Dehydration trifluoroacetic acid

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55° and followed by hydrolytic workup (Eq. 205).203... 

Many novel features emerged. The acid was the strongest organic acid then known, and the / -oxo ester was unusually stable, and contained a high proportion of the enol form. The tertiary alcohol was very resistant towards dehydration, in sharp contrast to tert-butyl alcohol. In 1931, Swarts reported the Kolbe-type electrolysis of trifluoroacetic acid and its salts, isolating hexafluoroethane for the first time, and demonstrating that it was very stable. 

Reduction by metal hydrides (LiAlH4, NaBH4) of these benzofuran-ones gives 3-hydroxy-2,3-dihydrobenzofurans which are dehydrated by distillation or by treatment with an acid or with P205 or treating the 3-acetoxy derivative with trifluoroacetic acid.39 The intermediates are more or less stable depending on their structures or their degree of purity 3-hydroxy-2,3-dihydrobenzofuran, described by Stoermer as... 

Addition of protic or Lewis acids to 76 leads to immediate isomerization. Thus 76 is transformed by picric acid or zinc chloride in dry benzene to the bicyclic acetal 322. Stronger acids such as trifluoroacetic acid isomerize 322 further to the unstable isobenzofuran derivative 323, which can be trapped with NMM in chloroform as a mixture of endo and exo adducts 324 and 325, respectively, and the in situ dehydration product 326. 

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...

Phosphoric acid ester amides suffer insertion into the N—H bond (770). Dehydration of 42 with trifluoroacetic acid anhydride and triethylamine yields the ketimide 43. Decomposition of 42 at 170°C leads to recovery of the starting material. 

Carbon disulfide has been found to be inert toward attack of HFA even at elevated temperatures (195). Thiocarboxamides react with two molecules of HFA. The intermediates with the likely structure 134 can be dehydrated with phosphorus oxychloride, pyridine (44), or trifluoroacetic acid anhydride (49) to yield A -l,3,5-oxathiazines 135. A retro Diels-Alder reaction takes place with evolution of HFA when 135 is heated to 140°C (44, 45). The heterobutadienes 136 are in equilibrium with the thiazetes 137, which are more stable at ambient temperature (45). 

Four TES ethers were cleaved in the final step of an approach to N1999-A2, a member of the highly unstable enediynes.20 After low temperature dehydration of 17.1 via its triflate [Scheme 4.17], deprotection was implemented by treatment with trifluoroacetic acid in aqueous THE at 0 °C to give the target epoxy-dienediyne 17.2 in 45% yield for the two steps. rtrf-Butyldimethytsilyl ethers could not be removed without total destruction of the molecule. 

Trifluoroacetic acid is a nonoxidizing acid whose aqueous solutions are comparable in strength with those of the mineral acids 115), but as a bulk solvent it is weakly acidic and does not even protonate water (236). Trifluoroacetic acid is also weakly basic and is a nonelectrolyte in 100% sulfuric acid (21). One of the major difficulties of using pure trifluoroacetic acid is its remarkable affinity for water and, to maintain an anhydrous medium, a small quantity of trifluoroacetic anhydride is usually added. This affinity for water is so pronounced that trifluoroacetic acid will dehydrate oxyacids and, for example, converts sulfuric acid into polysulfuric acid. 

Water was found to decrease the rates of polymerisation, but not to inhibit the process. Moreover, the four corresponding carbinols were successfully polymerised by trifluoroacetic anhydride. These reactions went throu a dehydration stage, and since polymerisation occurred even with about 50 times more carbinol than anhydride it was again proved that excess of water did not impede the polymerisation of these monomers by trifluoroacetic acid. It was concluded that two types of active species coexist in these systems, one sensitive to moisture (carbenium ions ) and one insensitive to it (ester ). 

As a test of the intermediacy of the divinyl dichloride (44) in the solvolysis of dichlorocyclopropylcar-binols, Hiyama prepared the homoallylic alcohols (48) by additirai of l,l-cyclic ketones. Treatment of (48) with trifluoroacetic acid produced the cyclopentenones in very good yield (equation 31). This reaction presumably proceeds by dehydration to the divinyl dichloride followed by a similar ionization-cyclization sequence, foterestingly the regioisomeric dichloride also underwent closure to a cyclopentenone. ... 

Reactions of phenylthiocyclopropyl lithium with alkyl halides and epoxides have also been reported to deliver products opened to a variety of carbonyl derivatives jS-(l-Phenylthio)cyclopropyl enones have been prepared by using lithium salts of a-hydroxymethylene ketones as electrophiles and dehydrating with acid (equation 110). Rearrangement to cyclobutanones occurs with trifluoroacetic acid, whereas thermal vinylcyclopropane-cyclopentene expansion sometimes gives mixtures of regioisomers . 

Protection for primary amines. Sheehan and Guziec1 have introduced this reagent for replacement of both hydrogens of a primary amine function by incorporation into the very stable 4,5-diphenyl-4-oxazoline-2-one ring system (3).2 These Ox-protected derivatives are obtained by treatment of a primary amine or amino acid tetramethyl-ammonium salt with (1) in DMF. After stirring for 0.5 hr., the mixture is acidified (HC1) and extracted with ethyl acetate to obtain a diastereomeric mixture of hydroxy-oxazolidinoncs (2). The mixture is dehydrated to the Ox derivative (3) by trifluoroacetic acid (TFA). Ox derivatives are stable to aqueous base, refluxing ethanolic hydrazine,... 

Preparation of carbamates. Carbamates of alcohols, even tertiary (which are easily dehydrated), can be obtained in good yield by stirring the alcohol with 2 equivalents each of sodium cyanate and trifluoroacetic acid in benzene or methylene chloride at room temperature for a few hours (Loev and Kormendy ). A mildly CH, CH, o... 

Modification of the ketal substituents involved deketalization of RE 39571 with aqueous trifluoroacetic acid followed by reaction with the appropriately substituted ketone or aldehyde and anhydrous copper sulfate as the dehydrating agent (Scheme 3). If the glycoside-ether is the desired product, this can readily be obtained by glycosidation with methanol in the presence of hydrogen chloride followed by alkylation of the 2-hydroxyl group with the appropriate halide. 

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