Utilizing Acetyl Hypofluorite for Chlorination, Bromination, and Etherification of the Pyridine System

Acetyl hypofluorite, which is easily made from F₂, possesses a strong electrophilic fluorine. This electrophile is able to attach itself to the nitrogen atom of pyridine and activate the ring toward nucleophilic attacks. The ultimate elimination of HF results in an overall easy nucleophilic displacement of the hydrogen of the important 2-position. The nucleophiles used; Cl^δ-, Br^δ-, and RO^δ-, originate from solvents such as CH₂Cl₂, CH₂Br₂, and various primary alcohols. Thus, 2-halo- or 2-alkoxypyridines were formed. The reaction conditions (room temperature, very short reaction times, and good yields) transform the task of direct substitution of the pyridine ring from an extremely difficult to a very easy procedure.