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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: AlphaScent on May 02, 2013, 10:10:50 AM

Title: Preferred Bromination
Post by: AlphaScent on May 02, 2013, 10:10:50 AM
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!!
Title: Re: Preferred Bromination
Post by: opsomath on May 02, 2013, 10:26:43 AM
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.
Title: Re: Preferred Bromination
Post by: Archer on May 03, 2013, 09:02:59 AM
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.

Title: Re: Preferred Bromination
Post by: opsomath on May 03, 2013, 09:57:23 AM
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.
Title: Re: Preferred Bromination
Post by: orgopete on May 03, 2013, 10:21:41 AM
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).
Title: Re: Preferred Bromination
Post by: opsomath on May 03, 2013, 10:26:02 AM
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.
Title: Re: Preferred Bromination
Post by: TwistedConf on May 03, 2013, 11:16:08 AM
Triphenylphosphine / NBS is my favorite combination and also avoids dealing with Br2.

Title: Re: Preferred Bromination
Post by: Archer on May 03, 2013, 11:22:01 AM
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!
Title: Re: Preferred Bromination
Post by: discodermolide on May 03, 2013, 12:14:11 PM
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.
Title: Re: Preferred Bromination
Post by: AlphaScent on May 04, 2013, 03:53:07 PM
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!!