mczee - 13-1-2011 at 18:13
Greetings,
I am trying to synthesize oxazoles that are substituted with an alkyl chain (not a phenyl ring) only at the 2-position. I am having a hard time
finding easy methods that only have groups at the 2-position. Most of the methods I found contain either only substituted phenyl rings at the
2-position or other groups at the 4 and 5 position. Anyone have any experience with oxazole synthesis that could help me?
Thanks!
Nicodem - 16-1-2011 at 11:00
2-Alkyl and 2-aryl substituted oxazoles are probably best prepared by the aromatization of the corresponding 2-substituted oxazolines. These are
easily accessible via the cyclocondensation of carboxylic acids or nitriles with 2-aminoethanol. There are plenty of methods for their synthesis in
the literature and some were already discussed on this forum. If I remember correctly, the aromatization can be done with some oxidants such as nickel peroxide, etc.
Likely it can be done with haloimide reagents in the presence of bases (the cheap and highly available trichloroisocyanuric acid is sometimes used on
related nitrogen containing heterocycles). I'm not going to waste time searching the literature as that is up to you, but I suggest you to first check
a review paper on oxazoles and their preparation (start searching in obvious places, like volumes of Comprehensive Heterocyclic Chemistry,
Chemistry of Heterocyclic Compounds and Advances in heterocyclic chemistry). I would also speculate it might be possible to do an
oxidative condensation of ethanolamine with aldehydes that goes all the way to 2-alkyloxazoles. Anyhow, check the literature first and ask questions
later.
mczee - 16-1-2011 at 15:01
I appreciate the information. Thank you very much for taking the time to reply. I, of course, do not expect anyone to do my literature searching for
me. I was simply asking if anyone had tried anything that worked well in their hands. I thought of oxidizing 2-alkyl oxazolines to 2-alkyl oxazoles,
but I can find no useful examples of this procedure (using Scifinder) where the 2-substituent is an alkyl group. I do find a some examples where the
2-substituent is an aromatic ring. Perhaps the aryl ring is necessary for oxidation to work in any appreciable yield. Maybe the oxidants will work
with an alkyl group at the 2-position, but I was looking for some examples before I give it a go in the lab.