Lead compounds trifluoromethyl

A type iii-d reaction leads to the formation of (69). Trifluoromethyl radicals generated electrochemically from triflu-oroacetate can attack electron-deficient olefins leading to trifluoromethylated carbon radicals whose chemical and electrochemical follow-up reactions can be controlled by current density, reaction temperature, and substituents of the olefins. With fumaronitrile (86) at 50 °C the monotri-fluoromethylated compound (87) was obtained in 65% yield (Scheme 31) [110]. 

Various reactions of thiocarbonyl compounds leading to trifluoromethyl compounds are described in the literature. Most of them lead to hetero-substituted trifluoromethanes, e.g. 

Trifluoromethyl derivatives of azomethine imines are effective 1,3-dipoles in reactions with unsaturated compounds. Thus, RCH = CHR type olefins and azinehexafluoroacetone react to form azomethineimine, transformed into 1/7-3-pyrazoline (75JCS(P1)538, 79T389) (Scheme 26). Heating the latter with AIBN leads to trifluoromethyl derivatives of pyrazole (82JFC(19)437) (Scheme 26). 

The lead compound for SB 204741 was the [3-(trifluoromethyl)phenyl] urea analogue, having a 100-fold greater potency for the 5-HT receptors in rat stomach fundus than in rat jugular preparations [45] (Table 17, compound 1). Replacement of the trifluoromethylphenyl moiety by a 3-pyridyl group and removal of the alkyl substituents at the 2- and 3-positions of the indole nucleus increases the affinity of the rat stomach fundus receptors 2-fold (Table 17, SB 200646). 

Oryzalin (6) is an anal( e of trifluralin (4) where the trifluoromethyl group is replaced with a sulfonamide group. This functional group replacement aids aqueous solubility, making oryzalin (6) a more attractive lead compound. Oryzalin (6) has been shown to inhibit the assemb of 7.5 pM leishmanial tubulin assembly by approximately 54% at a concentration of 25 pM."... 

Furthermore, compound 3, 4-phenoxy-2-(trifluoromethyl)phenyl 3,3-dichloro-2-propenyl ether, showed unique lethal symptoms as well as insecticidal activity against S. litura at 500 ppm, motivating us to use this 3 as the next lead compound (Fig. 30.3.2) [4, 5]. 

In a recent paper, 5-(trifluoromethyl)diphenylsulfonium triflate (545) in the presence of copper was proposed as an efficient reagent for trifluoromethylation of heteroaromatic compounds [282]. In particular, 3-chloro-6-iodopyridazine smoothly reacted with this reagent to give the product of the iodine selective substitution (546) in 98 % yield (Scheme 109). The proposed mechanism for the formation of active species included reduction of 545 leading to trifluoromethyl radicals, which in turn reacted with copper to give CFjCu. 

At present our knowledge of fluorocarbon-lead compounds is limited to (CH3)3PbCF3 and (CH3)3PbC2Fs (46). These substances can be obtained by heating at 150° C mixtures of tetramethyllead and trifluoromethyl iodide or pentafluoroethyl iodide, respectively. Considerable quantities of fluoro-form and pentafluoroethane are produced in these reactions and vapor phase chromatography was used to separate the desired lead compounds from unreacted tetramethyllead and methyl iodide. 

This formulation is supported by the proton resonance spectrum of the trifluoromethyl compound 101 which shows that it exists in the CH form shownd However, strong electron-withdrawing groups in the 4-position apparently lead to enolization, and compound 102, for example, gives an intense color with ferric chloride, - Other 4-acylated oxazol-5-ones are often formulated as 103 (see, e.g, reference 113). Tautomerism of the type illustrated by the equilibrium 104 103 has been discussed (see reference 115 for further references). 

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. 

The sediment concentrations of anthropogenic compounds in the cove were somewhat less variable than upstream this probably reflects the greater bottom uniformity of the cove. Fewer of the plant s compounds were detected in sediment from the channel where the cove leads into the brackish river (Point 18, Figure 1). Found at this location were various phenols (no. 28, 30a, 30b, 31, 33, 38, 39), di-t-butyl-benzoqui-none (no. 57), 3,5-di-t-butyl-4-hydroxy-benzaldehyde (no. 35), three benzotriazoles (no. 6, 10, 12), 4,4 -dichloro-3(trifluoromethyl) carbanilide (no. 77), and 2-chloro-4,6-bis-isopropylamino-s-triazine (no. 14). The only compounds from the plant detected in the sediment sample from the brackish river (Point 19) were the two high molecular weight benzotriazoles (no. 10 and 12) and methyl 3-(3 ,5 -di-t-butyl-4 -hydroxphenyl) propionate (no. 46). 

The bioreduction of carbonyl compounds with reductases has been exploited for many years, especially in the case of ketones, with baker s yeast Saccharomyces cerevisiae) being the most popular biocatalyst [45]. For instance, yeast treatment of 3-chloropropiophenone affords the expected (lS)-3-chloro-l-phenylpropan-l-ol, which was treated with trifluorocresol in tertrahydrofuran in the presence of tri-phenylphosphine and diethyl azodicarboxylate at room temperature to give (3R)-l-chloro-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propane and the later reaction with methylamine leads to (R)-fluoxetine that is an important serotonin uptake inhibitor (Scheme 10.19) [46]. 

In a study being conducted at Case Western Reserve University under the direction of Dr. Lawrence Sayre, trifluoromethyl-substituted analogs of 2,5-hexanedione will be synthesized, compared with the parent compound in chemical model studies, and evaluated for neurotoxicity in rats. This is part of an effort to address how gamma-diketone-induced pyrrole formation at neurofilament-based lysine epsilon-amino groups leads to neurofilament accumulations. Nuclear magnetic resonance (NMR) studies will provide direct visualization of the nature of chemical modification. 

To date, however, only few reactions between phosphine and a non-metal halide, in which a chemical bond is formed between phosphorus and a non-metal by HCl condensation, are known. To these, apart from the above-mentioned reactions, belongs also the reaction with CF3SCI which, depending upon the chosen proportions of the reactants, in a sealed tube at -95 °C leads to the formation of (CF3S)2PH or (CF3S)3P Both compounds are not very stable thermally and decompose at 40-50 °C. Tris(trifluoromethylthio)-phosphine forms an unstable adduct with chlorine, which decomposes at 0 °C to give a mixture of PCI3, bis(trifluoromethyl)-disulphide and trifluoromethyl-sulphenyl chloride. 

Racemic jS-fluoroalkyl tyrosines and phenylalanines have been prepared by classical methods starting from the corresponding fluoroacetophenones. Synthesis of the nonracemic compounds is much more difficult, as exemplified by the preparation of jS-difluoromethyl meta-tyrosines (Figure 5.14). jS-Trifluoromethyl tryptophan is prepared by alkylation of ethyl acetamido malonate with indolyl-2,2-trifluoroethanol. Surprisingly, the decarboxylation reaction leads stereoselectively to the syn isomer (Figure 5.15). ... 

S -Mono-, di-, and trifluoro derivatives of methionine and 5-fluoroalkyl derivatives of cysteine are accessible through fluorination. Thus, fluorination of methionine sulfoxide with xenon fluoride, or more easily using DAST, provided 5-monofluor-omethionine. Photochemical trifluoromethylation of homocysteine leads to 5-trifluoromethionine. These S -fluoroalkyl compounds are also available through fluoroalkylation of homocysteine. Thus, the addition of difluorocarbene (formed from Freon 11 (CHF2CI)) affords S -difluoromethionine. ... 

When the trifluoromethylation occurs on aketonic carbonyl (such as position 2 or 3 in furanose series), it must be followed by a Barton-McCombie deoxygenation of the hydroxyl. It thus leads to the 2- or 3-C-trifluoromethyl deoxyfuranoses. The transformation of these latter compounds into deoxynucleosides has been reported. Trifluoromethyl 2, 3 -dideoxynucleosides and A-2 3 -vinylic nucleosides have also been prepared according to this approach (Figure 6.34). The CF3 group protects the glycosyl base bound from proteolysis in acidic medium, especially in the case of A-2 3 compounds. ... 

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