Solvent‐Free Fluorination of Electron‐Rich Aromatic Compounds with F‐TEDA‐BF₄: Toward “Dry” Processes

Abstract

An effective protocol for the solvent‐free fluorination of electron‐rich aromatic compounds with 1‐chloromethyl‐4‐fluoro‐1,4‐diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F‐TEDA‐BF4) is described. The protocol allows the easy and efficient isolation of fluorinated products in high yields and purities with low E factors (kgwaste kgproduct–1) by vacuum‐sublimation without the use of any solvent. The solid‐state fluorination of naphthalen‐2‐ol was studied by differential thermal analysis, and scanning electron microscopy was used to obtain evidence for the solid‐state process. The crucial influence of alkali‐metal carbonates on the rate of the solvent‐free fluorination of hydroxynaphthalenes and estrone was demonstrated.

Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors

“…When fluorinations were carried out at 80 °C in acetonitrile, the same 10-fluoro products ( 9 or 17 ) were formed, but the reaction was complete within 1 h (Table 1, Entries 2 and 8). Our results are not consistent with those obtained for monosubstituted phenols [13], but they show good correspondence with chemoselectivities obtained earlier for fluorinations of estrone derivatives with Selectfluor [14,15,16,17]. In methanol, however, ortho-fluorinations also occurred (15–16%: 15 : 16 =1:0.9 or 18 : 19 =1:1.5) at both reaction temperatures (Table 1, Entries 4,5,10 and 11).…”

“…: 104–102 °C, R f = 0.42 a ). Compound 9 is identical with compound described in the literature [15]. 1 H-NMR (DMSO- d 6 ) δ ppm 0.86 (s, 3H, 18-H 3 ); 2.41 and 2.53 (2 × m, 2 × 1H, 6-H 2 ); 6.10 (s, 1H, 4-H); 6.22 (d, 1H, J = 10.2 Hz, 2-H); 7.27 (dd, 1H, J = 10.2 Hz, J = 7.4 Hz, 1-H).…”

“…According to the literature, 17β-estradiol ( 6 ), estrone ( 7 ) or their certain ring D-substituted derivatives can be converted to 10β-fluoroestra-1,4-dien-3-one analogues ( 8 and 9 ) with Selectfluor in different solvents (acetonitrile or bmimBF 4 :MeOH = 1:1, H 2 O) or under solvent-free conditions (Scheme 2) [14,15,16,17]. Independent of the nature of the solvent, all reactions resulted in dienones 8 and 9 as main products.…”

Core remodeling leads to long wavelength fluoro-coumarins

“…2), reported previously as a pharmaceutical precursor in a single study, was resynthesized. 34 To generate the diethylamino derivatives, the rst step involved a scalable Brucherer reaction of naphthalene 1 with diethylamine at 150 C to provide 2 in modest, albeit reproducible, yield (27%). Aer signicant screening, the combination of acidic conditions (TFA, H 2 O) and Selectuor was found to regioselectively uorinate 2 providing FC2 in high yield (82%) on gram-scale.…”

Fluoride Ion Interactions in Alkali-Metal Fluoride–Diol Complexes

“…25,26 Most organic cations are unstable when combined with F − . Such salts are hard to isolate due to β-hydrogen elimination, 1,[27][28][29] although this can be avoided with [TMA]F because the β-hydrogen atoms are absent (as in the exceptional case of N-methylquinuclidinium salt) 5 . Reactive anhydrous F − is sometimes created in an unusual way, as in the in situ generation of [TBA]F from hexafluorobenzene and [TBA]CN.…”