Pyridines substituent increments 323

Substituent increments have been compiled for several heterocyclic systems, such as six-membered heteroalicyclic rings [408], pyrrole [435], indole [445], thiazole [437], and pyridine [452],... 

Increments for a larger number of substituents in various positions permit 13C shift predictions of pyrroles [435], thiazoles [437], indoles [445], and pyridines [452], Similarly to benzene, substituted carbon shifts essentially are related to substituent electronegativity, while ortho- and para-like carbons are predominantly affected by mesomeric (resonance) effects of donor (( — )-M) or acceptor substituents as shown for methoxy... 

Increments of selected substituents in positions 2, 3 and 4 of the pyridine ring are listed in Table 4.83 (b). The 13C shifts of C-2,6 (149.7 ppm), C-3,5 (124.2 ppm) and C-4 (136.2 ppm) have been used as references. As can be seen in Table 4.67, N-oxidation causes a significant shielding (— 10 ppm) of the carbons a and y to nitrogen, while those in the / position are slightly shielded. This analogy to the behavior of pyridine-N-oxide towards electrophilic substitution can be rationalized by remembering the known canno-nical formulae of this molecule in contrast to pyridine itself. 

Table 4.83. Nitrogen Increments (a) and Substituent Effects of Selected Groups (b) in Pyridine [452] (in ppm).

Despite the fact that d is not a simple quantity, but a function oi AH and A S, its variation with change of structural parameters obeys a simple relationship, as may be seen from the additivity of A O values. This term is used here in the sense that the thermodynamic quantities for disubstituted compounds may be predicted from the changes produced when single substituents are introduced separately. The free energies of ionization of some methyl disubstituted pyridines, anilines and phenols are shown in Table 4 (to which we shall refer in detail later). From A G values for the parent and mono-substituted compounds it is possible to estimate A G values for disubstituted compounds. Thus, from the A G values for p ridine and the picolines, the following increments are calculated 2-methyl 1 01, 3-methyl 0-56, 4-methyl 1 03. 

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