Trifluoromethyl group general considerations

The differences in local fluorine environment are reflected in the i i [20] and T2 values reported in Table 19.3. In theory, the trifluoromethyl groups found in dexfenflura-mine, fluoxetine, fluvoxamine, and niflumic acid undergo less restrictive internal rotation and should also be less sensitive to their local environment than monofluorinated aromatic rings such as in tecastemizole or 5-FU. However, these compounds all have quite short in vivo T2 values except for niflumic acid [12], Because these T2 values are significantly shorter than those found in solution, it is fair to anticipate that all the compounds, except potentially niflumic acid, interact with their environment. However, as demonstrated with fluoxetine and FBAL (Table 19.3), reported T, values may vary considerably. This illustrates the difficulty of making a robust in vivo T, measurement under conditions of low SNR and broad resonance lines [8, 11, 12, 20, 24, 28, 31, 32, 35, 41 43, 50, 56, 68], In addition, the variable bioavailability, due to the small number of patients generally evaluated, compounds the measurement difficulty. 

The utility of this compound in organic synthesis considerably expanded the possibility of synthesizing derivatives with two trifluoromethyl groups. The general Scheme 3 is as follows. 

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