Gualterio_Malatesta - 2-9-2024 at 23:17
There's this paper where authors offer a "highly practical procedure for the preparation of bromoanilines by using copper-catalyzed oxidative
bromination has been developed. Treatment of free anilines with readily available NaBr and Na2S2O8 in the presence of
a catalytic amount of CuSO4·5H2O enabled regioselective bromination."
DOI: 10.1055/a-1441-3236
The procedure looks like this:
2-Nitroaniline (1.0 g, 7.24 mmol) was added to a suspension of CuSO4·5H2O (0.452 g, 1.81 mmol, 25 mol%) in a mixture of
CH3CN (20 mL) and H2O (10 mL) at 25 °C, and the mixture was stirred at 25 °C for 15 min. NaBr (1.34 g, 13.0 mmol, 1.8 equiv.)
and Na2S2O8 (2.41 g, 10.1 mmol, 1.4 equiv.) were then added simultaneously in three portions at 7 °C over 15 min.
After addition was complete, the mixture was further stirred at 7 °C for 2 h and at 25 °C for 22 h.
Now they use CH3CN, which I would like to avoid.
So I wanted to ask if anyone thinks acetone could be used here?
Or any other more common and readily available solvent?
clearly_not_atara - 3-9-2024 at 09:50
Cu2+ is more strongly oxidizing in nitrile solvents versus other solvents due to complex formation. Benzonitrile can be a substitute, but it is harder
to remove due to high bp (~180 C). Other aliphatic nitriles are much more toxic than acetonitrile. Pyridine might be an effective substitute, but it
has a terrible odor.
It's likely that acetonitrile is a non-innocent solvent in this reaction, so it can't be easily replaced.
Also, nitroaniline is much less reactive than other anilines, so it seems like a poor choice of example.
Gualterio_Malatesta - 3-9-2024 at 22:53
Awesome, thanks. I will do this procedure with CH3CN first, and then experiment with other solvents, see how it goes.
Also what do you think about proportions of solvent to nitroaniline (20:1), if I scale this up to 10g of nitroaniline does it really call for 200 ml
(
) of acetonitrile? That is an ungodly amount!
clearly_not_atara - 4-9-2024 at 11:16
Using more solvent can be a way to avoid exothermic issues or side-reactions. In this case, the proportions seem a little more defensive than might be
necessary, but the bromination of aniline is an exothermic reaction. I guess you could try 10:1? You could add the brominating reagents more gradually
(less per addition) to compensate.