N-Trifluoroacetylation

Nonvolatile analytes must be chemically converted to a volatile derivative before analysis. For example, amino acids are not sufficiently volatile to analyze directly by gas chromatography. Reacting an amino acid with 1-butanol and acetyl chloride produces an esterfied amino acid. Subsequent treatment with trifluoroacetic acid gives the amino acid s volatile N-trifluoroacetyl- -butyl ester derivative. 

When aziridine-2-carboxylic ester 124 (Scheme 3.44) was treated with 1 equivalent of TFA, 125 was formed as a single diastereomer in 80% yield [57]. Use of 10 equivalents of TFA resulted in the formation of N-trifluoroacetyl product 126. This... 

TRIFLUOROACETYLATION OF AMINES AND AMINO ACIDS UNDER NEUTRAL, MILD CONDITIONS N-TRIFLUOROACET ANILIDE AND N-TRIFLUOROACETYL-l-TYROSINE... 

Polymeric reagents, oxidation with, 99 Potassium cyanide, 20 L Proline, N bcnzyloxycarbonyl-3-hydroxy-[1,2-Pyrrohdinedicarboxyhc acid, 3-hydroxy, 1 (phenylmcthyl) ester], 89 L Proline, N trifluoroacetyl [2-Pyrrohdine-carboxylic acid, 1 (trifluoroacetyl), (5)-], 125... 

N-[l-ethyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-N-[l-ethyl N-(benzyloxycarbonyl)glycyl-L-aspart-4-oyl]-N-[ 1 -ethyl N-(trifluoroacetyl)-L-aspart-4-oyl]-N-[ 1 -p-nitrobenzyl N-(benzyloxycarbonyl)-L-seryl-L-aspart-4-oyl]-N-[2-N-(L-tyrosyl)-L-aspart-4-oyl)-2-acetamido-2-deoxy-N-(N-acetyl-L-aspart-4-oyl)-... 

N-Trifluoroacetylations of amino acid esters by a pyrazolide are described in reference [121]. 

The use of N-trifluoroacetyl in place of the piotonated N-methyl function in these oxidative cyclization reactions has been explored. Generally these substrates lead to products of the O-methylflavinanthine type. In one instance, the delocalised carbonium ion intermediate 34 was found to undergo a competitive rearrangement when lack of a nucleophile in solution led to a slow demethylation step [137],... 

The energy barriers and relative conformer stabilities have also been obtained and interpreted for a number of N-trifluoroacetyl derivatives (84BSB927) 119 in all those examined the Z-conformer prevails. 

Finally, a recent example on the biocatalyzed synthesis of new cytotoxic derivatives of the anthracycline doxurobicin (8) deserves to be mentioned. In the presence of Mucorjavanicus lipase or subtilisin Carlsberg ion-paired with Aerosol , the primary C-14 OH was chemoselectively acylated to give the corresponding derivatives, such as the valerate 8a [19]. However, optimization of this enzymatic synthesis did not provide a synthetic approach suitable for the preparative synthesis of gram quantities of Valrubicin (N-trifluoroacetyl doxurobicin-14-valerate, 8b)... 

G. Fronza, C. Fuganti, and G. Pedrocchi-Fantoni, Synthesis of the four configurational isomers of a protected form of N-trifluoroacetyl-4-C-methyl-2,4,6-trideoxy-4-amino-L-hexose from L-threonin, J. Carbohydr. Chem. 8 85 (1989). 

N-trifluoroacetyl amino acids have been reported as stable at -10°C over a 2-week period (53) and the TFA n-butyl esters are stable for about 72 hr when stored at 0 C in a nitrogen atmosphere (32). Reasonable stability of derivatives is necessary for repetitive analyses when many samples are prepared and stored prior to chromatography. Instability of silyl derivatives to hydrolysis has been a major problem which has led to decreased activity in research on these materials. The efficient treatment of amino acids with N,0-bis(trimethylsilyl)acetamide (51) and subsequent GLC of the derivatives is now used only occasionally as a result of instability of the derivatives. 

The naturally occurring amino acids are very polar, and cannot be separated as the free compounds by GC at a temperature below decomposition. If the polar groups in the molecule are chemically modified to produce a more volatile derivative a suitable temperature is then possible. Weinstein (25) reviews all the various derivatives which may be formed from amino acids and the GC conditions necessary to separate them. In actual practice only three derivatives are in popular use. These include the N-heptafluorobutyryl n-propyl ester derivatives, the N-trimethyl-silyl ether derivatives, and the n-trifluoroacetyl n-butyl ester derivatives. 

Gas chromatography (GC) for amino acid analysis is the alternative to HPLC that has found the greatest acceptance. It requires the preseparation derivatization of the amino acids to render them volatile. For this purpose, amino acids are frequently converted into acylated esters. N-Trifluoroacetyl-n-butyl esters and /V-heptafluorobutyrylisobutyl esters are most commonly employed. There have been comparative studies (3,4) that document similar (if not equivalent) analytical results for GC and the classic ion-exchange chromatographic method applied to a variety of food samples. Comparison (5) of GC to the reversed-phase HPLC determination of amino acids (phenylisothiocyanate derivatized) also shows excellent agreement. 

Fig 1 Association of N-trifluoroacetyl (N-TFA) amino acid derivatives and diamide phases (left l,l right l,d )... 

Using chemical Ionization with Isobutane and selected Ion monitoring of the M + H peak, the detection limit of the methyl ester of N-trifluoroacetyl-melphalan was less than 500 pg [41]. 

Although CDI was applied as early as 1972 as reagent for the esterification of starch and dextran, it has only scarcely been used up to now. Its renaissance during the last few years may be due to the fact that it became an affordable commercially available product. Among the first attempts for the esterification of polysaccharides via CDI is the binding of amino acids onto dextran. Besides CDI, -(thiocarbony diimidazole can be utilised to obtain the corresponding imidazolide [198]. The amino acids bound via this path are glycine, L-leucine, L-phenylalanine, L-histidine and L-alanyl-L-histidine. They are protected with N-trifluoroacetyl, N-benzyloxycarbonyl... 

Amino acids Concentration by ion and ligand exchange chroma tography 0.7% XE-60 0.5%OV-101 0.2% QF-1 on Diatoport S Flame ionisation After preliminary concentration prepare N-trifluoroacetyl methyl esters [332]... 

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