Trifluoroacetic acid nitriles

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

Acid derivatives that can be converted to amides include thiol acids (RCOSH), thiol esters (RCOSR), ° acyloxyboranes [RCOB(OR )2]. silicic esters [(RCOO)4Si], 1,1,1-trihalo ketones (RCOCXa), a-keto nitriles, acyl azides, and non-enolizable ketones (see the Haller-Bauer reaction 12-31). A polymer-bound acyl derivative was converted to an amide using tributylvinyl tin, trifluoroacetic acid, AsPh3, and a palladium catalyst. The source of amine in this reaction was the polymer itself, which was an amide resin. 

Miscellaneous Unsaturated Substrates. Exposure of l,l -bis(trans-2-cyanovinyl)ferrocene to a mixture of two equivalents of triethylsilane and 320 equivalents of trifluoroacetic acid at 50° for three hours gives a product with the carbon-carbon double bonds reduced in 83% yield, but leaving the nitrile groups intact (Eq. 122).179... 

Rice and Nuss report that the Argopore MB-CHO polymer-supported amidoximes 282 (readily available from the nitrile 281), shown in Scheme 46, can be acylated with acid chlorides in the presence of excess pyridine to give the O-acylamidoximes 283. Cyclization was carried out with TBAF in THF at ambient temperature, to give the polymer-supported 1,2,4-oxadiazoles 284. Release of the 1,2,4-oxadiazoles 285 from the polymer support was achieved by treatment with 95% trifluoroacetic acid <2001BML753>. 

Lithium aluminium hydride has also been used for the reduction of nitriles to amines a recommended procedure involves the slow addition of the nitrile to at least one molar proportion of the reducing agent in a cooled ethereal solution.205 The reduction of nitriles is also effected by the use of sodium trifluoro-acetoxyborohydride (from sodium borohydride and trifluoroacetic acid) in tetrahydrofuran solution.206... 

Wear nitrile rubber gloves, laboratory coat, goggles, a face shield, and, if necessary, a self-contained breathing apparatus. Cover the spill with a 1 1 1 mixture by weight of soda ash or calcium carbonate, clay cat litter (bentonite), and sand. When the trifluoroacetic acid (anhydride) has been absorbed, scoop the mixture into an appropriately labeled container for recycling or disposal by burning.4-6... 

By interaction of 7-amino-8-oxo-3-vinyl-5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid 4-methoxyphenyl ester with 4-bromoacetyl bromide was prepared 7-(4-bromo-3-oxo-butyrylamino)-8-oxo-3-vinyl-5-thia-l-azabicyclo (4.2.0)oct-2-ene-2-carboxylic acid 4-methoxyphenyl ester. The active methylene group in that product was then nitrosated with sodium nitrite. The initial product spontaneously tautomerizes to afford 7-(4-bromo-2-hydroxyimino-3-oxo-butyrylamino)-8-oxo-3-vinyl-5-thia-l-azabicyclo(4.2.0) oct-2-ene-2-carboxylic acid 4-methoxyphenyl ester. By the reaction of that compound with thiourea and then with trifluoroacetic acid was obtained (6R,7R)-7-(2-(2-amino-4-thiazolyl)glyoxylamido)-8-oxo-3-vinyl-5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid sodium nitrite, (Z)-oxime (Cefdinir sodium nitrile). 

In a recently reported synthesis of pyridines, lithiated methoxyallenes react with nitriles in the presence of trifluoroacetic acid (Scheme 107) <2004CEJ4283>. The mechanism is postulated to proceed via initial protonation followed by nucleophilic addition of the trifluoroacetate ion with subsequent intramolecular acyl transfer and aldol condensation to give the pyridine. An additional pyridine formation starting from azaenyne allenes forms a-5-didehydro-3-picoline diradicals, which can be trapped by 1,4-cyclohexadiene, chloroform, and methanol to produce various pyridines <20040L2059>. 

Fig. 7.3. Trifluoroacetic acid an hydride-mediated dehydration of plvallc acid amide (A) to plvallc acid nitrile (B) with the reagent forming tri- E...

In contrast to other methods, functional groups such as esters, amides, nitriles, alkenes, alkynes, etc. were unaffected, under these conditions. In pure methanol, ethanol or ethylene glycol, thioacetals were converted to acetals. The use of [bis(trichloroacetoxy)iodo]benzene gave equally good results [44]. Generally, since trichloroacetic acid is 3 times cheaper than trifluoroacetic acid on a mole basis, [bis(trichloroacetoxy)iodo]benzene may be an alternative to BTI. 

The Beckmann rearrangement of oximes may be induced by means of dicyclohexylcarbodi-imide and trifluoroacetic acid in dimethylsulphoxide. The oxime (256) of a 17-oxo-steroid gave the usual lactam (257) and seco-nitrile (258). The oxime of a 3a,5a-cyclo-6-ketone gives the ring-B lactam resulting from migration of C(5) (c/. p. 273). A kinetic study of the Beckmann rearrangement... 

Some hydrolyses will first be described, then the preparatively important reductions, and finally some addition reactions. 5-Cyano-4-formamido-2-methyltriazole, refluxed with trifluoroacetic acid, gave 4-formamido-2-methyltriazole-5-carboxamide (1 hr, 85%). The same nitrile, set aside in 2 Af sodium hydroxide was hydrolyzed to 4-amino-2-methyltriazole-5-carbo-xamide (25°C, 15 hr, 95%) [73JCS(P1)2659], 5-Cyano-4-dimethylaminomethylenamino-1 -methyltriazole, in alkaline hydrogen peroxide solution, yielded the amide (25°C, 12 hr, 87%)... 

Addition of solid disodium hydrogen phosphate as a buffer to seavenge trifluoroacetic acid from the system did prevent the side. eaction leading to the nitrile but very little nitroalkane was formed. However, further study of the reaction conditions led to the finding that nitroalkanes can be obtained in good yield by peracid oxidation with acetonitrile in the presence of a buffer (NajHP04, NaHCO., NaCO-O- For example,... 

Synthesis of phenols and aromatic nitriles.3 In a new phenol synthesis, an aromatic hydrocarbon is first thallated with the reagent in trifluoroacetic acid to give an arylthallium ditrifluoroacetate (which can be isolated) and then oxidized with lead tetraacetate in the presence of 1 equivalent of triphenylphosphine. The resulting aryl trifluoroacetate is then hydrolyzed with dilute base. The triphenyl-... 

From their extensive mechanistic studies on the asymmetric dihydroxylation reaction, the Corey group extended the utility of these catalysts to the Strecker reaction.35 Treatment of their dihydroxylation catalyst with trifluoroacetic acid generated a stable crystalline solid 63 that was demonstrated to catalyze the asymmetric Strecker reaction. The TV-allyl moiety was found to be preferred to benzyl as a protecting group for the nitrogen atom. Thus, when 64 was treated with catalyst 63, nitrile product 65 could be obtained in excellent yield. A solvent effect on the % ee was noted such that CH2CI2 was optimal compared to toluene that may compete with the aldimine for the catalyst s binding site. 

Rickborn and co-workers ° ° isolated the cycloadduct 164 from 4-phenylox-azole through careful manipulation of the experimental conditions (Fig. 3.50). They generated benzyne at 0°C from 1-aminobenzotriazole and lead tetraacetate. Compound 164 was stable at room temperature but, on heating, eliminated benzo-nitrile to give isobenzofuran 162, which could be trapped with A -methylmaleimide to afford a quantitative yield of the tetracyclic derivative 166 as an 88 12 mixture of endo and exo isomers. The cyclic aminal 164 was also sensitive to acid and rearranged to 4-hydroxy-3-phenyl-isoquinoline 165 on exposure to silica gel or a catalytic amount of trifluoroacetic acid. The benzyne cycloadditions were also carried out on 4-(4-nitrophenyl)oxazole and 4-(4-methoxyphenyl)oxazole. A fourfold rate increase was seen for the cycloaddition of the nitrophenyl-substituted oxazole relative to the methoxyphenyl analog, indicating a concerted process with little contribution from a polar intermediate. 

Olah et al. reported the triflic acid-catalyzed isobutene-iso-butylene alkylation, modified with trifluoroacetic acid (TFA) or water. They found that the best alkylation conditions were at an acid strength of about//q = —10.7, giving a calculated research octane number (RON) of 89.1 (TfOH/TFA) and91.3 (TfOH/HaO). Triflic acid-modified zeohtes can be used for the gas phase synthesis of methyl tert-butyl ether (MTBE), and the mechanism of activity enhancement by triflic acid modification appears to be related to the formation of extra-lattice Al rather than the direct presence of triflic acid. A thermally stable solid catalyst prepared from amorphous silica gel and triflic acid has also been reported. The obtained material was found to be an active catalyst in the alkylation of isobutylene with n-butenes to yield high-octane gasoline components. A similar study has been carried out with triflic acid-functionalized mesoporous Zr-TMS catalysts. Triflic acid-catalyzed carbonylation, direct coupling reactions, and formylation of toluene have also been reported. Tritlic acid also promotes transalkylation and adaman-tylation of arenes in ionic liquids. Triflic acid-mediated reactions of methylenecyclopropanes with nitriles have also been investigated to provide [3 + 2] cycloaddition products as well as Ritter products. Tritlic acid also catalyzes cyclization of unsaturated alcohols to cyclic ethers. ... 

Aldoximes 419 are selectively oxidized by (diacetoxyiodo)benzene in methanol containing a catalytic amount of trifluoroacetic acid to give nitrile oxides 420, which can be trapped in situ with olefins in a bimolec-ular or an intramolecular mode to give the synthetically valuable isoxazoline products 421 (Scheme 3.169) [509]. A similar reaction of a-oxo-aldoximes with PhI(OAc)2 affords a-oxo-nitrile oxides, which can be further trapped with norbornene or styrene [510]. 

Kim et al. have reported a facile one-pot stereoselective synthesis of ( )-cinnamyl alcohols 113 via the treatment of MBH adducts, derived from aryl aldehydes and ethyl acrylate, with TFA. However, a similar reaction of MBH adducts derived from aryl aldehydes and acrylonitriles with TFA gave the ( )-allyl alcohols 111 in low yields (Scheme 3.40). " Since Basavaiah s method works well for nitrile-containing adducts [for ( )-selective nitriles] and the trifluoroacetic acid method works well with ester-containing adducts [for ( )-selective esters], these two methods are considered to be complementary for the preparation of stereochemically defined cinnamyl alcohols. 

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