pyro2525
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5-Bromovanillin and atom economy
My question is about the 5-bromovanillin synthesis, but via HBr and H2O2 to avoid repeated sulphuric acid and free Br2. I've tried looking at
analogous mechanisms for this but still have some questions based on molar ratios others have used (1)(2)(3). From those refs and mechanisms I've
inferred they typically have:
Br2(equiv) + Ar-H --> Ar-Br + HBr
One paper (4) vaguely talks about using H2O2 to reclaim the HBr. The reaction 'I' am 'proposing' is:
H2O2 + 2 HBr --> Br2 + 2 H2O
Br2 + Ar-H --> Ar-Br + HBr
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H2O2 + HBr + Ar-H --> Ar-Br + 2 H2O
a) No one who uses any salt/H2O2 or Br2 system uses my proposed stoichiometry, is it because of: equilibrium, wrongly assumed mechanism, or because
HOBr is actually the active species?
b) Why is this reaction (and others) often done in GAA? I've read speculations about its role with bromine but I'm not sure, especially since it's
also done in MeOH so I don't think it's pKa. Is GAA better than MeOH?
(1) http://www.sciencemadness.org/talk/viewthread.php?tid=18948
(2) http://www.lambdasyn.org/synfiles/bromovanillin.htm
(3) Rhodium
(4) Choudary et al. (2003) The first example of bromination of aromatic compounds with unprecedented atom economy using molecular bromine
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Nicodem
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Quote: Originally posted by pyro2525  | | a) No one who uses any salt/H2O2 or Br2 system uses my proposed stoichiometry, is it because of: equilibrium, wrongly assumed mechanism, or because
HOBr is actually the active species? |
You need a 1 : 1 ratio of H2O2 vs. HBr. You can easily see this if you count the electrons and set the redox equation
accordingly.
| Quote: | | b) Why is this reaction (and others) often done in GAA? I've read speculations about its role with bromine but I'm not sure, especially since it's
also done in MeOH so I don't think it's pKa. Is GAA better than MeOH? |
Acetic acid is a good polar inert solvent. You could try with methanol, but it is not completely inert (though probably still useful for such a
reactive phenol) and electrophilic brominations proceed more slowly in it. Though performing a bromination of an aldehyde in methanol is likely going
to give you substantial amount of -CHO oxidation to -COOMe. I would rather avoid it.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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pyro2525
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This I definitely agree with, but it seems like everyone uses 1 equivalent of Br2 or 2 equivalents of xBr to Vanillin. This would leave an unused 1
equivalent of xBr.
Is its polarity required for polarizing the bromine? i.e. would DCM work?
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Nicodem
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| Quote: Originally posted by pyro2525 | | This I definitely agree with, but it seems like everyone uses 1 equivalent of Br2 or 2 equivalents of xBr to Vanillin. This would leave an unused 1
equivalent of xBr. |
There is no need for such an excess. If someone used 2 equivalents of the oxidant, that was most likely an arbitrary choice, rather than a reactivity
issue. Besides, above a certain point, the higher the excess, the lower the yield and purity.
Vanillin is as reactive toward bromine as it is. No need to enhance the reactivity of any of the reactants. It should react with bromine in
dichloromethane, but I thought you wanted to use a bromide salt with hydrogen peroxide, which would make it a biphasic liquid mixture with this
solvent (not that anything is wrong with that). Besides, 5-bromovanillin is well soluble in dichloromethane, which makes the isolation less simple, so
why not rather use water as the solvent in the first place?
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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pyro2525
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| Quote: Originally posted by Nicodem |
Vanillin is as reactive toward bromine as it is. No need to enhance the reactivity of any of the reactants. It should react with bromine in
dichloromethane, but I thought you wanted to use a bromide salt with hydrogen peroxide, which would make it a biphasic liquid mixture with this
solvent (not that anything is wrong with that). Besides, 5-bromovanillin is well soluble in dichloromethane, which makes the isolation less simple, so
why not rather use water as the solvent in the first place? |
Ah, I didn't know 5-bromovanillin was that soluble in DCM, as much as vanillin?
I have been playing around with using DCM because bromine is very soluble in it (making Br2 more pleasant to use), and HBr as the bromine
source (also eliminating Na+ and SO42- from the reaction mixture).
My protocols in general have been as follows,
Bromine:
In graduated cylinder or sep funnel is added HBr (~1.5 g/mL), and a few mL of DCM (~1.3 g/mL). H2O2 (~1.1 g/mL) is added
dropwise, preferably with cooling. This forms a weird situation with the layers and gentle swirling is required. It gets more interesting because the
HBr layer slowly gets less dense and the DCM/Br2 layer gets more dense, and the layers switch (allowing DCM/Br2 to be used in
the sep funnel). As I wrote this I realized that dropwise HBr instead could be worth investigating to prevent the weird layers.
Solvents:
MeOH + DCM/Br2. DCM basically ruins the whole product precipitation with water thing which is the largest problem, as you mentioned. The
water causes the DCM to separate out and the 5-bromovanillin falls into it creating some oily bs.
DCM + DCM/Br2. Prevents the water issue, but now the reaction mixture needs to be evaporated off, which has its own drawbacks.
Yields with various combinations are often poor but I've yet to take any m.p.'s. Anyway, I've procured some GAA and I'll see if I can bring these two
methods together, any other feedback or advice would be appreciated. 
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