Modular Synthesis of Tetraurea and Octaurea Macrocycles Encoded with Specific Monomer Sequences

Intermolecular hydrogen bonding among urea units grants prominent mechanical strength to polyurea elastomer materials. However, such interactions can cause significant solubility problems when synthesizing oligourea macrocycles with a large number of urea units, and it remains unknown for macrocycles containing more than six urea units. Here, we demonstrate a two-step, modular strategy for making a new class of tetraurea and octaurea macrocycles using commercially available building blocks. Intramolecular hydrogen bonding within the fundamental o-phenylene bis(urea) unit is the key to overcoming intermolecular hydrogen bonding to form favorable conformations for ring-closure reactions. The size and monomer sequences can be controlled by varying the flexibility of the spacers. Rigid diphenyl methylene and diphenyl ether linkers selectively afford tetraurea macrocycles, whereas the flexible hexylene linker produces octaurea macrocycles. Macrocycles encoded with two different spacers were also made. All these macrocycles are confirmed by X-ray diffraction structural analysis of the complexed forms with sulfate anions. Interestingly, a unique “figure-eight” structure is observed for the complex of MUH octaurea macrocycle with two encapsulated sulfate anions. Our study shows a paradigm of making large oligourea macrocycles with designer properties in a program-able manner with tunable monomer sequences.