10-10-04 17:16
No 535251
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: Good, Bad ("CC(O)/C=C/C(=O)O.CC(O)/C=C\C(=O)O")
So here is my idea:
Molecule: ketalize ("CC(=O)CCC(=O)O.C(OCC)(OCC)OCC>>C
1. convert levulinic acid into its ketal with acid/triethyl or trimethyl orthoformate. Yield 90%
Molecule: pyrolize ("CC(OCC)(OCC)CCC(=O)OCC>>CC(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: hydrolyze ("CC(OCC)/C=C/C(=O)OCC>>CC(O)/C=C/
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?
It's good to bee back! Don't trust your computer!!
