Carbon‐13 NMR studies of quinolines and isoquinolines. II. Chlorine–nitrogen interactions and N‐oxide effects

Abstract

AbstractCarbon‐13 chemical shift assignments are reported for four chloroquinolines, six chloroisoquinolines, one dichloroquinoline, four dichloroisoquinolines, four methylchloroquinolines, two methylchloroisoquinolines, quinoline N‐oxide, isoquinoline N‐oxide, five methylquinoline N‐oxides, two methylisoquinoline N‐oxides and three chloroisoquinoline N‐oxides. Chlorine substituent chemical shift (SCS) effects are reported for the alpha, ortho, meta, para and peri positions. Consistent patterns are observed for the para and peri positions, a vinylogous ortho pattern is reported and the additivity of these SCS effects is demonstrated. Alpha SCS effects vary widely from 1.1 ppm upfield in 1‐chloroisoquinoline to 6.7 ppm downfield in 4‐chloroquinoline. These results, together with those in the literature, permit the definition of steric and nitrogen lone‐pair contributions which modify the ‘normal’ chlorine SCS effect, and these modifying contributions are shown to be roughly additive.Large (6–16 ppm) upfield shifts are observed for the carbons ortho and para to the N‐oxide group. The individual magnitudes of these shifts and their sum are constant and the effects are additive in substituted systems. A 9.5 ppm upfield shift is also observed for C‐8 in quinoline N‐oxides which is attributed to a space–charge interaction. Substituent chemical shift (SCS) effects for the chloro and methyl groups and the chemical shifts of the methyl carbons are essentially the same in the N‐oxides as in the parent heterocycles and are additive, except for those molecules where the substituent is adjacent to the N‐oxide moiety, in which cases substantial interactions are observed.