I want to round up the approaches to alpha-brominated propionic acid. Can we get any concensus on what is most easily facilitated? Starting with alanine or lactic acid seems seems energetically favorable to brominating propionic acid directly. megamole gave a list of literature for alanine conversion, but since I'm not in range of a chem library the dates and citations show me little. lugh's abstract of one of these looks very promising:
(R)-2-Bromopropionic acid: 50 g D-Alanine (.56 mol) was dissolved in a mixture of 580 ml of 48% aqueous HBr and 1 L of water, and cracked ice added to give a total volume of 3 L. 104.3 g NaNO2 (1.51 mol ) was added in small portions with stirring, followed by 700 g of Na2SO4. When the stirred reaction had warmed to 15 degrees C, it was decanted from solids and extracted with five 500 ml portions of Et2O. Drying of Na2SO4 and then CaCl2 and concentration in vacuo gave 65 g of oil as residue. this was distilled at 25 torr collecting the forerun between 40-70 degrees C, and three fractions distilling at 104-8 degrees C (25 torr) totalling 51.3 grams.
Now I don't object to using sodium nitrite twice in the same synthesis (once for the nitrosyl bromide, then again to make nitroethane) but we don't need stereoselective processing. Usually if we buy alanine, we also pay for its being a stereospecific isomer. Also Fischer seems to use a whole lot of reagents to process 50 g of alanine. Why 700 g of sodium sulfate, it's too much.
Another contributor, foxy2, produced some interesting references from propionic acid, one or two of which look reachable. Bromine and PCl3 in a refluxing chlorinated solvent looks OK -- after making PCl3. (The alternative of bubbling with chlorine is also facile.)
In Post 227794
(megamole: "Re: Easy nitroethane in quantitative yield", Methods Discourse) megamole said, in reference to lactic acid:
Here are a couple instances of aliphatic alpha-hydroxy carboxylic acids being converted alpha-halo acids. They're old, but we're not exactly talking about high-tech chemistry with this reaction, are we?
Justus Liebigs Ann. Chem. (1864) vol. 130, Pp. 16.
Ber. (1879) vol.12, Pp. 178.
If Liebig could do it, I can too, but it would help to know just how Liebig did it. Are we talking about a water solution of dl-lactic acid and ~1.5-3.0 equivalents HBr, in which alpha-bromopropionic acid would be left in the still when the more volatile components were boiled out, after an appropriate reflux? I want to hear other beez confirm my judgment that yes, lactic acid is actually simplest to use. I can make calcium lactate in a bucket, which means lactic acid is practically free. It isn't robust, for it won't stand up to ambient pressure distillation, but being free makes it particularly valuable.
So who has preferences among alanine, lactic acid or propionic acid as the starting point for making alpha-bromopropionic acid?
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