Universal nucleophilicity scale

As already established for combinations of cations with n-nucleo-philes [33,160,219], the situation is less complicated for the reactions of carbocations with 7r-systems. Solvent polarity plays only a minor role (Section III.D.3) and, for many 7r-systems, the relative reactivity has been found to be electrophile-independent (Fig. 10, Section III.D.4.b). Also for these systems, the construction of a universal nucleophilicity scale is not unproblematic, however. Remember Fig. 11, which shows that An2CH + reacts 3.4 times faster with allyltrimethylsilane than with 2-methyl-2-bu-... 

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. 

There is no general rule relating the nucleophilic reactivity of cyclic monomer and linear polymer repeating unit, it depends on the nature of heteroatom and the size of the ring which affects the electronic structure of heteroatom. It is a common practice to estimate the order of nucleophilicities on the basis of basicities. Although it is only partly justified, this procedure enables semiquantitative comparisons of known pKa values whereas no universal scale of nucleophilicity exists. Some typical values of pKa for cyclic compounds and their linear analogs are given in Table 8 [99,100],... 

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