Ketones 2-phenyl-4-substituted oxazoles

Oxazoles have attracted considerable interest due their presence as subunits of several biologically active compoimds or as rigid mimetics of a peptidic ring. A first synthesis of 2-phenyl-4,5-substituted oxazoles 54 [47] was described by microwave-assisted reaction of enolizable ketones with benzoni-trile in the presence of mercury(II) p-toluenesulfonate (Scheme 17). 

TABLE 1.14. MICROWAVE ASSISTED SYNTHESIS OF 2-PHENYL-4-SUBSTITUTED OXAZOLES AND 4,5-DISUBSTITUTED 2-PHENYLOXAZOLES FROM ARYL KETONES, BENZONITRILE, AND MERCURY(II)TOSYLATE ... 

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). 

This method has afforded some 2-phenyl-4-(/3-aminoethyl)-, and 2-pheny 1-4- (/3-disubstituted-aminoethyl) oxazoles from benzamide and the appropriate substituted bromobutanones.90 A 5-oxazolylethanol derivative is obtained from the corresponding substituted a-chloro ketone and amide in the presence of calcium carbonate (to neutralize the generated hydrogen chloride.)91 Condensation of a-bromophenylacetaldehyde and p-bromo-benzamide at 110°-120° gives 50% yield of 2-p-bromophenyl-5-phenyl-oxazole.18... 

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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