[AlphaScent]

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!!

[opsomath]

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.

[Archer]

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.

[opsomath]

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.

[orgopete]

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).

[opsomath]

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.

[TwistedConf]

Triphenylphosphine / NBS is my favorite combination and also avoids dealing with Br₂.

[Archer]

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!

[discodermolide]

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.

[AlphaScent]

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!!