Preparation and Conversion ofN-Halomethylpyridinium Halides. Comparison with Related Compounds^†

N-Halomethylpyridinium halides 1a-f(X-CH2Py+X-, X = Cl, Br) have been synthesized from a three-component reaction mixture containing a thionyl halide 5, formaldehyde (6), and a pyridine 7. The salts 1a-f react readily with a variety of heterocyclic nucleophiles to yield (in general, nonsymmetrical) 1,1-bis(heteroarylium)methyl salts Sea-hb, (pathway a). The use of trichloroacetaldehyde (9) instead of formaldehyde in this three-component reaction leads to a salt 10 in which one of the CH2-hydrogens was replaced by the electron-withdrawing CCl3 substituent. This changes the standard reaction pathway a of 1 in solution toward nucleophiles completely: the chlorinated N-vinylpyridinium salts 11 and 12 were formed after the reaction of 10 with pyridine or triphenylphosphane. These are useful intermediates for the synthesis of new N- and 4-substituted 1,4-dihydropyridines 13-15 as could be demonstrated for compound 11. To explain the reactivity pattern of compounds 1 and 10 and the related structures (MeO-CH2Py+, 16, and Me3SiO-CH2Py+, 17) we calculated, using ab initio and DFT methods, reaction pathways a and b, both in the gas phase and in solution using ammonia as a model nucleophile. For all of these compounds, pyridine displacement (pathway b) dominates in the gas phase. As an example the energy gap between these two transition states for la turns out to be relatively small (11.6 kcal/mol in favor of pathway b, TS2). Solvation effects can therefore stabilize the corresponding transition state TS1 more effectively. In a MeCN solution, TS1 is 1.6 kcal/mol less energetic than TS2.