An efficient reagent-controlled approach for the regiospecific synthesis of new 2,2'-bipyridine derivatives in high-temperature water via microwave-assisted multicomponent reactions of aldehydes, 3-aryl-3-oxopropanenitrile, 2-acetylpyridine, and ammonium acetate is reported. Furthermore, aromatic aldehydes reacted with 1,2-diphenylethanone, resulting in structurally complex penta-arylpyridines. This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construct poly arylpyridine skeleton.