Estimation of the total range of 1J(CC) couplings in heterocyclic compounds: pyridines and their N-oxides, the experimental and DFT studies

A very large set of one-bond spin-spin carbon carbon coupling constants, 1J(CC), has been measured for 32 variously mono- and disubstituted pyridine N-oxides and for 14 substituted pyridines. The N-oxides studied were 2-, 3- and 4-monosubstituted isomers, and a series of disubstituted compounds. A variety of substituents has been employed (CH3, COCH3, C5H4NO, CN, F, Br, Cl, OH, OCH3, NH2, N(CH3)2 and NO2), which allowed us to study substituent effects thoroughly. Good linear relationships between 1J(C3C4) in 3- and/or 4-substituted pyridine N-oxides and 1J(CipsoCortho) in benzenes and between 1J(C2C3) in 2- and/or 3-substituted pyridine N-oxides and 1J(CipsoCortho) in benzenes have been found. An analogous linear relationship has been observed between 1J(C3C4) in 3- and/or 4-substituted pyridines and 1J(CipsoCortho) in benzenes. It has been also concluded that, by analogy to 1J(CC) couplings in substituted benzenes, those in pyridines and their N-oxides are the substituent electronegativity dependent. The estimated total range covered by 1J(CC), couplings in substituted compounds varies, in the case of 1J(C2C3) couplings for example, from 25 Hz in 2-lithiopyridine N-oxide to ca. 100 Hz in 2,3-difluoropyridine N-oxide and from 18 Hz in 2-lithiopyridine to 92 Hz in 2,3-difluoropyridine. The DFT calculations have been carried out for the parent compounds and for a set of their 2-lithio, and variously substituted fluoro derivatives. The DFT data reproduced very well the experimental coupling values and revealed that the Fermi contact contribution is the dominating factor which governs the magnitude of the CC coupling across one bond.