General Methods of Preparation, and Uses of Heterocyclic Compounds

Organic chemistry studies carbon and its bonds with several other elements like hydrogen, nitrogen, oxygen, halogens, etc. The importance of organic chemistry lies in several naturally occurring materials, including our bodies and plants, that have organic structures. So, studying it and the matter of organic compounds is crucial. One important branch of organic chemistry is heterocyclic chemistry. In this, we learn closed-ring systems, in which one or more than one carbon atom have been replaced by inorganic elements like oxygen, sulphur, or nitrogen.

Importance of Heterocyclic Compounds

We do not realise the unparalleled importance of heterocyclic compounds in our lives. Our body cannot function without vitamins, examples of natural heterocyclic compounds. Nucleic acids are an important class of heterocyclic compounds used in many applications. The use of these compounds makes the importance of organic chemistry even more significant in everyday life.

Whether isosteric or bioisosteric substituted carbon substructures in aliphatic structures or true heterocycles, heteroatoms are common components of many active medicinal components and excipients. Many heterocyclic scaffolds have the potential to be categorised as privileged structures. Nitrogen heterocycles, five- or six-membered rings with various positional combinations of nitrogen atoms, sulphur, and oxygen, are the most common. According to data, a heterocycle can be found in more than 85% of all physiologically active chemical entities.

They are used to resist corrosion in sanitisers and pesticides. They are also used in organic synthesis. One primary application is in the pharma sector, where antibiotics are prepared using heterocyclic compounds. They can interfere with the DNA synthesis of harmful bacteria and thus kill them eventually.

Now that we have a brief idea about the importance of heterocyclic organic compounds let’s move on to how they are prepared.

Preparation of Heterocyclic Compounds

Heterocyclic compounds can be classified into two types based on their structure – aliphatic and aromatic. Double bonds are not present in aliphatic heterocyclic compounds, whereas conjugated double bonds are present in planar aromatic heterocyclic compounds.

Examples of aliphatic heterocyclic compounds: pyrrolidine (a five-membered ring in which one carbon atom has been replaced by nitrogen), piperidine (a six-membered closed circle in which a nitrogen atom has replaced one carbon atom), 1,2-dioxane (a six-membered closed saturated ring in which oxygen atoms have replaced two adjacent carbon atoms), etc.

Examples of aromatic heterocyclic compounds: Furan (five-membered aromatic ring with oxygen atom), pyrrole (five-membered aromatic ring with nitrogen atom), thiophene (five-membered aromatic ring with a sulphur atom), pyridine (six-membered aromatic ring with nitrogen atom), etc. These are the most common heterocyclic compounds. 

Furan is prepared from a pentose that is first converted to furfural. When an aldehyde group is attached to the carbon next to the oxygen atom in furan, the compound is called furfural. Furfural was first synthesised in 1832 by reacting starch with sulphuric acid. Heating it in the presence of copper oxide yields furan.

Thus, furan can be prepared easily from corncobs and oat hubs (natural pentose containing materials). 

Pyrrole can be prepared by heating furan in ammonia and aluminium oxide catalyst. 

Thiophene can be prepared by the reaction of 1,3-butadiene with S8. When they are heated together at 600oC, thiophene is formed.

Properties of heterocyclic compounds

Heterocyclic compounds are indispensable when we talk about the importance of organic chemistry. They have slightly different properties because the heteroatoms are other than carbon atoms in lone pairs of electrons. The cyclic ring system has conjugated double bonds, and the lone pair of electrons on the heteroatom participate in conjugation via resonance. 

Nitrogen, oxygen, and sulphur – all of them have lone pairs. The resonating structures can be made, as shown above. The ring has an overall negative charge, due to which it can undergo electrophilic substitution reactions.

There is a generation of the dipole in the ring, making it more reactive than its benzene counterpart.

Important Reactions

Electrophilic substitution reactions are the most important reactions of these compounds. Due to their electronegative nature, they react with electrophiles. The substitution occurs primarily at the atom carbon next to the heteroatom, giving more resonating structures.

More is the number of resonating structures. The higher is the stability of the compound.

It is also to be noted that the reactivity order is: pyrrole >> furan > thiophene > benzene.

Pyrrole has nitrogen which is less electronegative due to which it donates electrons readily. Thiophene has a robust aromatic stabilisation that it becomes less reactive than furan even though furan is more electronegative. 

Conclusion

We cannot leave heterocyclic compounds out of the discussion when we talk about the importance of organic chemistry. They are the class of organic compounds in which one or more carbon atom(s) in the ring has/have been replaced by inorganic elements like sulphur, nitrogen, or oxygen. Furan, pyrrole, and thiophene are critical examples of such compounds and can be prepared easily in a laboratory. These compounds exhibit electrophilic substitution reactions because the rings are electronegative, having a resonating negative charge.