I am trying to prepare a Grignard reagent from 4-nitrobenzyl bromide

4-nitrobenzyl bromide

but the reaction just doesn't work. My conditions are:

  • 10 mL of THF (anhydrous);
  • 7.04 mmol of 4-nitrobenzyl bromide;
  • 7.04 mmol of Mg;
  • Argon atmosphere.

Water is not a problem since I left all my glassware in the oven overnight and flame-dried the round bottom flask + stir bar before adding Mg and the bromide. I also did everything under argon. I know the reaction is not proceeding because virtually all of the Mg turnings I added are still there and the solution is still clear. I tried adding two crystals of iodine but it didn't help either.

Is there something about this particular bromide that prevents/slows down the formation of the Grignard? I was wondering if the fact that the nitro group is electron withdrawing could make it more difficult to form the carbanion-like structure of the Grignard.

  • 2
    $\begingroup$ Has this particular Grignard been made previously in the literature? AFAIK, Grignards react with nitro groups, e.g. Bartoli indole synthesis. $\endgroup$ – orthocresol Mar 20 at 19:32
  • $\begingroup$ I could only find 4 references that use this compound, none of them describes its preparation (none of them are in very good journals also)... I took this as an red alert that it wouldn't work since this structure is not that complicated (someone would've tried doing it before). I decided to give it a shot though cause it would provide an important insight on the mechanism I am investigating. I will try again this with a milder EWG at this position. $\endgroup$ – Raul Luciano Mar 20 at 19:44
  • $\begingroup$ I also know grignards react with the nitro group, but in this case some reaction would occur and the Mg would be consumed to some extent. But nothing is happening... I decided to abort the reaction already following my advisor's advice. $\endgroup$ – Raul Luciano Mar 20 at 19:45
  • $\begingroup$ Yes, you are correct about that. I just wanted to mention it because it might not have been a productive use of time trying to troubleshoot this. So it was just a more general comment, not so much about the question itself. If you want an organometallic, Zn is compatible with nitros, but I think it's a real pain making them (I've no experience, though). $\endgroup$ – orthocresol Mar 20 at 20:42
  • 1
    $\begingroup$ Might be worth trying Knochel exchange conditions with iPrMgBr $\endgroup$ – Waylander Mar 20 at 21:50

This question has aged a bit with no other answers, so here I go.

The same nitro group that can oxidize Grignard reagents could be oxidizing the magnesium too, thus keeping it passivated. What you need is not so much a milder EWG but one with less oxidizing potential. Try your reaction with nonoxidizing EWGs like acetyl (watch for side reactions), a $\ce{CF3}$ group, or a chlorine atom attached to the aryl group.

  • 1
    $\begingroup$ CF3 is happily sfable under Grignard conditions and strongly electron withdrawing $\endgroup$ – Waylander Jun 8 at 19:53

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.