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

The nucleophilic addition of organic anions to aromatic compounds with halogens positioned both ortho and para to activating groups was studied in a variety of solvents. Substrates showed strong preferences for ortho substitution in most cases. Evidence is presented for activating group-dependent coordination, which contributes to very high ortho-selectivity in nonpolar solvents. This also drives the overall reaction rate in these solvents, and is of close to the same magnitude of rate increase derived from polar solvents. para-Products are maximized by using crown ethers in protic solvents. Solvent effects overall are very different from corresponding reactions with amine nucleophiles due primarily to the different charges present in the transition states, and to solvation of the nucleophile.