Ioxoi - 23-8-2009 at 15:13
Recently I bought a bottle of MSG (monosodium (L)-glutamate monohydrate) and was looking for uses for it. I eventually decided on a cyclocondensation
to (L)-2-pyrrolidone-5-carboxylate, aka "pyroglutamic acid," which was briefly mentioned, but not elaborated on in the earlier thread "Is MSG useful
for anything?"
Searching for ways to do so, I eventually found US Patent 4946968, which promised to condense MSG into the pyroglutamate salt almost quantitatively,
with no racemization. Most other papers and patents that used different methods (such as cyclocondensation of the free (L)-glutamic acid itself) noted
racemization. As such, US4946968 seemed like the best bet.
Afterwards, I planned on purifying the product by precipitating out the trihydrate, mentioned in another patent, US 4952706.
www.wikipatents.com/4946968.html
www.freepatentsonline.com/4952706.html
After some internet snooping, I found that (L)-2-pyrrolidone-5-carboxylic acid, aka pyroglutamic acid, has a number of uses, such as a humectant for
skin care products (reputedly works very well) as well as a vasodilator, as well as direct use, or use of derivatives, as an anti-dementia
pharmaceutical. For example,
http://www.freepatentsonline.com/4933354.html
It was even reported that the unmodified acid works pretty good as an anti-dementia drug as well.
Thus I was keen in turning my flavor enhancer into something more interesting. However, I have been having trouble at the crystallization step. Here
is what has been done:
80g of MSG hydrate were added to a 250ml beaker and heated on a hot plate, rather than the (probably better working) oil bath mentioned in the patent.
The hot plate had a temp readout and I kept the plate temp around 270-310C. The patent says to avoid temps above 270C to avoid racemization, but
because I wasn't using an oil bath I think the flask will have been cooler than 270-310C.
The melting process took several hours and finally gave a pale yellow syrup, which hardened to a glass on cooling. I assumed the reaction worked as
described, and added 34mL water to the glass and dissolved it. This would be a 65% sodium pyroglutamate 35% water mix, which according to the
trihydrate patent ought to form crystals at as high as room temp. I heated the liquid to about 55C and cooled it in a freezer, but so far I have no
crystals. And here I am stuck.
If you read carefully in the patent on forming the trihydrate, you will notice that the crystallizations work fine for pure L or pure D enantiomers,
but when they try to crystallize an 85% L 15% D mixture, the crystallization yield is miserable despite cooling to low temps. It would seem that the
solubility of the optically impure product is much higher than the pure enantiomers.
So then, might it be that I have an optically impure product? That is one worry I have, since I didn't use an oil bath for consistent heating, and my
reaction took forever (3-4hrs with occasional manual stirring).
Another possibility is incomplete reaction. There was still a small amount of water vapor coming from the melt even when it had completely clarified,
and bubbles were still coming off, despite the fact that the patent says gas evolution stops when the melt goes clear. I tried to test this by doing a
smaller 30g MSG batch and cooking it for a long time, even after it had clarified. However, the slow bubbling just didn't seem to stop, and it began
to get orange-brown and smell funny. I had no luck crystallizing that batch either.
Any ideas? Perhaps someone with better equipment than I do can replicate the patent more accurately than I have, and get the reaction done right.
Maybe I should try to do the reaction faster, rather than slowly.
jhullaert - 27-8-2009 at 04:27
I was planning the same synthesis, but I've found this method using a diazotation: http://www.hrhee-hanyang.net/board_file_img/Natural_Science_Technology_2000_2.pdf
In can't remember if you'll get a racemic mixture this way.