Separation of 2-bromo-3-methylthiophene and the corresponding 5-bromo isomer
I've been working on preparing bromothiophenes for a while now. The particular problem I am working on involves 2-bromo-3-methylthiophene. The
bromination, using NBS, always gives mixed products. I have experimented with many solvents, temperatures and rates of addition for the NBS. Presently
the optimized procedure gives the desired product around 88% to 90% but the 2,5-dibromo and 5-bromothiophene products are present to minor extents as
well as some starting material. The best method for analysis, I have found, is GC-MS.
While separation of the starting material and the 2,5-dibromothiophene bye-product is possible using silica gel chromatography, and or reverse phase
chromatography I have had limited success with separating the two brominated isomers. I have tried vacuum distillation without luck thus far, working
with 10g scale test batches. From this I would assume their boiling points are very close, as one might expect.
The best result I have been able to achieve thus far is down to approximately 4 to 5% of the 5-bromo-3-methylthiophene (by GC). Ideally, I would like
to obtain a clean sample of the minor isomer for analytical purposes to compare against the major isomer (physical properties, NMR, IR, etc...).
If anyone can offer some insight into improvements on separation for these types of compounds I would be most appreciative. I would like to use a
vacuum distillation process as I feel this could offer the best solution as I would like to have a reasonable quantity to use for analysis. I guess a
longer distillation column and testing rasching rings, plates etc... could be avenues of investigation. Ultimately I could go for repeated UHPLC runs,
but my sanity is also at stake then.
Again. Any useful contributions or musings would be appreciated.
- SmashGlass -
If it ain't broke don't fix it....
Now where are my screwdrivers?  |
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