Perfluoro-18-crown-6 ether

Simple and Complex Organic Molecules. Using modem direct fluorination technology, the synthesis of even the most complex perfluorocarbon stmctures from hydrocarbon precursors is now possible. For example, syntheses of the first perfluoro crown ethers, perfluoro 18-crown-6, perfluoro 15-crown-5, and perfluoro 12-crown-4 (54) have been reported. Perfluoro crown ethers (54,55) are becoming important as the molecules of choice for many F-nmr imaging appHcations (56) in humans and are particularly effective in brain and spinal diagnostics when... 

Perfluoro crown ethers from the hydrocarbon dibenzo crown ethers have also been synthesized (58) and the first perfluorocryptand molecule [2.2.2] has been reported (59). The perfluorocryptand is a stable, inert, high boiling clear oil. 

Hydrocarbon crown ethers coordinate cations however, both the perfluoro crown ethers and the perfluorocryptands coordinate anions. For example, perfluoro crown ethers and perfluorocryptands tenaciously encapsulate O and F (60,61). 

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],... 

Figure 14.8. Synthesis of perfluoro crown ether polymer.

The new perfluoro crown ether polymer is currently under investigation in regard to its binding abilities of several gas molecules. 

Several extraordinarily large perfluoro crown ethers have been synthesized examples are given by the formation of 6 and 7.24... 

Different classes of dimer perfluoro crown ethers connected with simple C-C bonds, such as perfluoro(bis[15]-crown-5) (9) and perfluoro(bis[12]-crown-4) (10) have also been prepared. 

Positively charged or neutral electron-deficient groups may serve as interaction sites for anion binding. Ammonium and guanidinium units, which form +N-H" X bonds, have mainly been used, but neutral polar hydrogen bonds (e.g., with -NHCO- or -COOH functions), electron-deficient centers (boron, tin, mercury, [3.6, 3.7] as well as perfluoro crown ethers and cryptands [3.8], etc.), or metal-ion centres in complexes also interact with anions. 

Brodbelt, J. Maleknia, S. Liou, C.C. Lagow, R. Selective formation of molecular oxygen/perfluoro crown ether adduct ions in the gas phase. J. Am. Chem. Soc. 1991, 113 (15), 5913-5914. 

Perfluoro macrocycles are a new development in organic and inorganic chemistry which has occurred in the last five years. The synthesis of perfluoro crown ethers and perfluorocryptands forecast the synthesis of many more perfluoro macrocycles in the next few years. The most surprising development to date with these new very chemically and thermally stable macrocycles has been the findings that they coordinate anions rather than cations and that they are extremely biocompatible materials. Perfluoro macrocycles have the potential for development as a new class of very thermally stable oxygen carriers which reversibly bind oxygen. 

A recent breakthrough in our laboratory has involved the synthesis of perfluorinated crown ethers and cryptands. We have previously reported the synthesis of the first perfluoro crown ethers, perfluoro [18]crown-6, perfluoro [15]crown-5 and perfluoro [12]crown>4 (1),... 

Perfluoro crown ethers have been synthetically inaccessible by conventional reactions of fluorocarbons and outside the capability of synthesis by fluorination using selective fluorination reagents. Examples of this potentially useful class of macrocycles have been prepared recently in our laboratory. These syntheses have been initially accomplished using the broadly applicable technique for controlling reactions of elemental fluorine (the La Mar process) developed in our laboratory. The reactions were conducted in the previously described cryogenic fluorination reactor (2),... 

Perfluoro crown ethers are very thermally and chemically stable. The reactions to produce perfluoro macrocycles are all illustrated in Figure 1. There are potential applications of such perfluoro macrocycles in biomedical... 

Perfluoro cis-syn-cis- and cis-anti-cis-Dicyclohexyl[18]Crown-6 Ether. Very recently we have synthesized perfluoro crown ethers from the hydrocarbon dibenzo crown ether (see Figure 8) (10). We have prepared two interesting isomers of perfluorodicyclohexyl[18]crown-6 ethers fi0),the cis-syn-cis and cis-anti-cis isomers. Their structures have also been established by X-ray crystallography. 

Each perfluoro macrocycle was ionized to form M then allowed to react with 02to successfully form + O2) adducts (11). lon/molecule reactions involving an acyclic perfluoro ether and hydrogenated crown ethers were also examined to determine whether the cyclic and/or perfluoro nature of the macrocycles played a role in the formation of the (M + O2)" adducts. Neither the perfluoro acyclic analog nor hydrogenated crown ethers reacted with 02to form (M + O2)" adduct ions. This result confirmed that the macrocyclic nature of the perfluoro crown ethers enhanced their ability to bind O2. 

Additionally, the ability of the perfluoro crown ethers to form complexes with CO, N2, CO 2, and Ar, species with similar sizes and some similar chemical and physical properties as O2, was examined. Adducts with these species were not observed (11). Thus, the tendency of the perfluoro crown ethers to form adducts exhibited striking selectivity for O 2 only. 

The ability to form and characterize new types of macrocyclic ion complexes involving perfluoro ethers holds great promise for future studies of host-guest complexation in the gas phase. Comparisons to the gas-phase chemistry of hydrogenated macrocycles may allow further insight into the influence of thermochemical and structural properties on the binding interactions of host molecules. All of the perfluoro crown ethers and perfluorocryptands to date have been found to coordinate 02 and F as well as some otii c anions (24). 

The CAD spectra of the molecular anions of two perfluoro dicyclohexyl crown ethers, the [18]crown-6 and [24]crown-8 ethers, also show characteristic fragmentation patterns (26). The CAD spectrum for the first one is shown in Figure 14. For these substituted perfluoro crown ethers, the molecular anions do not dissociate via simple loss of C2F4O units as was observed for the other... 

As previously discussed, perfluoro [15]crown-5 has great potential as a NMR imaging agent (4J. This crown ether has only one fluorine resonance making very sharp pictures during brain scans and spinal scans of animals possible. Perfluoro [15]crown-5 is also used successfully as an oxygen carrier in collaborative studies between our group and Dr. Leland Clark s laboratory. Work at Air Products has established that the perfluoro crown ethers are nontoxic in animals and are therefore very different from hydrocarbon crown ethers. 

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