Ketones 2-amino-4-substituted oxazoles

Oxazoles. N-Aroyl-a-amino ketones (I) can be cyclized to substituted oxazoles (2) in high yield by use of anhydrous hydrogen fluoride. ... 

Various preparation methods have been described. Wiley (1945, 1947) converted a-amino acids to acetdmido ketones by reaction with acetic anhydride in pyridine and obtained 2,5-dimethyl-4-substituted oxazoles after dehydration of the enol form of the intermediate. Theilig (1953) applied the reaction of a-bromoketones with the appropriate amides. 

The first iodine-catalyzed synthesis of 2-alkyl substituted oxazoles 130 by a decarboxylative domino reaction was reported. Aryl methyl ketones 128 were transformed in situ into a-iodo ketones and then, by the Kornblum oxidation, into 1,2-diketones. After the addition of the a-amino acid 129, an l2-mediated cyclization/decarboxylation gave oxazoles 130. The reaction proceeds better if the Ar has electron-donating substituents and if the R group is a branched alkyl chain or phenyl residue. The reaction used oxone to regenerate iodine (13JOC6065). 

Quaternized oxazoles are readily attacked by hydroxide, ammonia, and amines. Cleavage of the oxazole ring is observed by attack of hydroxide, undoubtedly at position 2, and iV-methyl-a-acylamino ketone (169) is formed.319 Treatment of 2-amino-5-phenyl-3-phenacyloxazolium bromide with ammonia gives 4-phenyl-l-phenacyl-2-imidazolone (170) by ringopening and reclosure. A similar reaction with aliphatic amines (RNH2) leads to 1-substituted 2,6-diphenylimidazo[l, 2-a]imidazoles (171).320... 

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