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 '19 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 '19 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 '19 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 '19 at 20:42
  • 1
    $\begingroup$ Might be worth trying Knochel exchange conditions with iPrMgBr $\endgroup$ – Waylander Mar 20 '19 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 '19 at 19:53

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