The Vespiary

The Hive => Novel Discourse => Topic started by: yei on October 10, 2004, 05:16:00 PM

Title: 4-Me 4-hydroxy trans crotonic acid, OTC?
Post by: yei on October 10, 2004, 05:16:00 PM
4-alkyl 4-hydroxy trans-crotonic acids & their salts are potent GHB receptor ligands. How about an OTC synthesis from levulinic acid?

The problem is slightly tricky, because just heating levulinic acid will produce a lactone with the wrong stereochemistry, even if hydrolyzed.












Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)

Good, Bad ("CC(O)/C=C/C(=O)O.CC(O)/C=C\C(=O)O")




So here is my idea:














Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)

ketalize ("CC(=O)CCC(=O)O.C(OCC)(OCC)OCC>>CC(OCC)(OCC)CCC(=O)OCC")


1. convert levulinic acid into its ketal with acid/triethyl or trimethyl orthoformate. Yield 90%













Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)

pyrolize ("CC(OCC)(OCC)CCC(=O)OCC>>CC(OCC)/C=C/C(=O)OCC.OCC")


2. Pyrolyze the ketal in the presence of acidic catalyst to produce an enol ether, which will isomerize (I think) at the temperature employed (~250 C)to conjugate with the carbonyl group. Yield probably about 90% (so says organicum)













Molecule: (https://www.the-hive.ws/forum/faq.pl?Cat=#applet)

hydrolyze ("CC(OCC)/C=C/C(=O)OCC>>CC(O)/C=C/C(=O)O")


3. Hydrolyze the ether and ester under acidic conditions to yield the desired compound. Consume and enjoy. Yield ??

At worst, I suppose this method would produce a racemic mixture, but in actuality, the steric hinderance would probably make the trans-isomer the predominant one. Hopefully.


Ketalization of levulinic acid:
JACS 1955, 4069
Leibig's Annalen 1983, 913
Carbohydrate Research #319,63

I will link the last article shortly.

Would this work?