orthohalogenation

Orthohalogenation refers to a specific type of electrophilic aromatic substitution reaction where a halogen atom is introduced onto an aromatic ring at the ortho position relative to an existing substituent. This regioselectivity is often influenced by the nature of the directing group already present on the aromatic ring. Activating groups, such as hydroxyl or amino groups, typically direct incoming electrophiles to the ortho and para positions. In orthohalogenation, conditions are often optimized or specific reagents are employed to favor substitution at the ortho position over the para position.

The mechanism involves the generation of an electrophilic halogen species, such as Br+ or Cl+, which then attacks the electron-rich aromatic ring. The directing effect of the existing substituent plays a crucial role in determining the site of attack. Steric hindrance can also contribute to favoring ortho substitution in some cases, although it can also disfavor it depending on the size of the directing group and the incoming halogen. The choice of solvent, temperature, and halogenating agent are important parameters for controlling the regioselectivity and yield of orthohalogenation reactions. Common halogenating agents include N-bromosuccinimide (NBS), N-chlorosuccinimide (NCS), and elemental halogens (Br2, Cl2) often in the presence of a Lewis acid catalyst. Orthohalogenation is a valuable synthetic tool for preparing substituted aromatic compounds with specific substitution patterns, which are important intermediates in the synthesis of pharmaceuticals, agrochemicals, and other fine chemicals.