Fabrice Cottet

Trifluoromethyl-substituted pyridines through displacement of iodine by in situ generated (trifluoromethyl)copper

A literature method reported for the prepn. of trifluoromethyl substituted benzenes from iodobenzene and congeners was successfully extended to the pyridine series. 2-Iodopyridines can be converted into 2-(trifluoromethyl)pyridines almost quant. by displacement of iodide by (trifluormethyl)copper generated in situ from (trifluoromethyl)trimethylsilane in the presence of cuprous iodide and potassium fluoride. In contrast, yields are moderate at best if 3- and 4-iodopyridines or 2-bromopyridines are used as the starting materials. [on SciFinder (R)]

Silyl-mediated halogen/halogen displacement in pyridines and other heterocycles

Heating with bromotrimethylsilane converts 2-chloropyridine into 2-bromopyridine and 2-chloro-6-methylpyridine into 2-bromo-6-methylpyridine. Both 2-chloropyridines and 2-bromopyridines give the corresponding iodo compd. when treated with in situ generated iodotrimethylsilane. Although 3- and 4-chloropyridine are completely inert, 2,4-dichloropyridine undergoes the halogen/halogen exchange simultaneously at the 2- and 4-position. Halogen displacement takes place exclusively at the 2-position with 2,3-dichloropyridine and 2,5-dichloropyridine. In agreement with the intermediacy of N-trimethylsilylpyridinium salts as a prerequisite for the occurrence of halogen exchange, neither 2-fluoropyridine and 2-fluoro-6-methylpyridine nor any 2,6-dihalopyridine reacts. Finally, bromine/chlorine and iodine/chlorine substitution can also be accomplished with 2- or 4-chloroquinoline, 1-chloroisoquinoline, 2-chloropyrimidine, chloropyrazine, and 2,3-dichloroquinoxaline as substrates. [on SciFinder (R)]

The Acidity of Chloro‐Substituted Benzenes: A Comparison of Gas Phase, Ab Initio, and Kinetic Data

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.

Halogen shuffling in pyridines: Site selective electrophilic substitutions of 2-chloro-6-(trifluoromethyl)pyridine

When treated with lithium diisopropylamide in THF at -85 Deg and subsequently with iodine, 2-chloro-6-(trifluoromethyl)pyridine is neatly converted into its 3-iodo deriv. The latter can be quant. isomerized to afford 2-chloro-4-iodo-6-(trifluoromethyl)pyridine. Either iodo compd. can serve as the starting material for further manipulation in reaction sequences consisting of halogen/metal exchange and electrophilic trapping. [on SciFinder (R)]