Trifluoromethylthio groups

The trifluoromethoxy and the trifluoromethylthio group are highly lipophilic substituents (91CC993). Therefore, their introduction into biologically active compounds is of current interest. 

A trifluoromethylthio group can be introduced into an aromatic ring by coupling of trifluoromethylthio copper (I) and an aryl bromide or iodide.1 Aryl chlorides are inert. 

The trifluoromethylthio group can be generated either from the corresponding thiols [27], rhodanides [28] or disulfides, or by reaction of nucleophilic [29] or electrophilic SCF3-transfer reagents with suitable aromatic, aromatic, or olefin substrates [30] (Schemes 2.175 and 2.176). 

Scheme A.17 Introduction of the trifluoromethylthio group using CUSCF3 [23].

The presence of trifluoromethylthio groups on the pyrrole ring changes the direction of reaction of such an jV-chloropyrrole with nucleophilic agents. 1-Chloro derivative 3a reacts with nucleophiles to form the products of N-substitution (85CB4588 89JFC265) (Scheme 40). 

Reaction of N-chloropyrrole with silver phthalimide proceeds to introduce the phthalimide moiety in position 2 with the simultaneous migration of trifluoromethylthio group to nitrogen (85CB4588) (Scheme 40). 

Amphiphilic heptakis(6-alkylthio)- 8-CyD derivatives were synthesized and their monolayer behavior on a water surface was studied on the basis of surface-molecular area [n-K) isotherms [61]. j8-CyD functionalized at the 6-position with trifluoromethylthio groups have been obtained from the native j8-CyD [62]. Heptakis(2,3-dihexanoyl)-yS-CyD, heptakis(6-hexanamido)-j8-CyD, and heptalds(6-myristamido)-j8-CyD have been synthesized and nanocapsules prepared by nanoprecipitation [63]. Heptakis(6-0-amphiphilic)-jS-CyDs with substituents of varying chain lengths (C and C14) and bond types (ester or amide) have been studied [64]. 

From Table 2, which contains the results for several systems for which the geminate element effect is possible, it seems that the competition between two leaving groups results, in most cases, in expulsion of the less basic one. Thus, the highly basic amino or alkylamino groups always remain attached to the double bond while the bonds to the less basic methylthio, trifluoromethylthio, cyano, fluoro, chloro or ethoxy groups are cleaved. However, the amino group is expelled in preference... 

Carcenac, Y., Tordeux, M., Wakselman, C. and Diter, P. (2006) Experimental determination of the conformational free energies (A values) of fluorinated substituents in cyclohexane by dynamic 19F NMR spectroscopy. Part 2. Extension to fluoromethyl, difluoromethyl,pentafluor oethyl, trifluoromethylthio and trifluoromethoxy groups. New J. Chem., 30, 447 -57. 

R = Bu ) has been prepared from tetra-t-butylcyclotetraphosphine by heating with excess sulphur, and (155 R = Ph) from bis(trifluoromethylthio)phenyl-phosphine and sulphur. These anhydrides, particularly (155 R=p-anisyl), have been exploited for the preparation of thiocarbonyl groups from the corresponding carbonyls (replacing the more obnoxious P2S5) e.g., thioketones, ... 

Malonodinitrile derivative 807, as well as compounds with phosphonate (808) and trifluoromethylthio (809) groups were used in reactions with NCN binucleophiles, including Af-alkylamidines, 3-aminopyrazoles and 2-aminopyridines to form 707 (Table 39). Activated aUcenes 807-809, unlike the compound 777 containing COOMe group, gave amino or imino derivatives of pyrimidines, which arose from attack of the nucleophile at the nitrile group. Analogous reaction was observed in case of 810 as a result dihydropyrimidine derivatives 811 or 812 were formed (Scheme 161) [497-500]. 

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