ABSTRACT
Measured substituent parameters for the trifluoromethylthio group in aromatic molecules suggest that the group is generally electron withdrawing, as might be expected. The direct inductive electron-withdrawing ability is smaller than, or at best comparable to, that of F, CF,, OCF,, and even Cl, but it is clearly greater than that of SCH, or OCH,' (Table 6.2). The ability of the group to stabilize negative charge through resonance effects can be thought of in terms of the three valence bond structural descriptions:
While OCF, and SCH,, as well as F, show significant contributions from structures similar to I (i.e., destabilizing negative charge in the ring), SCF, appears to encourage large contributions from IIL7
The trifluoromethylsulfonyl group is the strongest neutral electron-withdrawing group. Like the nitro group, its electron-withdrawing power is a result of significant resonance interaction as well as the inductive mechanism. Generally, the acidities of substituted phenols, for example, increase in the order of substituents, H < OCF, < SCF, < S0,CF3.7 Generally, the replacement of aliphatic hydrogens by fluorine
Halogen exchange fluorination of trichloromethylthioaromatics prepared by photoinitiated chlorination of the corresponding arylmethyl sulfides is a well-established route to trifluoromethylthioaromatics and is essentially based on traditionally Swartstype chemistry (Figure 6.3).13-l8 The fluorination reaction, which can proceed in reasonable yield, requires the Lewis acid, SbF,, and is reminiscent of the halogen exchange reaction route to trifluoromethylaromatics. This route is effective for aromatic rings containing inert substituents, such as chloro and nitro, but more severe conditions, along with the use of catalytic quantities of boron trifluoride, may be required in some cases18 and ortho substituents can render the route ineffe~tive.~
ca. 90°/0 ca. 70%
(R = inert group - see text)
Trifluoromethylthiophenothiazines have pharmaceutical utility and can be synthesized by using the SbF, reaction in the first, key fluorination step (Figure 6.4).19 It is interesting to note that the fluorinating agent, being a Lewis acid and hence electrophilic, does not substitute the ring fluorine (which would require a nucleophilic reagent).
