Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: AlphaScent on May 02, 2013, 10:10:50 AM
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Hey guys,
Beautiful day here in upstate NY. Today I am doing a bormination of a primary alcohol using triphenylphosphine and bromine. I am just wondering what is your preferred method to brominate a primary alcohol. Totally subjective answers. This is my second time and first on a large scale. I know the triphenylphosphine oxide is going to be a pain, so just was wondering what your thoughts were??
Cheers!!
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Honestly I've never bothered with this reaction, I always just made the tosylate instead (a very, very easy reaction) and then either used it directly with a nucleophile or else I turned it into the iodide with a Finkelstein reaction.
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Beauty in Old Blighty too
I don't like to handle elemental bromine, it is too volatile to weigh accurately (i.e. can't use a bench top balance) and the density makes it difficult to measure an accurate volume in small quantities.
I would personally go for a solvent free chlorination with SOCl2 with a catalytic drop of DMF (all gaseous biproducts so very little work up) then Finkelstein as opsomath suggested if this is not reactive enough.
If you must make an alkyl bromide I would opt for PBr3 as it is much easier to handle than bromine also PPh3 can be difficult to remove from your product in some cases without distillation or chromatography.
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I haven't done alkyl chlorination with SOCl2 but I have done acyl chloride formation in the neat stuff, it is one of my favorites. So easy and clean; reflux, then remove excess SOCl2 by hivac or distillation.
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In that case, while we're at it, I have done the Ph3P/CBr4 reaction. It was quite lovely, though not a good atom efficiency with 18 carbons used without contributing to product. I had a nice oil so removal of the phosphine oxide was not a problem.
For acid chlorides, I came to like oxalyl chloride with a pinch of DMF (Vilsmeier rgt). Lower temperature reaction and more volatile reagents. Also less thionyl chloride to deal with, if solvent and ugly quench for disposal. I suppose the SOCl2/DMF would also increase reactivity, but once I switched to oxalyl chloride, I never went back. Perhaps those favoring thionyl chloride could comment on the Vilsmeier reactivity for acid chlorides (without high jacking the thread, which I guess I am doing).
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Unfortunately I never got to try oxalyl chloride, we had a bad lab accident with it (cracked bottle) which led to its falling out of favor in the lab afterwards. Pure coincidence, a thionyl chloride spill would have been equally bad.
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Triphenylphosphine / NBS is my favorite combination and also avoids dealing with Br2.
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I got my sinuses filled with oxalyl chloride while supervising an undergraduate project lab. For a few hours I thought I had seriously and permanently impaired my sense of smell!
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To chip in here from a process point of view. I prefer thionyl chloride on large scale for the formation of acid chlorides. But without the DMF.
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Hi jack away, dont bother me none.
Another beautiful day here. Had to come into the lab to check my zinc reduction after an overnight reflux, only about 70% complete.
I talked to my professor/boss and he said that they have tried making a tosylate of cis-3-hexen-1-ol and the following alkylation with methylaceto acetate did not proceed as nicely a with a bromide.
The work up on a 2 mole scale was a pain in the ass, so I am thinking that making the iodide via finkelstein (NaI) would be a good option.
My question is, is the iodide made without purifying the chloride first. Does the HALEX reaction occur as a cascade type reaction??
Thanks guys, enjoy the weather!!