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.
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asked Apr 12, 2016 at 16:23
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1$\begingroup$ Amine or amide? $\endgroup$– orthocresolApr 12, 2016 at 16:34
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$\begingroup$ Amine. The picture shows the conversion to be done, and I'm with TriBromo anilene trying to replace it's Br s with D $\endgroup$– Ramith HettiarachchiApr 12, 2016 at 16:41
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2$\begingroup$ Yes, it will deprotonate tribromoaniline $\endgroup$– MithoronApr 12, 2016 at 17:02
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1$\begingroup$ you can never use Grignards in presence of acidic protons. $\endgroup$– gannexApr 13, 2016 at 6:37
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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_blackApr 13, 2016 at 15:48
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1 Answer
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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.
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.
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$\begingroup$ What about alpha hydrogens? Why don't Grignard reagents deprotonate these acidic protons? $\endgroup$ Nov 26, 2018 at 9:35
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$\begingroup$ 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. $\endgroup$– gannexNov 29, 2018 at 1:01