A-Trifluoromethyl-substituent

A potentially profitable discovery was that dibromide 74 will undergo an Ullman-type coupling to give the corresponding bis(l,2,4-triazole) 76 in 51% the reaction conditions employed were chosen in order that a trifluoromethyl substituent could be introduced but this reaction did not occur, the biaryl bond formation being preferred (Equation 27) <2006T3301 >. 

The bonding forces involved in hydrophobic interaction can be quite specific to the structure of the dye ions involved. A series of isomeric derivatives of 2-phenylazophenol-4-sulphonic acid, each containing a trifluoromethyl substituent, was synthesised recently. The aqueous solubility of these monosulphonated acid dyes was found to be dependent on the location of this specific grouping in the dye molecule [4]. 

Thioxanthenes lack the ring nitrogen of phenothiazine, and the side chain is attached by a double bond. In all cases, the cis isomer (relative to the substituted phenyl ring) is more active. Electron-attracting substituents seem to have a cumulative effect. For instance, pifluthixol (4.89), with a fluorine and a trifluoromethyl substituent, is 5-10 times more potent than its parent flupenthixol (4.90), and has an inhibitory effect (IC50 = 9.7 X 10 ° M) on the DA-sensitive adenylate cyclase of the striatum. 

A rather more complex scheme is required for the preparation of a derivative that bears a trifluoromethyl substituent on one of the benzene rings. The scheme starts with the condensation of the nitrile group in (32-1) with phenyhnagnesium bromide to give the corresponding imine treatment with aqueous acid leads to the substituted benzophenone (32-2). The future methyl on one of the bridges is introduced in a sequence involving the addition of a trimethylsulfonium yhde. 

Phenols with a trifluoromethyl substituent on the ring are hydroxylated with potassium persulfate,167 while oxidation with chloric acid causes oxidation to quinonc and ring contraction together with incorporation of chlorine in the product.176 A detailed study of the oxidations of 2-, 3-, and 4-(trifluoromethyl)phenols shows that the oxidation with chloric acid at 5 to 10°C for 0.5 hours gives complex mixtures of products 1 77 5-chloro-l-hydroxy-4-oxo-5-(tri-fluoromethyl)cyclopent-2-enecarboxylic acid (12) being isolated as the major product from the 2-isomer. 

In order to sec the influence that a trifluoromethyl substituent has on cyclopropane reactivity, l-(trifluoromethyl)-2-vinylcyclopropane (18) was prepared and its thermal reactions studied.13 Both the cisitrans isomerization and the vinylcyclopropane rearrangement were slower than those of any 2-substituted vinylcyclopropane previously reported. When m-18 is heated at 275 C, a clean and reversible cisitrans isomerization takes place (Kequi, = 5.33). At 332-364 C, 18 undergoes normal vinylcyclopropane rearrangement to 4- and 3-(tri-fluoromethyl)cyclopentenc (19) and (20). respectively. 

However, note that the values of pAR in Scheme 29 were measured in 50-50 v v TFE-water mixtures rather than water. In general, for anionic nucleophiles pAR is expected to be highly sensitive to solvent. Results of Pham and McClelland222 indicate that pAR pA 1 increases by 8 log units between water and 2% aqueous acetonitrile. The effect of a change from water to TFE-water will be much less than this, but a comparison for the /)-mcthoxybcn/yi cation shows that pAR decreases by 1 log unit.223 Thus neglecting any difference between pAR values in the two solvents the estimate of pAR for the a-trifluoromethyl-substituted /7-methoxybenzyl cation is increased to —22.5. This value has been considered at some length because equilibrium measurements for the ions summarized as 58 are relevant to the effects of a-trifluoromethyl substituents on reactivity discussed later in the chapter (p. 80). 

Substantial effects on both stability and metabolism might be expected from the presence of a trifluoromethyl substituent at C-10 in DHA and its ethers. The following effects were anticipated ... 

A different type of fungicide for use on rice, cereals, and vegetables is Flutolanil [22], which is based on a benzamide substructure with a trifluoromethyl substituent. 

When the substrate contains a trifluoromethyl substituent, the reaction is anomalous and forms a bis-aziridinylketone. This is probably explained by factors other than steric effects. For example, the electron-accepting influence of the CF3 group sharply accelerates dehydrobromination relative to dehydration and leads to a three-membered ring (96IZV3026, 95IZV1599, 96IZV2795) (Scheme 95). 

Quinze, K. Laurent, A. Mison, P. Synthesis of five-membered nitrogen heterocycles bearing a trifluoromethyl substituent. J. Fluorine Chem. 1989, 44, 233. 

There has been an increasing interest in the synthesis and properties of heterocycles bearing a trifluoromethyl substituent a selection of these is given in the Table. 2,6-Bis(trifluoroinethyl)pyridin-4-ol is readily prepared by the reaction of l,l,l,7,7,7-hexafluoroheptane-2,4,6-trione with aqueous anunonia at 125—130 °C its sodium salt reacts with halogens to give herbicidal 3,5-dihalogeno-derivatives. ... 

The first selective monoarylation of (W-pyridin-2-yl)piperidme was made possible by introduction of a trifluoromethyl substituent at the 3-position of the pyridin-2-yl directing group (Scheme 24) [16]. The steric hindrance brought by this substituent favoured the sole formation of monoarylated piperidines. A beneficial effect of metal salt additives to the Ru3(CO)i2-based catalyst was observed on... 

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