High atomic yield bromine-less benzylic bromination
Mestres, Ramon; Palenzuela, Jesus
Green Chemistry 4(4), 314-316 (2002)
DOI:10.1039/b203055a (http://dx.doi.org/10.1039/b203055a)
Abstract
A two-phase mixture (sodium bromide, aqueous hydrogen peroxide/carbon tetrachloride or chloroform) under visible light provides a simple and convenient system for benzylic bromination of toluenes. A high atomic yield for bromine atoms is attained. Substitution of the chlorinated solvents by other more environmentally benign organic solvents has been attempted and good results are obtained for methyl pivalate.
My problem was that the THF that one can get from pipe cement contains acetone. If you try and form Br2 and react it with "mostly pure" THF, you will get bromoacetone. The bromoacetone formed left me crying. It's highly irritating shit to deal with, even in small qty's. Post 363729 (https://www.thevespiary.org/talk/index.php?topic=7630.msg36372900#msg36372900)
(Chromic: "bromoacetone", Chemistry Discourse)
I'd absolutely love to see someone work on this who has access to reagent grade thf... (well, I do, but I have to go thru a chem supplier--and THF isn't really watched, so, perhaps I'm just complaining)
Moo, in the Deno paper that you dug up, J. Am. Chem. Soc.; 1967; 89(14); 3550-3554, mentioned in Post 308130 (https://www.thevespiary.org/talk/index.php?topic=11867.msg30813000#msg30813000)
(moo: "THF oxidations", Novel Discourse) I noticed that they use 4x equivilants of Br2 and conduct this experiment cold and in the dark.
If I've got this right, the paper mentioned in this post uses 1.2 eq Br2 (.4eq added as Br2 and .8eq generated catalytically as in H2O2 + 2 Br- + 2 H+ -> Br2 + 2 H2O) and conducts it at reflux with no mention of protecting from light. This is just strange. 1.2eq versus 4eq? They also change the solvent system from just water (as in the Deno paper) to a mix of DCM and water. Can anyone think of any reasons for changing the conditions so much?!?
Of course, there's also the great Tetrahedron; 2000 56; 1905-1910 ref as well that uses bromate... they talk about over-oxidizing the THF and forming small amounts of succinic acid... although they do isolate most of the product, 75% yield, thru atmospheric distillation.
Also, can you guys see anywhere if the 75% yield in this paper is an isolatable yield, or is it a GCMS yield? (like the GABA->GHB/GBL is a 100% yield by GCMS--but of that only 75% can be isolated) They just say that "the mixture was analyzed"--which doesn't say much.
P.S. why is there three bromine/THF refs and one H2O2/THF refs on the hive and no one but me as reported results on them? Am I just unaware of other people working on these routes?
Moo, in the Deno paper that you dug up, J. Am. Chem. Soc.; 1967; 89(14); 3550-3554, mentioned in moo: "THF oxidations" (Novel Discourse) I noticed that they use 4x equivilants of Br2 and conduct this experiment cold and in the dark.
In that ref they tried the ratios of THF:Br2 1:5, 4:1 and about 5:1. The focus of the article was on studying the kinetics and mechanism of this reaction, so I guess they weren't so interested in seeing if the reaction works with stoichiometric ratios of the reactants. In that post I say that they did the reaction in dark to avoid free-radical bromination -- this is a claim I must take back not only because of the article posted in this thread, but because of the following quote from the Deno article:
It was evident from qualitative observations that irradiation, even by simple sunlamps, greatly increased the rate of disappearance of Br2. Where the irradiated reaction gives the same products as the dark reaction, it would presumably be preferable from a synthetic viewpoint. However, in the one case investigated with care, benzyl isopropyl ether, the irradiated reaction gave different products. In retrospect we regret that we did not examine the light-catalyzed reaction more extensively.
It might be that this reaction can proceed both by ionic and free-radical mechanisms but evidently it doesn't matter in practice.
If I've got this right, the paper mentioned in this post uses 1.2 eq Br2 (.4eq added as Br2 and .8eq generated catalytically as in H2O2 + 2 Br- + 2 H+ -> Br2 + 2 H2O) and conducts it at reflux with no mention of protecting from light. This is just strange. 1.2eq versus 4eq? They also change the solvent system from just water (as in the Deno paper) to a mix of DCM and water. Can anyone think of any reasons for changing the conditions so much?!?
In the table 13 they say "Conversion based on oxidant", so not all THF gets oxidised in that example. The other example of an ether oxidation uses 2 equivalents of hydrogen peroxide in addition to 0.1 equivalents of elemental bromine.
Why the two-phase system? That is one of the key features of their article, the fact that the two-phase system affects certain reactions positively and eliminates unwanted side reactions, so they go on and try the same system with other substrates. In other refs DCM is not needed at all. It could be that this reaction is not so fickle and various reaction conditions can lead to good results.
Also, can you guys see anywhere if the 75% yield in this paper is an isolatable yield, or is it a GCMS yield? (like the GABA->GHB/GBL is a 100% yield by GCMS--but of that only 75% can be isolated) They just say that "the mixture was analyzed"--which doesn't say much
The 73% yield is the isolated yield, GC says 80%.
https://www.thevespiary.org/rhodium/Rhodium/pdf/thf2gbl.pdf (https://www.thevespiary.org/rhodium/Rhodium/pdf/thf2gbl.pdf)
P.S. why is there three bromine/THF refs and one H2O2/THF refs on the hive and no one but me as reported results on them? Am I just unaware of other people working on these routes?
I think there have been mentions of the H2O2/Fe(II) method being horribly messy but no actual results. It might be that as the doses of GHB are so high that a good GBL method is characterised by good volume efficiency, and there is no simple worked-out volume-optimised method, nobody has wanted to start messing with the scary peroxide-forming THF and the possibility of failure. By the way, there are five Br/THF refs, two of them mentioned in Post 381459 (https://www.thevespiary.org/talk/index.php?topic=8946.msg38145900#msg38145900)
(moo: "THF -> GBL patents etc.", Methods Discourse). It is possible to use chlorine too. Maybe a possibility for a H2O2/HCl method? Or an electrolytic cell with NaCl as the electrolyte with sulfuric or hydrochloric acid added so that the pH is 1 as recommended (Post 243610 (https://www.thevespiary.org/talk/index.php?topic=11867.msg24361000#msg24361000)
(foxy2: "Re: Easy Oxidation of THF to GBL", Novel Discourse))?
I still haven't found out if lead oxide (PbO2 aka lead peroxide in older literature) is suitable for an anode in oxidation of halogen ions. Both graphite and platinum are used for this purpose.