Reactions of Crown Ethers

Reactions of Crown Ethers. - Irradiation of the unsaturated crown ether (67) in benzene, containing catalytic amounts of iodine, and with oxygen bubbling through the solution, gave (68) in 50-60% yield. There were no products arising from intramolecular [2 + 2] cyclization of the two alkene moieties in 

5-furo-18-crown-6 with singlet oxygen via the intermediate ozonide. The mode of opening of the furan is in marked contrast to that of 2,5-dimethyl-furan, which forms a hydroperoxide under similar conditions. 3,4-Diaminobenzo-15-crown-5 reacts with EtOCH=CCHMe2CHO to form (70), 

Eichner and A. Merz, Tetrahedron Lett., 1981,22,1315. B. L. Ferringa, Tetrahedron Lett., 1981, 22,1443. 

In a similar way, crown ethers bearing a photoresponsive anionic cap have been synthesized. The cis form (73) extracts sodium and calcium ions more efficiently than the trans form. This increase has been attributed to arvintra- 

The crown ether (74) has been used to determine the mode of cis to trans isomerization of derivatives of azobenzene. The process occurs via an inversion mechanism rather than a rotation mechanism, as was shown by the small effect of pressure on the course of the reaction. The azo system (75) also photoisomerizes by inversion in this case, steric factors exclude the possibility of a rotation mechanism.  

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The foregoing sections have dealt with the nucleophilic properties of anionic species whose salts were solubilized in apolar solvents with the aid of cation-complexing agents. Apart from the nucleophilic character of the anion, however, its basic strength is also expected to increase with decreasing extent of solvation. This section will deal with hydrogen-abstraction reactions of crown ether-solubilized bases. 

It is clear from Table 44 that the E2/SN2 ratios observed for reactions of crown ether-separated KOt-Bu ion pairs will greatly depend on the type of substrate and solvent. Di Biase and Gokel (1978) have recently reported many examples of the use of this reagent either as a nucleophile [for example, in its reaction with benzyl chloride and in the reaction with isatoic anhydride (34)] or as a strong base [for example, in the basic oxidation of fluorene to 2-carboxybiphenyl (35)]. 

Cacciapaglia, R. and Mandolini, L. (1993) Catalysis by metal ions in reactions of crown ether substrates. Chem. Soc. Rev., 22, 221. 

Reactions of crown ethers catalyzed by metal ions 93CSR221. 

Table 1.7 Rate constants for reaction of crown ethers with metal ions in aqueous ...

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]. 

With the discovery of the crowns and related species, it was inevitable that a search would begin for simpler and simpler relatives which might be useful in similar applications. Perhaps these compounds would be easier and more economical to prepare and ultimately, of course, better in one respect or another than the molecules which inspired the research. In particular, the collateral developments of crown ether chemistry and phase transfer catalysis fostered an interest in utilizing the readily available polyethylene glycol mono- or dimethyl ethers as catalysts for such reactions. Although there is considerable literature in this area, much of it relates to the use of simple polyethylene glycols in phase transfer processes. Since our main concern in this monograph is with novel structures, we will discuss these simple examples further only briefly, below. 

Isomerization of fluoroolefins by a shift of a double bond is catalyzed by halide 10ns [7] The presence of crown ether makes this reaction more efficient [74] Prolonged reaction time favors the rearranged product with an internal double bond (equations 3-5) Isomerization of perfluoro-l-pentene with cesium fluoride yields perfluoro-2-pentenes in a Z ratio of 1 6 [75] Antimony pentafluoride also causes isomenzation of olefins leading to more substituted products [76]... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

A typical phase transfer catalytic reaction of the liquid/liquid type is the cyanation of an alkyl halide in an organic phase using sodium or potassium cyanide in an aqueous phase. When these phases are stirred and heated together very little reaction occurs. However, addition of a small amount of crown ether (or cryptand) results in the reaction occurring to yield the required nitrile. The crown serves to transport the cyanide ion, as its ion pair with the complexed potassium cation, into the organic phase allowing the reaction to proceed. 

Scheme 18. Asymmetric Michael reaction by use of crown ethers.

As the initial sulfonyl fluoride groups can be easily modified by the reaction with corresponding amino derivatives, e.g., those of crown ethers, the composites obtained can be used as polymeric reagents for a wide range of organic reactions. 

Since Pedersen s original work on the use of cations to template the formation of crown ethers [18-20], a large number of different templating agents for macro-cyclization reactions have been reported. While the initial work concentrated on the use of metal cations, further developments demonstrated that species with hydrogen bonding donor or acceptor properties could be equally useful to template the synthesis of macrocyclic molecules. 

The unique ability of crown ethers to form stable complexes with various cations has been used to advantage in such diverse processes as isotope separations (Jepson and De Witt, 1976), the transport of ions through artificial and natural membranes (Tosteson, 1968) and the construction of ion-selective electrodes (Ryba and Petranek, 1973). On account of their lipophilic exterior, crown ether complexes are often soluble even in apolar solvents. This property has been successfully exploited in liquid-liquid and solid-liquid phase-transfer reactions. Extensive reviews deal with the synthetic aspects of the use of crown ethers as phase-transfer catalysts (Gokel and Dupont Durst, 1976 Liotta, 1978 Weber and Gokel, 1977 Starks and Liotta, 1978). Several studies have been devoted to the identification of the factors affecting the formation and stability of crown-ether complexes, and many aspects of this subject have been discussed in reviews (Christensen et al., 1971, 1974 Pedersen and Frensdorf, 1972 Izatt et al., 1973 Kappenstein, 1974). 

Reactions performed under two-phase conditions are further complicated by the partitioning of the reactants and catalyst over the two phases. In the case of quaternary ammonium phase-transfer catalysis, the mechanistic aspects have received a great deal of attention (Brandstrom, 1977 Makosza, 1975 Starks and Owens, 1973). In contrast, the mechanism of crown ether-type phase-transfer catalysis has hardly been investigated at all, despite its... 

The arylation of potassium phenoxide has been studied by Litvak and Shein (1976). In the absence of crown ether the rate of reaction with p-nitrobromobenzene in various solvents increases in the order dioxan < methanol < pyridine < DMSO. In the presence of either 18-crown-6 [3] or dibenzo-18-crown-6 [11], the order of the reaction rates in dioxan and methanol is reversed (Table 22). The effect of crown ether addition on the rate... 

The small effect on reaction rates of the addition of crown ethers to the lower alcohols was also observed in the reaction of potassium acetate with 1-bromobutane in ethanol (Hirao et al., 1978a,b). The displacement of fluorine in either o-nitro- or p-nitro-fluorobenzene by a methoxy group, by reaction with potassium methoxide in methanol was hardly influenced by the presence of dicyclohexyl-18-crown-6 (Del Cima et al., 1973). Mariani et al. (1978), too,... 

The effect of crown ethers on the rates and stereochemistry of the alkylation of metal acetoacetates has been studied by Cambillau et al. (1976, 1978) and Kurts et al. (1973, 1974). Since the enolate can adopt various conformations ([96]—[99]), O-alkylation may produce either the cis ([100]) or the trans ([101]) isomer, whereas C-alkylation affords [102]. The reaction of the sodium... 

The acceleration of the reaction between benzyl chloride and metal acetates in acetonitrile has been studied using several crown ethers (Dorn et al., 1977 Knochel et al., 1975). Very surprisingly, the overall reaction was found to be first order in the presence of cryptands and second order in the presence of crown ethers. The order in benzyl chloride was one in both cases, indicating a zero-order dependence on acetate concentration for the cryptand-catalysed reaction. Unfortunately, the authors did not give all the details of the experiments on which these conclusions were based. Hence, no explanation can be offered for the apparent discrepancy between their results and those of Cambillau et al. (1976, 1978), who observed a first-order dependence on the concentration of metal acetoacetates in alkylations, irrespective of whether or not they were performed in the presence of crown ethers or cryptands. 

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