Fluoro radicals

Nitrated fluoro compounds are synthesized by electrophilic (NOz+), radical (NO2 ), or nucleophilic (NO2-) methods Indirect nitration routes can suppress the side reactions associated with severe reaction conditions and some nitration reagents Novel fluoronitro compounds, unobtainable by direct nitration, can also be pre pared For example, the nitration of (2-fluoro-2,2-dinitroethoxy)acetaldoxime followed by oxidation of the nitroso intermediate with hydrogen peroxide yields 2-fluoro-2,2-dinitioethyl 2,2-dinitroethyl ether [f] (equation 1)... 

Electrochemically generated trifluoromethyl radicals add to 1-hexyne to give a 1 4 mixture of ( )- and (Z)-l,l,l-trifluoro-2-heptene [22] Kinetic data on the addition of photochemically generated trifluoromethyl radicals to acetylene and substituted acetylenes were reported [2J]. Alcohols and aldehydes add to hexa-fluoro-2-butyne in the presence of peroxide and y-ray initiation [24] (equations 16 and 17). 

Examples of perfluoroalkyl iodide addition to the triple bond include free radical addition of perfluoropropyl iodide to 1 -heptyne [28] (equation 21), thermal and free radical-initiated addition of lodoperfluoroalkanesulfonyl fluorides to acetylene [29] (equation 22), thermal addition of perfluoropropyl iodide to hexa-fluoro 2 butyne [30] (equation 23), and palladium-catalyzed addition of per-fluorobutyl iodide to phenylacetylene [31] (equation 24) The E isomers predominate in these reactions Photochemical addition of tnfluoromethyl iodide to vinylacetylene gives predominantly the 1 4 adduct by addition to the double bond [32] Platinum catalyzed addition of perfluorooctyl iodide to l-hexyne in the presence of potassium carbonate, carbon monoxide, and ethanol gives ethyl () per fluorooctyl-a-butylpropenoate [JJ] (equation 25)... 

The first example of a cyclization of fluorine-containing 5-hexenyl radicals was the study of the radical-iniOated cyclodimenzation reaction of 3,3,4,4-tetra-fluoro-4-iodo-1-butene. In this reaction, the intermediate free radical adds either to more of the butene or to an added unsaturated species [54, 55] (equation 56). Electron-deficient alkenes are not as effective trapping agents as electron-nch alkenes and alkynes [55]. 

Results of studies of the electrocyclic ring opening of 3 fluoro-, 3,3-difluoro-, and 3-tnfluoromethylcyclobutene are consistent with the theoretical predictions of the effect of fluonne on this reaction [142] Surpnsingly, fluonnated analogues of hexa tnene-cyclohexadiene systems undergo complex rearrangements mainly via free radical mechanisms and not by electrocyclic nng operung as expected [143] (equation 35)... 

Extensive reviews of the effects of fluonnation on stmeture and bonding are available [75, 76, 77], and only the charactenstic trends in bond strengths will be covered here. The bond energies cited are average values corrected for the revised heats of formation of alkyl radicals [78], but their precision is seldom better than 2 kcal/mol for the fluoro compounds. 

First examine the geometry of methyl radical. Is it planar or puckered Examine the geometries of 2-methy 1-2-propyl radical, trifluoromethyl radical, trichloromethyl radical and tricyanomethyl radical. Classify each of the substituents (methyl, fluoro, chloro and cyano) as a n-electron donor or as a Tt-electron acceptor (relative to hydrogen). Does replacement of the hydrogens by 7t-donor groups make the radical center more or less puckered Does replacement by Jt-acceptor groups make the radical center more or less puckered Justify your observations. 

Bamford and coworkers [24] also investigated the kinetics and mechanism of free radical polymerization of bulk MMA photoinitiated by Mn2(CO)io or Re2(CO)io in the presence of a series of fluoro-olefms such as ... 

The overall trend of reactivities for t-butoxy radicals with the fluoro-olcfins more closely parallels that for methyl radicals than that for the electrophilic trifluoromethyl or trichloromethyl radicals. 

The behavior of methyl and halomethyl radicals in their reactions with the fluoro-olefms (Table 1.2), can thus be rationalized in terms of a more dominant role of polar factors and the nucleophilic or electrophilic character of the radicals involved." Methyl radicals are usually considered to be slightly nucleophilic, trifluoromcthyl and triehloroincthyl radicals arc electrophilic (Tabic 1,4). 

For olefins with Ji-substitucnts, whether electron-withdrawing or electron-donating, both the HOMO and LUMO have the higher coefficient 021 the carbon atom remote from the substituent. A predominance of tail addition is expected as a consequence. However, for non-conjugated substituents, or those with lone pairs (e.g. the halo-olefins), the HOMO and LUMO are polarized in opposite directions. This may result in head addition being preferred in the case of a nucleophilic radical interacting with such an olefin. Thus, the data for attack of alkyl and fluoroalkyl radicals on the fluoro-olefins (Table 1.2) have been rationalized in terms of FMO theory.16 Where the radical and olefin both have near neutral philicity, the situation is less clear.21... 

The fraction of head-to-head linkages in the poly(fluoro-olefms) increases in the series PVF2 < PVF PVF3 (Tabic 4.2). This can be rationalized in terms of the propensity of electrophilic radicals to add preferentially to the more electron rich end of monomers (i.e, that with the lowest number of fluorines). This trend is also seen in the reactions of trifluoromethyl radicals wilh the fluoro-olefins (see 2.3). 

Radical-mediated silyldesulfonylation of various vinyl and (a-fluoro)vinyl sulfones 21 with (TMSlsSiH (Reaction 25) provide access to vinyl and (a-fluoro)vinyl silanes 22. These reactions presumably occur via a radical addition of (TMSlsSi radical followed by /)-scission with the ejection of PhS02 radical. Hydrogen abstraction from (TMSlsSiH by PhS02 radical completes the cycle of these chain reactions. Such silyldesulfonylation provides a flexible alternative to the hydrosilylation of alkynes with (TMSlsSiH (see below). On oxidative treatment with hydrogen peroxide in basic aqueous solution, compound 22 undergoes Pd-catalyzed cross-couplings with aryl halides. 

The radical-promoted reaction between polyethylene and hexafluoro-acetone is shown in Equation 1. It had been demonstrated previously in the case of simple hydrocarbons (8) that the addition of a carbon radical to the carbonyl group of hexafluoroacetone can take place in two modes, to yield the product, of substitution with either a fluoro-... 

Tram-anular interactions, which would create an active radical site via hydrogen transfer through 98, cannot be invoked to explain the specific loss of a CH3 radical from the ether side chain. This conclusions is based upon the following experimental observations. The radical cation of the tetrafluoro substituted compound 101 eliminates CH3, but loss of CH3 from the para-isomer 102 is not observed. If a transanuiar process according to 97- 98 were operative, then such a reaction is not expected to be suppressed upon substitution of H by F as is known for many examples from the field of photochemistry of fluoro substituted compounds41 (23). 

The Jacobson thioanilide radical cyclization chemistry has been extensively used for the synthesis of benzothiazoles as shown by the preparation of 4-fluoro-2-(3,4-dimethoxy-phenyl)benzothiazole 47 <06JMC179>. The harsh reaction conditions (K3Fe(CN)6, NaOH,... 

Second, metabolism of 6-fluoroBP by rat liver microsomes yields the same BP quinones obtained in the metabolism of BP (23). This suggests that these products are formed by an initial attack of a nucleophilic oxygen atom at C-6 in the 6-fluoroBP radical cation with displacement of the fluoro atom. In fact, when 6-fluoroBP is treated with the one-electron oxidant Mn(0Ac)3, the major products obtained are 6-acetoxyBP and a mixture of 1,6- and 3,6-diacetoxyBP (15), indicating that reaction occurs via an initial attack of acetate ion at C-6 of the 6-fluoroBP radical cation. On the other hand electrophilic substitution of 6-fluoroBP with bromine or deuterium ion shows no displacement of fluorine at C-6, although in both cases substitution occurs at C-l and/or C-3. These results indicate that... 

Acyl Halides. Acyl halides, in which the hydroxyl portion of a carboxyl group is replaced by a halogen, are named by placing the name of the corresponding halide after that of the acyl radical. When another group is present that has priority for citation as principal group or when the acyl halide is attached to a side chain, the prefix haloformyl- is used as, for example, in fluoro-formyl-. 

Under similar reaction, the action of XeF2 on PBN and DMPO led to similar spin adducts, proving the radical cation mechanism (524). Unlike this reaction, the formation of fluoro-containing spin adducts when using a weaker oxidant such as /V-lluorodibenzsulfonamide [(PhSC>2)2N-F] is believed to involve the Forrester-Hepburn mechanism (524). 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

The effects of substituents in the -position to the radical center are mostly inductive in nature. Comparison of the RSE values for the ethyl radical (- 13.8 kj/mol) with those of the propyl, 2-hydroxyethyl, 2-fluoroethyl, and 2-chloroethyl radicals with RSE values of - 11.9, - 8.5, - 5.5, and - 6.7 kj/mol also indicates that electronegative substituents in the -position uniformly destabilize the radical center, the effect being larger for more electronegative substituents. Comparison of the RSE values of the 2-fluoro, 2,2-difluoro, and 2,2,2-trifluoroethyl radicals of - 5.5, + 3.0, and + 8.1 kj/mol also indicate that these effects can accumulate to yield overall destabilized radicals relative to the methyl radical. Even less favorable RSE values are found for positively charged substituents directly attached to the radical center such as - NH3+ (+ 18.3 kj/mol) or-SH2+ (+ 12.8 kj/mol) (Table 1). 

From a study of the fluoroacetates so far mentioned, it appears that any compound which can give rise to fluoroacetic acid (or the fluoroacetate ion), either by hydrolysis or by oxidation (or both), is toxic. The toxic grouping is thus F-CH2-CO, and any substitution in this radical destroys the toxicity as far as relatively simple compounds are concerned. We had reached this conclusion by May 1943.1 We subsequently showed that esters of / -fluoropropionic acid were non-toxic, whereas esters of y-fluorobutyric acid were shown by American workers to be toxic. In 19442 we reported the synthesis of ethyl 5-fluoro-pentanecarboxylate, F,[CH2]g C02Et (I). This is a stable, colourless liquid and we showed that it possessed very potent toxic properties of the fluoroacetate type. By subcutaneous injection of the propylene glycol solution into mice the l.d. 50 was 4 mg./kg. Methyl fluoroacetate (II) may be taken as a convenient standard (p. 115) and has a l.d. 50 of about 6 mg./kg. for saline solutions, and 15 mg./kg. for propylene glycol solution.3 Therefore ethyl 5-fluoropentanecarboxylate was about 7 times as toxic as methyl fluoroacetate (molecule for molecule).4... 

As already mentioned in Section 1, the radical ion-mediated mechanism, often to be denoted as inverted spin trapping in the following, was discussed and experimentally supported in several isolated cases in the period between 1975 and 1990, but was not subjected to systematic study. In addition, numerous studies were performed on systems which, in the light of later developments, must have involved inverted spin trapping, but which were interpreted differently. Two particularly interesting cases involve the formation of fluoro and acetoxy spin adducts. 

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