Pyrrolidine, 2- trifluoroacetate

Mannich-type reactions, an organocatalyst such as pyrrolidine/trifluoroacetic acid (TFA) or L-proline was employed to assist in the additions of ketones. 

The Hofmann-Loffler-Freytag reaction represents formation of pyrrolidines or piperidines by thermal or photochemical decomposition of protonated A -haloamines in the presence of strong acid such as sulfuric acid or trifluoroacetic acid. " The Hofmann-Loffler-Freytag reaction may also be carried out in milder conditions, for example, PhI(OAc)2,12, hv as shown in section 2.3.4. 

Pyrrolidines have been prepared by 1,3-dipolar cycloaddition of N-(benzyli-dene)trimethylsilylamine/TMSOf 20 and methyl acrylate, N-methylmaleimide, or dimethyl maleate [35]. More recently, methyl trans-3-cyanociruiamate 1479 was reacted with N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether 1480 and trifluoroacetic acid in CH2CI2 at 0°C and 24°C to afford, via 1481, the pyrrolidine derivative 1482 in high yield and MeOSiMe3 13a [35a] (Scheme 9.20). Several... 

Solubility - The oxidized polymer (VIII) has a greater solubility than the original polymer (VII). It was found to be soluble in acetone, chloroform, benzene, DMF and DMSO. Unlike the polymer (VII), (VIII) was not soluble in formic acid or trifluoroacetic acid that was expected since the pyrrole moiety is less basic than pyrrolidine. In the oxidized polymer, the pair of unshared electrons on the nitrogen atom are contributing to the pyrrole ring aromaticity, therefore, unavailable for protonation as in the case of polymer (VII). A comparison of the solubilities is given in Table I. 

Treatment of 329, the A-butyl-A-4-pentenyl analogue of 327, with trifluoroacetic acid and r-butylthiolate radicals (from r-butylthiol) under irradiation with visible light gives the aminyl radical 330, which cyclizes to the pyrrolidine 331 and a r-butylthiolate radical is regenerated (equation 115). It is believed that the process involves, at least partially,... 

Type iii-a The formation of (66) is found in the electrolysis of partially neutralized trifluoroacetic acid in the presence of diallylamine (78). It provides the crystalline hydrochloride of ds-3,4-bis-(2,2,2-trifluoroethyl)pyrrolidine (79) in 8% yield (Scheme 28) [101]. 

The pyrrolidine derivative 1 was treated with trifluoroacetic anhydride in the expectation that intramolecular cyclisation would result. The only products isolated, however, were the isomeric enamines 2a and b. 

Heating or photolytic treatment of A,A-dialkyl-A-haloamine in sulfuric acid or trifluoroacetic acid, followed by neutralization with a base, generates a pyrrolidine or piperidine skeleton. This is the Hofmann-Loffler-Frey tag reaction, and the reaction comprises of the formation of an electrophilic aminium radical, 1,5-H shift (6-membered transition state) or 1,6-H shift (7-membered transition state), formation of 4-haloalkyl ammonium or 5-haloalkyl ammonium, and its polar cyclization by neutralization with a base. Eq. 6.16 shows the formation of A-alkyl pyrrolidine (31) from A-chloro-A-alkyl-A-butylamine (30) in sulfuric acid [46, 47]. 

In a study of the Hofmann-Loffler reaction, the jV-chloro-amine (8a) was irradiated in trifluoroacetic acid solution and underwent photolysis to yield the pyrrolidine (9a) together with the 205-isomer (9b) in a ratio 8 1. The starting amine (8b) was prepared by hydrogenation of (8c), followed by von Braun demethylation and hydrolysis of the JV-cyano-amine (8d) which was so formed. The n.m.r. spectrum of (8b) and of related amines in the presence of lanthanide shift reagents was discussed.10... 

Preparation of (S)-[l-(3-hydroxyadamantan-l-yl)-2-oxo-2-pyrrolidin-l-ylethyl]-amine, trifluoroacetic acid salt... 

Direct N-nitration of secondary amines by nitric acid is possible only for weakly basic amines. The more basic amines can be nitrated under neutral conditions widi reagents such as dinitrogen pentoxide and nitronium tetrafluoroborate, but nitrosamines are significant by-products. The nitrate ester CF3CMe20N02 has been recommended as a nonacidic nitrating agent for secondary amines which avoids the problem of contamination of the products by A(-nitrosamines piperidine and pyrrolidine were nitrated in yields of 75% and 72%, respectively. Amides and imides are efficiendy N-nitrated using ammonium nitrate in trifluoroacetic anhydride. ... 

ALDOL CONDENSATION (+)-(R)-l-Amino-2- methoxymethyl)pyrrolidine. Boron trichloride. Dialkylboron tri-fluoromethanesulfonates. Dibenzyl-ammonium trifluoroacetate. Di- -butylboryl trifluoromethanesulfonate. Dichlorodiethylaminoborane. Diiso-propylaluminum phenoxide. Diisopropyl-aminomagnesium bromide. Lithium diisopropylamide. Morpholine-Camphoric acid. Proline. 

Our ongoing research on (aminomethyl)(lithiomethyl)silanes focuses on modification of the substituents at the nitrogen center. The unprotected 2-silyl-substituted pyrrolidine 5 is a very useful starting point for the synthesis of different A -substituted pyrrolidines like rac-6. The racemic compound rac-S and the enantioenriched compound (iS)-5 could be s)mthesized by reaction of the Af-Boc-protected compound rac-2 or (S)-2 trifluoroacetic acid (TFA) [10]. In subsequent reactions it was possible to introduce a methyl group at the nitrogen center by conversion of rac-S with methyl... 

For pyrrolidine N-oxides, one might a priori anticipate iminium ion formation to occur by a syn elimination process, since the N—O and adjacent Co—bonds cannot become antiperiplanar to each other. However, the N-oxide (29a) of the steroid alkaloid conanine reacts with acetic and trifluoroacetic anhydride exclusively by the anti pathway to give the exocyclic enamine (30 Scheme 6). Release of steric strain between the C-16 methylene and the ring methyl substituent is undoubtedly a major driving force in this reaction. More revealing is the reaction of N-oxide (29b), which would give the same enamine product if a syn pathway is favored. The observed formation of compounds (31) and (32) argues in favor of the anti elimination. 

Lhommet and co-workers synthesized (- )-436 by the route shown in Scheme 66 [422). Wittig-Homer reaction between the 2,5-rrans -disubstituted pyrrolidine aldehyde 509, made from (S)-pyroglutamic acid [423), and the protected keto-phosphonate 510 introduced all the skeletal carbon atoms of the target. Simultaneous hydrogenation and //-deprotection of enone 511 gave the aminoketone 512, which spontaneously formed the bicyclic enamine 513 in 98% yield when exposed to trifluoroacetic acid—apparently the first time that such an intermediate has actually been isolated en route to indolizidines. Reduction with sodium cyanoborohydride in acidic medium acid produced a diastereomeric mixture (92 8) of (- )-436 and (+ )-437. The former was isolated in 84% yield after chromatography on silica gel. The overall yield of this 15-step sequence was 8% based on (S)-pyroglutamic acid. 

Biogenic amines are usually detected by LC with a pre- or postcolumn derivatization with o-phthalaldehyde in the presence of mer-captoethanol, and fluorimetric detection of derivatives. A sample derivatization also has to be done to perform GC/MS analysis of grape juice or wine. Amines are distilled from the alkalized sample and trapped in an acidified solution. After concentration under vacuum, salts of ethylamine, dimethylamine, ethylamine, diethyl-amine, n-propylamine, isobutylamine, a-amylamine, isoamylamine, pyrrolidine, and 2-phenethylamine are derivatized with trifluoroacetic (TEA) anhydride. Their derivatives are extracted with ethyl ether. GC/MS is performed using a capillary fused silica PEG column with an oven temperature programmed for 8 min at 70 °C, l°C/min to 160°C, isotherm for 90min (Daudt and Ough, 1980). 

Hydroxylactam 9 rapidly rearranges on treatment with trifluoroacetic acid to pyrrolidine 12. which possesses E geometry at the double bond963. Cyclization of 12 in the presence of formic acid produces pyrrolizidine 13 stereoselectively together with small amounts of indolizidine 14, Hydroxylactams of type 9 are readily prepared from vinyloxiranes. 

These anhydro-iminosugars proved to be valuable synthetic intermediates for the preparation of some derivatives of synthetic and biological interest. Thus, the opening of the pyrrolidine ring of 9 in the presence of aqueous trifluoroacetic acid led to the stereoselective migration of the protected amino moiety from the anomeric position to C-4, as depicted in Scheme 4 [43]. By this procedure 4-aminoaldoses such as 10 can be obtained, in an efficient alternative to nucleophilic displacement of 4-sulfonyl-oxy groups by azide. 

When a mixture of acetic anhydride and trimethylsilyl triflate was used, the opening of the Cl - O bond took place to yield the corresponding acy-lated polyhydroxy pyrrolidines 11 as mixtures of a- and b-anomers [43], compounds of interest as potential glycosidase inhibitors. However, when the opening of the pyranose ring is carried out in methanol containing lithium perchlorate, followed by addition of a 2 1 mixture of TFA and trifluoroacetic anhydride, only 12 was obtained as a single diastereoisomer (Scheme 4). 

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