Acylation 5- -4-methyloxazoles

Oxazoles react with amines to form imidazoles. As more examples have been documented, the critical role that the oxazole substitution pattern plays in the reaction outcome has become apparent. For example, 5-acetyl-2-aminooxazole reacts with amines to give imidazoles as the predominant products <84TL2957>. With the addition of a 4-methyl group, as in 5-acyl-4-methyloxazoles or 5-acetyl-2,4-dimethyloxazole, pyrimidines are formed instead <60CB1998,85IJC(B)535>. The reaction of... 

Mekonnen and Crank also found the same reaction dichotomy in Friedel-Crafts reactions of 622 (X = O) with acid chlorides or acid anhydrides. In general, acylation of 622 (X = O, R = CH3) with acetic anhydride or benzoyl chloride/ pyridine afforded the corresponding 2-(acylamino)-4-methyloxazole 630a and 630b (Scheme 1.174). However, low-temperature acetylation or aroylation of 622 (X = O, R = CH3) in the presence of two equivalents of AICI3 produced a 5-acyl-2-amino-4-methyloxazole 631 in low to modest yield. The authors reported that AICI3 was the most effective Lewis acid (SnCLj and TiCL) and that the reaction required two equivalents of Lewis acid. Selected examples are shown in Table 1.48. 

Both 1005 and 1008 (X = H) are readily acylated by an activated ketene, e.g., dichloroketene or f-butylcyanoketene (Scheme 1.271). The authors isolated excellent yields of the a,a-disubstituted 2-acyl-5-phenyloxazoles 1015a/b (X = H). In contrast, the a,a-disubstituted 2-acyl-4-methyloxazoles 1014a/b were isolated in modest to good yield. Nonethless, the yield of 1014a was an improvement over direct acylation of 3 using dichloroketene. ... 

TABLE 1.76 2-ACYL-4-METHYLOXAZOLES AND 2-ACYL-5-ARYLOXAZOLES FROM 4-METHYL-2-(TRIMETHYLSILYL)OXAZOLE OR 5-ARYL-2-(TRIMETHYLSILYL) OXAZOLES AND ELECTROPHILES, 223... 

The original method for the synthesis of triflnoromethyl-snbstitnted oxazoles is based on the transformation of acyloxazolin-5-ones. Thus, 2-acyl-2-trifluoromethyl-A -oxazolin-5-ones 38 undergo cycloelimination of CO2 on heating at 200-230 °C to yield trisubstituted oxazoles 39. In this case snbstituents at positions 2 and 4 of the oxazole ring are formally interchanged [37]. Flash vacnnm pyrolysis (540-600 °C/0.01 mm Hg) of N-trifluoroacetylisoxazole-5-one also leads to 2-trifiuoro-methyloxazole [38]. 

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