The synthesis of halogenated pyridines substituted at the carbon atom C-3

Arylation of α-methyleneglutaronitrile (MGN) occurred when arylamines, aminopyridines and 3-aminothiophene were treated with alkylnitrites and copper(I) chloride in dimethyl methylphosphonate (DMMP) solutions. Results from this study exemplified the synthetic advantage of DMMP as a solvent in Meerwein reactions with an olefin of low reactivity, yielding 1-aryl-2 chloro-2,4-dicyanobutanes, and its 3-pyridyl- and thiophen-3-yl analogues. Partial hydrolysis, followed by subsequent ring closure of the substituted 2,4-dicyanobutanes to 2,6-piperidinediones (glutaric acid imides) was effected with a solution of sulfuric acid in acetic acid. The aromatization of the substituted 2,6-piperidinediones with phosphorus oxychloride in the presence of hexamethylphosphoric acid triamide (HMPT) yielded the 2,6-dichloropyridine moiety substituted at the carbon atom C-3.