Racemic synthesis of 2′‐substituted nicotine analogs

The chemical and pharmacological properties of 2′‐substituted nicotines are poorly understood relative to other substituted nicotines. We developed a practical synthesis of the key intermediate (±)‐2′‐cyanonicotine using the Polonovski reaction . Alkylation of (±)‐2′‐cyanonicotine with Grignard reagents led to several 2′‐alkylnicotines; (±)‐2′‐aminomethylnicotine, (±)‐2′‐hydroxymethylnicotine, and (±)‐2′‐carbamoylnicotine were also synthesized. J. Heterocyclic Chem., (2012).