In the formation of ethyl 4-(6-chloro-3-nitropyridin-2-yl)piperazine-1-carboxylate G, why is the substitution favoured at the 2-position? I would have said that the 6-position substitution is preferred as:
- In pyridines, nucleophilic substitution occurs at the 2/6th or 4th position, and as chlorine is an effective leaving group compared to hydride this rules out position 4, leaving 2 and 6 as the most feasible...
- The electron withdrawing nature of the nitro group on the ring would favour nucleophilic substitution at the positions ortho or para to itself. The chlorine at the 2 -position is ortho, and the chlorine at the 6-position is para so both are feasible...
- If I didn't know what the product was, I would have said that position 6 is therefore the site of substitution as the amine reagent is quite bulky and the 6-position is less sterically hindered due to the absence of an adjacent nitro group
However, this evidently isn't the case! I found another similar reaction where the same thing occurs:
Is it something to do with the nitrogen in the pyridine ring hindering the electron density transfer to and from the para nitro group? I'm really stuck!
