2.2.2- Trifluoroethyl derivatives

The solvolyses of the secondary l-aryl-2,2,2-trifluoroethyl derivatives I and HI-V would be more likely candidates for kinetically significant solvent... 

On heating with sodium borohydride in glacial acetic acid. 5//-dibenz[/t,/ azepine (5) undergoes sequential acylation and reduction to yield 5-ethyl-5/7-dibcnz[A,/ ]azepine (8, R = Et).192 Similarly, reduction in trifluoroacetic acid produces the trifluoroethyl derivative 8 (R = CF3CH2 61% mp 69-70 C).193... 

Other biodegradation intermediates, such as sulfophenyl carboxy-lates (SPCs) and alkyltetralin carboxylates, can also be analysed by this method. In the latter case, the carboxylates are converted into their acid chlorides and, in a second step, into their trifluoroethyl derivatives as... 

LAS and dialkyltetralin sulphonates are converted to their sulphonyl chlorides by reaction with phosphorus pentachloride and then to their trifluoroethyl derivatives by reaction with trifluoroethanol. These derivatives are separated on a 15 m x 0.25 mm i.d. (0.25 micron film) of DB-5 temperature programmed from 125°C (1 min) to 230°C at 5°C per min with a final hold of 5 min. Helium is the carrier gas and detection is by negative-ion chemical ionisation mass spectrometry [3]. 

Chemical ionization. Yield of molecular ions of trifluoroethyl derivatives is much higher under positive Cl conditions than negative Cl conditions, making positive Cl more useful for trace analysis than either El or negative Cl (7,8). Negative ion CI-MS of trifluo-roethanol derivatives of LAS and dialkyltetralinsulfonate shows predominantly the parent ion, [parent - 100] , due to loss of trifluoroethanol, and mjz 163 due to O3SCH2CF3" (9). The intensity of the rather uninformative 163 ion is increased by increasing the source temperature. 

Other important derivatives for the preparation of (i-aminoacids are the corresponding P-aminonitriles. Lipase-catalyzed N-acylations of racemic cis-2-aminocyclopentane and cyclohexane carbonitriles with 2,2,2-trifluoroethyl butanoate have been successfully carried out in organic solvents and ionic liquids [53], PSL yielding better results than CALB (Scheme 7.29). 

In contrast to the cathodic reduction of organic tellurium compounds, few studies on their anodic oxidation have been performed. No paper has reported on the electrolytic reactions of fluorinated tellurides up to date, which is probably due to the difficulty of the preparation of the partially fluorinated tellurides as starting material. Quite recently, Fuchigami et al. have investigated the anodic behavior of 2,2,2-trifluoroethyl and difluoroethyl phenyl tellurides (8 and 9) [54]. The telluride 8 does not undergo an anodic a-substitution, which is totally different to the eases of the corresponding sulfide and selenide. Even in the presence of fluoride ions, the anodic methoxylation does not take place at all. Instead, a selective difluorination occurs at the tellurium atom effectively to provide the hypervalent tellurium derivative in good yield as shown in Scheme 6.12. 

Trifluoroethyl chloride, bromide, and iodide (but not fluoride) react with thio-late ions in DMF under laboratory illumination at 30-50 °C to give high yields of 2,2,2-trifluoroethyl thiol derivatives. Various features of the reactions show that they occur by the 5 rnI mechanism. The initiation may be spontaneous or thermal electron transfer between thiolate and halides, because the reactions can occur in the dark. 

The Corey synthesis began with an asymmetric Diels-Alder reaction between butadiene and 2,2,2-trifluoroethyl acrylate in the presence of the 5-proline-derived catalyst ent-59 to form the adduct ent-69 in excellent yield (97%) and with >97% ee (Scheme 7.10). Ammonolysis of 60 produced amide 61 quantitatively, which underwent iodolacta-mization using the Knapp protocol to generate lactam 62. A-Acylation of 62 with... 

A number of variations on this type of coating have been prepared and offer some improvement over the original phase. Figure 11.11 shows the volatile pentafluoropropionamide-trifluoroethyl ester (PFP-TFE) derivatives of L and D phenylalanine. Figure 11.12 shows the separation of PFP-TFE derivatives of the D and L enantiomers of the amino acids phenylalanine and p-tyrosine on a Chirasil Val column, the D(/ )-enantiomers elute first. Chirasil Val generally performs best for the separation of enantiomers of amino acids, for many other compounds it is not as effective. 

The rather complex furylvinylcarbinol derivative 76 shown in Scheme 4.28 was required in enantiopure form as a key intermediate in the synthesis of the natural product cneorin. The carbinol moiety is heavily substituted with sterically demanding groups. Therefore attempts to resolve the furylvinylcarbinol with CALB or lipase PS-II led to very slow reactions. However, the rarely used enzyme Candida antarctica lipase A (CALA), which is known to act on sterically hindered substrates offers an alternative. Thus acylation of the furylvinylcarbinol 76 with 2,2,2-trifluoroethyl butanoate catalyzed by CALA (immobilized on celite with sucrose at pH 7.9) furnished the enantiomerically enriched propanoate of S-76 and R-76 (Scheme 4.28) [90]. Small-scale experiments gave E > 300. 

Derivatives of trifluoroethanethiol have limited though interesting chemistry. Unfortunately, metallated difluorothioenol chemistry has not been reported, because rapid nucleophilic attack occurs even by hindered bases such as LDA. Nakai et al. exploited this high electrophilicity in a tandem addition/elimina-tion-rearrangement sequence [146], but more recent applications have concerned free radical chemistry (Eq. 46). Chlorination of trifluoroethyl phenyl sulfide followed by exposure to tin hydride in the presence of an allylstannane resulted in C-C bond formation with a reasonable level of stereocontrol [147]. 

Using similar methodology, constant potential electrolysis, Et3N 3HF/CH3CN electrolyte, platinum anode, Fuchigami prepared the a-fluorinated derivatives of a series of different aryl 2,2,2-trifluoroethyl sulphides. 

A good example of the fact that a considerable number of fluorinated chemicals are not toxic per se, but elicit toxicity only after metabolic modifications, is the toxic behavior of tri-fluoroethanol and/or its derivatives, e.g. the anesthetic Fluoroxene (CF3CH2OCH = CH2)4 43 and analogs, 2.2,2-trifluoroethyl ethyl ether and others.44,45... 

Triethylamine over cobalt(III) fluoride gives90 over 10 products, all of which could have been derived from tris(l,2,2-trifluoroethyl)amine [(CHF2CHF)3N] the 1,2,2-trifluoroethyl motif is the same as that which occurs in the fluorination of ethyl ethers (Section 25.1.1.3.), and presumably arises via a similar mechanism. 

A number of steroids have been regioselectively acylated in a similar manner (99,104). Chromobacterium viscosum lipase esterifies 5a-androstane-3p,17p-diol [571-20-0] (75) with 2,2,2-trifluoroethyl butyrate in acetone with high selectivity. The lipase acylates exclusively the hydroxy group in the 3-position giving the 3p-(monobutyryl ester) of (75) in 83% yield. In contrast, bacillus subtilis protease (subtilisin) displays a marked preference for the C-17 hydroxyl. Candida cylindracea lipase (CCL) suspended in anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Once bearing some substituents, the decrease of polarity of the sucrose derivatives makes them soluble in less-polar solvents, such as acetone or tert-butanol, in which some lipases are able to catalyze esterifications. Unlike proteases, which necessitate most often the use of an activated acyl donor (such as vinyl or trifluoroethyl esters), lipases are active with simple esters and even the parent carboxylic acids in the presence of a water scavenger. The selectivity of the lipase-catalyzed second esterification is specific for OH-6 allowing the synthesis of mixed T,6 -diesters.123,124 For some lipases, a chain-length dependence on the regiochemistry was observed.125 Selectively substituted monoesters were thus prepared and studied for their solution and thermotropic behavior.126,127 Combinations of enzyme-mediated and purely chemical esterifications led to a series of specifically substituted sucrose fatty acid diesters with variations in the chain length, the level of saturation, and the position on the sugar backbone. This allowed the impact of structural variations on thermotropic properties to be demonstrated (compare Section III.l).128... 

The same reaction, originating from the non-fluorinated compound (i.e. ethylammonium chloride) yields the borazine after refluxing for only 15 to 20 hours in the same solvent. The postulated formation of [CF3CH2NBC1]3 69> could not be confirmed 64>. However, 2,4,6-organo-and fluoroorgano-substitituted derivatives of l,3,5-tris(trifluoroethyl) borazine have been made from [CF3CH2NBC1]3 by Grignardalkyla-tions 64>. 

Aromatic primary amines are not only binucleophiles at the amino group, but they also exhibit the properties of C,N-binucleophiles. Their reactions with internal perfluoroolefins lead to quinoline derivatives (98JFC(88)169, 94JCS(CC)134, 98T4949). Thus the reaction of aniline with 2//-heptafluorobut-2-ene yields phenyl(2-trifluoromethylquinolin-4-yl) amine (00ZOR109) when the reaction is carried out with the tetrafluoro-ethylene trimer, it leads to 2-trifluoromethyl-3-(l-N-phenylimino-2,2,2-trifluoroethyl)-4-(N-phenylamino)quinoline (98JFC(88)169). 

An enantioselectivity of 45% e.e. (at 15% conversion) was observed in the enzymatic transesterification of 2,2,2-trifluoroethyl palmitate by the [60]full-eroproline-derived alcohol ( )-209 (Figure 1.45), catalyzed by lipoprotein lipase (LPL) from Pseudomonas specie.350 The modest enantioselectivity may be related to the distance between the stereogenic center of the substrate and its reactive OH group. If, on the other hand, the group reacting with the enzyme is located closer to the fullerene spheroid, reaction rates slow down... 

Substitution reactions involving 3/S-hydroxy-A -steroids and their derivatives require special mention. Cholesterol reacts with a variety of halogenating agents, including thionyl chloride / StJ, phosphorus pentachioride [81], haHdes of aluminium or titanium [82], 2-chloro-i,i,2 trifluoroethyl di-ethylamine [83] and triphenylphosphine dibromide [55], to... 

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