Isophthalamide anion receptors

Isophthalamide anion receptors, for example, compound 96, were originally synthesized by Crabtree and coworkers as a binding motif with little rigidity or preorganization. However, reasonable binding affinities with halides were observed in the range of 10 -1(1 M in dichloromethane. The molecnlar strncture determined by X-ray diffraction shows a distinctly nonplanar binding mode. ... 

Fig. 12 Isophthalamide anion receptors with and without tiiazoles...

Figure 2. The isophthalamide motif has been employed in a variety of receptors possessing high affinities for anions.

In receptor 32 Gale and co-workers have exploited the electron-withdrawing properties of Cr(CO)3 [27]. The coordination of this metal unit to the arene substituents of the isophthalamide increases the acidity of the NH protons and hence their affinity for anions. H NMR titrations with 32 in CD3CN provided stability constants of the same order of magnitude as those for the non-metal-lated receptor in the far less competitive solvent CD2C12. 

Four years later, in 1997, Crabtree and co-workers reported that simple isophthalamide receptors e.g. 2 can bind anions in organic solution [12]. These receptors, even simpler than Reinhoudt s tren-based anion binders, were found to bind smaller halides selectively in dichloromethane solution. 

Almost contemporaneously, B.D. Smith and co-workers reported the use of functionalized isophthalamide receptors for the coordination of anions [13]. Smith appended boronate groups to the peripheral aryl groups in order to form interactions between the Lewis acidic boron and the carbonyl oxygens of the amides therefore pre-organizing the receptor into the syn-syn conformation (preferable for anion coordination) and presumably increasing the acidity of the NH group. Proton COSY and NOE difference experiments indicated that the receptor did indeed adopt the desired syn-syn conformation in DMSO-de. NMR titration experiments in DMSO-de at 295 K showed that re-... 

Stability constants were obtained for receptors 13a, 13b and 13c using analogous conditions to those employed for receptors 12a, 12b and 12c. As with the pyridine-2,6-dicarboxamide macrocydes, the stability constants for the isophthalamide macrocydes appear to be influenced by the size and flexi-bihty of the system with the higher constants observed in the 20-membered receptor 13a with notable decreases in the assodation constants with the 22-and 24-membered receptors 13b and 13c. The greatest decreases where observed in the stability constants obtained with the carboxylate anions. In the case of acetate the constants decreased from 3130 M for 13a to 552 M and 205 M for 13b and 13c, respedively. hi the case of benzoate a constant of 601 M was calculated for 13a decreasing to 302 M and 82 M for 13b and 13c, respectively. Unexpectedly lower binding constants were obtained for the isophthalamide macrocydes (13a-13c) compared to the pyridine-... 

A series of diamide-based cryptands derived from bis(m-phenylene)-[32]crown-10 have been synthesized to complex divalent salts such as paraquat (N,N-dimethyl-4,4 -bipyridinium) dichloride. The synthetic project started from the observation that readily prepared bicyclic crown ether 23 containing two 1,3,5-phenylene units linked by three tetra(ethyleneoxy) units forms a pseudorotaxane-like inclusion complex with Af,Af-dimethyl-4,4-bipyridinium bis(hexafluorophosphate), with an association constant /fa = 6.1 X 1() M that is 100-fold greater than that of the analogous simple crown ether. On this basis, additional anion-binding moieties, such as isophthalamide or 2,6-pyridinedicarboxamide unit, were intfoduced in the third chain of the cryptand receptor. The anion-assisted complexation of bypyridinium dications was analyzed by a combination of different techniques ( H NMR,... 

To exploit this ion pair receptor for rotaxane formation, Smith utilized a discrete potassium template bound within the crown ether group of 17 to aid the association of an anionic phenolate half-axle 19 in the adjacent isophthalamide cleft (Scheme 10.10). Successive esterification reactions between this complex, isophthaloyl dichloride (18), and a further equivalent of the half-axle 19 are necessary to form a fully stoppered axle component. The templated arrangement promotes formation of this axle within the macrocycle, yielding uncharged rotaxane 20. 

As a seminal contribution to anion recognition, in 1997, Crabtree and co-workers reported the synthesis and anion-binding properties of isophthalamide-linked bidentate amide-based receptors 4a,b [21]. Crystal stmcture of 4a Br showed 1 1 complexation with Br (Fig. 5.2). In the stmcmre, the bromide was held with two H-bonds by the amide NH groups at N Br distances of 3.436 and 3.634 A, and N-H—Br angles of 116 and 172 . The isophthalamide spacer could be replaced with a 2,6-diamidopyridine unit to give 4b, which was selective for fluoride anion in CD2CI2 ( Ta = 2.4 x 10 M ) [22]. 

Davis and co-workers designed isophthalamide receptors with appended hydroxyl (4c) or methoxyl (4d) groups [23]. In the solid state, the hydroxyl groups of 4c formed intramolecular OI 1—0=C H-bonds with the amide carbonyls to stabilize the syn—syn conformation, which complexed Cl (K = 5,230 M ) in its cleft. On the other hand, 4d did not bind halide anions, because the methoxy groups promoted the formation of the anti-anti conformation. 

Sessler and co-workers further synthesized strapped calixpyrroles, including isophthalamide strapped system 74 [136, 137]. The aliphatic bridges were found to increase the binding affinity for halide anions in acetonitrile, but failed to provide size-based selectivity amongst anions (Br, CF and F) due to the tilt of the strap to one side of the receptor, which allowed the formation of 2 1 (receptor anion) complexes. 

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