Cryptands, conformers

Analysis of solid-state structures has played an important role in understanding crown and cryptand conformation. A variety of interactions between these heteromacrocyclic receptors and metal cations, ammonium ions, and other species have been revealed. The earliest work in this area revealed that crowns and cryptands crystallize in conformations in which one or more methylene group(s) rotate inward to fill the molecular void, if this is permitted by the overall size of the macroring. In fact, molecules such as 12-crownM are remarkably congested and have little or no internal cavity (i.e., hole). This is apparent in Figure 8, which shows space-filling molecular models of 12-crown-4 (left) and 15-crown-5 (right). 

The similarity between the cryptands and the first of these molecules is obvious. Compound 7 7 is a urethane equivalent of [2.2.2]-cryptand. The synthesis of 7 7 was accomplished using a diacyl halide and l,10-diaza-18-crown-6 (shown in Eq. 8.13). Since amidic nitrogen inverts less rapidly than a tertiary amine nitrogen, Vogtle and his coworkers who prepared 7 7, analyzed the proton and carbon magnetic resonance spectra to discern differences in conformational preferences. Compound 7 7 was found to form a lithium perchlorate complex. 

For larger cryptands [6] (Cox et al., 1978), the protonation/deprotonation kinetics have also been measured. Table 4 lists the kinetic and the equilibrium data for such cryptands. When compared to the neutralization of protonated tertiary amines by OH, the reaction of the second smallest protonated cryptand [2.1.1] H is 10 to 10 times slower (Cox et al., 1978), indicating a strong shielding and possibly an i -orientation of the proton. For the [2.2.1] cryptand, no k and k-i values could be calculated, probably due to a fast pre-equilibrium between in,in- and m,OMt-conformations. 

Rate constants for reaction of Ca2+aq with macrocycles and with cryptands (281,282,291) reflect the need for conformational changes, considerably more difficult for cryptands than for crown ethers, which may be considerably slower than formation of the first Ca2+-ligand bond. Ca2+aq reacts with crown ethers such as 18-crown-6 with rate constants of the order of 5 x 107M 1 s, with diaza crown ethers more slowly (286,326). The more demanding cryptands complex Ca2+ more slowly than crown ethers (kfslow reaction for cryptands with benzene rings fused to the macrocycle. The dominance of kA over kt in determining stability constants is well illustrated by the cryptates included in Table X. Whereas for formation of the [2,1,1], [2,2,1], and [2,2,2] cryptates kf values increase in order smoothly and gently, the k( sequence Ca[2,l,l]2+ Ca[2,2,l]2+ Ca[2,2,2]2+ determines the very marked preference of Ca2+ for the cryptand [2,2,1] (290). 

The proportion of the /rans-O-alkylated product [101] increases in the order no ligand < 18-crown-6 < [2.2.2]-cryptand. This difference was attributed to the fact that the enolate anion in a crown-ether complex is still capable of interacting with the cation, which stabilizes conformation [96]. For the cryptate, however, cation-anion interactions are less likely and electrostatic repulsion will force the anion to adopt conformation [99], which is the same as that of the free anion in DMSO. This explanation was substantiated by the fact that the anion was found to have structure [96] in the solid state of the potassium acetoacetate complex of 18-crown-6 (Cambillau et al., 1978). Using 23Na NMR, Cornelis et al. (1978) have recently concluded that the active nucleophilic species is the ion pair formed between 18-crown-6 and sodium ethyl acetoacetate, in which Na+ is co-ordinated to both the anion and the ligand. 

The preferential stabilization of conformation [96] by the cation is annulled upon binding of the cation with a cryptand. Similar effects have been observed with crown ethers. The sodium salt of acac in methanol at —58°C consists of 35% [104] and 65% [105]. The addition of 18-crown-6 [3] shifts the... 

Scheme 3.27 represents a case when the odd-bond formation governs the geometry of an anion-radical (Chona et al. 2004). The substrate was reduced on an alkali mirror in the presence of a cryptand, giving the anion-radical, which is not coordinated to the counterion. Such a species undergoes internal rotation to adopt a conformation in which the two phosphine rings occur to be bound with a weak but real one-electron bond. 

Figure 14, Schematic drawings of conformational changes upon cation binding by glymes, crown ethers, and cryptands (D denotes donor atom) also shown are the slopes (a) and intercepts TASo oi AH-TAS plots as measures of conformational change and desolvation.

Thermodynamic behaviour of the complexes should be differentiated from their kinetic behaviour. For instance, conformationally most rigid cryptands form their complexes very slowly. 

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