Downfield 1 H NMR shifts induced by electron‐rich substituents

The 1 H NMR signal due to the peri proton H‐5 in imidazo[1,2‐ a ]pyridines exhibits large downfield shifts when the 3‐position bears a substituent (−XY) containing an electron‐rich atom (Y) two bonds removed from C‐3. Such shifts are observed not only when the ring electron density can be decreased by resonance interaction [from −1.29 to −1.87 ppm for 3‐COR, 3‐(2′‐quinoxalyl) and 3‐No in CDCl 3 ], but also when electron withdrawal must be minimal: −1.10 ppm when X is an sp 3 center [3‐CH(OH)CCl 3 in CDCl 3 ], −1.0 ppm when the 3‐substituent is negatively charged (3‐CO 2 − Na + in D 2 O), and −1.32 to −1.46 ppm when the ring system is protonated (3‐COR and 3‐NO 2 in TFAA). The effect is largest in those compounds for which orientation of lone‐pair electrons on atom Y toward H‐5 can be invoked. The desielding is attributed primarily to a through‐space electric field effect.