David Aurelio - 16-9-2010 at 09:56
I'm trying to add an alkyl chain to a carbonyl compound and then somehow introduce a carbonyl group on the alpha carbon of the new chain (e.g.,
1-acetyl-1-hydroxycyclohexane from cyclohexanone). So, I need a Grignard with something on the alpha C that can easily be converted to C=O. Any
suggestions?
madscientist - 16-9-2010 at 11:27
If you could prepare a Grignard from methylacetylene and add that, it should do the trick - the resulting compound will hydrolyze to yield the
compound you have in mind.
Only other thing related to Grignards that's coming to mind for me is something vaguely along the lines of preparing the cyanohydrin and adding this
to a CH3MgX Grignard, then refluxing with a bit of acid... probably would be left with hideously low yields though, assuming you were even able to
stabilize the cyanohydrin enough for the reaction to proceed (it exists in equilibrium.)
As for other routes:
1-acetyl-1-hydroxycyclohexane from cyclohexanone, with tetraethylammonium p-toluenesulfonate in isopropyl alcohol electroreduction (Sn-cathode), 67%
yield:
Journal of Organic Chemistry, 1992 , vol. 57, # 28 p. 7175 - 7187
1-acetyl-1-hydroxycyclohexane from cyclohexanone and acetyl chloride, with HCl and samarium diiodide in THF, 48% yield:
Journal of Organic Chemistry, 1991 , vol. 56, # 9 p. 3118 - 3122
EDIT:
Looks like you can do the Grignard reaction I proposed - the addition to the cyanohydrin (hope you can read French, because I can't):
Bulletin de la Societe Chimique de France, 1964 , p. 2908 - 2916
Something else interesting I just found too: if you hydrolyze that cyanohydrin to the carboxylic acid, supposedly methyl lithium in ether will yield
your target compound:
Journal of the Chemical Society, 1951 , p. 3067,3069
[Edited on 16-9-2010 by madscientist]
DJF90 - 16-9-2010 at 15:44
What you need is an "Acyl anion equivalent". Anions of dithianes (use 6 membered ring, not 5) and terminal acetylenes (followed by hydration to the
enol <=>ketone) are good methods. Other methods can be found in a good textbook
ziqquratu - 16-9-2010 at 17:15
If you wanted to hydrolyse the nitrile of a cyanohydrin, here's a reference to the reaction of 1-hydroxy cyclohexane carboxylic acid with methyl
lithium to give your ketone:
Simple analogs of cortisone. I. Some monocyclic compounds. Journal of the Chemical Society (1951), 3067-72
You could also try alkylating cyclohexanone with lithium acetylide to give a propargylic alcohol and treating that with mercuric sulfate or similar to
form the ketone - this is what I'd look into. Lithium acetylide is easy enough to prepare, and the yields should be good. There's probably other
methods for the hydration, but mercury jumps to mind.