A Ditopic Azacryptate Proton Cage Paula Morehouse, Md. Alamgir Hossain, Jose ´ M. Llinares, Douglas Powell, and Kristin Bowman-James* Department of Chemistry, UniVersity of Kansas, Lawrence, Kansas 66045 Received August 15, 2003 A tosylated azacryptand readily protonates at the bridgehead amines, becoming a potential ditopic anion receptor. The in-in conformation of the amines facilitates encapsulation of two bromide guests and represents the first structural evidence that a proton cage cryptate can bind two anions internally. The concept of a proton cage emerged with the introduc- tion of macrobicyclic diaza katapinands, 1, of Park and Simmons, 1 and was exploited even further with the introduc- tion of the proton cryptates, 2. 2 The bridgehead amines of these two classes of macrocycles readily become protonated and can form in-in, in-out, and out-out conformers. Further- more, because of the more rigid structure imparted by the arms joining the two tertiary amines, the protons in the in- in conformation are shielded, and hence rates of deprotona- tion are diminished. The effect has been termed “proton cage”. 3 This type of shielding of the protonated amines allows for more control on their chemistry and has led to explora- tions in the photoinduction of long-lived proton transfer states in cryptands 3 and in the membrane transport of anions using katapinands and tosyl-protected azacryptands. 4 Indeed with the exception of this latter report, protection by tosyl groups has been primarily viewed as an undesirable nuisance, but a necessary part of the synthetic pathway to many aza- containing macrocycles. While Lehn and co-workers pos- tulated binding of a halide within the proton cage in membrane transport, 4 this is the first structural evidence that tosylated azacryptands bind not just one, but two halides simultaneously within the bicyclic cavity. One focus of our research group is the binding of anions by polyaza macrocycles. 5 More recently we have explored systematic ways to increase the affinity of anion receptors, including exploring the binding capabilities of new amide and thioamide macrocycles and cryptands, 6 and mixed amide/ quaternized amine receptors. 7 It is this latter aspect that led us to revisit the tosylated azacryptands, with the possibility of introducing charge complementarity in these ligands by altering the protonation tendencies of the secondary amines. As a result, we synthesized the protected azacryptand, L, derived from a simple Schiff base condensation between tren and isophthalaldehyde, and isolated crystals of the free base, L, and the dihydrobromide salt, H 2 L(Br) 2 . L was synthesized from the reaction of the precursor amine 8 with p-toluenesulfonyl chloride in CH 3 CN using * Author to whom correspondence should be addressed. E-mail: kbowman-james@ukans.edu. (1) (a) Park, C. H.; Simmons, H. E. J. Am. Chem. Soc. 1968, 90, 2428- 2429. (b) Simmons, H. E., Park, C. H. J. Am. Chem. Soc. 1968, 90, 2429-2431. (2) (a) Cheney, J.; Lehn, J.-M. J. Chem. Soc., Chem. Commun. 1972, 487- 489. (b) Cheney, J.; Kintzinger, J. P.; Lehn, J.-M. NouV. J. Chim. 1978, 2, 411-418. (c) Smith, P. B.; Dye, J.; Cheney, J.; Lehn, J.-M. J. Am. Chem. Soc. 1981, 103, 6044-6048. (3) Kuldova `, K.; Corval, A.; Trommsdorff, H. P., Lehn, J.-M. J. Phys. Chem. A 1997, 101, 6950-6854. (4) Dietrich, B.; Fyles, T. M.; Hosseini, M. W.; Lehn, J.-M.; Kaye, K. C. J. Chem. Soc., Chem. Commun. 1988, 691-692. (5) Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem. ReV. 2003, 240, 57-75. (6) (a) Kang, S. O.; Llinares, J. M.; Powell, D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem. Soc. 2003, 125, 10152-10153. (b) Hossain, A. Md.; Kang, S. O.; Llinares, J. M.; Powell, D.; Bowman- James, K. Inorg. Chem. 2003, 42, 5043-5045. (7) Hossain, M. A.; Kang, S. O.; Powell, D.; Bowman-James, K. Inorg. Chem. 2003, 42, 1397-1399. Inorg. Chem. 2003, 42, 8131-8133 10.1021/ic034972u CCC: $25.00 © 2003 American Chemical Society Inorganic Chemistry, Vol. 42, No. 25, 2003 8131 Published on Web 11/13/2003