Cryptands preparation

The spherand prepared by Cram and coworkers was designed to have a relatively small molecular cavity and appeared to prefer complexation with Li and Na over larger cations like K", Rb, etc. Tlie spheroidal cryptand prepared by Lehn ° involved strategy employed previously but the spherand 24 was prepared by quite a different approach. 

A number of bridged crown ethers have been prepared. Although the Simmons-Park in-out bicyclic amines (see Sect. 1.3.3) are the prototype, Lehn s cryptands (see Chap. 8) are probably better known. Intermediates between the cryptands (which Pedersen referred to as lanterns ) and the simple monoazacrowns are monoazacrowns bridged by a single hydrocarbon strand. Pedersen reports the synthesis of such a structure (see 7, below) which he referred to as a clam compound for the obvious reason . Although Pedersen appears not to have explored the binding properties of his clam in any detail, he did attempt to complex Na and Cs ions. A 0.0001 molar solution of the clam compound is prepared in ethanol. The metal ions Na and Cs are added to the clam-ethanol solutions as salts. Ultraviolet spectra of these solutions indicate that a small amount of the Na is complexed by the clam compound but none of the Cs . 

The synthesis of 1,10-diaza-l 8-crown-6 (9) has been an important problem because this is the key starting material in the synthesis of numerous cryptands (see Chap. 8). Although first synthesized some years ago, the process has recently been patented. Di-azacrown 9 is prepared by a high dilution condensation of 1,8-diamino-3,7-dioxaoctane with ethylene glycol diacetyl chloride. The resulting diamide is then reduced with lithium aluminum hydride to give 9 in 56% overall yield from the open-chained diamine. The synthesis is illustrated In Eq. (4.8), below. 

Although a large number of such compounds have been prepared, many of the mixed nitrogen-sulfur macrocycles are included in other tables, most notably in Chap. 4. Some have also been recorded in Chap. 8 as monocyclic precursors to bi- or polycyclic ligands (i.e., cryptands). The reader is directed to the tables of other chapters where the desired compound, if known, may be reported. 

In later work, Vogtle and his coworkers prepared analogs of both crown ethers and cryptands. These molecules are designed to have a terminal donor group which is capable of offering a complexed cation additional binding sites. Numerous... 

Although Lehn and his coworkers prepared a large number of cryptands and derived complexes over the years, the synthetic approach to these compounds remained essentially similar for most of them. Details are presented for a number of such compounds in ref. 26. The essential features of these syntheses were use of amide-forming reactions in the absence of templating ions with reliance on a high dilution step to form the second ring. An alternative approach for the synthesis of cryptands was developed by Dye and his coworkers. Their approach involved the use of a flow synthesis to replace the high dilution step. 

It should also be noted that l,10-diaza-18-crown-6 is a key intermediate in the preparation of numerous cryptands. Considerable attention has been given to the synthesis of this molecule and is noted in Sect. 4.4 to which the reader is referred. 

By incorporating trisubstituted aromatic rings, Vogtle has prepared what he calls endo-lipophilic cryptands . Such a compound is illustrated below as 8. The synthetic approach to these systems parallels those outlined in previous discussion . 

Similar pentaerythritol cryptands have been prepared by a slight modification of the above approach. Although the general strategy is as illustrated in Eq. (8.11), atfetal formation is accomplished by reaction of pentaerythritol with paraformaldehyde. This reaction leads to diacetal 12 which is hydrolyzed in dilute H2SO4 to yield the monoacetal, 13. The latter is then used in a fashion similar to that described in Eq. 8.10, above. 

Krespan has utilized these substances in the preparation of a variety of azacrowns and cryptands . Note that this material is also mentioned by Coxon and Stoddart . The strategy and techniques utilized with 14 are similar to those discussed above and are not noted here in detail. An overall transformation is illustrated in Eq. (8.12). 

Lehn and his coworkers have prepared a number of chiral cryptands based upon the 2,2 -binaphthyl unit " . In a typical preparation, the binaphthyl units are treated with bromoacetic acid to form the phenoxyacetic acid derivatives which are then converted into the corresponding diacyl chlorides (75). Reaction of 15 with l,10-diaza-18-... 

A number of bi- or polycyclic structures have been prepared over the years which are somewhat difficult to classify within the narrow confines of crown and cryptand nomenclature. Nevertheless, these molecules deserve mention and are noted here. 

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. 

The in-out bicyclic amines prepared by Simmons and Park bear a remarkable semblance to the cryptands but lack the binding sites in the bridges. As a result, these molecules interact with electrophiles in a fashion similar to other tertiary amines and generally do not exhibit strong interactions with alkali or alkaline earth metal ions. The in-out bicyclic amines are prepared by reaction of the appropriate acid chlorides and amines in two stages to yield the macrobicyclic amine after reduction of the amidic linkages. A typical amine is shown above as compound 18. 

Tomoi, Kihara and Kakiuchi " have prepared a cryptand with a hydroxymethyl group in one of the strands and then utilized this as nucleophile in a reaction with chlo-romethylated polystyrene. The type of compound prepared by this method is illustrated in Eq. (8.16). 

The Na is 555 pm from the nearest N and 516 pm from the nearest O, indicating that it is a separate entity in the structure. Potas-sides, rubidides and caesides have similarly been prepared. The same technique has been used to prepare solutions and even crystals of electrides, in which trapped electrons can play the role of anion. Typical examples are [K(cryptand)]+e and [Cs(18-crown-... 

The influence of electron-count on cluster geometry has been very elegantly shown by a crystallographic study of the deep-red compound [K(ctypt)]g [Ge9]- [Ge9] .2.5en, prepared by the reaction of KGe with cryptand in ethylenediamine. [Ge9] has the C4, unicapped square-antiprismatic structure (10.10c) whereas [Ge9]- , with 2 less electrons, adopts a distorted Dit, structure which clearly derives from the tricapped trigonal prism (p. 153).The field is one of... 

F-Labeled pirenperone (9) was prepared with high radiochemical yield (72%) and high purity (99%) for PET studies from pirenperone using a [ F] fluoride-cryptand-oxalate system (95CL835). 

Under carefully controlled conditions even complex molecules can be fluorinated. For example, the preparation of perfluoro-crown ethers (85CC1350) and perfluoro(2.2.2.)-cryptand (90JOC5933) has been described. Branched morpholines and piperazines have been directly fluorinated to their perfluoro analogues [90JFC(50)15],... 

A new type of calixarene-capped calixpyrrole (9) has been generated (32 %) in one-step from p-fe/t-butylcalix[4]arene tetramethylketone as the template <96TL7881>. A cylindrical calix[4]-fois-cryptand, in which the central calix[4]arene possesses two 1,3-altemating diaza-tetraoxa macrocycles on each face, has been synthesized <96TL8747>. A series of substituted l,4-(2,6-pyridino)-bridged calix[6]arenes has prepared and studied <96LA1367>. 

The tin homolog of 49, distannene anion radical 50, was successfully prepared employing the same synthetic protocol the direct reduction of distannene (t-Bu2MeSi)2Sn=Sn(SiMer-Bu2)2 with potassium mirror in THF in the presence of [2.2.2]cryptand (Scheme 2.38). ... 

The reduction of the stannyl radical (t-Bu2MeSi)3Sn with alkali metals produces a variety of structural modifications depending on the solvent used (Scheme 2.55). Thus, in nonpolar heptane, a dimeric stannyllithium species [58c Li ]2 (E = Sn) was formed, whereas in more polar benzene, the monomeric pyramidal structure 58c [Ti -Li (C6H5)] was produced. In the latter compound the Li+ ion was covalently bonded to the anionic Sn atom being at the same time n -coordinated to the benzene ring. A similar monomeric pyramidal CIP 58c [Li (thf)2] was prepared by reduction in polar THE the addition of [2.2.2]cryptand to this compound resulted in the isolation of the free stannyl anion 58c K+([2.2.2]cryptand), in which the ion lacked its bonding to the Sn atom. ... 

The ions having five tin or lead atoms are prepared by the reaction of a solution containing sodium and the cryptand reacting with alloys of sodium and tin or lead, respectively. It should also be mentioned that numerous derivatives of these materials have been prepared that contain alkyl and other groups. 

A typical synthesis. The preparation of (213 m, n = 1) serves to illustrate the general synthetic strategy used to obtain this class of polyether cage. Starting from diaza-18-crown-6 and the required diacid chloride, condensation followed by reduction yields the corresponding cryptand, 2.2.2 (Dietrich, Lehn Sauvage, 1970 Dietrich, Lehn, Sauvage Blanzat, 1973)-see [4.8],... 

Attracted by the benefits of the cryptand effect, Coxon and Stoddart (1975, 1977) prepared the bicyclic compound [39]. Compared with the monocyclic crown ether [40], the bicyclic compound showed no increased ion binding... 

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