Design and Synthesis of Urea‐Linked Aromatic Oligomers—A Route Towards Convoluted Foldamers

Abstract

Herein we report the design and synthesis of crescent-shaped and helical urea-based foldamers, the curvature of which is controlled by varying the constituent building blocks and their connectivity. These oligomers are comprised of two, three or five alternating aromatic heterocycles (pyridazine, pyrimidine or pyrazine) and methyl-substituted aromatic carbocycles (tolyl, o-xylyl or m-xylyl) connected together through urea linkages. A crescent-shaped conformational preference is encoded within these pi-conjugated urea-linked oligomers based on intramolecular hydrogen bonding and steric interactions; the degree of curvature is tuned by the urea connectivity to the heterocycles and the aryl groups. NMR characterization of these foldamers confirms the intramolecular hydrogen-bonded conformation expected (Z,E configuration of the urea bond) in both the pyridazyl and pyrimidyl foldamers in solution. An X-ray crystal structure of the N(3),N(6)-diisobutylpyridazine-4,6-diamine-o-tolyl urea-linked foldamer (4) confirms the presence of N-H...N hydrogen bonds between the heterocyclic nitrogen atom and the free hydrogen of the urea linkage. Additionally, the tolyl methyl group interacts unfavourably with the urea carbonyl oxygen, thus destabilising the alternate planar conformation.

Folding and self-assembly of aromatic and aliphatic urea oligomers: Towards connecting structure and function

“…94 The folded nature of pyridazyl urea-linked oligomers was confirmed by X-ray crystal structure determination of 18 and by studies of open-chain oligomers in solution and in the crystal state. 96 Conformational control through H-bonding (Fig. 4b) has also been used to generate extended linear strands.…”

Conformational Control of Hydrogen-Bonded Aromatic Bis-Ureas

“…For instance, the hydrogen bond donor ability of phenylureas has been exploited in the fields of anion complexation [1][2][3] and foldamer conformational control. 4 Most importantly, the self-complementarity of the phenylurea synthon is a reliable design element in crystal engineering [5][6][7][8] and the main driving force for the self-assembly of numerous organogelators, [9][10][11][12] liquid crystals, 13 supramolecular polymers, [14][15][16][17][18][19][20][21][22][23] nanostructured polymers, [24][25][26][27][28][29] selfassembled monolayers [30][31][32] and dimeric capsules. [33][34][35][36] Scheme 1.…”

Structure and conformational dynamics of an aromatic sulfonamide: NMR, X-Ray and computational studies

“…3,4 It is worth of mention that the 1,4-tosylation of 2,3-dimethyl-4-amino aniline revealed to be not a trivial task. In fact, after the easy introduction of the first tosyl group, the second tosylation occurred either in 1,4-and in 1,1-position.…”