Aromatic Trifluoromethyl Compounds

The c -dihydrodiols have been prodnced from a nnmber of triflnoromethylbenzoates  

Both trifluoromethylbenzoates and trifluoromethylphenols prodnced 2-hydroxy-6-keto-7,7,7-trifluorohepta-2,4-dienoate, which is the immediate ring-fission prodnct. The triflnoromethyl group of the original substrates was retained in the terminal metabolites. 

FIGURE 9.37 Anaerobic transformation of 6-fluoro-3-methylphenol. (From Neilson, A.H. and Allard, A.-S., The Handbook of Environmental Chemistry, Vol. 3R, Springer Verlag, 2002, pp. 1-74. With permission.) 

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Aryl ortho thioesters, which can be readily prepared from the corresponding acid chlorides or methyl esters, react with A-halo compounds, such as 1,3-dibromo-5,5-dimethylhydantoin (DBH) or A-bromosuccinimide, and hydrogen fluoridc/pyridine to give aromatic trifluoromethyl compounds,i.e. formation of... 

Aromatic thio orthoesters are successfully converted into trifluoromethyl arenes by treatment with a pyridinium polyhydrogen fluoride-A -halo imide reagent. The reactions are conducted at -30 to -20 °C, and the nature of A-halo imide is critical both 1,3-dibromo-5,5-dimethylhydantoin and A-bromosuccin-imide give similar yields of trifluoromethyl compounds [5] (equation 7)... 

In addition to military uses, it should be noted that aromatic nitro compounds such as trifluralin (2,6-dinitro-A,A-dipropyl-4-(trifluoromethyl)aniline and dinoseb (2,4-dinitro-6-5 ec-butylphenol)... 

All derivatives, sulfenylated at the nitrogen atom, are stable for a prolonged period of time only at low temperature. 5-Trifluoromethyl-mercaptouracil is an extraordinarily stable compound. In contrast to 5-bromouracil (129), the substituent cannot be exchanged by amines. Nevertheless, a complete fluorine-chlorine exchange can be brought about with the aid of boron trichloride, just as with other aromatic CF3S compounds (170) ... 

Howdeshell and Hites [102] identified three aromatic fluorinated compounds associated with the production of 4-(trifluoromethyl)-chlorobenzene in sediment core samples from Lake Ontario in 1993. These compounds were specifically associated with the Hyde Park dumpsite near the Niagara River [97], which was also likely to be the main source of 2378-TeCDD (Fig. 9). The average maximum years for concentrations of these fluorinated compounds was 1969-1971 in the Niagara, Mississauga, and Rochester Basins, and 1975 in the Kingston Basin. Pearson et al. [19] noted that the peak PCDF concentration in Lake Ontario sediments corresponded to that of the fluorinated compounds, suggesting that Hyde Park may be the source of the unusual PCDF contamination of Lake Ontario as well as 2378-TeCDD. 

Sulfides with a hydrogen atoms like dimethyl sulfide, dimethyl disulfide, and tetrahydrothiophene form diols under UV irradiation (795). In the tetrahydrothiophene-2HFA2 adduct the hydroxyhexafluoropropyl groups are in trans positions and the trifluoromethyl groups show nonequivalence (795). Aromatic thio compounds like thiophenols (77), diaryl sulfides (779, 180, 207), and thiophene (95) add HFA in an ortho position, as does furan (95). 

Trifluoromethylation This reagent converts aliphatic and aromatic halides into the corresponding trifluoromethyl compounds in moderate yield ( 10-65%). 

Trifluoromethyl ketones have generated much interest as potent enzyme inhibitors [1]. A series of trimethylsilylated aliphatic and aromatic trifluoromethyl ketones were synthesized and evaluated for anti-acetylcholinesterase activity. One compound in this series — 3-(trimethylsilyl)trifluoro-acetylbenzene (MDL-73745, Zifrosilone) — was selected for further investigation for the treatment of Alzheimer s disease [1 - 3]. 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

The accumulation of the cycloaddition product is related to its thermal stability in regard to nitrogen elimination. Here, elimination of nitrogen is even more pronounced because of two reasons the presence of the double C-C bond instead of a cyclopropane moiety (Scheme 11) and because it can produce corresponding furan derivatives. Furan is actually one of the rare aromatic heterocyclic compounds that easily participates in Diels-Alder reactions as a moderately active diene. Therefore, it is also reasonable to postulate that the furan derivative obtained after elimination of nitrogen is more reactive than 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole. Additionally, the cycloadduct with a second molecule of cyclooctyne would be a final product of the cycloaddition reaction. To explore this possibility further, a semiempirical study of cycloadduct stability and activation barrier needed for cyclooctyne to react with furan was performed. 

Majority of known perfluoroalkylated aromatic heterocyclic compounds contain one or several nitrogen atom(s) in the aromatic ring. Examples of fluoroalkylated aromatic six-membered heterocycles containing atoms, such as phosphorous or antimony are extremely rare and this is the reason why this chapter is mostly limited to preparation and chemical transformations of nitrogen-cotitammg aromatic heterocycles, providing limited number of references to only few known examples of trifluoromethyl s-1,3,5,2,4,6-triazatriphosphinines. 

Trifluoromethyl ketones (TFKs) have been found to inhibit various hydrolytic enzymes (1-6 ). Series of aliphatic and aromatic trifluoromethyl ketone sulfides (7-10 ) proved to be exceptionally powerful inhibitors of insect juvenile hormone esterase (JHE), an enzyme of key importance in insect metamorphosis. The trifluoroketone moiety is believed to behave as a transition state mimic (11,12) of juvenile hormones (JHs), substrates of the enzyme. The /3 sulfur atom is anticipated to mimic the a-/3 double bond present in all natural JH substrates. In earlier structure-activity relationship (SAR) studies (7,11) clear correlation was found among the molar I50 values of these compounds against JHE and the calculated molar refractivlty of the inhibitors. 

The radiopartltlon assay (2fi.2 ) was applied to monitor the in vitro inhibitory activity of the title compounds against JHE. The enzyme activity Is monitored by measuring the hydrolysis rate of the substrate, juvenile hormone. Diluted hemolymph from L Dj larvae of Trlchonlusla nl (cabbage looper) was the source of the enzyme, a mixture of H-labeled and unlabeled JH-III was used as a substrate. Ethanol or acetone were used as solvents for the TFK inhibitors in the assay. The chemical structures and Inhibitory potencies of the aromatic trifluoromethyl ketones Involved in this study are summarized in Table I. 

Trifluoromethyl)diphenylsulfonium triflate can be reduced by Cu metal, converting iodo-substituted aromatics and heteroaromatics into the corresponding trifluoromethylated compounds in high yield (eq 1). ... 

Dehydration of pyronecarboxamide 22 with trifluoroacetic anhydride in the presence of pyridine leads to the formation of 2-cyano-6-(trifluoromethyl)-4-py-rone (40) in 61 % yield. The reactions of this cyanopyrone with A(-nucleophiles can proceed with or without substitution of the cyano group to give a wide range of novel trifluoromethylated compounds. Thus, cyanopyrone 40 easily reacted with aliphatic and aromatic amines in EtOH at -20 °C and o-phenylenediamine in... 

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED AROMATIC COMPOUNDS] (Volll) (+)-N-Methyl-g-[4-(trifluoromethyl)phenoxy]ben-zenepropanamine hydrochloride [54910-89-3]... 

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