18-Crown-6 derivatives

Tomoi and coworkers adopted a somewhat more direct approach in their synthesis of 16-crown-5 derivatives bearing a single alkenyl residue. They hoped to obtain precursors to polymers which could be used as phase transfer catalysts. In this approach I,I-bis-chloromethylethylene (a-chloromethallyl chloride) was allowed to react with the dianion of tetraethylene glycol (NaH/THF). By this method, methylene-16-crown-5 could be isolated in 66% yield after vacuum distillation. Ozonolysis led, in almost quantitative yield, to the formation of oxo-16-crown-5 as shown in Eq. (3.38). These authors prepared a number of other, closely related species by similar methods. 

Many other cyclic and noncyclic organic carriers with remarkable ion selectivities have been used successfiilly as active hosts of various liquid membrane electrodes. These include the 14-crown-4-ether for lithium (30) 16-crown-5 derivatives for sodium bis-benzo-18-crown-6 ether for cesium the ionophore ETH 1001 [(R,R)-AA -bisd l-ethoxycarbonyl)undecyl-A,yVl-4,5-tctramcthyl-3,6-dioxaoctancdiamide] for calcium the natural macrocyclics nonactin and monensin for ammonia and sodium (31), respectively the ionophore ETH 1117 for magnesium calixarene derivatives for sodium (32) and macrocyclic thioethers for mercury and silver (33). 

Inoue, Y. Ouchi. M. Hososyama, K. Hakushi. T. Liu, Y. Takeda. Y. Molecular design of crown ethers. Part 8. Substitution and lariat effect upon cation complexation with 1,4,7,10,13-pentaoxacyclohexadecane (16-crown-5) derivatives in solvent extraction and in homogeneous solution. J. Chem. Soc.. Dalton Trans. 1991. 1291-1293. 

Suzuki K, Hayashi K, Tohda K, et al. (1991) Sodium ion-selective electrodes based on lipophilic 16-crown-5-derivatives. Analytical Letters 24 1085-1091. 

This is a term introduced by Gokel and co-workers only very recently. The compounds included in this class are those which have single macrorings like crowns but additional pendant donor groups which make them similar in some respects to crytands. The presumption from which the name derives is that a complexed cation will be bound by both the macroring and the sidechain in much the same fashion as a lasso binds an animal. The compounds are named as simple crown derivatives and are illustrated as 16 a 17 below. 

One approach, pursued by two groups in particular, is to use model nucleobases that feature an additional metal-ion binding group. Gokel and co-workers have used this strategy with aza-crown derivatives (50,51). X-ray crystallography of 6is-(3-(l-thyminyl)propyl)-4,13-diaza-18-crown-6, 4, reveals the Na+ is coordinated by T-02 [Na-0 distances 2.488 and 2.468 Al (51). Aza-crown derivatives with multiple base substi-... 

Figure 46 The structure of the inverse crown derivative, [Na4Mg4(NPr 2)8Fe(C5H3)2] 95.

Further comments. The preceding discussion outlines typical syntheses for simple polyether crown rings. It needs to be noted that a considerable number of other types of crown derivatives, displaying a variety of molecular architectures, has also been synthesized. Many of these types parallel the structurally developed macrocycles (which incorporate mainly donor atom types other than ether oxygen) discussed in Chapter... 

A range of crown derivatives have been developed in which colour-inducing functional groups are incorporated in the overall struc-... 

Crown derivatives which are able to bind simultaneously to more than two metal ions have been synthesized such species have been termed multiloop crowns (Weber, 1982). Polynuclear cation receptors of this type provide yet another series of novel crown derivatives whose metal complexes tend to exhibit a range of unusual properties. Because of the diversity of the structures falling in this category, only a brief mention of this ligand type is presented here. 

The stability of cryptate complexes. The cage topology of the cryptands results in them yielding complexes with considerably enhanced stabilities relative to the corresponding crown species. Thus the K+ complex of 2.2.2 is 105 times more stable than the complex of the corresponding diaza-crown derivative - such enhancement has been designated by Lehn to reflect the operation of the cryptate effect this effect may be considered to be a special case of the macrocyclic effect mentioned previously. 

Figure 5.17. Formulas of some donor-acccptor and donor-donor stilbene-Crown derivatives. Emission spectra of (a) DCS-Crown in...

The introduction at the C- or N-terminal position of a crown ether unit has been used as a strategy to control the aggregation of poly(benzyl glutamate) derivatives 19 The incorporation of the crown unit at the C-terminal position is performed using (benzo-15-crown-5)-4-amine as initiator of the polymerization of l-G1u(OBz1)-NCA. Physical properties of such crown derivatives can be modulated by the formation of sandwich 2 1 complexes driven by the addition of specific alkali metal ions. In the reported case, the formation of K+ sandwich complex between two C-terminal benzo-15-crown-5 modified helical polypeptides induced aggregation. In a similar approach,f20 addition of Cs+ to 18-crown-6 terminated helical peptides results in the formation of supramolecular assemblies having membrane ion conductivity activities. 

In a subsequent study [30], cholesteryl-substituted 18C6 derivative 11 and diaza [18]crown-6 12 (Scheme 6) were used to create solid-supported bilayer lipids. The liquid crystalline crown derivatives 11,12 were dissolved in chloroform and mixed with squalene or squalene saturated with cholesterol. The solid-supported bilayers were prepared in freshly cut stainless steel wires. A 10-4 to 10-1 mol L-1 solution of MCI (M = Li, Na, K, Rb, Cs) or MgCl2 was used as aqueous phase. Measurement of the membrane potential revealed a Nemst response to the concentration of M+ in solution. It was possible to differentiate between the different cations which might be used for the preparation of new ion sensors. For the detection of K+ and Rb+, aza crown derivative 12 proved to be the most selective. A problem was the presence of traces of Fe2+/3+ that made the measurements difficult. It was also not... 

Inokuma, S. Okada, H. Kuwamura, T., (1989) Surface active crown ethers. XV. Syntheses and properties of amphiphilic aza crowns derivatives possessing cation-ligating double side chains Yukugaku 38, 705-709 [Chem. Abstr. 112 58794],... 

More recently, bis-crown derivatives of the diastereo-isomeric fullerenocrowns 55a/b have been prepared, and their electrochemical properties have been measured as well [64,65], It is important to note that these bis-crown compounds (( )-57a/b, Figure 20), were successfully obtained at 30 % yield when the five... 

Thus, we have studied theoretically the tautomerism of pyridones and 1,2,4-triazoles related to two crown ethers and two crown esters derived from these heterocycles [209], For the four macrocycles 262-265, Bradshaw identified a single tautomer by X-ray crystallography [210-213], To rationalize these findings, a series of calculations from simple models to crown derivatives were carried out. The most interesting case concerns the observation, for the first time, of a 4H-1,2,4-triazole tautomer 265b. 

In the last two decades, chiral receptors containing amidic functions were designed almost exclusively for binding protected amino acids [49-57], oligopeptides [54,58], and lactic [59], tartaric [60,61] or camphoric acid derivatives [62]. Usually, chiral building blocks such as spirobifluorene [49, 60], binaphthalene [51,57],or amino acid chains containing macrocycles [52-56,58] were employed. An interesting receptor was synthesized via connection of the calix[4]arene moiety with an aza-crown derivative [61]. 

Oxa-crown porphyrazines (21) were synthesized by the Mg(II) template cyclization of crown ether derivatives of dithiomaleonitrile and shown to possess ligation of eight Ag(I) ions by utilizing both the crown ether and meso-pocket coordination sites [95AG(E)2020]. An improved preparation and the coordination chemistry with Ag(I) of oxa-crown derivatives of dithiomaleonitrile have been reported [95IC2300]. 

Baek, S. H., et al. (2004), Surface plasmon resonance imaging analysis of hexahistidine-tagged protein on the gold thin film coated with a calix crown derivative, Biotechnol. Bioprocess. Eng., 9,143-146. 

Hoffman et al. have reported the synthesis of tetrakis-, tris-, and monothiacrown ethers containing a tetra-azaporphyrin unit 139-152. The first porphyradine crown ethers were prepared by the Mgz+ template cyclization of the appropriate crowned derivative of dithiomaleonitrile 32 and 33 to afford 139 and 143, respectively, in ca. 35% yields. Treatment of 139 and 143 with trifluoroacetic acid provided the metal-free porphyrazines 140 and 144, respectively. Subsequent reaction with Ni(OAc)2 or Cu(OAc)2 quantitatively produced 141, 142, 145, and 146 (Scheme 21). 

Scheme 7-42 shows three ferrocene-crown derivatives that are able to incorporate silver(i) ions [195],... 

Demonstration of the photorelease has been done in particular with Sr + [46]. This process was monitored on several time scales providing evidence for (1) the delayed formation in 9 ps of the charge transfer state of the merocyanine chromophore following ultrafast photodisruption of the nitrogen - cation interaction, (2) the cation movement away from the excited chromophore into the bulk in 400 ps, (3) recombination of the complex in the ground in about 120 ns. These three steps are respectively illustrated in Fig. 7.17a, b, c (see caption for details). Similar transient absorption studies have been carried out on a PDS-crown-Ca + complex, where PDS is an aza-crown derivative of a substituted stilbene [47]. The spectrodynamics observed on the short time scale are very similar to those found in step (1) of the above description, with in particular a delayed rise of a stimulated emission band attributed to a solvent-separated cation-probe pair. Although the full scenario of the cation photoejection from the DCM-crown-Sr, is complex [46], the spectra shown in Fig. 7.17 demonstrate that at least part of the photoexcited complexes does eject the ion into the bulk. 

Isoaromatization of dienone macrocycles afforded Horning-crown macro-cycles - flexible macrocycles bearing structural elements reminiscent of those found in both calixarenes and crown ethers. In some cases the Horning-crown macrocycles exhibited solvent-dependent and switchable conformations. For macrocycles with the same short linker, self-complementarity was observed, and dimers tended to crystallize as solvates or inclusion compounds. This tendency was suppressed with longer linkers and in some Horning-crowns derived from trapezoidal macrocycles. These properties suggest potential applications in analysis, separation and detection (Figure 6.8). ... 

In 1977 and 1978, analyses of the complexing properties of crown derivatives with p-phenylene or 2,3-naphthyl units were carried out by several groups. They found out that the aromatic ring acts as a 7c-donor and thus contributes to the binding of the guest (usually an alkali metal cation) [14, 15, 16, 17, 18]. 

Curtis, W. D., D. A. Laidler, J. F. Stoddard, J. B. Wolstenholme, and G. H. Jones Enantiomeric Differentiation by a Chiral Symmetrical Crown Derived from L-Iditol. Carbohyd. Res. 57, C 17 (1977) Laidler, C. L., and J. F. Stoddard Chiral Asymmetrical Crown-Ethers. Carbohyd. Res. 55, C 1 (1977) Laidler, D. A., and J. F. Stoddard Stereoselectivity in Complexation of Primary Alkylammonium Cations by the Diastereotopic Faces of Chiral Asymmetric Crowns. Chem. Commun. 1977, 481. 

Fig. 2.13 (a) Cyclic voltanunograms of indimn tin oxide electrode coated with the crown derivative reported in the inset, recorded in ethanol solntion eraitaining 0.1 M [CH3(0H2)3]4NC104 and different amount of alkali metal salts (ftom 0 to 50 mM in the direction of the arrow) (b) relevant plot of the anodic peak currents as a function of the concentration of the alkali metal salt (Reproduced from Ref. [126] with the permission of Elsevier)... 

Reductive amination of the aldehyde 3 with various amines provides a ready route to the preparation of derivatives. For example, reductive amination of 3 in methanol using 1,10-diaza-18-crown afforded the water soluble crown derivative Similarly, the PEG-carbohydrate conjugates 7 and were obtained by reductive amination with glucosamine and chitosan, respectively. PEG-coated glass beads 9 were obtained from aldehyde sodium cyanoborohydride, and aminopropyl-derivatized, controlled-pore glass. We are presently examining this same reaction for coupling PEG and proteins. Also, as mentioned above, PEG amine was prepared by reductive amination with ammonium acetate. 

Diederich F, Jonas U, Gramlich V, Herrmann A, Ringsdorf H and Thilgen C 1993 Synthesis of a fullerene derivative of benzo[18]crown-6 by Diels-Alder reaction complexation ability, amphiphilic properties, and x-ray crystal structure of a dimethoxy-1,9-(methano[1, 2]benzomethano)fullerene[60] benzene clathrate Helv. Chim. Acta 76 2445-53... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

---