Fluoro-effects

Our intuition derived from the per and 7r-fluoro effects suggests that fluorination of the nonplanar ethane should be accompanied by an increased ionization potential. Reference 3 corroborates this C2H6 and C2F6 have ionization potentials of 11.52 and 13.4 eV respectively. Likewise, our intuition suggests that the ionization energies of planar CH3 and planar CF3 should be comparable. From the definition of the inversion barrier, AE nv. as the energy difference of the planar and pyramidal forms and the identity for adiabatic ionization potentials (equation 3),... 

We have just derived D (C2F4) D (C2H4) 174 kcal mol 1. As befits the "perfluoro" and "7r-fluoro" effects on "normal", closed-shell species, we expect that the ionization potential of tetrafluoroethylene, the parent hydrocarbons, and the various fluorinated species to be "similar." Table II, with all its numbers in eV, documents this. 

It is interesting to point out that the lowest proton affinity in polyfluorinated naphthalenes is found for ipso protonation (viz. systems 33, 35 and 36). It is a consequence of the out-of-plane shift of fluorine and the accompanying ring puckering. However, this is at the same time a manifestation of the rr-electron fluoro effect put forward by Liebman et al. [45]. It is very well known that multiply fluorinated compounds possess considerably stabilized a-MOs if the systems are planar, the 7r-manifold being almost unaffected [46]. However, in nonplanar systems all MOs at the carbon skeleton are significantly stabilized [45,46] which is exactly the ceise for the ipso protonation. Now, it can be easily shown... 

Fig. 14 The i)>n-p-fluoro effect can be used to refine piT, predictions for amines containing P-fluoro substitution [88]...

Additionally, the n-p-fluoro effect may, in part, account for the difficulty in predicting the p T of imperfectly staggered heterocycles such as fluoro-substi-tuted pyrroUdines [88],... 

Fluoropyridine. This isomer can be prepared in 54—81% yield by dia2oti2ation of 4-aminopyridine in anhydrous hydrogen fluoride (370,371,400). Eree 4-fluoropyridine readily undergoes self-quaterni2ation to give pyridyl pyridinium salts (401) stabili2ation can be effected as the hydrochloride salt (371,400). Numerous 4-fluoropyridinium salts, eg, 4-fluoro-l-methylpyridinium iodide, have been converted to novel penicillins (387,402). 

Composite Resins. Many composite restorative resins have incorporated fluoride into the filler particles. One commonly used material, yttrium trifluoride [13709-49-4] is incorporated as a radiopaque filler to aid in radiographic diagnosis, and is also responsible for slow release of fluoride from the composites (280). This same effect is achieved with a barium—alumina—fluoro-siUcate glass filler in composite filling and lining materials. Sodium fluoride [7681-49-4] has also been used in composites by incorporating it into the resin matrix material where it provides long-term low level release (281-283). 

The results obtained with methoxypyrazole (247) are attributed to an electronic effect, whereas those obtained with (246) can be explained by taking into account the angular strain in the minor isomer. Reaction of 3(5)-nitropyrazole with l-fluoro-2,4-dinitrobenzene affords exclusively l-(2,4-dinitrophenyl)-3-nitropyrazole (70JHC1237). 

The axial-equatorial conformational equilibria for 2-fluoro- and 2-chlorotetrahydropyran have been investigated with several MO calculations, including calculations at the MP2/6-31G level. The MP2/6-31G calculations give values of 3.47 and 2.84kcal/mol, respectively, for the energy favoring the axial conformer. Solvent effects were also explored computationally and show the usual trend of reduced stability for the axial conformation as solvent polarity increases. 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

Trimelhylsilyl enol ethers are effective substrates in fluorination with fluo-roxytrifluoromethanefor the preparation of a-fluoro esters, amides and aldehydes [J7] (equations 13-15)... 

The anions of malonaldehyde [106, 107] and of organophosphonates [108, 109, 110] are fluorinated in good yields to provide interesting fluorinated intermediates The At-fluoro compound B in Table 3a is also effective in the fluonnation of phosphonate anions [109] (equations 60 and 61). 

The effect of the substituent group can be seen in the reactions of the following senes of halogenated esters Methyl 2,3 dichloro-3-fluoro-2-methylpropionate and chlorine monofluoride first form methyl 2-chloro-3,3-difluoro-2-methylpro-pionate An additional equivalent of chlorine monofluoride produces methyl 2 methyl-2,3,3-trifluoropropionate (equation 14)... 

This topic has been reviewed [2, pp 94, 100-111, 130-134] All of the standard approaches to the synthesis of a compound like methyl 2-fluorostearate from methyl 2-bromostearate result mall yield of the 2-fluoro ester and the unsaturated esters. Although silver fluoride is not a new reagent, its use moist in wet acetonitrile to convert methyl 2-bromostearate to its fluoro ester is a departure from the traditional set of anhydrous conditions (Procedure 6, p 194) [71] In contrast, silver tetrafluoroborate converts a-chloroketones to their respective fluoroketones under anhydrous conditions. The displacement of less activated halogen groups by silver tetrafluoroborate to form their respective fluorides is novel Although silver tetrafluoroborate could not be used to convert an aliphatic terminal dichloromethyl or trichloromethyl group to its corresponding fluoro derivative, it is an effective fluorine source in other situations [72] (Table 8)... 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

A powerful solvent effect is observed in the reaction of /j-nitrobenzaldehyde with sulfur telrafluonde The reaction conducted in a benzene solution gives the expected p nitrobenzyhdene fluoride, without a solvent, bis(p-nitro a fluoro-benzyl) ether is formed as the sole product [171 (equation 86)... 

High-yield deaminative fluorination of a-atmnocarboxylic acids to a-fluoro-carboxylic acids can be effected with sodium nitrite in Olah s reagent [5, 6] (equation 3 and Table 2)... 

Ultrasound promoted (17 kHz) decomposition of arenediazonium fluoro borates can also be effected m the presence of tnethylamine tnhydrofluoride in Freon 113 media For example, fluorobenzene can be obtained in 92-95% yield by this method [39] (equation 10)... 

Anhydrous hydrogen fluoride can also effect fluorodenitration of nitrohetero-cyclics such as 3(5) mho 1,2,4 triazoles and 8-nitropurine to give 3(5)-fluoro-1,2,4-triazoles and 8-fluoropurine, respectively [iiS] (equation 35)... 

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. 

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