Can I add Mg/dry ether to 2,4,6-tribromoaniline followed by $\ce{D2O}$ in order to replace the bromines with deuterium?

The reaction I'm proposing is part of a synthetic route as shown below.

Overall transformation

  • 1
    $\begingroup$ Amine or amide? $\endgroup$
    – orthocresol
    Apr 12 '16 at 16:34
  • $\begingroup$ Amine. The picture shows the conversion to be done, and I'm with TriBromo anilene trying to replace it's Br s with D $\endgroup$ Apr 12 '16 at 16:41
  • 2
    $\begingroup$ Yes, it will deprotonate tribromoaniline $\endgroup$
    – Mithoron
    Apr 12 '16 at 17:02
  • 1
    $\begingroup$ you can never use Grignards in presence of acidic protons. $\endgroup$
    – gannex
    Apr 13 '16 at 6:37
  • 1
    $\begingroup$ @gannex Usually true, but if you have an excess of Grignard and the deprotonated species still reacts with the surplus Grignard, you might be able to get away with it. It is a wasteful way to use Grignard reagents, though. And in this case it risks throwing away a lot of the substrate. $\endgroup$
    – matt_black
    Apr 13 '16 at 15:48

If you really wanted to start with the substituted aniline, you could probably oxidize, deuterate, reduce to get the product if you indeed want the amine and not the amide, but the yield would be poor. Various peroxides and peroxybenzoic acids will do this for you. Lui, Li, et al. indicated that oxidation of substituted anilines would work best in dichloroethane or THF with 4-5 equivalents of m-CPBA, with little difference produced by electronic effects. Then you could use your metal reagent, deuterate, and reduce using a method of your choice.

enter image description here

Of course it's probably easier to just nitrate your 1,3,5-tribromobenzene directly with nitric acid.

If this is a question from a book, they're probably trying to make sure you notice that you can't use organometal chemistry when you have acidic protons, so yes, grignard reagents do deprotonate amines.

  • $\begingroup$ What about alpha hydrogens? Why don't Grignard reagents deprotonate these acidic protons? $\endgroup$ Nov 26 '18 at 9:35
  • $\begingroup$ α-hydrogens are not that acidic (pka = 20-30) and Grignard reagents are strong nucleophiles, so if a carbonyl is present in the molecule, nucleophilic attack will be preferred over proton-abstraction. $\endgroup$
    – gannex
    Nov 29 '18 at 1:01

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.