Trifluoromethyl Derivatives of the

Trifluoromethyl Derivatives of the Transition Metal Flements 1984 Synthesis and Properties of Aryl... 

At the present time the preparation of the trifluoromethylated derivatives of low valent transition metals by ligand-exchange reactions appears to be quite general. However, as exemplified by the nickel reaction above, the utility of the method is obviously subject to the inherent stability of the desired product. In many cases, such as the preparation of the trifluoromethyl derivatives of the cyclopentadienyl cobalt system, (CF3)Co(Cp)(CO)I and (CF3)2Co(Cp)(CO), the reaction of the dihalide with (CF3)2Cd glyme represents the simplest reaction... 

Although these methods did result in the preparation of a number of then new compounds, they are inherently limited by the fact that the amount of material afforded by a typical reaction is often only in the tens of milligrams range, which is ample for product characterization but insufficient for a reasonably thorough examination of the chemistry of the new compounds. Additionally, while metal atom reactions have been successfully utilized on the elements of groups 10-12 (see below), the synthesis, isolation, and characterization of trifluoromethyl derivatives of the elements from earlier periods of the periodic table is yet to be established. 

Trihalomethyl groups have a-constants similar to those of the halogens but seem to be generally much less reactive than chlorine. However, convenient displacement of the former is often possible. Chlorine is more reactive than the trifluoromethyl group in 4-chloro-and 4,6-dichloro-2-trifluoromethylpyrimidine and the 5-nitro derivative of the latter thus ammonia or hydrosulfide ion gave the 4-and 4,6-analogs. In the isomeric 2,6-dichloro-5-nitro-4-trifluoro-... 

The sodium derivative of the 2-trifluoromethylphenothiazine was prepared from 26.7 g (0.1 mol) of 2-trifluoromethylphenothiazine and 2.3 g (0.1 g atom) of sodium in 500 ml of liquid ammonia. After the reaction was completed, the ammonia was driven off and 500 ml of dry toluene were added. A solution of 25 g (0.09 mol) of N-(3-chloropropyl)-N -[2-(1,3-dioxanyl)-ethyl] -piperazine In 200 ml of toluene was added drop by drop to this solution which was then refluxed with stirring for 1B hours. After cooling, the precipitate which had formed was filtered and the filtrate was washed with water, dried and concentrated in vacuo. 33 g of brown oil, the N-3-(2-trifluoromethyl-10-phenothiazinyl)-propyl-N -2-[2-(1,3-dioxanyl)] -ethyl-piperazine, were obtained. 

Attempted syntheses of trifluoromethyl derivatives of germanium, tin, and lead by thermal decarboxylation either resulted in decomposition of the trifluoroacetate without forming carbon dioxide (22,39,40) or gave carbon dioxide but no trifluoromethyl organometallic (22). In the latter case, the metal fluoride was detected. This suggests that the trifluoromethyl compound is thermally unstable and decomposes by fluoride abstraction. 

Chen and coworkers have developed two new phosphorescent blue emitters, which have two identical 2-(2,4-difluorophenyl)pyridine ligands and are derivatives of the Firpic compound, iridium(III) bis(4,6-difluorophenylpyridinato)-3-(trifluoromethyl)-5-(pyridin-2-yl)-1, 2,4-triazolate (Firtaz) and iridium(III) bis(4,6-difluorophenylpyridinato)-5-(pyridin-2-yl)-l//-tetrazolate (FirN4) (Scheme 3.90) [314]. Both these two blue emitters show a 10-nm blue-shift of the emission compared with Firpic. Unfortunately, the efficiency of such blue emitters is inferior to those of Firpic and Fir6. There is no lifetime data reported for such devices. 

The reaction of (trimethylsilylamino)(trifluoromethyl) methylene-malonate (1532) and /erf-butyl hypochlorite or N./V-dibromobenzene-sulfonamide in benzene afforded 2-halogen derivatives of the malonate (1538) in 92% and 85% yields, respectively (81ZOR439). 

Trifluoromethyl derivatives of aziridine are intensively studied as biologically active substances. (Trifluoromethyl)aziridines 4 were prepared from (trifluoromethyl)ketoximes 3 and Grignard reagents (equation 2). However, this reaction is not general. For example, reaction does not occur with phenyl and allyl Grignard reagents, but when it works the Z stereoisomer is formed . 

Support for this concept is provided by H NMR studies which have identified a downfield resonance of the hydrogen-bonded proton in this pair at 18 ppm in chymotrypsinogen and chymotrypsin at low pH and at 14.9-15.5 ppm at high pH values.246 247 Similar resonances are seen in the a-lytic protease,248 in sub-tilisin,249 in adducts of serine proteases with boronic acids250 251 or peptidyl trifluoromethyl ketones,252 in alkylated derivative of the active site histidine,253 and in molecular complexes that mimic the Asp-His pair in the active sites of serine proteases.254... 

This indirect, two-step procedure for the synthesis of trifluoromethyl derivatives of transition metals was developed after it had become evident that the reaction of CF3I with metallate ions such as Mn(CO)5 resulted in the formation of the iodide rather than the expected trifluoromethyl derivative, as indicated in Eq. (3) (16). 

The second area of contemporary interest is the attempted formation of fully substituted trifluoromethyl derivatives of high valent transition metal species. At -30°C in ether, the reaction between hexabro-motungsten and (CF3)2Cd glyme proceeds smoothly, but the product decomposes at temperatures near 0°C with the formation of C2F4, WF6, and WOF4. The decomposition of the presumed W(CF3)6 appears to be... 

Irradiation of a 4,6-dien-3-one (312) in pyridine containing CF3I gives the 4-trifluoromethyl derivative (313) the corresponding reaction of a 3,5-dien-7-one gives both the 6-trifluoromethyl-dienone and the 3/3-trifluoromethyl-5-en-7-one.247... 

Extensive Step 2 derivatives of the current invention including N-hydroxy-2,3-dimethoxy-6-[[4-[4-(trifluoromethyl)phenoxy]-l-piperidinyl)sulfonyl]benzamide (3) and l-(2-furanylcarbonyl)-N-hydroxy-4-[[4- [4-(trifluoromethyl)phenoxy] -1 -piper idiny 1] sulfony 1]-4-piperidinecarboxamide, (III), (4) are provided for review. 

---