Protonated cryptates

There is considerable interest in the properties of macrobicyclic cryptands, for example [78] to [81], and particularly in their ability to complex protons, metal ions, and small molecules (Lehn, 1978). In the proton cryptates there exists the possibility of intramolecular +N—H N hydrogen bonding as well as interaction of the proton with the oxygen atoms, and the properties are also strongly influenced by the size of the molecular cavity. In the [l.l.l]-cryptand [78] the molecular cavity is small (Cheney et al., 1978) and... 

For cryptands in which the molecular cavity is larger than in the case of the [l.l.l]-species [78], proton transfer in and out of the cavity can be observed more conveniently. Proton transfer from the inside-monoprotonated cryptands [2.1.1] [79], [2.2.1] [80], and [2.2.2] [81 ] to hydroxide ion in aqueous solution has been studied by the pressure-jump technique, using the conductance change accompanying the shift in equilibrium position after a pressure jump to follow the reaction (Cox et al., 1978). The temperature-jump technique has also been used to study the reactions. If an equilibrium, such as that given in equation (80), can be coupled with the faster acid-base equilibrium of an indicator, then proton transfer from the proton cryptate to hydroxide ion... 

The hexaethylenetetraamine 12 has been created as a proton cryptate and proven by its X-ray structure<99ACIE956>. Related but larger macrocyclic cages have been formed in order to encapsulate metal ions<99ACIE959>. 

Proton cryptates are obtained by internal protonation, the cavity concealing the protons very efficiently especially in the case of the protonated forms 11 and 12 of the smaller cryptand 6 [2.29,2.30]. 

Diaza[12]coronand-4 (21) was condensed with diethylene glycol bismesylate 22 in the presence of butyllithium. Precipitation, occuring during the reaction course, afforded the proton cryptate 24 H+ c= [1.1.1] in 40% yield. It should be noted that [1.1.1] was obtained only in 10% yield via the high-dilution method 23). Lithium promoted cyclization was excluded (as an alternative mechanism) by an additional experiment in which KH served as a base instead of BuLi. Identical yield was achieved, indicating that intramolecular hydrogen bonding was responsible of the cyclization. 

A derivative of the (bpy.bpy.bpy) cryptand, obtained by modifying one of the chains, Lbpy, forms a di-protonated cryptate with EuCb in water at acidic pH, [EuCl3(H2Lbpy)]2+ in which the metal ion is coordinated to the four bipyridyl and two bridgehead nitrogen atoms, and to the three chlorine ions (Fig. 4.25). The polyamine chain is not involved in the metal ion coordination, due to the binding of the two acidic protons within this triamine subunit. In solution, when chlorides are replaced by perchlorate ions, two water molecules coordinate onto the Eu(III) ion at low pH and one at neutral pH, a pH at which de-protonation of the amine chain occurs, allowing it to coordinate to the metal ion. As a result, the intensity of the luminescence emitted by Eu(III) is pH dependent since water molecules deactivate the metal ion in a non-radiative way. Henceforth, this system can be used as a pH sensor. Several other europium cryptates have been developed as luminescent labels for microscopy. 

Fig. 4.25. Structure of the protonated cryptate [EuCl3(H2L)]2+. Redrawn from C. Bazzicalupi et al., Chem.

The endo-endo conformation of cryptands can be internally protonated to form proton cryptates. With the small cryptands, e.g. [1.1.1]- and [2.1.1]-cryptand (15a and 15b), the two internal protons are so efficiently shielded from H2O and OH that deprotonation only very slowly occurs even in strong base (8UA6044). Alkali cation cryptates are able to stabilize unusual species as their counterions. Dye and coworkers have isolated several alkali metal anions by this method. The sodium species (Na [2.2.2]cryptand Na ) was obtained as gold metallic crystals and gave a Na NMR with a broad Na -cryptate resonance and a narrow, upheld Na resonance. The other alkali metals show similar behavior and an electride salt (Na [2.2.2]cryptand e l has even been isolated (B-79MI52105). Crystalline anionic clusters of the heavy post-transition metals (such as Sb7 , Pbs , Sng ) were first obtained with alkali metal cryptates as the counterions (75JA6267). 

Howard, S.T. (2000) Relationship between basicity, strain and intramolecular hydrogen-bond energy in proton sponges. Journal of the American Chemical Society, 122, 8238-8244. Smith, P.B., Dye, J.L., Cheney, J. and Lehn, J.-M. (1981) Proton cryptates. Kinetics and thermodynamics of protonation of the [ 1.1.1 ] macrobicyclic cryptand. Journal of the American Chemical Society, 103, 6044-6048. 

The small cryptand 11 (Fig. 11) was obtained with difficulty, because the major compound obtained was a macrotricyclic tetraamide resulting from a dimerization reaction. It was observed that stable proton cryptates of 11 can be obtained. The [1.1.1] bicycle binds one or two protons inside its intramolecular cavity. The diprotonated cryptate 11, 2H. has a high resistance to deprotonation. The monoprotonated cryptate may be obtained with difficulty but this latter species cannot be fully depro-tonated by base to afford the free cryptand. Smaller analogues of 11 containing only carbon atoms in the three chains were also described. They present similar behavior toward the proton. Another class of cryptands able to strongly bind the proton was developed more recently. 

An exception is the extremely slow proton transfer involving certain proton cryptates, Cheney, J. and Lehn, J. M. 1972, J. Chem. Soc., Chem. Comm., p. 487. 

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