Macrocyclic compound

(organic chemistry) An organic compound containing a large ring, that is, a closed chain of 12 or more carbon atoms; examples include crown ethers, cryptands, spherands, carcerands, cyclodextrins, cyclophanes, and calixarenes. Also known as macrocycle.

An organic compound that contains a large ring. In the organic chemistry of alicyclic compounds, a closed chain of 12 carbon (C) atoms is usually regarded as the minimum size for a large ring; crown ethers are similarly defined. Macrocyclic compounds may be a single, continuous thread of atoms, as in cyclododecane [(CH₂)₁₂], or they may incorporate more than one strand or other ring systems (subcyclic units) within the macrocycle or macroring. In addition, macrocycles may be composed of aromatic rings that confer considerable rigidity upon the cyclic system. These aromatic rings may be joined together or coupled by spacer units consisting of one or more carbon atoms. See also Aromatic hydrocarbon.

Classes of macrocyclic polyethers

Crown ethers are generally composed of repeating ethylene (CH₂CH₂) units separated by noncarbon atoms such as oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), or silicon (Si). By far, the most common heteroatom present in the macrorings of crowns [X in (XCH₂CH₂)_n] is oxygen; but as more intricate structures are prepared, nitrogen, sulfur, phosphorus, silicon, or siloxy residues are becoming much more common.

By adding a third strand to the simple macrocyclic polyethers, three-dimensional compounds based on the crown framework are formed. Typically, two of the oxygen atoms across the ring from each other are replaced by nitrogens, and a third ethyleneoxy chain is attached to them. Known as cryptands, these structures completely encapsulate cations smaller than their internal cavities and strongly bind the most similar in size.

Two crown ether rings may be held together by a crown-ether-like strand to give a bicyclic cryptand. These have sometimes been referred to as ditopic receptors because they possess two distinct binding sites.

Lariat ethers, spherands, calixarenes, cavitands, and carcerands are other types of macrocyclic compounds, all of which are capable of encapsulating “guest” molecules in their interior cavities.

Cyclophane is the name given to macrocyclic compounds that contain organic (usually aromatic) rings as part of a cavity-containing structure. The first such compound was [2.2]-paracyclophane. In it, two benzene rings are joined by ethylene (CH₂CH₂) chains in their para positions. See also Cyclophane.

Complexation phenomena

It is the ability of these macrocyclic host compounds to complex a variety of guest species that makes these structures interesting. A crown ether can be described as a doughnut with an electron-rich and polar hole and a greasy or lipophilic (hydrophobic) exterior. As a result, these compounds are usually quite soluble in organic solvents but accommodate positively charged species in their holes.

A variety of organic cations have been found to complex with crown ethers and related hosts. It has been suggested that for a host-guest interaction to occur, the host must have convergent binding sites and the guest must have divergent sites. This is illustrated by the interaction between optically active dibinaphtho-22-crown-6 and optically active phenethylammonium chloride. The crown ether oxygen atoms converge to the center of a hole and the ammonium hydrogens diverge from nitrogen. Three complementary OHN hydrogen bonds stabilize the complex. In this particular case, different steric interactions between the optically active crown and the enantiomers of the complex permit resolution of the salt.

Other organic cations have also been complexed, either by insertion of the charged function in the crown's polar hole or by less distinct interactions observed in the solid state. See also Coordination chemistry; Coordination complexes.

Applications

The striking ability of neutral macrocyclic polyethers to complex with alkali and alkaline-earth cations as well as a variety of other species has proved of considerable interest to the chemistry community. Crown ethers may complex the cation associated with an organic salt and cause separation of the ions. In the absence of cations to neutralize them, many anions show considerably enhanced reactivity. See also Organic reaction mechanism.

One of the important modern developments in synthetic chemistry was the use of the phase-transfer technique. Nucleophiles such as cyanide are often insoluble in media that dissolve organic compounds with which they react. Thus 1-bromooctane may be heated in the presence of sodium cyanide for days with no product formation. When a crown ether is added, two things change. First, solubility is enhanced because the crown wraps about the cation, making it more lipophilic. This, in turn, makes the entire salt more lipophilic. Second, by solvating the cation, the association between cation and anion and the interactions with solvent are weakened, thus activating the anion for reaction. This approach has been used to assist the dissolution of potassium permanganate (KMnO₄) in benzene in which solvent permanganate is a powerful oxidizing agent. One striking example of solubilization is the displacement of chloride (Cl⁻) by fluoride (F⁻) in dimethyl 2-chloroethylene-1,1-dicarboxylate by using the KF complex of dicyclohexano-18-crown-6. In this reaction, a crown provides solubility for an otherwise insoluble or marginally soluble salt. Use of crowns to transfer a salt from the solid phase into an organic phase is often referred to as solid-liquid phase-transfer catalysis. See also Catalysis; Phase-transfer catalysis.

Since crown ethers and related species complex cations selectively, they can be used as sensors. Crowns have been incorporated into electrodes for this purpose, and crowns having various appended chromophores have been prepared. When a cation is bound within the macroring, a change in electron density is felt in the chromophore. The chromophores are often nitroaromatic residues and therefore highly colored. The color change that accompanies complexation can be easily detected and quantitated. See also Ion-selective membranes and electrodes.