Saturday, November 24, 2012

MARKOVNIKOV DIBROMIDE

I am contemplating some hypothetical difficulties in the synthesis of 2,5-dibromohexane from 1,5-hexadiene. I am aware that this is a simple reaction that can be achieved in many ways but I would like to accomplish it in such a way that a messy separation is minimally necessary, be it via selective chemical extraction, column chromatography, or fractional distillation. The main unwanted side-products in this synthesis would be the mixed-Markovnikov product and the full anti-Markovnikov product. My first option is simple bromination with (aq) HBr and an appropriate phase transfer catalyst or a similar reaction involving hydrogen bromide gas. My second option is oxymercuration-demurcuration yielding hexane-2,5-diol which can then be subjected to a high yielding and selective bromination with PBr3. The third option is acid catalyzed hydration to the diol with H2SO4 and water followed by bromination with PBr3.

I would prefer not to use hydrogen bromide gas or mercuric acetate (which will require recycling of the metallic mercury liberated during demercuration) and so I lean toward acid catalyzed hydration. Would anyone with practical experience using the above methods enlighten me regarding their relative regioselectivity for the Markovnikov product? I believe it would be something like this: oxymercuration-demurcuration>acid catalyzed hydration>HBr addition.

8 comments:

Nick said...

The only other option I see is H2SO4 and water, followed by TsCl and pyridine to make good leaving groups, and then substitute the bromines in with NaBr.

However, simple bromination with HBr is probably your best bet.

Hamilton Morris said...

H2SO4 and water is one of the three I suggested, acid catalyzed hydration. Tosylation is unnecessary as 2ยบ alcohols are converted to a suitable SN2 leaving group by PBr3 (an intermediate phosphorus-oxygen bond forms inferring a positive charge to the alcohol and allowing for nucleophilic substitution by bromide in solution) so the conversion of an alcohol to an alkyl-bromide can take place in a single step.

streamfortyseven said...

Cleave 1,2-dimethyl-cyclobut-1-ene with ozone to get the diketone, reduce the carbonyl to hydroxyl, substitute hydroxyl to bromine using tosylate, or maybe there's a quicker way to get a carbonyl to bromide, just not thinking of it at 2am, just got in from photographing the tail end of a punk rock show...

streamfortyseven said...

Btw, the 1,2 dimetylcarboxylate-cyclobut-1-ene is a common starting material... And streamfortyseven is Hudson Luce...

Hamilton Morris said...

I already have 1,5-hexadiene to work with. One reason I have chosen that as the precursor as opposed to the diol, which is also available, is the extremely low cost. Conversely 1,2-dimethyl-cyclobut-1-ene is not commercially available. Ozonolysis of an unavailable (or expensive) material to yield ketones that will require reduction before bromination makes for a expensive and time consuming four step synthesis!

EDIT: Hudson I see that you were referring to the carboxylate, but I don't see it offered anywhere. Also do you have practical experience with ozonolysis? I don't know anyone that has actually done it.

streamfortyseven said...

Just buy the stuff, you get a mixture of erythroa and threo diastereomers, but you'll end up with that any way. Five grams costs $40: https://us.vwr.com/store/catalog/product.jsp?product_id=7989081

Jerebear said...
This comment has been removed by a blog administrator.
RM said...

Hello Mr. Morris. Love your work, brother. Wishing you many positive 'trips' for the future. Keep exploring those mystical frontiers.