Many reagents useful for organic synthesis are soluble in water because of their ionic nature, but are insoluble in organic solvents for the same reason. However, most organic syntheses are performed in organic solvents, and it would therefore give chemists more flexibility to be able to use ionic reagents in these media.
Solubility in water is generally driven by hydration of cations to separate them from their associated anions, as pointed out in previous installments of this series. Hydration in turn is driven by the formation of non-covalent bonds (complexing, coordination); see Part XXVI. Nonpolar organic solvents such as benzene or aliphatic hydrocarbons are unable to coordinate with ions and therefore cannot dissolve ionic substances.
In 1967, Charles J. Pederson at du Pont found that cyclic polyethers can coordinate with metal ions such as K+ in nonpolar solvents, thus separating them from their associated anions and rendering their salts soluble in these solvents. When potassium permanganate (KMnO4), a useful oxidizing agent, was subjected to the action of such a cyclic polyether, it became soluble in benzene and was then available for use in an extended range of reactions. Pederson assigned the trivial name "crown ethers" to this class of coordinating agents, a nomenclature that has become standard.
Shown below are some typical crown ethers.
||12-crown-4 (12-membered ring with 4 oxygen atoms)|
The potassium permanganate complex of dicyclohexyl-18-crown-6 (a host-guest complex) has the structure:
Pederson synthesized about 60 different crown ethers in the 1960s, and found that the size of the central "cavity" determined which metal ions would be complexed most strongly, depending on their size. Donald J. Cram at UCLA then synthesized a large number of functionalized crown ethers of all sizes and shapes and "delineated the principles of molecular architecture needed for optimal binding and specificity" [Chem. Eng. News, January 2, 1984, p. 33].
Modified crown ethers with some of the oxygen atoms replaced by nitrogen atoms are called cryptands.
The concept of size- and shape-selective trapping, complexing, and catalysis, analogous in some respects to the use of crown ethers, has been extended to using natural and synthetic inorganic zeolites (aluminosilicates) as selective adsorbents. These materials have cavities of diverse sizes and shapes that selectively trap ions and molecules as a function of their specific dimensions. They have found wide industrial use. Interested readers may refer to Chem. Eng. News, December 13, 1982, pp. 9-15 for details on their early uses and development.
Calixcrowns and calixarenes
The incorporation of benzene rings into crown ethers has led to the synthesis of more complex ring systems such as bis(p-phenylene)-34-crown-10:
In turn, this has led to the development of calixarenes, cyclic complex-forming polyphenols such as calixarene, shown below:
Further information on these and other novel complexing agents, as well as novel structures of potential use in nanotechnology, is available at
a dissertation by Volker Wendel, with abstract in English and German and full text in German, in HTML and PDF formats. Check out Chapters 4 and 7.
The structure of ciguatoxins, toxic compounds present in 400 species of fish, has long been conjectured. However, definite proof has just been presented by Prof. Masahiro Hirama of Tohoku University in Japan. In a project lasting 12 years, he and his graduate students synthesized a ciguatoxin, CTX3C, from simple starting materials (Chemical & Engineering News, 79 No. 49, 12/3/01, p. 9). The compound has 13 rings with from five to nine members, and 30 chiral centers. Surprisingly, none of the intermediates en route to the compound were toxic. Toxicity was found only after the final step of removing protective groups. The synthesis is all the more remarkable since about a billion stereoisomers could exist, and the group produced the only one found in fish.