The N-carbamoyl squaramide dimer: a compact, strongly associated H-bonding motif Anthony P. Davis,* a Sylvia M. Draper, a Gavin Dunne a and Peter Ashton b a Department of Chemistry, Trinity College, Dublin 2, Ireland. E-mail: adavis@tcd.ie b School of Chemistry, University of Birmingham, Edgbaston, Birmingham, UK B15 2TT Received (in Cambridge, UK) 6th September 1999, Accepted 1st October 1999 N-Carbamoyl squaramides 3, readily available from dialkyl squarate 5, form hydrogen-bonded dimers in solution and in non-polar organic solvents; in CDCl 3 they show no sig- nificant dissociation down to concentrations of ~ 0.5 mM. The continuing development of supramolecular self-assembly requires accessible subunits which can be relied upon to associate strongly and predictably through non-covalent inter- actions. Particular attention has recently been paid to systems capable of forming four intermolecular hydrogen bonds, 1–4 such as the self-complementary ‘DDAA’ units 1 and 2 studied by the groups of Meijer 1 and Zimmerman, 2 respectively. These units self-associate essentially completely in solvents such as CDCl 3 , and are only disrupted by significant quantities of polar solvents such as DMSO. Herein we report a new homodimer which is related to 1 and 2 but with significant geometric differences. It is nearly as strongly bound, while being exceptionally compact and easy to construct. The new system 3·3 is based on the squaramide unit, previously shown by Ballester, Costa and co-workers to provide a distinctive array of H-bonding sites for molecular recogni- tion. 5,6 Unlike the earlier squaramides, monomer 3 possesses a ureidyl substituent capable in principle of intramolecular hydrogen bonding to the neighbouring NH. The result should be a well-defined, roughly planar structure with an intriguing resemblance to guanine derivatives 4. Planning to investigate the interaction of 3 with nucleobases, we synthesized examples 3a and 3b from diisopropyl squarate 5 as shown in Scheme 1. Preliminary 1 H NMR binding experiments in CDCl 3 gave unexpected results, leading us to suspect that the squaramides self-associated to some degree. However, dilution studies in this solvent showed no substantial changes in the spectra of 3a or 3b (Dd < 0.1 ppm) over a wide range of concentrations ( ~ 25–0.5 mM), suggesting either that association was not taking place or that it was very strong indeed. Suspecting the latter, we obtained crystals of 3a from CH 2 Cl 2 –light petroleum and subjected them to X-ray crys- tallography.† As shown in Fig. 1, 3a exists as a centrosym- metric dimer in the crystal, apparently maintained by four NH…ONC hydrogen bonds. The carbamoylsquaramide units are essentially planar, and exhibit the expected intramolecular hydrogen bond. The hypothesis that 3 dimerises strongly in CDCl 3 was tested by NMR studies in the presence of ‘competitive’ co-solvents. Addition of CD 3 CN (up to 40% v/v) to CDCl 3 solutions of 3a resulted in upfield movements of all three NH signals. For H(1) and H(3) the motions were moderate (Dd ~ 20.7 ppm), while Scheme 1 Reagents and conditions: i, NH 3 , MeOH–CH 2 Cl 2 , room temp.; ii, R 1 NCO, Et 3 N, MeCN, room temp.; iii, R 2 NH 2 , CH 2 Cl 2 , room temp. Fig. 1 Crystal structure of 3a showing the relationship between adjacent H- bonded molecules. Selected distances (Å) and angles (°) are H(1)…O(5) 2.120(2), H(2)…O(3) 1.936(1), H(3)…O(3) 2.204(6), H(1)–N(1) 0.869(6), H(2)–N(2) 0.900(3), H(3)–N(3) 0.832(2); N(1)–H(1)…O(5) 136.65(6), N(2)–H(2)…O(3) 160.96(8), N(3)–H(3)…O(3) 149.03(9), H(2)…O(3)…H(3) 60.81(9). This journal is © The Royal Society of Chemistry 1999 Chem. Commun., 1999, 2265–2266 2265