[3H]imidacloprid: Synthesis of a candidate radioligand for the nicotinic acetylcholine receptor

Imidacloprid is an exceptionally potent insecticide known from physiological studies to act at the nicotinic acetylcholine receptor. To prepare [3H]imidacloprid as a candidate radioligand, 6‐chloronicotinoyl chloride was reduced with NaB2H4 (in model studies) or NaB3H4 in absolute ethanol to 2‐chloro‐5‐pyridinylmethanol which was transformed to 2‐chloro‐5‐chloromethylpyridine on refluxing with thionyl chloride. Coupling with 4,5‐dihydro‐N‐nitro‐1H‐imidazol‐2‐amine then gave [2H2]imidacloprid incorporating about 95% of the deuterium or [3H2]imidacloprid (25 Ci/mmol) in 80% radiochemical yield. In studies not detailed here [3H]imidacloprid was found to undergo high affinity, specific and saturable binding to a site in insect brain.