Potassium template synthesis

This dinitrile 25 was obtained by heating of commercially available 4,5-dichlorophthalodinitrile 19 with dry potassium fluoride in DMF in the presence of 18-crown-6 (54 %) and used in the template synthesis of the Zn complex [ZoPci Fg] (26) in the presence of Zn" acetate in 1-chloronaphthalene (IClNp) (Scheme 7). 

The template effects of potassium and lithium ions are responsible for the efficiency of the synthesis of macrocyclic ligands in 18-CROWN-6 and2,2.7,7,12,12,17,l 7-OCTAMETHYL-21,22,23,24-TETRAOXAPER-HYDROQUATERENE. 

An early synthesis of [18]crown-6 (1) involved the cyclization of hydroxychloride (30) via a Williamson ether synthesis. The yield was 2%. In an adaptation of this approach ethylene oxide was oligomerized in the presence of an alkali cation template. By varying the cation template from lithium to sodium to potassium the major macrocyclic product changed from [12]crown-4 to [15]crown-5 to [18]crown-6, albeit only in about 10% yield (76CC295). 

The observations made here are not sufficient to prove any particular synthesis mechanism. However we may speculate as to mechanisms that are consistent with the observations. The synthesis of LTA probably proceeds by formation of sodalite units from D4R. This mechanism has been postulated before(14,15). D4R are present in silicate solutions containing sodium(16), potassium(17), and TMA(18) and in aluminosilicate solutions containing TMA(19). In TMA silicate solutions the fraction of Si in D4R decreases with dilution(20) and in TMA aluminosilicate solutions D4R s decrease with decreasing Si/Al(21). D4R with strict alternation of Si and Al, as required for zeolite A, can join in only one way and this is apparently facile as no template... 

Higher yields of crown ethers are generally obtained if the cyclisation reaction can be templated by a metal ion of appropriate size. Thus, potassium ions are well known to enhance the yields of 18-crown-6 derivatives,1,3 while addition of the smaller lithium ion enhances the yields of reactions giving 13-and 14-membered tetraoxa rings.4b4c Such a reaction has been used to good effect in the synthesis of the chiral 14-crown-4 dibenzyl ether, L-ll, which can be prepared in a yield of 65% (Scheme 4.7) (cf. 11% for the untemplated 18-crown-6 analogue) by co-condensation of l-7 with the appropriate linear ditoluenesulfonate. 

Lower rim substitution can also be used to link cahxarene molecules. An elegant example was produced by linking two calix[4]arenes with four ethylene bridges to produce what was termed as a calix[4]tube (102). The synthesis was templated by the potassium ion, and the product was found to bind this cation selectively. 

Greene observed that the formation of 18-crown-6 from a ditosylate and a diol in the presence of f-butoxide salts was enhanced when a potassium cation was used (Greene, 1972). This template effect was operative for the synthesis of other polyether crown compounds using alkali or alkaline-earth metal cations. Template effects have also been observed for the preparation of aza-crown ethers, although the effect is less pronounced because the softer A-donor atoms form weaker complexes with the alkali metal cations (Frens-dorff, 1971). Richman and Atkins reported that high-dilution techniques were not required for the cyclization reaction of the disodium salt of a pertosylated oligoethylenepolyamine with sulfonated diols to form medium and large polyaza-crown compounds (Richman and Atkins, 1974 Atkins et al., 1978). 

The yield for and jS increases in passing from LiF to KF. This fact can be associated with increasing basicity of the solid supports not with an appreciable template effect for which the maximum yield should be observed when NaF on alumina was employed. Potassium fluoride on alumina turned out to be the most efficient in the synthesis of... 

Smith and coworkers have also harnessed related anunonium ion/crown ether interactions to template the assembly of two Boc-protected L-lysine dendrons (Scheme 9)." It was observed that the addition of potassium ions, a competitive gnest of the crown ether hosts, triggers disassembly of the snpramolecniar dendrimer (41) to its component parts (42 and 43). This example of stimuli-responsive dendritic architectures that release small molecules on demand clearly demonstrates advantages inherent in non-covalent dendrimer synthesis over conventional, covalent approaches. 

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