Kryptofix

Other complexing agents sometimes advocated are cryptates, especially the compound dubbed [2.2.2] (Kryptofix 222) [23978-09-8] (see Chelating agents). Crown ethers were originally advocated for reactions in the presence of soHd reagents (Uquid-soHd PTC). It is now known, however, that onium salts are equally suitable in many cases. 

Cleavage of mesyl or tosyl esters with K F in the presence of 18-crown-6 ether [46] or Kryptofix 222 [47] provides a reliable method for the preparation of F-labeled biologically active compounds... 

In the case of Kryptofix 221D, a cryptand able to complex the alkali metal cations [141-143], it has been observed that it is solubilized mainly in the palisade layer of the AOT-reversed micelles. And from an analysis of the enthalpy of transfer of this solubilizate from the organic to the micellar phase it has been established that the driving force of the solubilization is the complexation of the sodium counterion. In addition, the enthalpy... 

Deoxy-2-[ F]fluoro-D-galactose can be prepared through an addition reaction to tri-O-acetyl-D-galactal (465), but better through Sn2 reaction (K F-Kryptofix 222 in MeCN) of methyl 3,4-0-isopropylidene-2-0-triflyl-6-0-trityl-y -D-talopyranoside (220 see Section 11,2), according to the cold synthesis. 

Thiocyanate Human urine, saliva Derivatization of basic pH sample with pentafluorobenzyl bromide in the presence of Kryptofix 222 B polymer and extraction into methylene chloride then back extraction into isooctane GC with ECD 0.0115 nmol (in 0.2 mL) 83-106 Chen et al. 1994... 

Compounds 33(67) and 34 (Kryptofix 5, Merck)(68, 69) are also based on methoxyquinoline fluorophore. The geometrical contraints in 33 explain the excellent selectivity for the small lithium ion, and as in the previous example, binding is accompanied with an increase in fluorescence intensity. 

Radical anions of acyclic vicinal oligo-ketones with up to five CO units, generated by reduction of the parent compounds with potassium in the presence of Kryptofix 222, were shown to be extended rr-systems by ESR measurements. ... 

Nucleophilic substitution on methyl / -nitrobenzenesulfonate in CH2CI2 has been studied with a series of chloride salts with different structures and solvations BU4NCI, PPNCl [bis(triphenylphosphoranylidene)ammonium chloride], KCl complexed by 18-crown-6 or Kryptofix 2,2,2, and for comparison PPNBr. ° Rate constants and activation parameters are in accordance with an S 2 mechanism. The results were treated by the Acree equation. There are two reaction paths the first, involving the chloride ion, has the same rate for all the salts, whereas the second slower path, involving the ion pair, has a rate related to the dissociation constant of the salt. 

In the early days of fluorine-18-chemistry the low reactivity of p F]fluoride ion in aqueous solution constituted a major obstacle to the advance of nucleophilic radiofluorination with high specific radioactivity, a problem that would later be solved with the introduction of the cryptand Kryptofix-222 , giving the highly reactive K[ F]F-K222 complex (see Section 4.1) [3], For this reason active research for anhydrous reactive fluorine-18 labelling species continued. Scheme 1 reviews a number of these early reagents. 

Since non-bound or non-coordinated nucleophiles are even more reactive, crown-ethers [138] and cryptands (polyaminoethers) [139,140] have been used to chelate the alkali metal cations, notably the potassium ion of K[ F]F. This allows the [ F]fluoride anion to be less tightly paired with the cation and therefore to be more reactive, which has been coined the naked ion effect. In practice, the crown-ether (e.g. 18-crown-6) or better the polyaminoether Kryptofix-222 (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) is added to the aqueous K[ F]F/K2C03 solution which is then concentrated to dryness [139,140]. The complex (KP FIF-K ) can be further dried, if needed, by one or more cycles of addition of dry acetonitrile and azeotropic evaporation. 

Aromatic nucleophilic radiofluorinations are usually performed in aprotic polar solvents, such as dimethyl sulfoxide (DMSO), sulfolane or dimethylacetamide, and often under basic conditions (because of the presence of Kryptofix-222 / potassium carbonate). Completion of the p F]fluoride incorporation often requires moderate to high temperatures (100-170 °C) for 10-30 min. Microwave technology can be a successful application here, resulting in improved yields and shorter reaction times [29,170-173],... 

Another route to introduce the 1-[ F]fluoroisopropyl residue into the propanol-amine radioligands is represented by the model radiotracers listed in Table 3. [ F]Fluorometoprolol 6 exemplifies the less affine F-labeled counterpart of the )Si-AR-selective radioligand [ C]metoprolol [103]. 1-[ F]Fluoroisopropyl tosylate is the building block of choice used to prepare (+/ )-p F]fluorometopro-lol 6. 1-[ F]Fluoroisopropyl tosylate itself is accessible via the reaction of 1,2-propanediol di(p-toluenesulfonate) with [ F]K(Kryptofix 2.2.2)F. (+/ )-[ F]Fluorometoprolol 6 was proven to possess a similar Pt-AR selectivity like [ C]metoprolol, but its affinity appeared to be too low to potently visualize p-ARs in the heart with PET. 

The nucleophilic aromatic substitution of 6-nitropiperonal with [ F]K(Kryptofix 2.2.2)F yielded 6-[ F]fluoropiperonal that was condensed with nitromethane. Reduction and subsequent hydrolysis of the intermediate nitroalkene provided the target compound 6-[ F]FDA. In comparison to more direct approaches which utilize electrophilic aromatic substitution with positive polarized p F]fluo-rine [140-142], this type of preparation is characterized by high specific radioactivity, which is requested for human PET studies with vasopressor compounds, like 6-FDA [139,143]. 

Influence of the Additives. Complexing agents like Kryptofix 222 and Kro-nenether are known to effect a dramatic change in the interactions of cations with their counter ions. The addition of these macrocycle compounds to a micellar Na(AOT) solution is supposed to gather alkaline cations (Na+) within macrocycle cavities near the interface. 

Addition of Kryptofix 222 and Kronenether to reverse micellar system induces no changes in the droplet size and an increase in the droplet-droplet interactions. The complexation of cations Na of AOT led to a decrease in counterion binding, and consequently repulsive interactions between polar head groups of AOT surfactant are increasing. This could induce a more flexible interface of reverse micelles. 

The addition of macrocycles on CdS synthesis in reverse micelles induces a strong change in absorption spectra. For a given water content, a red shift of absorption onset is observed in presence of macrocycles. This effect is more pronounced in presence of Kryptofix 222 and when the CdS nanocrystallite synthesis is realized in presence of an excess of sulfide S2 ions (x = ). This red shift is characteristic of an increase in the average nanocrystallite size. It can be noticed that absorption of CdS particles synthetized in reverse micelles in presence of an excess of cadmium Cd2+ ions (x = 2) is reduced in presence of macrocycles. This indicates a decrease in the yield of CdS particles and is attributed to complexation of functionalized... 

CC BB Kryptofix 221B, 22B Parish Chem. Co. Utah. CILIA... 

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