An overview of radio or stable isotope‐labeled cis‐neonicotinoid analogs

To support the metabolism and toxicology study of cis‐neonicotinoids, radio or stable isotope was introduced into different sites of the key intermediate 2‐chloro‐5‐((2‐(nitromethylene)imidazolidin‐1‐yl)methyl)pyridine (6‐Cl‐PMNI). ³H₂]‐ and ¹⁴C]‐label were successively prepared from initial materials NaB³H₄ and ¹⁴C]‐nitromethane, respectively. Similarly, D₂]‐6‐Cl‐PMNI was prepared from NaBD₄ in four steps, with 52.6% overall isotopic yield, and dual‐labeled D₂, ¹³C]‐target was obtained from NaBD₄ and ¹³C]‐nitromethane, affording overall isotopic yield of 42.5%. Moreover, ¹⁴C₂] was introduced from U‐¹⁴C]‐ethylenediamine dihydrochloride in three steps, with a 58.3% overall chemical yield. Finally, typical labeled cis‐neonicotinoids paichongding and cycloxaprid were prepared and characterized. The methods were proved to have good generality in the synthesis of other cis‐neonicotinoids, and all results would be useful in metabolism studies of new cis‐neonicotinoids. Copyright © 2012 John Wiley & Sons, Ltd.