Perfluoroacyl derivatives

Although the anhydride may be used on its own, the acylation reactions go most smoothly and quickly in a solvent and with a catalyst. The precise nature of the solvent is not important, but it is common to use a solvent such as acetonitrile which can act in both capacities. The following conditions are satisfactory for phenols, amines, phenolic amines and alcohols. 

studying the acylation of anilines and chloroanilines, found that reaction with TFAA was complete for most of them in 5 minutes at room temperature, and in 15 minutes for all of them with PFPA the reaction was complete for most in 15 minutes at room temperature, and after two hours for all and with HFBA anhydride for most in 18 hours at room temperature and for 30 minutes at 60 °C [54]. 

The reactivity of the compounds to be derivatized clearly plays an equally important part. Thus, for example, ephedrine, pseudoephedrine and analogues were acylated with TFAA for 5 minutes at 60 C [57], tricyclic antidepressants with HFBA for 10 minutes at 60 °C [58], the methyl esters of pipecolic acid, proline, glutamic acid and y-aminobutyric acid with HFBA for 20 minutes at 150 °C [59], and catecholamines (after methylation of the j8-hydroxyl) with PFPA for 15 minutes at 80 °C [60]. 

In the second procedure for amino adds (first converted to the n-butyl esters), acylation is done with a 1 3 mixture of TFAA and methylene chloride (1 ml for each 10 mg of amino add mixture) in a readion vial with a PTFE-lined screw-cap seal at 150 °C for 5 min. Excess of the reagents is evaporated in a stream of nitrogen, but not to complete dryness, to avoid evaporative losses [61], Conditions for GC analysis of amino acids as the N-TFA amino add n-butyl esters have been carefully optimized, and details may be found in the summarizing paper [62]. 

The acylation procedures as described are equally applicable to PEP and HFB derivatives however, for amino groups, only the N-HFB derivatives capture really well in the ECD for significantly more sensitive detection than with the flame ionization detedor (63, 64), although the derivatives of the hydroxyl amino acids can be detected with much better sensitivity because, as mentioned already, O-perfluoroacyl derivatives are more electron-capturing. 

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Diethyl perfluoroacylphosphonates, e.g. (129), undergo easy solvolysis and hydra-zinolysis with P—C bond fission to give the perfluoroacyl derivatives (130).108 The... 

Concentrations of major carbohydrates in other physiological fluids are usually sufficiently high to permit a reliable profile analysis with the flame-ionization detector. Thus, the GC carbohydrate analyses have been described for plasma [412,413] as well as the seminal fluid from both normal and sterile men [164]. Several attempts have been made to relate the polyol concentrations in the human cerebrospinal fluid to certain pathological conditions [414-416]. If higher sensitivities are needed in the carbohydrate determinations, it is of advantage to consider perfluoroacyl derivatives and the electron-capture detector [402]. 

Many different derivatives have been suggested over the years. The most important include acetylated [418,419], and various perfluoroacylated, derivatives [420-423], trimethylsilyl compounds [424-427], enamines [428] and isothiocyanates [429,430]. Because of the non-uniform reactivity of the different functional groups within the studied molecules, the mixed derivatives are quite common these include trimethylsilylenamines [431], trimethylsilyl-perfluoroacyl [233,427,432], carbamate-trimethyl silyl [236], A -2,6-dinitro-4-trifluoromethylphenyl-trimethylsilyl [433], and isothiocyanate-trimethylsilyl [430] derivatives. Numerous newer attempts for optimized derivatization [427] and less conventional derivatives [434,436] demonstrate the methodological challenge of this area. 

Brenneisen and Borner (1985) identified and quantified thebaine, morphine, and codeine in different plant parts of Papaver somniferum and P, bracteatum. GC-MS of the acetate derivatives was used to confirm the identification obtained by HPLC. Perfluoroacylation was found to give, besides the usual derivatives, C-perfluoroacyl derivatives in the case of the presence of an enamine moiety in the ring D of the morphine-type molecule (Moore et al. 1984). 

Trimethylamine has been used as a basic catalyst for the derivatization of phenols. The phenols (up to 1 mg) in benzene (500 /il) were mixed with 0.1 M trimethylamine in benzene (100 /il) and acylated with HFBA (10 /il) at room temperature for 10 minutes. Excess reagents were removed by a 30 second wash with pH 6 phosphate buffer, the phases were separated by centrifugation, and the benzene solution was taken for gas chromatography. As with other O-perfluoroacyl derivatives, these compounds could be analysed with excellent sensitivity using the ECD [92]. 

The derivatization of amides has been mentioned. Although amides form either TMS or perfluoroacyl derivatives, PFBzO is probably the derivative of choice it is stable [108] and readily prepared in good yield, and the products chromatograph well. The amide (0.2 mg) in hexane (500 (A) is mixed with 1.4 M trimethylamine in hexane (200 /il) and PFBzO-Cl (25 (A) is added. If the amide does not completely dissolve, acetone (100/rl) may be added. After 2 hours at room temperature excess reagents are removed in vacuo, and the residue is dissolved in ethyl acetate for analysis by GC with electron capture detection [108). 

Even such high molecular weight compounds as thyroxine may be pertrimethylsilylated [27] for GC-MS analysis, but this derivative shows mainly lower m/z fragment ions. Thus most thyroxine assays tend to be carried out with perfluoroacyl derivatives, which have more abundant higher m/z fragments (see Section 5, below). 

Perfluoroacyl derivatives such as trifluoroacetyl (TF.A), pentafluoropropionyl (PFP) and heptafluorobutyryl (HFB) are very commonly employed in GC-MS. Much of their popularity arose from their ease of preparation and their useful employment in GC with ECD. Workers then employed them directly in the GC-MS system and in many cases excellent results were obtained—high mass increments which can be conveniently adjusted by choice of derivative (see Table 3) and high abundance fragment ions. All this is in addition to their advantages for negative-ion chemical ionization mass spectrometry, where their electron capturing properties can enable highly sensitive analyses to be carried out. 

Table 3. Stmchire and mass increments obtained with the commonly used perfluoroacyl derivatives...

It is recommended that these reactions be conducted in the presence of bases without active hydrogen atoms (pyridine, triethyl amine, etc.). These basic media are necessary for the conversion of acidic by-products into non-volatile salts to protect the acid-sensitive analytes from decomposition and to avoid the appearance of extra peaks of by-products on the chromatograms. Exceptions are indicated by reagent/(H ). Phenols can be converted into Na salts before acylation. A large variety of anhydrides of perfluormated carboxylic acids are recommended for derivatization because of the favorable chromatographic properties of perfluoroacyl derivatives. 

Mn(CO)5] reacts with allyl halides at room temperature to produce the hexacoordinate a-allyl derivative C3H5Mn(CO)5 which must be heated to 60° C before carbon monoxide is lost at an appreciable rate to form the ir-allyl derivative C3HsMn(CO)4 (99,100). In addition, the pentacoordinate perfluoroacyl derivatives of cobalt, RfCOCo(CO)4 (38, 111, 112), lose carbon monoxide to form RfCo(CO)4 at a lower temperature than the hexacoordinate perfluoroacyl derivatives of manganese, RfCOMn(CO)5 (38,113), form the perfluoroalkyl derivatives, RfMn(CO)s. On the basis of present data, however, it is diflicult to separate the effect of coordination number on the general stability of the molecule from the effect of coordination number on the stability of the metal-carbon monoxide bond. 

No stable compounds of the type R2Fe(CO)4 with iron-carbon a bonds have been isolated by the reaction between [Fe(CO)4] and alkyl halides such as methyl iodide. However, the perfluoroalkyl derivatives (Rf)2Fe (CO)4 (Rf = C2F5 and C3F7) have been obtained as air-stable very pale yellow crystals by the reaction between Na2[Fe(CO)4] prepared in tetra-hydrofuran and the perfluoroacy/ chlorides RfCOCl. The intermediate perfluoroacyl derivatives (RfCO)2Fe(CO)4 were not isolated, but instead were decarbonylated spontaneously in the boiling tetrahydrofuran 50). For reasons which are not clear at the present time the yields of the perfluoroalkyl compounds (Rf)2Fe(CO)4 in this reaction were only about 15%. Attempts to prepare (CF3)2Fe(CO)4 by this technique have been unsuccessful. A related compound is the extremely stable perfluorotetramethylene derivative C4FgFe(CO)4 (XXIX) 182) obtained from tetrafluoroethylene and iron pentacarbonyl. This fluorocarbon derivative was first erroneously formulated as a tricarbonyl derivative 183). 

There is only one example of trifluoroacylation in the series of benzoindolizines. 3-Perfluoroacyl derivatives 15 and 16 were obtained in high yield [12] using trifluo-roacetic and perfluorosuccinic anhydride as acylating agents. 

Analytes that are not suitable candidates for electron capture can often be made so by suitable derivatization. Perfluoracyl, pentafluorobenzyl, pentafluorobenzoyl and nitrobenzyl derivatives are often used not only to increase the electron capture rate constants but also to enhance chromatographic properties. However, in contrast to electron capture gas chromatography, it is not sufficient that electron capture be facile in addition, ions characteristic of the analyte must be formed since ions characteristic only of the derivatizing agent leaves the identity of the analyte in question. This is illustrated by the data in Table 4 for derivatization of phenols, where it can be seen that the perfluoroacyl derivatives yield ions characteristic only of the derivatizing agent, whereas the pentafluorobenzyl and pentafluorobenzoyl derivatives yield ions characteristic of the analyte. Also... 

In some cases, thermal decarbonylation is preferable to photochemical techniques [51]. Using this synthetic approach, perfluoroacyl and alkyl complexes of Mn(CO)s [210, 211, 212, 213, 214], Re(CO)s [210], iron carbonyls [51, 215, 216], cobalt carbonyls [211, 213, 217, 218] and jr-C5HsMo(CO)3 [51] have been isolated. Perfluoroacyl derivatives may also be prepared using perfluoroacid anhydrides [213]. 

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