space efficient, easy 2-Br-propionic acid prep

[ChemicalSolution]

Tetrahedrone: Asymmetry Vol. 4. pp 1141-1152, 1993

(2R)-Alanine (4.0g, 45 mmol) was added to a saturated solution of KBr (10 ml), followed by the dropwise addition of 15ml of 47% HBr.  The resulting mixture was then cooled to 0C and NaNO2 (6.21g, 90 mmol) was added over 1hr.  The reaction mixture was maintained below 5C for a further 1hr and then allowed to warm to room temperature.  The resulting solution was then extracted with et2O (3 X 25ml), the combined ether extracts were then dried over MgSO4 and concentrated in vacuo to give a pale yellow oil (6.54g) in 95% yield.  This was distilled under reduced pressure to give pure (2R)-bromopropionic acid B.P. 68/70C/0.1 mm Hg.

A 1 molar batch could easily be done in a litre flask.

About the workup...  Ether is the shyte if you live galaxies from neighbors.  For SWIM (and probably most other bees), DCM is her choice for solvent.  With all the in-organics remaining in this reaction.. Would the DCM not be on top?  This weirds her out a bit since she's always used to the DCM being on bottom.. She wonders if DCM will cause any problems...

Regardless, she will give this a shot in the next few days and let her bees know.  Rh's etNO2 synthesis from 2-Br-propionic acid looks to bee a bloody sweet rxn..

XOXO!!!

Julia

[ChemicalSolution]

Does it seem a bit odd to have a reaction proceed w/out stirring?

SWIM is going to assume that she may use a saturated NaBr solution instead of a KBr solution..  Any bees see a problem with this?

Julia

[halfapint]

You suppose stirring wasn't done if it wasn't mentioned?

Distillation's easy, with a 100 micron vac.
a half a pints a half a pound a half a world a half a round
demimonde, n. Half world.

[Rhodium]

Use an equimolar amount of either KBr or NaBr - it shouldn't make a difference. And to everybody who have asked - it does not matter which stereoisomer or stereoisomer mixture that is used in this reaction. The distillation temperature at a more usual vacuum of 25 mmHg would be about 150°C, which seems okay to me.

[ChemicalSolution]

You suppose stirring wasn't done if it wasn't mentioned?

Weeeeelllllllll

A paper ususally drops little clues such as "to a stirred solution of_____" or "stirring is maintained while the solution warms to room temperature.."

So you think stirring is assumed?

xoxo

[Rhodium]

It depends on how much space they are allotted in the publication, sometimes they need to truncate a little. Always assume stirring in all reactions which does not explicitly say "DON'T STIR". It is much like the use of boiling stones are never mentioned in journals, but you should always use them when distilling (or preferably magnetic stirring, especially under vacuum).

[ChemicalSolution]

Rh-  What do you think about using DCM as an extracting solvent.  SWIM's saturated NaBR solution is in the range of 1.5g/ml.  This will be diluted in the reaction with the addition of 48%HBr.. But what happens (stoichiometrically) with the NaNO2?  Do you think the final solution will have a density of more or less than 1.32 (DCM)?

xoxo-Julia

[ChemicalSolution]

One more thing about this bromo-compound..

This mother has a density of 1.7!!  SWIM remembers failing in steam distilling of bromosafrole.. She wonders if this will steam..

Or-- if all distillations fail, what about an a/b extraction?  SWIM imagines extracting the organic layer with NaOH and then acidifying with HCL and hoping the product will drop out.

xoxo-Julia

[Rhodium]

DCM will be just fine for the extraction. The NaNO2  reacts with the -NH2 group on alanine, forming N2, H2O and OH^-.