Cryptands sulfur

Although a large number of such compounds have been prepared, many of the mixed nitrogen-sulfur macrocycles are included in other tables, most notably in Chap. 4. Some have also been recorded in Chap. 8 as monocyclic precursors to bi- or polycyclic ligands (i.e., cryptands). The reader is directed to the tables of other chapters where the desired compound, if known, may be reported. 

Shortly after their first report of all-oxygen bridged cryptands, Dietrich, Lehn and Sauvage reported incorporation of sulfur in the strands. The experimental methods used were essentially similar to those applied in the syntheses of the parent cryptands. As in previous cases, a diacyl chloride was condensed with a diamine under high dilution conditions. In this case, however, the diamine contained sulfur atoms rather than oxygen. The synthesis of compound 5 was accomplished in two stages as illustrated below in Eq. (8.3). The first cyclization step affords the macrocyclic amine in 55% yield. The macrobicyclic product (5) is formed in 25% yield from the monocyclic diamine and the acid chloride. 

The cryptands (490) coordinate by three sulfur and three nitrogen donors only, forming distorted octahedral Ni11 complexes.1336... 

As in the coronands, binding site identity plays an important role in the complexation preferences of cryptands. Replacement of oxygens by sulfur or nitrogen in the bridges (45b-d) results in decreased stability and selectivity for alkali metal and alkaline earth cations (as was also noted for the coronands).66,164 Selectivity is then shifted toward softer metal ions such as Ag+, Tl+, Cd2+ and Pb2+. 

Guests with polar N—H bonds include amides, ureas and related sulfur compounds, substituted hydrazines, and aromatic amines.21-264,265 Complexes with these substrates exhibit a wide variety of stoichiometric and nonstoichiometric associations. A particularly popular association is the 1 2 guest host relationship as typified by the structure of the benzenesulfonamide complex with [18]crown-6 (84).266-267 The weak complexes formed between crown ethers and cryptands with certain proteins allow for solubilizing these species in organic solvents.268... 

To monitor tumor response to capecitabine therapy noninvasively, Zheng and co-workers, from the Indiana University School of Medicine, developed the synthesis of the fluorine- 18-labeled capecitabine as a potential radiotracer for positron emission tomography (PET) imaging of tumors.28 Cytosine (20) was nitrated at the C-5 position with nitric acid in concentrated sulfuric acid at 85°C, followed by neutralization to provide 5-nitrocytosine (27) in moderate yield. This nitro pyrimidine was then carried through the glycosylation and carbamate formation steps, as shown in the Scheme below, to provide the 6/s-protected 5-nitro cytidine 28 in 47% for the three-step process. Precursor 28 was then labeled by nucleophilic substitution with a complex of 18F-labeled potassium fluoride with cryptand Kryptofix 222 in DMSO at 150 °C to provide the fluorine-18-labe led adduct. This intermediate was not isolated, but semi-purified and deprotected with aqueous NaOH in methanol to provide [l8F]-capecitabine in 20-30% radiochemical yield for the 3-mg-scale process. The synthesis time for fluorine-18 labeled capecitabine (including HPLC purification) from end of bombardment to produce KI8F to the final formulation of [18F]-1 for in vivo studies was 60-70 min. 

Another important type of complex is formed between metal ions and cyclic organic compounds, known as macrocycles. These molecules contain nine or more atoms in the cycle and include at least three heteroatoms, usually oxygen, nitrogen, or sulfur. Crown ethers such as 18-crown-6 and dibenzo-18-crown-6 are examples of organic macrocycles. Some macrocyclic compounds form three-dimensional cavities that can just accommodate appropriately sized metal ions. Ligands known as cryptands are examples. Selectivity occurs to a large extent because of the size and shape of the cycle or cavity relative to that of the metal, although the nature of the heteroatoms and their electron densities, the compatibility of the donor atoms with the metal, and several other factors also play important roles. 

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