Preparation and conversion of N-halomethylpyridinium halides. Comparison with related compounds

N-Halomethylpyridinium halides 1a-f(X-CH2Py+X-, X = Cl, Br) have been synth esized 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 trichlor oacetaldehyde (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 el ectron-withdrawing CCl3 substituent. This changes the standard reaction pat hway a of 1 in solution toward nucleophiles completely: the chlorinated N-v inylpyridinium salts 11 and 12 were formed after the reaction of 10 with py ridine or triphenylphosphane. These are useful intermediates for the synthe sis of new N- and 4-substituted 1,4-dihydropyridines 13-15 as could be demo nstrated for compound 11. To explain the reactivity pattern of compounds 1 and 10 and the related structures (MeO-CH2Py+, 16, and Me3SiO-CH2Py+, 17) w e calculated, using ab initio and DFT methods, reaction pathways a and b, b oth 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 st ates for la turns out to be relatively small (11.6 kcal/mol in favor of pat hway b, TS2). Solvation effects can therefore stabilize the corresponding t ransition state TS1 more effectively. In a MeCN solution, TS1 is 1.6 kcal/m ol less energetic than TS2.