Ortho selectivity in SNAr substitutions of 2,4-dihaloaromatic compounds. Reactions with piperidine

A broad survey of aromatic compounds with halogens positioned both ortho and para to activating groups was studied in S_NAr reactions with piperidine. Regioselectivities varied with the substituent group and the polarity of the solvent. Many activating groups exhibited an overall bias toward ortho-substitution, and this led in nonpolar solvents to very high ortho selectivity. More polar solvents uniformly shifted the product ratio toward para substitution. Evidence is presented that argues for coordination via hydrogen bonding as a driver of much of the ortho selectivity observed. The data presented show ample evidence of the generality and synthetic utility of the ortho-directing ability of several common activating groups for this reaction type.