Improved synthesis of bis(chloromethyl)arene monomers

Abstract

We report here on the experimental conditions for radical chlorination that provide improved yields of 2,5-bis(chloromethyl) pyridine and pyrazine, as well as on theoretical calculations which were performed in order to gain some insight regarding the factors that affect reactivity in these systems. The difficulties encountered previously in the methyl functionalization of N-heteroarenes are not due to radical selectivity that produces low yield of the dichlorides or to lower reactivity of this type of compounds, but to the post-halogenation reactions that occur on the desired products. Therefore, a careful handling during and after the reaction allowed us to find conditions for product optimization of α, α -dichlorinated monomers.

Synthesis, Structural Studies, and Oxidation Catalysis of the Late-First-Row-Transition-Metal Complexes of a 2-Pyridylmethyl Pendant-Armed Ethylene Cross-Bridged Cyclam

“…Attaching 2-pyridylmethyl N-pendant arms to ethylene cross-bridged tetraazamacrocycles would most efficiently be accomplished by reaction of a halomethylpyridyl moiety with a cyclam–glyoxal bisaminal following the teachings of Weisman et al ,, and Handel et al Initial attempts with picolyl chloride under the typical acetonitrile conditions for such reactions resulted in unsatisfactory red products where the color appeared because of reaction of the picolyl group with itself rather than bisaminal. Literature investigation of the reactivity of halomethylpyridines and halomethylpyrazines led to work where these compounds were stabilized by storage in nonpolar chlorinated solvents . Unsuccessful at alkylation of the bisaminals in typical S N 2 solvents like acetonitrile, we explored the chlorinated solvents and found successful, although low-yielding, monoalykylation of the bisaminal 1 with picolyl chloride in chloroform at room temperature.…”

“…Literature investigation of the reactivity of halomethylpyridines and halomethylpyrazines led to work where these compounds were stabilized by storage in nonpolar chlorinated solvents. 44 Unsuccessful at alkylation of the bisaminals in typical S N 2 solvents like acetonitrile, we explored the chlorinated solvents and found successful, although low-yielding, monoalykylation of the bisaminal 1 with picolyl chloride in chloroform at room temperature. It should be pointed out that others have alkylated cyclam− glyoxal condensates successfully in chloroform, as well.…”

Towards Halomethylated Benzene-Bearing Monomeric and Polymeric Substrates

“…It is worth recalling that, at the molecular level, side bromination of methyl groups of mesitylene and o-xylenes with NBS was also reported [121,122]. In the same vein, p-xylene, 2,5-dimethypyrazine and 2,5-dimethypyridine were subjected to the reaction with NCS in the presence of BPO or under UV irradiation and in chlorobenzene as solvent to give mixtures of chloromethylated products in yields of 70-86, 68 and 46-54%, respectively [123].…”

Synthesis, structural studies, and oxidation catalysis of the manganese(II), iron(II), and copper(II) complexes of a 2-pyridylmethyl pendant armed side-bridged cyclam

“…So, we explored the chlorinated solvents [40] to stabilize this reagent in the presence of the bisaminal and found successful, although low- yielding, monoalykylation with picolyl chloride in chloroform at room temperature. [41] We raised the yields of the monoalkyl salt 5 to 66% by addition of KI and increasing the temperature to reflux over 6 days.…”