An improved method of synthesizing a macrocyclic tetraamido compound includes protecting the amino portion of an amino carboxylic acid to form a protected amino carboxylic acid; exposing the protected amino carboxylic acid to a first solvent, preferably a hydrocarbon solvent, such as toluene or 1,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane. The carboxylic acid portion of the protected amino carboxylic acid is then converted to an activated carboxylic acid by one of esterification or acid halide formation, to form a protected amino activated carboxylic acid derivative. The protected amino activated carboxylic acid derivative is reacted with a diamine in the presence of a second solvent, such as THF or ,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane, to form a protected diamide diamine intermediate. Following deprotection, the diamide diamine intermediate is reacted with an activated diacid, such as an activated malonate, oxalate or succinate derivative to form the macrocyclic tetraamido compound. The macrocyclic tetraamido compound may further be complexed with a transition metal.