I am attempting to prepare 6,6'-dibromo-6,6'-dideoxy-a,a-trehalose by taking d-trehalose and dissolving it in anhydrous DMF followed by addition of triphenylphosphine and N-bromosuccinamide (may use CBr4 instead) and heating to 60o C under an inert atmosphere. This should (overnight) convert the two primary alcohols to bromines.
Ref: M. Wang et al. Bioorg. Med. Chem. Lett. 14 (2004) 2585-2588
I then want to take this reaction mixture and add it to an aqueous (water/acetone) system. Will the newly added bromines survive the aqueous system?
The alkyl bromides as a class are certainly susceptible to hydrolysis: primary bromides undergo rapid Sn2 cleavage of the C-Br bond at pH > 8-9, whereas prim, sec and tert bromides rapidly hydrolyze at low pH by the Sn1 process, in both cases usually forming alcohols or alcohols, rarely olefins except at high temp..
Your bromides might have special reactivity or unreactivity owing to neighboring group effects, but putting these bromides into water/acetone should not lead to rapid loss.
We prepared a critical review of these reactions for alkyl halides: Mabey and Mill, Physical and Chemical Reference Data 7: 383-415 (1978)
Theodore has provided the answer. 1,1-Dibromides (gem dibromides) may be a little more stable, because the C-Br bonds are not so polarised. as a single C-Br bond.
Good luck!
After the reaction your reaction mixture is acidic (if you have not used amine in the reaction). Under acidic aq. conditions the hydrolysis (CH2Br) is less probable. But the glycosidic bond is sensitive for the acidic aqueous system.
In many carbohydrate cases (after e.g. Br2/TPP bromination) the reaction mixture is neutralized with NaOMe(!, until pH ~10) without considerable decomposition of the formed halide.
Please, note that in case of glucose derivatives (like trehalose) under basic conditions the formation of 3,6-anhydrosugar can be more expressed than the hydrolysis of the CH2Br.
Using the NBS/TPP (or Br2/TPP, or CBr4/TPP) the most difficult is to remove the residual TPP and TPPO. From my experiences the TPP/O removal from aqueous systems is difficult because of the very fine powder of TPP/O. I would avoid the use of aq, system. I assume that your product is soluble in water, this is why you might want to use the mentioned system.
Probable your product is not soluble in MeOH. If this is the case, concentrate the DMF solution as much as possible (high vacuum , moderate temp), then dilute your solution with MeOH (~ 9:1 or more MeOH: DMF) and check the pH, then neutralize the MeOH solution with 1 M NaOMe/MeOH. When the solution becomes basic the your product starts to crystallize but the TPP/O remains in solution. Too much residual DMF may prevent the crystallization.
It might happen that the best TPPO removal is the Soxhlet extraction with MeOH or nPrOH first then MeOH (many times the nPrOH is difficult to completely remove) - of course if your product is not soluble in these solvents. But, you can also use acetone or DCM for the soxhlet extraction too.
Raymond, you are right. But 6,6'-dibromo-6,6'-dideoxy-a,a-trehalose does not contain geminal dibromide.
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