J. zyxwvutsrq Am. Chem. SOC. zyxwv 1992, zyxwvu 114, 365-366 Acknowledgment. Support of this research by the National Science Foundation is gratefully acknowledged as is support of early stages by NIH Grant GM07487. "I zyx J5( & >o;oq Registry No. 5, 137570-31-1; 6, 79919-09-8; 7, 3263-79-4; 8, 137570-32-2; 9, 137570-33-3; 10, 4400-53-7; 11, 2892-41-3; 15, 137570-34-4; 16, 137570-35-5; 17, 137570-36-6. Supplementary Material Available: Details of the general photolysis conditions and preparative information as well as quantum yield determinations and runs and a table of thioxanthone sensitized quantum yields (3 pages). Ordering information is given on any current masthead page. Figure 1. 365 Molecular Recognition: Bis-Acylguanidiniums Provide a Simple Family of Receptors for Phosphodiesters Robert P. Dixon, Steven J. Geib, and Andrew D. Hamilton* Department of Chemistry, University of Pittsburgh Pittsburgh, Pennsylvania 15260 Received August 14, 1991 Recent reports from this' and other laboratories2have shown that molecules containing several hydrogen-bonding groups di- rected into a cleft or cavity can effectively recognize neutral substrates. For example, 2-(acy1amino)pyridine derivatives form strong complexes with carboxylic acidsla via a neutral bidentate hydrogen-bonding interaction (1). We were interested in extending this directed hydrogen-bonding approach to anionic substrates such as phosphate and carboxylate. A straightforward strategy would involve protonating the pyridine to form the bidentate ion pair 2. However, crystals grown from a 1:l mixture of 2,6-dib~tyi- amidopyridine (3) and diphenylphosphoric acid3 show, in the solid state (Figure l), that while proton transfer occurs the cyclic bidentate complex does not. Instead, the N-pyridine bonds rotate 1 80° to form two intramolecular hydrogen bonds between the pyridinium H and amide CO and two intermolecular hydrogen bonds between the amide NHs and two phosphate unitsS4 An intramolecular hydrogen bond of this type might be ex- ploited as a rigidifying element in receptor design if an additional binding group were positioned at a site corresponding to the pyridine 3-carbon in 3. This arrangement exists in 2-(acyl- amino)imidazolines, 4, and a crystal structure of 2-(benzoyl- (1) (a) Garcia-Tellado, F.; Goswami, S.; Chang, S. K.; Geib, S.; Hamilton, A. D. J. Am. Chem. SOC. 1990,112,7393. (b) Goswami, S.; Van Engen, D.; Hamilton, A. D. J. Am. Chem. SOC. 1989, 111, 3425. (c) Chang, S. K.; Hamilton, A. D. J. Am. Chem. SOC. 1988, 110, 1318. (b) Muehldorf, A. V.; Van Engen, D.; Warner, J. C.; Hamilton, A. D. J. Am. Chem. SOC. 1988,110, 6561. (2) Jeong, K. S.; Tjivikua, T.; Muehldorf, A.; Deslongchamps, G.; Famu- lok, M.; Rebek, J., Jr. J. Am. Chem. Soc. 1991, 113, 201. Liu, R.; Sanderson, P. E. J.; Still, W. C. J. Org. Chem. 1990.55, 5184. Hegde, V.; Madhukar, J. D.; Thummel, R. P. J. Am. Chem. SOC. 1990, 112, 4549. Jeong, K.-S.; Muehldorf, A. V.; Rebek, J., Jr. J. Am. Chem. SOC. 1990,112,6144. Tanaka, Y.; Kato, Y.; Aoyama, Y. J. Am. Chem. SOC. 1990, 112, 3910. Whitlock, B. J.; Whitlock, H. W. J. Am. Chem. SOC. 1990, 112, 3910. Rebek, J., Jr. Acc. Chem. Res. 1990, 23, 399. Adrian, J. C.; Wilcox, C. S. J. Am. Chem. Soc. 1989,111,8055. Chapman, K. T.; Still, W. C. J. Am. Chem. SOC. 1989, 111,3075. Zimmerman, S. C.; Wu, W. J. Am. Chem. SOC. 1989,111,8054. Bell, T. W.; Liu, J. J. Am. Chem. SOC. 1988, 110, 3673. Kelly, T. R.; Maguire, M. P. J. Am. Chem. SOC. 1987, 109, 6549. (3) Dissolved in CH,CI,-hexane. (4) This solid-state hydrogen-bonding motif appears to be general for 2,6-di(acylamino)pyridinium diphenylphosphate salts: Geib, S. J.; Hirst, S. C.; Vicent, C.; Hamilton, A. D. J. Chem. SOC., Chem. Commun. 1991, 1283. H O H 4 Figure 2. amin0)imidazoline (Figure 2) showed that an intramolecular hydrogen bond between one ring N H and the benzoyl CO was present. In addition, the other N H and the acyl N were positioned to form a cyclic bidentate interaction with a second molecule. On the basis of our earlier studies of phosphorodiamidate recognition? we reasoned that linking two protonated aminoimidazolines through an isophthalic acid spacer should lead to a simple receptor for phosphate ester anions. Reaction of dimethyl isophthalate with 2-aminoimidazolinium p-toluenesulfonate in MeOH and NaOMe6 followed by alumina chromatography (CH2C12-MeOH, 50: 1 eluent) gave the corre- sponding bi~-2-(acylamino)imidazoline in 16% yield. The basicity of (acy1amino)imidazolines (pK, = 7.09) is reduced relative to aminoimidazolines (pK, = 13.58);' however, they can be readily protonated, and treatment with picric acid gave the dicationic receptor 5. An even simpler receptor, 6,8 containing two acyl- H .P&o%H b H ' " ,HN$", HN+$H ,HNHb HNH < , " H ""3 H 5 ( ( picrate)2 5 guanidinium groups can be formed from the reaction of guani- dinium hydrochloride and dimethyl i~ophthalate.~ Both 5 and 6 could be converted into their tetraphenylborate (TBP) salts by treating the corresponding bis-hydrochloride with sodium tetra- phenylborate. The 'H N M R spectrum of 6 in CD3CN shows three broad signals due to guanidinium hydrogens a, b, and c at 7.4, 8.2, and 11.2 ppm, respectively.1° The large downfield shift of the b protons is consistent with the formation of an intramolecular hydrogen bond to each of the isophthaloyl carbonyl groups, as depicted in 6.'" These provide additional rigidity to the molecule, (5) Tecilla, P.; Chang, S. K.; Hamilton, A. D. J. Am. Chem. SOC. 1990, (6) Bicking, J. B.; Robb, C. M.; Kwong, S. F.; Cragoe, E. J. J. Med. Chem. (7) Storey, B. T.; Sullivan, W. W.; Moyer, C. L. J. Org. Chem. 1964, 29, 112,9586. 1967, 10, 598. 3118. (8) ' H NMR of 6 (CD,CN): d 11.16 (br s, 2 H, CONH), 8.73 (s, 4 H, picrate), 8.49 (s, 1 H, 2-isophth), 8.26 (br s, 4 H, endo NH), 8.17 (dd, J = 8, 2 Hz, 2 H, 4,6-isophth), 7.69 (t. J = 8 Hz, 5-isophth), 7.40 (br s, 4 H, exo NH). (9) For other examples of guanidinium-containing synthetic receptors, see: Dietrich, B.; Fyles, D. L.; Fyles, T. M.; Lehn, J. M. Helu. Chim. Acta 1979, 62, 2763. Muller, M.; Riede, J.; Schmidtchen, F. P. Angew. Chem., Int. Ed. Engl. 1988, 27, 1516. Echaverren, A.; Galan, A,; Lehn, J. M.; de Mendoza, J. J. Am. Chem. Soc. 1989,111,4994. Schmidtchen, F. P. Tetrahedron Lett. 1989, 4493. 0002-7863/92/1514-365$03.00/0 0 1992 American Chemical Society