The effect of the molecular structure on the reactivity of four first-generation linear-dendritic block copolymers derived from Jeffamines and bearing amine end groups is presented and discussed. Different parameters were investigated via chemical modifications and nuclear magnetic resonance analysis, showing that chain length, hydrophilic/hydrophobic character, and flexibility of the central oligoether block did not produce any change in the amine moiety reactivity. In contrast, the type of branches and the nature of the amine end groups strongly affected the reactivity in an unusual manner. In fact, the copolymer bearing aromatic amine end groups showed better reactivity than those based on aliphatic counterparts.