Submitted by Nick K / University of Michigan-Flint on Tue, 06/12/2012 - 14:30

I reach out to the VIPEr community with a few questions.

How familiar is anyone with using dibenzoyl peroxide as a catalyst for brominations with NBS? 

If so did you use 75% remainder water or pure peroxide for the reactions?

We have been trying to reproduce the synthesis of a 2-bromo-methyl-indole derivative and the reaction is being incredibly finicky to us.  We have ruled out almost every possibility except for the catalyst.  Everyone uses dibenzoyl peroxide for this reaction but I have yet to find anyone who mentions the purity of what they are using.  Any help anyone could offer would be greatly appreciated.



Kyle Grice / DePaul University

Radical reactions are finicky by nature. I know i've seen some NBS brominations that worked in the presence of water, but I can't seem to find them right now.  They were in wierd journals (not ACS or RSC if I remember correctly), but they worked.  I think they were in biphasic DCM/water solution and were heterocycles. 

The lab purifications book has a warning benzoyl peroxide being explosive when dry (as most peroxides and similar reagents are).  It has a few methods of purification (I would avoid using acetone or ether during purification, just for safety). Maybe make a solution in something like DCM and dry with mole seives?

Have you tried AIBN as the catalyst? It's easy to handle in my (very limited) experience, and comes pretty darn pure usually.

Check the refs and forward search this on ISI for more info? 

Let me know if that helps,


Tue, 06/26/2012 - 20:47 Permalink
Nancy Williams / Scripps College, Pitzer College, Claremont McKenna College

I'd echo what Kyle said. We've used benzoyl peroxide and AIBN in our NBS brominations, and I've never found any real advantages to the benzoyl peroxide. Recently, we've gone to using thermal activation of AIBN, and using benzene as a solvent. Nice strong bonds that won't get activated, boiling point at a good level for thermolysis of AIBN, easy to remove. Yields are good, but finicky. 

Fri, 07/20/2012 - 09:21 Permalink
Kyle Grice / DePaul University

I found the papers I mentioned earlier while looking up brominations to help a student.  Here's two relevant papers, the first being the most applicable to doing radical reactions "on water"... they use mixed water/organic solvents (including benzene as one of the solvents). The second one shows examples of comparing various radical initiators with photolysis, and photolysis works out well in some cases.

Tetrahedron Letters 2002, v43, p1697

Tetrahedron Letters 2006, v47, p1097

I hope this is useful, I know this thread is a little old.


Wed, 09/19/2012 - 15:43 Permalink
Sheila Smith / University of Michigan- Dearborn

Ha!  I think it's funny that Kyle thinks TetLett is some "weird journal".

Fri, 09/28/2012 - 15:49 Permalink
Adam Johnson / Harvey Mudd College

Ha! I think it's funny that Kyle thinks that this thread (at 3 months) is "old." I bet Nick hasn't even found a student to run the reaction yet :)

Fri, 09/28/2012 - 17:09 Permalink
Kyle Grice / DePaul University

Heh, Tettlett is definitely not some wierd journal, i thought the papers I was thinking of were in really esoteric journals for some reason... the sad thing is I think many people in the department are probably unaware that it even exists (silly young grad students).

and also for some reason I thought this thread was older than it is. My grasp of time is clearly getting even more shaky that it was in college and grad school.

In order to not derail the thread.... Nick (if you get a chance to see this), let us know if you figure out something that works for what you are trying to do.

I'll throw another reference out there... you can use H2O2/HBr in water to brominate with high selectivity:

Tetrahedron 2009, v65, p4429

-KyleFinder (its kinda like Scifinder, but you just ask Kyle)*

*my labmate came up with that at group meeting when he was presenting

Sat, 09/29/2012 - 15:23 Permalink
Nick K / University of Michigan-Flint

Thanks to everyone who has contributed to this thread as it has been very insightful for us.   Kyle, thanks for the great references they will be very helpful when we come back to this project in a few months.

The brief whole story is that this reaction didn't work for 6 moths and we finally got it working and thought we knew the reasons for why it wasn't working.  Everything went great for the next 6 months and we made great progess. 

Then literally the day my student was awared the outstanding student research award (mainly for his ambition and hard work in getting this reaction to work) it quite working again and hasn't since.  

The sad news is we can not find out what is causing the problems in our reaction.  We have at least identified the byproduct and it is a result of the bromination step but are not sure why it isn't going as planned/reported.  The other problem is that it is well documented that it is pretty much impossible to separate the two products once the impurity has formed.  

As a result of this we have put this project on the back burner for now as one of our other projects is yielding much better results.  I am going to keep coming back to this thread though since I have a student starting in Jan. that will be trying to work through our difficulties on this.

Mon, 10/01/2012 - 12:07 Permalink