Bedlasky
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Bromination of aromatic compounds without catalyst
Hi.
I did some research for my analytical chemistry and I came across some bromination reactions of aromatic compounds without need of a catalyst.
Strongly activating groups like -OH and -NH2 afford direct bromination even in aqueous solution. For example phenol is brominated to
2,4,6-tribromophenol, aniline to 2,4,6-tribromoaniline, 8-hydroxychinoline to 5,7-dibromo-8-hydroxychinoline etc. Some labile groups like -COOH and
-SO3H are completly removed from the ring as CO2 or H2SO4. So salicylic acid is brominated to 2,4,6-tribromophenol and sulfanilic acid is brominated
to 2,4,6-tribromoaniline.
Aromatic compounds with -OR, -NHR and -NR2 groups cannot be brominated in aqueous solution. However they can be brominated in certain organic solvents
like glacial acetic acid or DCM. For example anisole in GAA can be brominated to p-bromoanisole, N,N-dimethylaniline in DCM or GAA to
p-bromo-N,N-dimethylaniline etc.
Here is some literature:
https://copharm.uobaghdad.edu.iq/wp-content/uploads/sites/6/...
https://sci-hub.se/https://pubs.acs.org/doi/10.1021/ja01493a...
https://sci-hub.se/https://doi.org/10.1002/slct.201702023
https://chemistry.sites.clemson.edu/organic/Labs/2280Docs/Br...
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Bedlasky
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So, I tried to utilize these reactions to determine O-alkylated phenols and N-alkylated anilines.
Determination of anisole went great. I used 5 ml of 0,1M KBrO3 and 5 ml of 0,55M KBr as bromine source + 90 ml glacial acetic acid as reaction medium.
Excess of bromine was determined by iodometry.
I tried the same procedure to determination of N,N-diethylaniline. But this compounds behave with bromine very strangely. It consumed all bromine,
which was unexpected, I did my calculations well. So I reduced weight of diethylaniline three times, just for the case that it form di or
tribromoderivative. Still it consumed all bromine. So I added extra 5 ml KBrO3 and 5ml KBr. This time some bromine remain in the flask even after 20
minutes. So I added some KI and water, left it for 10 minutes and titrated it with 0,1M Na2S2O3. When I reached the end point, solution started darken
because of formation of new iodine. I left it for few minutes and add few drops of thiosulfate. Solution decolorize but after a while it started
darken again. I repeated the same procedure, the same result.
I really don't understand that. Every article about bromination of N-alkylanilines says that p-bromoderivative is formed. One article mentioned
formation of dibromoderivatives as minor byproducts. Any ideas what's going on in this reaction?
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Metacelsus
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Maybe run a GC and see what happened?
Did you let the bromate and bromide react to form bromine, before you added the diethylaniline? I wonder if there are any possible side reactions with
bromate.
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Bedlasky
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I don't have standards and suitable colone for GC analysis of this product.
I mixed bromate and bromide, add diethylaniline and acid as last. Once I tried add diethylaniline as last (so bromine was formed before addition). But
behavior was the same.
Edit: I find interesting note when googling some answers for this mystery. In this procedure on orgsyn, there is mentioned this:
Aromatic amines are usually polybrominated on treatment with bromine. Several mild brominating agents have been introduced in attempts to achieve
partial bromination without the necessity of protecting and deprotecting the amino group, but these give variable results when applied to a large
variety of amines. Dioxane dibromide4 monobrominates tertiary aromatic amines, but gives poor yields with primary and secondary aryl amines. The use
of N-bromosuccinimide5,6 (1-bromo-2,5-pyrrolidinedione) leads to monobrominated compounds frequently contaminated with decomposition products.
The dienone, which is prepared essentially as described by Benedikt7 and Caló,8 monobrominates a wide range of primary, secondary, and tertiary
aromatic amines almost exclusively in the para-position. The procedure described is of general synthetic utility for the preparation of
para-brominated aromatic and heteroaromatic amines in high yields and frequently in a high state of purity. The submitters have used this technique to
para-brominate many compounds in quantities ranging from 0.01–0.1 mole, including the following (yields after one crystallization): aniline (92),
N-methylaniline (94), N,N-dimethylaniline (91), N,N-diethylaniline (94), o-toluidine (88), N,2-dimethylaniline (91), N,N,2-trimethylaniline (90),
m-toluidine (90), N,N,3-trimethylaniline (86), 2,3-dimethylaniline (91), 2,5-dimethylaniline (91), 3,5-dimethylaniline (81), 2-chloroaniline (86),
3-chloroaniline (86), 2-bromoaniline (78), 3-bromoaniline (82), 2-nitroaniline (91), 3-nitroaniline (85), m-phenylenediamine (82), o-anisidine (85),
3-methoxyaniline (58, 4-bromo; 30, 6-bromo), diphenylamine (90), 1-aminonaphthalene (86), 1-dimethylaminonaphthalene (84), 2-(trifluoromethyl)aniline
(85), 2-aminopyridine (75), 2-dimethylaminopyridine (70), 3-dimethylaminopyridine (60),9 2-amino-6-methylpyridine (76). Where solubility of the amine
in dichloromethane is low, chloroform may be used as solvent. For example, 2-aminopyrimidine gave 2-amino-5-bromopyrimidine (82%) in this manner,
compared with 41% when the amine is brominated conventionally in aqueous solution.10 In the case of anthranilic acid, 2-amino-5-bromobenzoic acid
(82%) precipitated from the chloroform reaction medium. In addition to its use with amines, the dienone reagent monobrominates a variety of phenols,11
and behaves as an oxidizing agent toward sulfides, converting them to sulfoxides.12
Preparation of 2,4,4,6-tetrabromo-2,5-cyclohexadien-1-one is easy, just direct bromination of phenol or salicylic acid in aqueous solution and
filtering the product. Diethylaniline can be then brominated by this compound, after reaction DCM solution will be shaken with aqueous KI, which will
react with excess of ketone to form iodine and 2,4,6-tribromophenol (I am sure about this reaction, because this tetrabromoketone is intermediate in
determination of phenol or salicylic acid).
[Edited on 26-12-2021 by Bedlasky]
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karlos³
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Three letters: NBS
Try this instead, ist so much cleaner because of... someone else should explain this.
But this is from experience myself, try this instead, the mechanism works just one way not both(or more?) that are possible and thus you'll end up
with a far cleaner result in higher yields.
I tried in-situ brominations the one or other way from bromides and an oxidant, or with HBr/DMSO and the like, it all sucked.
Compared to NBS.
I know its quite OT here, I still suggest it because this reagent is a heaven sent alternative to bromine, in-situ, from the bottle,doesn't matter.
Screw elemental bromine.
You never achieve that cleanliness and purity, and ease, with bromine, no matter how.
Join team NBS!
We always recruit former "elementarded brominators" who got enlighted 
No seriously, NBS is a superior alternative to brominations and so much easier to handle, so much more predictable, please look into this to avoid any
further frustration.
[Edited on 26-12-2021 by karlos³]
verrückt und wissenschaftlich
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Bedlasky
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Thanks, Karlos!
I was thinking about NBS too, but I don't know where to get it. I ask my friend Fery, he do lot's of organics and he is from the same country, so
maybe he know where to get NBS here. I read about utilizing NBS in determination of sorbic acid. I have some issues with sorbic acid too, I will try
to change conditions today, maybe it will help.
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Fery
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Here they sell it:
https://shop.es-drei.de/imide/230/n-bromsuccinimid-min.-99?n...
But I have more than 4 kg Br2 in stock  which I won't be able to use in my
whole life...
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karlos³
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My ideal source for the stuff, if Bedlasky is in europe, he should buy from them.
Pro-tip: buy at least a pound, ideally a kilo, it lasts and will not go bad for years, and at these quantities, it will become so cheap, it does not
make sense to buy just a little.
Also, their prices can hardly be beat, I looked around because I became very fond of NBS and ought to include it into some order elsewhere... they all
astonished me with their prices
S3 is just great for NBS, no but's or if's, I haven't found any better supplier so far.
Buying succinimide is more expensive actually... no joke, I bought 50g's of succinimide once, for another purpose, and I paid as much as I would for
250g's of NBS from S3
PS: if any of you knows a better supplier innereuropean, for S3, that is below 40€ a pound, contact me to not derail his thread any further, please.
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Bedlasky
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45€ are money which I cannot afford to spent right now. And it is also little bit pointless buy half an kilo of NBS, because I don't have space
where I can do organic brominations (regular synthesis). I need just around 0,0015 mol of bromine in one reaction flask. This is just one-time
project, I normally don't need to determine content of N-alkylated anilines. I was just curious if it can be done similarily to determination of
normal anilines. I will probably try that tetrabromocyclohexadienone, preparation look easy. If it won't work, I'll probably give up on it.I still
have plans to try determination of halides and thiocynates (cheaper alternative to argentometry).
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Mateo_swe
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Bromine can brominate 3,4-dihydroxybenzaldehyde into 2,5-dibromo-3,4-dihydroxybenzaldehyde.
(2 mol eq. bromine to 1 mol eq. 3,4-dihydroxybenzaldehyde in chloroform).
Could NBS be used to get the same result?
Bromine is not the nicest chemical to work with and if NBS could do the same it would be intresting.
Sorry no refs, just something i remember reading somewhere.
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steadyhand
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Quote: Originally posted by Bedlasky  | Thanks, Karlos!
I was thinking about NBS too, but I don't know where to get it. I ask my friend Fery, he do lot's of organics and he is from the same country, so
maybe he know where to get NBS here. I read about utilizing NBS in determination of sorbic acid. I have some issues with sorbic acid too, I will try
to change conditions today, maybe it will help. |
It's really easy to make (though lengthy). I did so from MSG (see http://www.sciencemadness.org/talk/viewthread.php?tid=69635) Follow chemplayer's steps to get succinic acid, but use my dilutions (last post on
that thread) and use 10% ammonia (or I suppose household ammonia is fine too) instead of Baker's ammonia. I got to discover ammonia scrubbing and
high-melting point distillation. Super cheap too.
For succinic acid->succinimide:
http://orgsyn.org/demo.aspx?prep=cv2p0562
I got the bromination step from Rhodium, but I'm not happy with it. Not well contained imho.
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