Trifluoroacetaldehyde, reaction

Perfluoroketones are able to abstract hydrogen on irradiation in solution, producing the corresponding ketyl radicals which are detected by e.s.r. spectroscopy.11 Abstraction occurs from trifluoroacetaldehyde [reaction (11)] and from cyclopropane as hydrogen donors. E.s.r. studies also show that photoexcited... 

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Indole has also been demonstrated to undergo a thermally induced condensation with trifluoroacetaldehyde ethyl hemiacetal to give a variety of products depending on the reaction conditions, e.g., the 6,12-dihydroindolo[3,2-f)]carbazole 172, which could be isolated in low yield from the mixture originating from the heating of equimolar amounts of the reactants in the absence of solvent. The formation of an intermediate indolenine species was suggested to account for the outcome (88JFC47). 

It has been shown to metabolize trifluoroethene to glyoxylate, difluoroacetate, and the rearranged product trifluoroacetaldehyde (Fox et al. 1990). The last reaction is analogous to the formation of trichloroacetaldehyde from trichloroethene by the same strain (Oldenhuis et al. 1989). 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

Diketones are reductively cyclized in a TFA-catalyzed reaction. The cycliza-tion of the cage structure shown in Eq. 236 illustrates this ring closure in the formation of an acetal of trifluoroacetaldehyde.409 The organosilane reduction of triketone 69 followed by Jones oxidation gives the cyclic ketoether in fair yield (Eq. 237).410... 

Analogously, the reaction of trifluoroacetaldehyde dimethylhydrazone 249 with TFAA gave 250, which condensed in situ with o-phenylenediamine to afford quinoxaline 251 in good yield <00TL9267>. 

A related catalyst 20 was used in the diastereoselective carbonyl-ene reaction between ethylidenecyclohexane, ethylidenecycloheptane, or 2-methyl-2-butene and trifluoroacetaldehyde (21, R = CF3, Equation (ll))19 or methyl glyoxylate (R = C02Me).20 The best results were obtained when X = Br 63-85% yields are obtained with syn/anti ratios of 95 5 or better, and ee s of the. qw-isomer of 74-89%. 

When trifluoroacetaldehyde ethyl hemiacetal [F3CCH(OH)OEt] is treated with enamines in hexane at room temperature, it provides a source of the aldehyde under mild conditions. Subsequent reaction with the enamine can be used to prepare -hydroxy-/ -trifluoromethyl ketones, F3CCH(OH)CH2COR. The enamine plays successive roles as base, ammonium counterion, and then carbon nucleophile as the sequence proceeds. 

Starting from Fluoral Fluoral (trifluoroacetaldehyde) is an unstable gas that must be prepared before use by dehydration of the corresponding hydrate (commercially available). In spite of this limitation, fluoral itself has been used as a substrate in various reactions. Among the most recent examples, carbonyl-ene and hetero-Diels-Alder reactions deserve mention. The use of chiral Lewis acid... 

Irradiation of hexafluorobiacetyl in the vapor phase produces a 2 1 mole ratio of carbon monoxide and hexafluoroethane, products consistent with an initial carbon-carbon bond cleavage.62 However, vapor phase irradiation of hexafluorobiacetyl in the presence of a large excess of 2,3-dimethylbutane vapor or in 2,3-dimethylbutane solution gave less than 1% carbon monoxide and trifluoromethane. No trifluoroacetaldehyde or hexafluoroacetone was produced in the latter reaction. Instead a complex mixture of products, which was not separated and identified but whose infrared showed the presence of a hydroxyl band and a diminished carbonyl band, was obtained. This observation is consistent with product formation via hydrogen abstraction. 

Male Fischer 344 rats were exposed by inhalation to 1% 2-chloro-1,1,1 -trifluoroethane for 2 h and then urine was collected for 24 h. Urinary metabolites identified by 19F nuclear magnetic resonance and gas chromatography/mass spectrometry were 2,2,2-trifluoroethyl glucuronide (16%), trifluoroacetic acid (14%), trifluoroacetaldehyde hydrate (26%), trifluoroacetaldehyde-urea adduct (40%) and inorganic fluoride (3%). A minor, unidentified metabolite was also detected. No covalent binding of fluorine-containing metabolites was observed in the liver and kidney from the exposed rats (Yin et al., 1995). In-vitro incubation of 2-chloro-1,1,1-trifluoroethane with rat liver microsomes and an NADPH-generating system has been shown to involve a dechlorination reaction (Salmon et al., 1981) that produced trifluoroacetaldehyde hydrate as the only metabolite (Yin et al., 1995). 

The photolysis of trifluoroacetaldehyde at a wavelength of 3130 A. has been shown by Dodd and Smith68 to follow a reaction scheme... 

A series of halogenated ethanes 1 containing the trifluoromethyl group has been oxidized under various conditions.5-7 When water is present in the reaction mixture, the acid 3 is usually formed during the reaction when water is absent, the acid halide 2 formed can be hydrolyzed in a trap with water. Trifluoroacetaldehyde hydrate 4 is formed6 as a minor product in addition to the acid when 2-chloro-l,l,l-trifluoroethane is treated with oxygen and chlorine under UV irradiation with subsequent reflux of the mixture with hydrogen peroxide. 

The results of the oxidations of polyfluoropropanes and higher alkanes are strongly dependent both on the structure of the substrate and the oxidation agent. Shorter chain compounds formed by degradative oxidation are usually present in the reaction mixture as byproducts. Thus, 1,1,1 -trifluoropropanecan be converted by nitric acid and oxygen into a mixture of trifluoroacetaldehyde (5) and l,l,l-trifluoro-3-nitropropane (6).8... 

A third approach to the preparation of allyl lluorovinyl ethers is the reaction of an allylic alcohol with trifluoroacetaldehyde, as illustrated by an alternative synthesis of 37a.17 Cinnamyl alcohol (47) forms with trifluoroacetaldehyde a hemiacetal, which is converted into bromide 48 via the mesy late. Reductive elimination affords 37a, which undergoes Claisen rearrangement within one hour in refluxing carbon tetrachloride to give 2,2-difluoro-3-phenylpent-4-enal (38a).17... 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

Single crystals of difluoromethane bis(sulfinic acid) anhydride 17 were isolated, after the cesium salt 119 was stored in the presence of traces of water vapor for several weeks <1998JFC(89)55>. Treatment of difluoromethane-l,l-bis(sulfonyl fluoride) 120 with liquid ammonia led to the formation of the cyclic ammonium imide 121 <1997ZNB359, 1997WO9731909>, while reaction of sulfamide 122 with trifluoroacetaldehyde O-ethyl hemiacetal afforded the cyclic aminal 60 (Scheme 41) < 1999S1731 >. 

In the case of the 9-catalyzed aldol reactions of ketones and aldehyde donors that have a high affinity for water (e.g., chloral, trifluoroacetaldehyde, aqueous formaldehyde or the corresponding hydrates of the aldehydes), the addition of 100-500 mol% water to the reaction mixture accelerated the reaction rate and afforded the products with higher enantiomeric excess (Scheme 2.13) [16]. The presence of a catalytic amount of water (20 or 50 mol%) or no addition of water... 

The reactions of allylindium reagents with trifluoroacetaldehyde hydrate or hemiacetal in water (Equation (79)), or with aldehyde dimethyl acetals in aqueous THF, give the corresponding homoallylic alcohols (Equation (80)). 313-315... 

Since Kagan s first report of N-N bond reduction using Sml2,39 the reagent is now routinely used for the transformation. The reaction has been used widely in asymmetric synthesis to reduce the products of asymmetric additions to, or reductions of,47 hydrazone derivatives. For example, Enders reported the nucleophilic addition of alkyllithiums to trifluoroacetaldehyde SAMP and RAMP hydrazones in an asymmetric approach to a-trifluoromethyl-sub-stituted amines.48 After activation of the adducts by benzoylation, Sml2-mediated N-N bond cleavage proceeded in high yield (Scheme 4.41). 

In the same way as a,a,(Z-trihalogenated carbonyl compounds are cleaved hydrolytically to produce haloforms, the fluorinated analogs also react by release of trifluoromethane. The fluoroform reaction has been described with aldehydes such as trifluoroacetaldehyde, alkyl trifluoromethyl ketones, and aryl trifluoromethyl ketones, e.g. l-(2,4-dihydroxyphcnyl)-... 

The continuous photochemical decomposition of trifluoroacetaldehyde closely resembles that of acetaldehyde, the main products at A 3130 A being tri-fluoromethane and carbon monoxide. A chain reaction involving trifluoromethyl radicals is probably involved... 

Condensation with ketones. The aminals serve as synthetic equivalent of trifluoroacetaldehyde. Thus, its condensation with ketones (catalyzed by aqueous HCl) gives 2-(l-hydroxy-2,2,2-trifluoroethyl) ketones and reaction with silyl enol ethers I catalyzed by ZnCl ) delivers the trifluoroethylidene ketones. 

Oxazolidine 134 is a masked trifluoroacetaldehyde imine that generates in situ the corresponding imine 135 under Lewis acid catalysis conditions. Lewis acid-catalyzed reactions of 134 with TMS-cyanide and ketene silylacetal provide adducts 136 in high yields with good diastereoselectivities (see Scheme 9.29) [56]. Conventional chemical transformation of 137 produces 3-amino-4,4,4-trifluorobutanoic acid 138. Similarly, tri-fluoroacetone oxazolidine 139 is used for the synthesis of 2-trifluoromethylalanine 142... 

Introduction of a trifluoroethyl group at the a-carbon of the nitro group of 280 by a sequence of reactions - (l,5-diazabicyclo[4.3.0]non-5-ene) (DBU)-catalyzed alkylation with trifluoroacetaldehyde hemiacetal in MeCN, dehydration with acetic anhydride-pyridine, and reduction of the C-C double bond with NaBH4 - produces 281. 6-Trifluoroethyl-L-lysine 282 can be prepared from 281 (see Scheme 9.60) [88]. 

In the presence of catalytic amounts of anhydrons potassinm carbonate, phenols react with trifluoroacetaldehyde ethyl hemiacetal to give the / ara-alkylated prodncts (C-aUcylation of the phenolate anions). Thns, phenol nnder these conditions gives 4-(2,2,2-trifluoro-l-hydroxyethyl)phenol as the predominant prodnct. The reaction catalyzed by zinc halides predominantly gave the ortto-snbstitnted prodnct (eqnation 4) . ... 

Although it has been stated that di- and tri-haloketones and a-haloaldehydes (irrespective of the degree of halogen substitution) tend to yield only enol phosphate esters, further qualification of this statement is appropriate. The formation of silyl ethers from aldehydes or ketones and silyl phosphites has already been noted (see section III.A). Reactions between silyl phosphites and trifluoroacetaldehyde or perfluoroacetone and other similar compounds initially lead to silyl ethers of (a-hydroxyalkyl)phosphonic diesters in which all the fluorine is retained, although subsequent change leads to fluorinated enol phosphate esters. Sekine et also observed the formation of (a-silyloxyalkyl)phospho-... 

Most of 4,5-diary 1-2-trifluoromethylimidazoles have been synthesized by the methods shown in Scheme 12.8. The imidazoles 60 are synthesized by the condensation of trifluoroacetaldehyde equivalent with applicable diaryl-1,2-diketones, where a carbonyl group is replaced with imino group in situ in the presence of ammonium acetate. The imidazole 63 is synthesized by the sequential substitution-condensation reactions of a-bromoketone 62 with trifluoroacetiminoa-mide 61. ... 

Kamachi and co-workers reported a base-induced transformation of trifluoroacetaldehyde azine 86 into 1,4-bis(2,2,2-trifluoroethyl)-3,6-bis(trifluoromethyl)-l,4-dihydro-l,2,4,5-tetrazine 92. The proposed reaction mechanism involves addition of triethylamine to the C=N bond followed by addition of the adduct 87 to another molecule of 86 to give the zwitterion 88. Intermediate 88 undergoes hydride shift and elimination to give the intermediate 90. Repetition of the latter part of the reaction sequence then results in cyclization to give dihydrotetrazine 92 (Scheme 22) < 1995BCJ2025>. 

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