Kryptofix 2.2.2, structure

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. 

Figure 3.40 X-ray crystal structure showing the wrapping of the podand Kryptofix-5 (3.60) around an Rb+ cation.

For a couple of years, polymer resins with [2b.2.1] and [2b.2.2] anchor groups have been commercially available (trade name Merck-Schuchardt Kryptofix 221B polymer and Kryptofix 222B polymer for their structures compare Fig. 6). In the meanwhile, a number of lithium i i> and calcium 139,142) isotopic separations have been investigated with these resins. 

F-FMISO is synthesized in one-step reaction between the protected precursor, l-(2/-nitro-l,-imidazolyl)-2-0-tetrahydropyranyl-3-0-toluenesulfonyl-propanediol (NITTP) and 18F-containing Kryptofix 2.2.2 in acetonitrile solution (Kamarainen et al, 2004). The labeled product is hydrolyzed with acid to give 18F-FMISO, which is further purified by column chromatography using a Sep-Pak cartridge. From an automated synthesis, the radiochemical yield is 34% at EOB after a synthesis time of 50 min. HPLC shows a radiochemical purity of 97%. The molecular structure of 18F-FMISO is shown in Fig. 8.2f. 

The entropically, and often enthalpically, unfavourable degree of host rearrangement is even more pronounced in podand hosts such as 3.33 and Kryptofix-5 3.60, which adopt extended conformations in the free state. The degree to which 3.60 has to rearrange in order to wrap itself about a Rb cation is evident from the X-ray crystal structure of the Rb+ podaplex (Figure 3.40). 

Later, in 1995, Pike and Aigbirhio applied for the first time diaryliodonium salts for the preparation of F-labeled aryl fluorides using potassium [ F]-fluoride in the presence of the diaza-crown ether Kryptofix (K2.2.2 structure 24 in Scheme 7.7) in acetonitrile at 85 °C or 110 "C [67]. Under these conditions, the reaction of diphenyliodonium chloride provided [ F]-fluorobenzene in 31-78% radiochemical yield. The use of Kryptofix is required for phase transfer of the [ F]-fluoride ion obtained by the nuclear reaction in the cyclotron as a solution in water enriched with oxygen-18. 

The structures of crown ethers used in this study are shown in Figure 1, In table 1 are shown the results of the qualitative test by the paper disc method. Some alkylbenzocrown ethers (type II and III) and dicyclo-hexylcrown ethers (type IV) showed certain activity. On the other hand, unsubstituted crown ethers (type I) and benzocrown ethers with a polar substituent were inactive. Kryptofix 221 (VI) and Kryptofix 222B, which are highly selective to sodium and potassium, respectively, proved to be inactive, whereas Kryptofix 22DD, which has long alkyl chains, showed some activity. 

To study XB donor strength of aliphatic nitrogen versus oxygen with activated iodine, 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane (Kryptofix 2.2., K.2.2) was cocrystalhzed with Q ,a)-DIPFAs. The result was ID chains with N- I XB synthons (Scheme 16, 9). In all cocrystals of a,nitrogen atoms were involved in XB no structural interference was observed from the oxygen atoms, which clearly demonstrates the selectivity of XB in the presence of potentially competing heteroatomic donor sites. ... 

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