lone Pairs of Pyridine Involved in sp2 Hybrid Orbitals

In contrast, pyridines are basic. Because pyridine has three double bonds, the unshared electron pairs (lone pairs) in pyridine need not be involved in aromaticity. Therefore, the lone pair of nitrogen atoms in the pyridine is involved in the sp2 hybrid orbital, not the 2p orbital.

Since the lone pair is involved in the sp2 hybrid orbitals and not in the aromaticity, the unshared electron pairs present in the nitrogen atom show a basic nature.

Also, unlike pyrrole, which is insoluble in water, pyridine is hydrophilic. Pyridine is water soluble because it forms hydrogen bonds in solution.

In the case of pyrrole, the lone pair of a nitrogen atom is involved in the aromaticity, and the nitrogen atom does not have the electrons to make hydrogen bonds. In pyridine, on the other hand, a nitrogen atom is negatively charged, allowing the lone pair to form hydrogen bonds with water molecules.

Therefore, pyridines are water-soluble. Even for the same aromatic heterocyclic compound, the properties of the 5-membered and 6-membered rings are quite different.

Reactivity of Electrophilic Substitution Reactions Differ Between 5 and 6-Membered Rings

How does the reactivity in aromatic heterocyclic compounds differ? Due to the difference in properties, the reactivity of aromatic compounds also differs between 5-membered and 6-membered rings.

For heterocyclic compounds that show aromaticity, the following points should be checked.

  • Reactivity of the compound: high or low electron density
  • Location of the reaction: orientation

In aromatic compounds with a benzene ring, the electron density and orientation change depending on the nature of the substituents. Even in aromatic heterocyclic compounds, the reactivity changes depending on the substituents. However, a more important factor is how the reactivity changes depending on the 5-membered ring and 6-membered ring.

The 5-membered Ring Has a Higher Electron Density and a Substituent Bound to the 2nd Position

An important synthetic reaction in aromatic compounds is the electrophilic substitution reaction. An electrophilic aromatic substitution replaces a hydrogen atom in a heterocycle with a substituent.

The higher the electron density of an aromatic ring, the more likely it is that an electrophilic aromatic substitution will occur. The higher the electron density of the aromatic ring, the more likely it is to attack the electrophilic agent.

In 5-membered heterocyclic compounds, the electron density of the aromatic ring is high because the aromatic ring has six π-electrons in spite of its 5-membered ring. Since there are six π-electrons in the 5-membered ring, it can be calculated as follows

  • 6 (π electrons) ÷ 5-membered ring = 1.2

One carbon atom has 1.2 pi-electrons in it. This is the reason why 5-membered ring heterocyclic compounds are highly reactive.

-The Orientation Is 2nd (α-Position)

For a 5-membered heterocyclic compound, there are two reaction sites: the 2nd (α-position) and the 3rd (β-position). At which position does the electrophilic aromatic substitution reaction take place?

The answer is that the 2nd position is where the electrophilic substitution reaction takes place. When an electrophilic agent reacts with an aromatic ring, the presence of a substituent in the second position allows more resonance structures to be written. The reaction mechanism is as follows.

The ability to write resonance structures allows the electrons to be dispersed in many places and the structure is easily stabilized. For this reason, electrophilic substitution reactions with 5-membered heterocyclic compounds occur in the 2nd position (α-position).

6-Membered Rings Have Low Electron Density and are meta-Oriented

On the other hand, what about the heterocyclic compounds with six-membered rings? Unlike the 5-membered heterocyclic compounds, the electron density is lower in the 6-membered ring. There are fewer electrons in the aromatic carbon atoms.

Writing a resonance structure, the double bond in the aromatic ring can be transferred to the nitrogen atom. The result is a resonance structure that looks like the following.

Thus, the carbon atom is positively charged. As a result of the transfer of electrons from the aromatic ring to the nitrogen atom, the electron density of the aromatic ring is lowered, making it less reactive. In fact, pyridines must be subjected to extreme conditions in order to undergo an electrophilic substitution reaction.

In addition, by checking the resonance structure, we can see that the ortho and para positions have a positive charge. Therefore, for six-membered heterocyclic compounds, such as pyridine, an electrophilic substitution always takes place at the meta-position. Because of the low electron density in the ortho and para positions, the reaction occurs in the meta position.

The reason for the meta-orientation in pyridines is that only in the meta position is the carbon atom not having a positive charge.

Nucleophilic Aromatic Substitution Reactions Understood by Pyridine

The reactions that occur in aromatic heterocyclic compounds are not limited to electrophilic substitution reactions. Electrophilic aromatic substitution reactions also occur. Nucleophilic substitution reactions in which the substituent on the benzene ring is replaced by an attacking nucleophilic agent are nucleophilic aromatic substitution reactions.

Aromatic compounds do not normally undergo nucleophilic substitution. Exceptionally, aromatic compounds with low electron density, such as pyridine, can undergo nucleophilic aromatic substitution reactions.

Specifically, nucleophilic substitution occurs when halogens such as fluorine (F) or chlorine (Cl) are bound to the pyridine in ortho or para.

As mentioned above, six-membered aromatic heterocyclic compounds have positive charges at the ortho and para positions. This makes it easier to attack by negatively charged nucleophiles. If these conditions are met, a nucleophilic substitution reaction to a halogen occurs.

Learn Reactivity and Orientation of Heterocyclic Compounds

One major genre in organic chemistry synthesis is heterocyclic compounds. There are many compounds that have heterocyclic rings in the molecule and you have to learn how they react chemically.

However, there is a big difference between heterocyclic compounds compared to benzene rings. Also, even though the compounds exhibit the same aromaticity, the characteristics of a 5-membered ring and a 6-membered ring are quite different. They have different properties such as basicity, reactivity and orientation.

There are many types of aromatic heterocyclic compounds, not only 5-membered rings and 6-membered rings, but also more complex ring structures are common. There are also many compounds that have more than one heteroatom in the same molecule. So, we have used simple heterocyclic compounds such as pyrrole and pyridine as examples.

Because they are aromatic compounds, the compounds undergo electrophilic and nucleophilic substitution reactions. However, there are specific aromatic reactivity and orientation properties unique to heteroatoms, so it is important to understand these features.