Substrate selectivity and orientation in aromatic Substitution by molecular fluorine

Abstract

Direct elemental fluorination of representative aromatic substrates, including PhH, PhCH3, PhF, PhCI, PhBr, PhN02, PhCN, and PhOCH3, has been investigated in inert solvents, e.g., CC13F and other fluorocarbons, over the temperature range - 154 to 40 OC. In order to achieve the necessary control of the extremely reactive electrophile, and to minimize unwanted modifications of the reaction environment, the fluorination has been carried out at extremely low rates and correspondingly low conversions, generally below 0.01%, using as a reagent gaseous mixtures of F2 highly diluted ( < I mol %) in N2 or Ar. The partial rate factors, calculated from a consistent set of relative reactivity and orientation data measured at -78 OC in CC13F, correlate smoothly with the u+ constants for all the substituents investigated, giving a p+ value of -2.45 for aromatic substitution by elemental fluorine with a correlation coefficient of 0.993. These results characterize F2 as a highly reactive, and correspondently unselective, reagent, and support a polar electrophilic substitution mechanism that is discussed and compared with other plausible fluorination pathways

Fluorinations, chlorinations and brominations of organic compounds in micro reactors

“…From the beginning of the 1960s or so, several experimental works deal with slowing down the fluorine conversion rate by extreme dilution of fluorine and the substrates and by decreasing the temperature down to a cryogenic level [16][17][18][19][20][21][22]. Indeed, by these measures control over product spectra and defined reaction paths were achieved.…”

The cleavage of aryl-metal bonds by elemental fluorine: synthesis of aryl-fluorides

“…Simple addition of fluorine to aromatic nuclei is rare (15,16), because the reaction is usually acconipanied by unselective partial or total replacement of hydrogen (15). One method of achieving site selectivity is to metallate one carbon atom in the ring, for which there is ample precedent in the literature (2.…”

“…OH). Connections from the manifold to glassware were made with Teflon tubing (11 16 or I /8 in. od) using Swagelok fittings (Crawford Fitting Co..…”

Electrophilic aromatic fluorination with fluorine: meta-Directed fluorination of anilines

“…Since this time, a steadily growing number of papers have appeared [15][16][17][18][19][20][21][22][23][24]. Concerning electrophilic aromatic fluorination [25][26][27][28][29][30], an outstanding contribution has been given again by Chambers et al, who demonstrated that aromatics bearing an electrondonating group in para-position to an electron-withdrawing group, can be cleanly fluorinated with F 2 at room temperature, provided that a strong acid, such as 98% sulfuric or formic acid, is used as solvent [20,31,32]. Such solvents are polar enough and, more importantly, protic enough to strongly polarize fluorine and avoid uncontrolled radical processes.…”