Pharmaceutical Organic Chemistry-I: Electrophilic Substitution

A substituent in a benzene ring that makes the ring more reactive towards electrophilic aromatic substitution (EAS) reactions by donating electrons.

A substituent in a benzene ring that makes the ring less reactive towards electrophilic aromatic substitution (EAS) reactions by withdrawing electrons.

A substituent in a benzene ring that increases the rate of electrophilic aromatic substitution (EAS) reaction compared to benzene itself.

A substituent in a benzene ring that decreases the rate of electrophilic aromatic substitution (EAS) reaction compared to benzene itself.

Electron donating groups that direct the incoming electrophile to the ortho and para positions of the benzene ring.

Electron withdrawing groups that direct the incoming electrophile to the meta position of the benzene ring.

The tendency of a substituent on a benzene ring to influence the position of the incoming substituent during an electrophilic aromatic substitution (EAS) reaction.

A type of chemical reaction in which an electrophile (electron-loving species) attacks an aromatic ring, replacing a hydrogen atom with a new substituent.

Groups that donate electrons through resonance, increasing electron density at the ortho and para positions of the benzene ring.

Groups that donate electrons through inductive effect, increasing electron density at the ortho and para positions of the benzene ring.

The +M effect (resonance donation) of -OH, -OR, and -NH2 groups stabilizes the σ-complex intermediate at the ortho and para positions. Thus, these groups direct electrophilic attack to these positions.

The +I effect (inductive donation) of alkyl groups stabilizes the σ-complex intermediate at the ortho and para positions, making these groups o/p-directing in electrophilic aromatic substitution.

Highly activating groups like -NH2, -NHR, -NR2, and -OH can react further with electrophiles, leading to more complex substitution patterns. Special conditions are required to control the reaction.

Groups that withdraw electrons from the benzene ring, decreasing its electron density and hindering electrophilic aromatic substitution. They direct the incoming electrophile to the meta position.

These groups are characterized by their strong electron-withdrawing effect due to their ability to pull electrons through resonance and inductive interactions. This withdrawal of electron density from the benzene ring makes it less reactive towards electrophilic substitution reactions.

These groups have an electron-withdrawing ability through their inductive effect, which involves the withdrawal of electron density through sigma bonds. Compared to strong deactivators, their electron-withdrawing power is less pronounced.

The nitro group, -NO2, is an example of a deactivating group that directs the incoming electrophile to the meta position.

Halogens, such as fluorine, chlorine, bromine, and iodine, are deactivating groups that direct incoming electrophiles to the ortho and para positions. Although they withdraw electrons inductively (-I effect), they also donate electrons through resonance (+M effect). The -I effect is stronger than the +M effect, making halogens overall deactivating.

A sigma complex is an intermediate formed during electrophilic aromatic substitution reactions. It involves a positive charge on the benzene ring, which is stabilized by resonance.

The +M effect, also known as the mesomeric effect, is a type of electron delocalization in molecules where electrons shift from a region of higher electron density to a region of lower electron density. In the case of halogens like chlorine, the +M effect is weaker compared to hydroxyl (OH) or amino (NH2) groups because the overlap between the 2p orbitals of carbon and the 3p orbitals of chlorine is less effective.

In disubstituted benzenes, the substituents can either reinforce or oppose each other's directing effects during electrophilic aromatic substitution reactions.

When the two substituents on a benzene ring direct the incoming group to the same position, they reinforce each other. This results in a single major product.

In disubstituted benzenes, activating groups are generally stronger directors than deactivating groups. This means they control the position of the incoming electrophile.

When the directing effects of the two substituents on a benzene ring oppose each other, the stronger activating group usually dictates the orientation of the incoming electrophile. This results in a single major product.

If the two opposing substituents have similar directing abilities, a mixture of products may form. This indicates that neither group has a strong enough influence to control the reaction completely.