Cryptands synthesis

Alder and Sessions have reported that reductive cleavage of hydrazinium dications is a useful approach to macrobicyclic amines of the type developed by Park and Sim-mons , but the method does not appear to have been successfully applied to any cryptand syntheses. 

Cryptand syntheses require ultrahigh purity reagents, water-free conditions, and highly dilute reaction conditions in order to quell partial reactions and polymerizations. Also, a template species such as metal ions or nonreactive guest species is useful. 

W. D. Curtis, D. A. Laidler, and J. F. Stoddart (1977), To enzyme analogues by lock and key chemistry with crown compounds. I. Enantiomeric differentation by configurationally chiral cryptands synthesized from L-tartaric acid and d-mannitol. J. Chem. Soc. Perkin Trans. 1,1756-1769. 

H-1,3,2- Diazaborole, 1,2-dihydro-reactions, 1, 641 synthesis, 1, 639, 640 transition metal complexes, 1, 641 Diazadiborine, tetrahydro-semi-empirical calculations, 1, 632 Diaza[2.2.2]cryptand synthesis, 7, 750 Diazacryptands bispyridine... 

The saturated aza-oxa crown ethers were first synthesised as intermediates in the synthesis of the nitrogen cryptands.1 The reaction conditions used for the formation of these macrocycles involved the high-dilution technique. In this versatile method, a diamine and a diacid chloride are simultaneously added in the presence of triethylamine to a large volume of solvent, usually toluene, over an extended period of time. The major product from such a reaction is the [1+1] cyclised product, although the [2+2] adduct can often be isolated as well, in low yield. Whilst this method is still sometimes used,2,3 particularly for cryptand synthesis (Chapter 5), it has been superseded by methods that are more convenient and which proceed under medium dilution. 

Polyaza macrobicyclic cryptands synthesis, crystal structures of a cyclophane type macrobicyclic cryptand and of its dinuclear copper(I) cryptate, and anion binding features, J. Jazwinski, J.-M. Lehn, D. Lilienbaum, R. Ziessel, J. Guilhem and... 

The commonly adopted methods for cryptand synthesis are (1) high dilution,... 

Mention has to be given to the synthetic aspects of cryptands. It is obvious that after the intellectual process of ligand design and despite the various new (efficient) modelization tools found for the computer, the necessity still exists to obtain the actual compound. Numerous methods were developed over the years. Many symmetrical cryptands can be obtained in a few steps and with high yields. For the more elaborate cryptands, synthesis is usually more cumbersome, and the number of steps is high. 

Bryant WS, Jones JW, Mason PE, Guzei I, Rheingold AL, Fronczek FR, Nagvekar DS, Gibson HW (1999) A new cryptand synthesis and complexation with paraquat. Oig Lett 1(7) 1001—1004... 

Synthesis by high-dilution techniques requires slow admixture of reagents ( 8-24 hrs) or very large volumes of solvents 100 1/mmol). Fast reactions can also be carried out in suitable flow cells (J.L. Dye, 1973). High dilution conditions have been used in the dilactam formation from l,8-diamino-3,6-dioxaoctane and 3,6-dioxaoctanedioyl dichloride in benzene. The amide groups were reduced with lithium aluminum hydride, and a second cyclization with the same dichloride was then carried out. The new bicyclic compound was reduced with diborane. This ligand envelops metal ions completely and is therefore called a cryptand (B. Dietrich, 1969). 

Synthesis of diaza-potyoxa-macrobicyciic compounds (cryptands). 

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 the principal application for 9 has been in the synthesis of cryptands (see Chap. 8), this material has also served as precursor to a number of nitrogen based lariat ethers , sometimes referred to as crown complexanes . Binding constants for such compounds have been measured for a few examples in a few cases , but... 

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. 

It should be noted here that the brevity of this section is due in part to the fact that essentially this single method is utilized in the synthesis of most cryptands which have... 

Shortly after their first report of all-oxygen bridged cryptands, Dietrich, Lehn and Sauvage reported incorporation of sulfur in the strands. The experimental methods used were essentially similar to those applied in the syntheses of the parent cryptands. As in previous cases, a diacyl chloride was condensed with a diamine under high dilution conditions. In this case, however, the diamine contained sulfur atoms rather than oxygen. The synthesis of compound 5 was accomplished in two stages as illustrated below in Eq. (8.3). The first cyclization step affords the macrocyclic amine in 55% yield. The macrobicyclic product (5) is formed in 25% yield from the monocyclic diamine and the acid chloride. 

Synthesis of cryptands which contain nitrogen atoms in the bridges has also attracted Lehn s attention. In general, a similar synthetic strategy was utilized, but ni-... 

An interesting alternative approach to the synthesis of a cryptand having nitrogen atoms in the bridges was presented by Newkome and coworkers. This group condensed triethanolamine with 2,6-dichloropyridine in a relatively straightforward but low yield (5%) nucleophilic aromatic substitution to form 7, illustrated below in Eq. (8.6). The identity of the compound was confirmed by X-ray structural analysis. 

Vdgtle and his coworkers have reported the synthesis of cryptands containing lipophilic structural elements like o-, m- andp-phenylene, biphenyl and pyridine nuclei. ... 

We have noted above (Sect. 8.3) that certain substituted benzoic acids have been used in the synthesis of endolipophilic cryptands but it is the glycerol and penta-erythritol units which have been used most commonly in this application. These are discussed separately, below. 

Haines and Karntiang later adopted a somewhat more symmetrical approach in the synthesis of glycerol-based cryptands when they utilized the six-membered benzylidene derivative of glyceroP. Details of the synthesis described in Eq. (8.8), above, are also presented in this paper. The symmetrical approach is quite similar to that described in Eq. (8.8), and is outlined below in Eq. (8.9). 

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