Trifluoroacetyl radicals

The successful nitration of purines by trifluoroacetyl nitrate was originally presumed to proceed through hetero-lytic dissociation of the reagent into nitroso and trifluoroacetyl radicals, followed by radical attack on the purine <1995TL7875>. However, detailed investigation has shown the reaction mechanism to be a combination of electrophilic and radical steps (see Section 10.11.5.2.3). 

In their original investigations, Ayscough and Steacie42 stressed the simplicity of the reaction scheme and were unable to identify any product which could arise from the reactions of a trifluoroacetyl radical. Further, the ratio of quantum yields of carbon monoxide and hexa-fluoroethane was always close to unity, a fact which has been confirmed by later workers. Recently, Tucker and Whittle43 have shown that when hexafluoroacetone is photolyzed in the presence of excess bromine, trifluoroacetyl bromide is formed, suggesting that the trifluoroacetyl radical must intervene. The absence of hexafluorodiacetyl in the photolysis products of hexafluoroacetone is explained by the assumption that it is not stable. In fact, however, hexafluorodiacetyl may be prepared by the chromium trioxide oxidation of l,l,l,4,4,4-hexafluoro-2,3-di-... 

In their original paper, Sieger and Calvert proposed the second of these routes as the predominant primary step. This is unlikely to be the case because no trace of products which could arise by the reactions of the trifluoroacetyl radical have been observed in the photolysis of either trifluoro- or hexafluoroacetone and it is assumed that this radical is unstable. In support of this is the evidence that the yield of ethane rises steadily with increase in temperature whereas that of hexafluoroethane remains approximately constant. Finally, in a recent re-investigation, Dawidowicz and Patrick49 have identified biacetyl in the products of the photolysis of trifluoroacetone. The most probable primary step is, therefore, the former, which provided the acetyl radical and a trifluoro-methyl radical. 

In their original paper, Ayscough and Steacie42 claimed that the photolysis was very simple and that only carbon monoxide and hexa-fluoroethane were formed as a result of a reaction of type B. Subsequent work has thrown some doubt on this simple interpretation, nevertheless, the ratio of the quantum yields of carbon monoxide and hexafluoro-ethane was close to unity for a temperature range of 25-300°C. (above which temperature, thermal decompositions become important) and at wavelengths of 3130 A. and 2537 A. No trace of perfluorobiacetyl was found, nor any other product which could arise from the reactions of the trifluoroacetyl radical. 

Once again, neither hexafluorodiacetyl nor hexafluoroacetone was detected, suggesting that the trifluoroacetyl radical, even when formed in thermal equilibrium with its environment, is too unstable to survive long enough to take part in combination reactions. The fate of the formyl radical is uncertain at low temperatures it may take part in wall reactions, while at higher temperatures it may decompose to yield hydrogen atoms capable of taking part in the chain reaction... 

Similarly, the perfluoroacyl radical CF3C (—O)203 was obtained by photolysis of a cyclopropane solution containing dw-butyl peroxide and trifluoroacetaldehyde below -80 °C after abstraction of the aldehydic hydrogen atom, the trifluoroacetyl radical is formed. It decarbonylates above -80 °C and exhibits a coupling of 11.54 G with three equivalent 19F nuclei. 

The atmospheric chemistry of trifluoroacetyl radical CF3CO is not well known. It was implicated to explain the products observed98 in photolysis of hexafluoroacetone in the presence of Br2 and Cl2, but its first direct observation came from rapid-scan infrared spectroscopic studies in a matrix99, and more recently its laser-induced fluorescence spectrum has been observed100 the band origin for the first excited state of the radical appears at 384 nm. A weak UV absorption band which onsets at 250 nm and continues to increase in intensity below 200 nm has been attributed to CF3C0101. 

The most abundant reaction partner for trifluoroacetyl radical is molecular oxygen. The product of addition (equation 107) is trifluoracetylperoxy radical CF3C(0)02, which may be converted into trifluoroacetyloxy CF3C(0)0 in two ways. The dominant process in the upper atmosphere is likely to be reaction with nitric oxide (equation 108). The alternative would be self-reaction (equation 109), resulting in disproportionation. 

Photodecomposition. Since the last review of photochemistry of HFA (61), there has been a great deal of effort expended in the study of the primary processes and decomposition modes of HFA. The photodecomposition products observed appear to be carbon monoxide and hexafluoroethane exclusively. The trifluoroacetyl radical, CF3CO, must be very unstable. As in acetone, it has been proposed that the decomposition processes must overcome an energy barrier, as temperature-dependent quantum yields were observed (252). A detailed mechanism that takes into account a vibrational deactivation cascade has been proposed by several authors (34,35,97,252). 

The e.s.r. spectrum of the trifluoroacetyl radical, generated by photolysis of a cyclopropane solution of trifluoroacetaldehyde and di-t-butyl peroxide at temper-... 

C2F3O Trifluoroacetyl radical F3C—c—0 TBO - +F3CCHO/ Cyclo-CjHg liquid EPR/ 176 2.00104 F 1.154 74Krl... 

Treatment of 3-acylacrylates and 2-acylfiimarates 208 with irifluoroacetic anhydride and PPhs yielded 3,4,5-substituted 2-(trifluoromethyl)furans 209. The plausible mechanism of the reaction includes slow Michael addition of triphenylphosphine to enone fragment with fast trifluoroacetylation of resulted adduct and subsequent intramolecular Wittig olefination. An alternative mechanism via trifluoroacetyl radical arising from interaction of irifluoroacetic anhydride and triphenylphosphine is also possible [133]. 

Studies in the photoinitiation of polymerization by transition metal chelates probably stem from the original observations of Bamford and Ferrar [33]. These workers have shown that Mn(III) tris-(acety]acetonate) (Mn(a-cac)3) and Mn (III) tris-(l,l,l-trifluoroacetyl acetonate) (Mn(facac)3) can photosensitize the free radical polymerization of MMA and styrene (in bulk and in solution) when irradiated with light of A = 365 at 25°C and also abstract hydrogen atom from hydrocarbon solvents in the absence of monomer. The initiation of polymerization is not dependant on the nature of the monomer and the rate of photodecomposition of Mn(acac)3 exceeds the rate of initiation and the initiation species is the acac radical. The mechanism shown in Scheme (14) is proposed according to the kinetics and spectral observations ... 

A tertiary radical can be formed by elimination during AF of ter/-butyl methyl and ethyl ethers thus, isolation of the respective perfluoro-/erf-butyl ethers, e.g. 1, occurs in only 36 and 42% yield.28 Significant quantities of perfluoro(2-methylpropane) (2) are also isolated. The longer alkyl chains (ethyl and larger) appear to be slightly less prone to scission than the methyl group. Apparently, carbonyl fluoride is more readily eliminated than trifluoroacetyl fluoride, a phenomenon observed during AF of esters.29 Elimination becomes most serious in the special class of polyethers called ortho esters, e.g. 3-5.30 Cyclic ortho esters, acetals and ketals are much less affected than acyclics. 

Following their syntheses of ( )-pancracine and related alkaloids (vide supra), Hoshino et al [106] had described a different approach involving radical cyclisation of an isoquinoline derivative which permitted a rapid assembly of keto-5,11-methanomorphanthridine skeleton. The syntheses of 413, 414 and 415 commenced with the known 4-hydroxy-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoIine (439) (Scheme 62). Subsequent to protection of the amino group as the trifluoroacetyl derivative, the amide alcohol 440 was converted into the amide thioether 441, by reaction with phenylthiol in the presence of zinc iodide. Alkaline hydrolysis of 441,... 

The mechanisms underlying hepatotoxicity from halothane remain unclear, but studies in animals have implicated the formation of reactive metabolites that either cause direct hepatocellular damage (eg, free radical intermediates) or initiate immune-mediated responses. With regard to the latter mechanism, serum from patients with halothane hepatitis contains a variety of autoantibodies against hepatic proteins, many of which are in a trifluoroacetylated form. These trifluoroacetylated proteins could be formed in the hepatocyte during the biotransformation of halothane by liver drug-metabolizing enzymes. However, TFA proteins have also been identified in the sera of patients who did not develop hepatitis after halothane anesthesia. 

Halothane is a volatile general anesthetic that was introduced into the practice of clinical anesthesia in 1956. Shortly after its introduction two forms of hepatic injury were noted to occur in patients who received halothane anesthesia. A subclinical increase in blood concentration of transaminase enzymes is observed in 20% of patients and has been attributed to lipid peroxidation caused by the free radical formed by reductive metabolism of halothane as shown in Figure 16.7 (39/ 40). The second form of toxicity is a potentially fatal hepatitis-like reaction that is characterized by severe hepatocellular necrosis and is thought to be initiated by the oxidative formation of trifluoroacetyl chloride (Figure 16.7). Fatal hepatic necrosis occurs in only 1 of 35/000 patients exposed to halothane/ but the risk of this adverse event is greater in females and is increased with repeat exposure/ obesity/ and advancing age (40). Because the onset of halothane hepatitis is delayed but is more frequent and occurs more rapidly following multiple exposures/ and because these patients usually are febrile and demonstrate eosinophilia/ this reaction is suspected... 

Figure 3 Halothane biotransformation. Approximately 80% of inhaled halothane is exhaled unchanged. The majority of the remaining 20% undergoes oxidative metabolism. This produces trifluoroacetic acid (TFA) as the major metabolite which is excreted in the urine, and smaller amounts of trifluoroacetyl chloride. The trifluoroacetyl chloride covalently binds to a variety hepatic proteins. Antibodies to these trifluoroacetylated proteins are thought to be a causative factor in the development of type II hepatotoxicity. Some reductive metabolism also occurs which involves the production of a free radical intermediate. It is believed that this intermediate is the hepatotoxic compound in type I hepatotoxicity. The metabolites chlorotrifluoroethane (CTF) and chlorodifluoroethylene (CDF) are exhaled and can serve as markers for reductive metabolism.

Other small molecules for which photodecarbonylation studies have been made include phosgene in both the gas phaseand as a solid,acetyl chloride, and oxalyl chloride though extrusion of CO is only one of the pathways observed for these species. Photodissociations of acetyl and propionyl radicals have been studied by IR emission spectroscopy of the vibrationally excited CO produced, and an ab initio study of the photodissociation of the formyl radical (HCO) has been made." Trifluoroacetylthiol (CF3COSH) and trifluoroacetyl-sulfenyl chloride (CF3COSCI) have been photolysed in noble gas matrices, to produce CF3SH and CO, and CF3SCI, CO and SCO, respectively." ... 

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