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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Babcock_Hall on February 04, 2017, 07:43:07 AM

Title: Krohnke pyridine synthesis and other heterocyclic catalysts
Post by: Babcock_Hall on February 04, 2017, 07:43:07 AM
In the Krohnke pyridine synthesis, pyridine is used as a catalyst of sort.  One makes a pyridinium ketone which (with the help of ammonium acetate) loses a proton and attacks a Michael acceptor, to ultimately make a substituted pyridine.  The ammonium ion provides the nitrogen for the substituted pyridine  But the original molecule of pyridine is not the source of the pyridine ring in the final product.  My question is would other heterocycles, such as oxazolium ketones or thiazolium ketones, be as effective?  My tentative answer is that there might be more side reactions.  For example, the hydrogen at C-2 of a thiazolium compound is somewhat acidic (the pKa of thiamin pyrophosphate is about 18).  My interest is not so much in the Kronhke synthesis as it is in other Michael additions that such substituted ketones might do.
Title: Re: Krohnke pyridine synthesis and other heterocyclic catalysts
Post by: kriggy on February 04, 2017, 08:21:02 AM
I think it should work. I never run the reaction but the pyridinium salt is there probably to increase the acidity of the α-proton, since you can run the reaction with β-diketones instead of those pyridinium derivatives
Title: Re: Krohnke pyridine synthesis and other heterocyclic catalysts
Post by: wildfyr on February 04, 2017, 08:58:51 AM
Seems like it might work, the krohnke reaction works because of the electron richness of the ring, which thiazole and oxazole have in spades as well As kriggy pointed out, they might be TOO electron rich. I'm sure someone has explored this idea though I couldn't find anything with a cursory search. Some deep and inventive Sci-findering and google scholar would be well worth it.