A systematic comparison between 1,3‐difluorobenzene, 1,3‐dichlorobenzene, and 1,3‐dibromobenzene did not reveal major differences in their behavior towards strong bases such as lithium diisopropylamide or lithium 2,2,6,6‐tetramethylpiperidide. Thus, all 2,6‐dihalobenzoic acids 1 are directly accessible by consecutive treatment with a suitable base and dry ice. In contrast, (2,6‐dichlorophenyl)‐ and (2,6‐bromophenyl)triethylsilane (2a and 2b) were found to undergo deprotonation at the 5‐position (affording acids 3 and, after deprotection, 4), whereas the 1,3‐difluoro analog is known to react at the 4‐position. The 2,4‐dihalobenzoic acids 7 were selectively prepared from either the silanes 2 (by bromination at the 4‐position, metalation and carboxylation of the neighboring position, followed by desilylation and debromination) or the 1,3‐dihalo‐2‐iodobenzenes 8 (by base‐promoted migration of iodine to the 4‐position followed by iodine/magnesium permutation and subsequent carboxylation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

As a rule, tri-, tetra-and pentahaloarenes readily undergo ortho-lithiation when treated with amide-type bases. However, halogen migration occurs whenever the substrate contains three or more contiguous halogen atoms, provided that at least one of them is bromine or iodine. Dismutation and reduction processes often take place concomitantly. In this manner, a variety of organometallic intermediates may be formed, the driving force always being a decrease in basicity.

No abstract

In a model study, 3‐fluorophenol and 3‐fluoropyridine were converted into the each time four possible carboxylic acids by passing through the corresponding organometallic intermediates. As an attempt to generalize the findings reveals, a restricted set of principles and methods suffices to cope with all standard scenarios. The most valuable and versatile tools for the regiochemically exhaustive functionalization of a great variety of substrate patterns are the optionally site‐selective metalation (either by reagent/substrate matching or by peripheral coordination control), the use of activating or congesting protective groups and the basicity gradient‐driven heavy halogen migration (followed by halogen/metal permutation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The deprotonation energies of benzene, chlorobenzene, all di-, tri-, tetrachlorobenzenes, and pentachlorobenzene have been determined in the gas phase using a Fourier transform ion cyclotron resonance mass spectrometer. The values measured differ only slightly, though significantly, from the corresponding data for oligofluorobenzenes. The heavier halogen acidifies orthopositions slightly less and meta-positions slightly more than fluorine does. Moreover, the contributions of three or more chloro substituents are not perfectly additive. In fact the accumulation attenuates the contributions somewhat. Quantum chemical calculations at the MP2/6-311+G* level reproduce the gas-phase acidities fairly well, but reveal special effects when extended to experimentally not observable benzenides carrying the halogens at anion-remote positions. Competition experiments have been performed to assess the relative reactivity of nine oligochlorobenzenes towards sec-butyllithium in tetrahydrofuran at -100 degrees C. An almost exact linear correlation between logarithmic rates and gas-phase acidities has been found.